diff --git a/Capstone Course Adrenal Nodule information/Adrenal Incidentaloma Practice Guidelines.pdf_semantic.json b/Capstone Course Adrenal Nodule information/Adrenal Incidentaloma Practice Guidelines.pdf_semantic.json deleted file mode 100644 index d9ba606f02a87f04eb455a54680ea15cda51858a..0000000000000000000000000000000000000000 --- a/Capstone Course Adrenal Nodule information/Adrenal Incidentaloma Practice Guidelines.pdf_semantic.json +++ /dev/null @@ -1,1507 +0,0 @@ -[ - { - "text": "1542 Clinical Pr actice From the Division of General Surgery, Department of Surgery, Stanford University School of Medicine, Stanford, CA.", - "tokenCount": 27, - "pageStart": 1, - "pageEnd": 1, - "hash": "c46323567ec46a950ecb1e8d34f3878e33b6eb5f55286c418738c6a0d925cd71" - }, - { - "text": "Kebebew at the Division of General Surgery, Department of Surgery, Stanford University School of Medicine, 300 Pasteur Dr.", - "tokenCount": 26, - "pageStart": 1, - "pageEnd": 1, - "hash": "f5881b763aaedc4a055490cf33f1a7c4613bb3dfcd955dcadfba25c58d1a53db" - }, - { - "text": ", H3642, Stanford, CA 94305-2200, or at kebebew@ stanford .", - "tokenCount": 24, - "pageStart": 1, - "pageEnd": 1, - "hash": "1476b67b4a3dc37b38ce2e862acaf8e1a7caa9795d58b1aa0858180dd6ca34a1" - }, - { - "text": "1056/NEJMcp2031112 Copyright 2021 Massachusetts Medical Society.", - "tokenCount": 17, - "pageStart": 1, - "pageEnd": 1, - "hash": "5ffe6ec7d95d09949e7d72bb5873501a887d04add228af92264ebba0a4c53127" - }, - { - "text": "A 42-yearold woman has been in a motor vehicle accident in which her seat belt tightened.", - "tokenCount": 20, - "pageStart": 1, - "pageEnd": 1, - "hash": "b48048454911f917c81b7b512a714e07721109aaca0129a0119c1464ab63991a" - }, - { - "text": "She has upper abdominal pain and is evaluated with computed tomography (CT).", - "tokenCount": 15, - "pageStart": 1, - "pageEnd": 1, - "hash": "8d711ab367d67cecf52846990a1f30b4d5413aa529d40671702734909419ea61" - }, - { - "text": "This imaging shows no evidence of intraabdominal trauma but reveals a wellcircumscribed and homogeneous left adrenal mass that is 3.", - "tokenCount": 29, - "pageStart": 1, - "pageEnd": 1, - "hash": "588e54acf468bf2ae12a0dfe5f773b4a4bcf8dc3a2e3d3e0be2c10139fc9848d" - }, - { - "text": "The mass has an attenuation value of 7 Hounsf ield units on unenhanced CT.", - "tokenCount": 21, - "pageStart": 1, - "pageEnd": 1, - "hash": "fe447d6890b76f9143085902b13bd400154f9f0f0dca4c8eebf82937e060601b" - }, - { - "text": "The patients history is remarkable for obesity and newly diagnosed mild hypertension.", - "tokenCount": 13, - "pageStart": 1, - "pageEnd": 1, - "hash": "71443fc90cd791670bf20da8700601ba055b13bb82770094676484c9c0e6c29c" - }, - { - "text": "On physical examination, the blood pressure is 142/90 mm Hg.", - "tokenCount": 15, - "pageStart": 1, - "pageEnd": 1, - "hash": "ff6b699da8c612eb8c262a4385925f63d7dbd99f5cd588eef712a08e803c682a" - }, - { - "text": "There is sternal and upper abdominal bruising but no striae, moon facies, or fat accumulation over the dorsocervical spine (buffalo hump).", - "tokenCount": 32, - "pageStart": 1, - "pageEnd": 1, - "hash": "cb227476ed01dbcba1be2a33774c473f0d53e8f5d6ad5732cac84f338ecf8f65" - }, - { - "text": "How should this patient be further evaluated and treated?", - "tokenCount": 10, - "pageStart": 1, - "pageEnd": 1, - "hash": "f84ad05c42669ce8b03569104ce9a3341ac2d891682b5e573d06a0ec88a33b4f" - }, - { - "text": "The Clinical Problem A drenal incidentaloma is defined as a clinically unapparent adrenal lesion (1 cm in diameter) that is detected on imaging performed for indications other than evaluation for adrenal disease.", - "tokenCount": 43, - "pageStart": 1, - "pageEnd": 1, - "hash": "129563aef529c74710432a379ef51da9667d4ef52f0ad916a5997b48a1f343f1" - }, - { - "text": "1 This definition excludes patients who are undergoing screening and surveillance because of hereditary syndromes or those with known extraadrenal cancer who are undergoing imaging for staging or during followup after treatment.", - "tokenCount": 39, - "pageStart": 1, - "pageEnd": 1, - "hash": "7d0272e30fefbdcf77dabaf2410e475ae9c85983f1a75bfbff2b30a4a121e38d" - }, - { - "text": "Among adults, the prevalence of adrenal incidentaloma has been reported to be 1 to 6%, 2,3 and the prevalence has increased with the growing use of and technological advances in imaging and with the aging of the population.", - "tokenCount": 45, - "pageStart": 1, - "pageEnd": 1, - "hash": "7a0fb64ac0e0b759ab5f566ca4fab0dd16bbaf10ec319df7554182245e09e425" - }, - { - "text": "4,5 The prevalence is higher among older adults, with a peak (7%) in the fifth to seventh decades.", - "tokenCount": 24, - "pageStart": 1, - "pageEnd": 1, - "hash": "240b8c565814751025712482a940e3f299ea7fe064e7ab293465b6e71df926f1" - }, - { - "text": "3 Most adrenal incidentalomas are nonfunctioning benign tumors; 75% are nonfunctioning cortical adenomas.", - "tokenCount": 24, - "pageStart": 1, - "pageEnd": 1, - "hash": "5fba47e93b58a141b12d2c3196fe7f230950e2109a19df3bba3517aa2f20aa65" - }, - { - "text": "6-9 However, there are important clinical consequences in a subset of these masses.", - "tokenCount": 17, - "pageStart": 1, - "pageEnd": 1, - "hash": "33268aeabaf57bc0cf4f07617c5a022e83c036739254b18acd8731e06f515460" - }, - { - "text": "For example, approximately 14% of adrenal incidentalomas are functional tumors that secrete excess cortisol, aldosterone, or (rarely) both.", - "tokenCount": 31, - "pageStart": 1, - "pageEnd": 1, - "hash": "32860386be3db61effa09e975b2f5f75744fb1ddb738e0a7245d6ed599937466" - }, - { - "text": "Other masses with clinical significance are pheochromocytomas (approximately 7%) and primary adrenal cancers or metastases to the adrenal glands (approximately 4%).", - "tokenCount": 34, - "pageStart": 1, - "pageEnd": 1, - "hash": "e79466b9e4a5142f56daaf8036fbac7b28867978530415e4842c79fc6d4da7b5" - }, - { - "text": "6-9 When an adrenal mass is incidentally identified, the key clinical questions are whether it is functioning and whether it is malignant.", - "tokenCount": 28, - "pageStart": 1, - "pageEnd": 1, - "hash": "f47d72baa51a07277c00f419f441dfd8ef5daba3045ad00a870dafbdbeb6af4d" - }, - { - "text": "These determinations are guided by clinical and radiographic features and biochemical assessments.", - "tokenCount": 15, - "pageStart": 1, - "pageEnd": 1, - "hash": "3761e81d2ccab8b7ca6c992a803ca4be43431fbeaa46d6bd58cd28d0d8674291" - }, - { - "text": "Str ategies and Evidence In the absence of randomized, controlled trials in which various approaches to evaluation are compared, the workup is guided by data from prospective and retrospective observational studies.", - "tokenCount": 37, - "pageStart": 1, - "pageEnd": 1, - "hash": "3dd2899a6aeca0bd6473206923e296ed462c37847dcc12df591aa854a67b8e75" - }, - { - "text": "A careful history taking and physical examination Caren G.", - "tokenCount": 11, - "pageStart": 1, - "pageEnd": 1, - "hash": "4a4d753ea4172db18a14b0b67a22a027894696d726bb108b2a155b548ad49055" - }, - { - "text": ", Editor Adrenal Incidentaloma Electron Kebebew, M.", - "tokenCount": 16, - "pageStart": 1, - "pageEnd": 1, - "hash": "2fec31e96ea6efc2af26299f3b3cb0aa1488ce00147c45c7c07b07ce586c93c3" - }, - { - "text": "This Journal feature begins with a case vignette highlighting a common clinical problem.", - "tokenCount": 16, - "pageStart": 1, - "pageEnd": 1, - "hash": "95d62c8a8d9bcebed9fe49a2cbc8d91b5b2517f8870213e1d087001f61e54ca0" - }, - { - "text": "Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist.", - "tokenCount": 20, - "pageStart": 1, - "pageEnd": 1, - "hash": "6c9634b4813b53ea28834a4827c5853b5be1f7f25eb116b55f369d25978eb404" - }, - { - "text": "An audio version of this article is available at NEJM.", - "tokenCount": 12, - "pageStart": 1, - "pageEnd": 1, - "hash": "7e541e7df0b3b1c8a5c3c617613e4b4e8d69ed35b0c1789fadac832e103197ce" - }, - { - "text": "All rights reserved, including those for text and data mining, AI training, and similar technologies.", - "tokenCount": 19, - "pageStart": 1, - "pageEnd": 1, - "hash": "91d5195352a80c18dd1684b75b4fa68010fdd3834aa9434004acea46388b39df" - }, - { - "text": "Clinical Pr actice 1543 focusing on signs and symptoms that may be associated with hormonal hypersecretion or cancer are essential (Fig.", - "tokenCount": 28, - "pageStart": 2, - "pageEnd": 2, - "hash": "55938d008cc6398f7e2dfaf054ff8b1fedef4dbd648582e8d9c68c96dc03e78e" - }, - { - "text": "1, and Table S1 in the Supplementary Appendix, available with the full text of this article at NEJM.", - "tokenCount": 23, - "pageStart": 2, - "pageEnd": 2, - "hash": "4adc667d5d63e7ec74243778b824149a2d739b4feac73a2c89ef83063dbb04c6" - }, - { - "text": "Hormonal Evaluation Mild Autonomous Cortisol Excess Abnormal cortisol secretion that is independent of normal hypothalamicpituitary control in the absence of overt clinical signs of Cushings syndrome is called mild autonomous cortisol excess (also known as subclinical Cushings syndrome).", - "tokenCount": 54, - "pageStart": 2, - "pageEnd": 2, - "hash": "8d8b7bf2747e00edaf43dd305172f2bde476dd464c5d8133bc3781110a489ee8" - }, - { - "text": "A careful history taking and physical examination should focus on determining whether the patient has had recent weight gain or has a history of easy bruising, general weakness, poor wound healing, or decreases in memory and cognitive function.", - "tokenCount": 42, - "pageStart": 2, - "pageEnd": 2, - "hash": "74207f2711770584ba6e39ffb5a044793b892e4d3911057401c9ab8ac9699157" - }, - { - "text": "The patient should also be evaluated for the presence of central obesity, purple striae, facial rounding and plethora, supraclavicular and dorsocervical fat pads, acne, and hirsutism.", - "tokenCount": 43, - "pageStart": 2, - "pageEnd": 2, - "hash": "dd2c2e7d6910fb1c858bffc49d5dbe235b898a510cfbaaf55f8fef84c85d7205" - }, - { - "text": "Mild autonomous cortisol excess, the most common functional disorder detected in patients with adrenal incidentaloma, occurs in approximately 10% of such patients (range, 1 to 29), depending on the diagnostic criteria used and the population studied. 3,6 ,7,9 Patients with mild autonomous cortisol excess have a higher incidence of coexisting conditions such as hypertension, obesity, glucose intolerance or type 2 diabetes mellitus, dyslipidemia, and osteopenia or osteoporosis than patients with nonfunctioning adrenal tumors.", - "tokenCount": 106, - "pageStart": 2, - "pageEnd": 2, - "hash": "4a89f7f8e996d92041f3230386063f5bab64af3dead3aa44e0057605db3df0d4" - }, - { - "text": "10 An overnight dexamethasone (1 mg) suppression test should be performed in all patients with adrenal incidentaloma (Table 1).", - "tokenCount": 29, - "pageStart": 2, - "pageEnd": 2, - "hash": "beaf26159318a4e5c5d826d98ddd4140bbffbebdec71598e4fe188da5a635bd4" - }, - { - "text": "The most appropriate cutoff value for the morning serum cortisol level to make a diagnosis of mild autonomous cortisol excess is controversial.", - "tokenCount": 23, - "pageStart": 2, - "pageEnd": 2, - "hash": "0b575dfcd68a44ddf92d68abef6c1f8369420e2cbfd1b2d874c36fbc737ce453" - }, - { - "text": "8 g per deciliter (>50 nmol per liter) has high sensitivity (95 to 100%) but low specificity (60 to 80%), whereas a level of more than 5. 0 g per deciliter (>138 nmol per liter) has lower sensitivity (86%) but higher specificity (92 to 97%).", - "tokenCount": 64, - "pageStart": 2, - "pageEnd": 2, - "hash": "1c9df1532d16d69aff01e197a9faa00856b314d6a751a3ebdbe0d958b2981c6c" - }, - { - "text": "3,7,11-1 3 Additional findings on biochemical tests (e.", - "tokenCount": 16, - "pageStart": 2, - "pageEnd": 2, - "hash": "0871297938122e384e3720d73ee1fae987b303a16b021746a6c65207cf38c9ac" - }, - { - "text": ", a low corticotropin level, an elevated 24-hour urinary cortisol level, a high latenight salivary cortisol level, and a low dehydroepiandrosterone sulfate level) may help to confirm the diagnosis and magnitude of cortisol excess (Table 1).", - "tokenCount": 58, - "pageStart": 2, - "pageEnd": 2, - "hash": "9f1916911041dc1b20a1175a3c195cde8471761bb047ca790ccf2d3d8cc2a0b8" - }, - { - "text": "14 In a metaanalysis assessing outcomes in 4121 patients with adrenal incidentalomas that were either nonfunctioning or were causing mild autonomous cortisol excess, the risk of progression to overt Cushings syndrome was low (<0.", - "tokenCount": 45, - "pageStart": 2, - "pageEnd": 2, - "hash": "b2065eca84694cf85f30f12f9ba799d474d42fa0b777dd6b5f9b80bb0ef49a24" - }, - { - "text": "1%) in both groups during a mean followup of 50.", - "tokenCount": 13, - "pageStart": 2, - "pageEnd": 2, - "hash": "e62ae774ca4583bc65c86b26c514f420a449033eb78805ee9a29f27efe6702be" - }, - { - "text": "15 Furthermore, mild autonomous cortisol excess developed in only 4.", - "tokenCount": 12, - "pageStart": 2, - "pageEnd": 2, - "hash": "48de180897e411dc64dca02c25c50c4be9af91cf79580b1fe688dc604e8d9767" - }, - { - "text": "3% of the patients with nonfunctioning tumors, and fewer than 0.", - "tokenCount": 16, - "pageStart": 2, - "pageEnd": 2, - "hash": "f5c514386ec4f7faa6afb52991f55d701d2de5f801abe385a2e81211dd1d1f42" - }, - { - "text": "1% of the patients with mild autonomous cortisol excess had spontaneous resolution during followup.", - "tokenCount": 17, - "pageStart": 2, - "pageEnd": 2, - "hash": "20211479969cfa8625b24340e523f5815268ac4210a8ddfa166dce140bf665fa" - }, - { - "text": "The prevalence of type 2 diabetes mellitus, hypertension, obesity, dyslipidemia, Key Clinical Points Adrenal Incidentaloma All patients with an adrenal mass that is discovered during diagnostic testing for another condition (an incidentaloma) should undergo biochemical testing to detect pheochromocytoma and excess cortisol secretion, and those who also have high blood pressure should undergo biochemical testing to detect primary hyperaldosteronism.", - "tokenCount": 87, - "pageStart": 2, - "pageEnd": 2, - "hash": "037d2efedc875095ac69c51aa19fee23931cff106535c3f25e73d28308590c0b" - }, - { - "text": "Patients with pheochromocytoma should undergo adrenalectomy after adequate presurgical alphablockade and betablockade, if necessary.", - "tokenCount": 33, - "pageStart": 2, - "pageEnd": 2, - "hash": "c258e08a75d51f270aca7711b277f6478c58b56a132ee69a9a84c3cc4fa37651" - }, - { - "text": "Patients with mild autonomous cortisol excess and primary hyperaldosteronism may benefit from adrenalectomy, but treatment should be individualized.", - "tokenCount": 28, - "pageStart": 2, - "pageEnd": 2, - "hash": "63066288bcd17f9e785c3e7fdd5e98c47bbe942a901adad7bd7768789af657a1" - }, - { - "text": "Nonfunctioning adrenal tumors that have an attenuation of 10 Hounsfield units or less on computed tomographic (CT) evaluation and that are smaller than 4 cm in greatest diameter generally do not warrant intervention or longterm followup.", - "tokenCount": 49, - "pageStart": 2, - "pageEnd": 2, - "hash": "4276df32758f7c143e13e506e69151fbc7fbf55bbab26b3dacc14c739df41285" - }, - { - "text": "All other adrenal incidentalomas with indeterminate features on imaging may warrant additional imaging with contrastenhanced CT, magnetic resonance imaging with chemicalshift analysis, positronemission tomographyCT with 18 Ffluorodeoxyglucose, or all of these tests.", - "tokenCount": 55, - "pageStart": 2, - "pageEnd": 2, - "hash": "51bd907f1f5e5003a304e155f2450f4e2460331fe4a11103597295255b494315" - }, - { - "text": "The management of these masses should be individualized and should involve a multidisciplinary team consisting of an endocrinologist, an endocrine surgeon, and a radiologist.", - "tokenCount": 34, - "pageStart": 2, - "pageEnd": 2, - "hash": "ecfbee70cc969c1db50da99dc1580aee9f9c29d560e1928e68676f635c4c30e4" - }, - { - "text": "Biochemical Evaluation in Patients with Adrenal Incidentaloma.", - "tokenCount": 12, - "pageStart": 4, - "pageEnd": 4, - "hash": "508e06afb4baef520bf7e7b38cb167837cddcb3e67ea688de56f2caf8007e7a7" - }, - { - "text": "* Clinical Diagnosis Screening Test Additional or Confirmatory Test Common Causes of False Positive or False Negative Findings Special Considerations Mild autonomous cortisol excess Overnight dexamethasone (1 mg) suppression test; an abnormal result is a serum cortisol level >1.", - "tokenCount": 55, - "pageStart": 4, - "pageEnd": 4, - "hash": "ef35a9c9cbcddc459d39f7c55a5374572530951614085d07c4c19b8408bee093" - }, - { - "text": "8 g per deciliter (50 nmol per liter) with confirmation of serum dexamethasone level (to ensure adherence); a higher serum cortisol cutoff level (e.", - "tokenCount": 37, - "pageStart": 4, - "pageEnd": 4, - "hash": "b6179874f5be669d1fd490b3fec50a2eb17b8c723e14e40bb14c8294aa6d0ab9" - }, - { - "text": ", 35 g per deciliter) can be used to reduce the risk of a false positive Measurement of levels of morning serum corticotropin and cortisol levels, 24-hr urinary cortisol, latenight salivary cortisol, midnight serum cortisol, and DHEAS False positives may occur in patients receiving medications that accelerate hepatic metabolism of dexamethasone and with nonadherence to dexamethasone Consider a pseudoCushings syndrome state due to diabetes, obesity, pregnancy, alcoholism, psychiatric disorders, or stress Pheochromocytoma Measurement of levels of plasmafree metanephrines or 24-hr urinary fractionated metanephrines Not applicable False positives may occur in patients with stress and illness warranting hospitalization; with medications that increase levels of endogenous catecholamines; with excessive caffeine; and with recreational drug use (e.", - "tokenCount": 183, - "pageStart": 4, - "pageEnd": 4, - "hash": "73dbfc4b18aeafb0dc6a47f3fe4380167ed43f79975e8511a003cd4422df6f6f" - }, - { - "text": ", amphetamines) Biochemical testing may not be necessary if the adrenal mass has CT attenuation of 10 Hounsfield units; genetic testing for inherited syndrome should be performed, regardless of family history, if screening test is positive Primary hyperaldosteronism Measurement of midmorning plasma aldosterone concentration and plasma renin activity; a ratio of plasma aldosterone concentration to plasma renin activity >20 confirms diagnosis If the ratio of plasma aldosterone concentration to plasma renin activity <20, confirmatory testing includes 24-hr urinary aldosterone excretion test with patient receiving highsodium diet, aldosterone suppression test, and testing with saline infusion while patient is sitting False positives can be caused by betablockers, methyldopa, clonidine, nonsteroidal antiinflammatory drugs, and oral contraceptives and estrogen; false negatives can be caused by angiotensinconvertingenzyme inhibitors, angiotensin II receptor blockers, and potassiumsparing diuretics (e.", - "tokenCount": 207, - "pageStart": 4, - "pageEnd": 4, - "hash": "75ebbc599ce2ff74585f0e5664cc78a252f5e738a99e1841c7dcd91ffa8af303" - }, - { - "text": ", spironolactone, eplerenone, and amiloride) If patient is a candidate for adrenalectomy and >35 yr of age, adrenal venous sampling is recommended to confirm lateralization of aldosterone to the side of the adrenal mass (some patients have bilateral aldosterone hypersecretion, or the contralateral adrenal gland may be the source of excess aldosterone and the tumor detected is nonfunctioning) * Reference ranges for specific assays based on age and sex should be used and may differ from the ranges shown here.", - "tokenCount": 119, - "pageStart": 4, - "pageEnd": 4, - "hash": "b243d5aa4c090744d89c9c0d59291d02129be2c4fe78ee5f3618f968a4ce0855" - }, - { - "text": "DHEAS denotes dehydroepiandrosterone sulfate.", - "tokenCount": 14, - "pageStart": 4, - "pageEnd": 4, - "hash": "1cc58631c479426fc29b0f8ef2ae0eee7e08aa0c7af5809ff6334d375edb7b09" - }, - { - "text": "Additional laboratory tests may include measurement of plasma chromogranin A levels, 24-hour urinary 3-methoxytyramine levels, or both, especially when a malignant pheochromocytoma is suspected because of the presence of potential metastatic disease sites or local invasion.", - "tokenCount": 60, - "pageStart": 4, - "pageEnd": 4, - "hash": "eb5380637e125702d0991bd95e6f90658e470653fea4ee2dc24b774a121e144c" - }, - { - "text": "Clinical Pr actice Primary Hyperaldosteronism Among patients with adrenal incidentaloma, primary hyperaldosteronism is less common than mild autonomous cortisol excess and pheochromocytoma; primary hyperaldosteronism accounts for 1.", - "tokenCount": 52, - "pageStart": 6, - "pageEnd": 6, - "hash": "50b750a609e10855e968504085ae93c82254d80ebc5c0c1f41d54780ba383eb1" - }, - { - "text": "9 However, any patient with adrenal incidentaloma and hypertension or hypokalemia should be screened for primary hyperaldosteronism with measurement of the midmorning plasma aldosterone concentration and plasma renin activity; patients should not be taking medications that could cause false positive or false negative results (Table 1).", - "tokenCount": 63, - "pageStart": 6, - "pageEnd": 6, - "hash": "2c75d3ddbc60ea2370a8aab4032c76007558546d2d7bf7dba79a8c1d55651394" - }, - { - "text": "31 Although studies have used various cutoff values to identify hyperaldosteronism, a ratio of the plasma aldosterone concentration to plasma renin activity that is higher than 20 is considered to be a reliable indicator of the diagnosis; if the ratio is high but below this level, confirmatory testing is recommended (Table 1).", - "tokenCount": 65, - "pageStart": 6, - "pageEnd": 6, - "hash": "d0802ef45a7998a085d13d19cf4b0ddd8b2a1aad254f46acb8c951ddefa7432f" - }, - { - "text": "31,32 Once the diagnosis is established, patientspecific factors guide decisions regarding medical versus surgical therapy (Fig.", - "tokenCount": 23, - "pageStart": 6, - "pageEnd": 6, - "hash": "b00d996c477840f784d66e0719fb21796ca449823fd6d6a33b64e469a1203f57" - }, - { - "text": "Additional Hormonal Secretion It is extremely rare for patients with adrenal incidentaloma to have sex hormone (estrogen or testosterone)secreting tumors without appreciable clinical manifestations.", - "tokenCount": 36, - "pageStart": 6, - "pageEnd": 6, - "hash": "b43028e13f4e35a8a71f32ce63833721eeae6fef26829890bf67837515955faf" - }, - { - "text": "In women, excess testosterone is associated with features of virilization such as facial hair growth, acne, and deepening of the voice, and excess estrogen is associated with irregular uterine bleeding and breast tenderness.", - "tokenCount": 42, - "pageStart": 6, - "pageEnd": 6, - "hash": "d76616e6a6648e1813d414cf96d48465631f0a9b12fcdc14f16ba5b931268581" - }, - { - "text": "In men, estrogensecreting tumors can cause gynecomastia, testicular atrophy, and decreased libido.", - "tokenCount": 27, - "pageStart": 6, - "pageEnd": 6, - "hash": "e565eeba9d6e10fd6ed93d0483706c3ed2a3814cf6b6f6e3d4f0fe2e7d4c2b89" - }, - { - "text": "Assessment for Cancer An adrenal incidentaloma may be a primary malignant tumor that has arisen from the adrenal cortex (adrenocortical carcinoma) or medulla (pheochromocytoma), or, rarely, a metastatic tumor.", - "tokenCount": 53, - "pageStart": 6, - "pageEnd": 6, - "hash": "7c42912cdc234a9486884055175f19f22ce40200c1bbc5c6dc16f52af5d5d181" - }, - { - "text": "Adrenocortical carcinoma, which accounts for 1.", - "tokenCount": 13, - "pageStart": 6, - "pageEnd": 6, - "hash": "1d8abb801411b6c03f7ca1ae68b6733fd12f00974b1f6f78fb6142b841c8d3a5" - }, - { - "text": "0% of adrenal incidentalomas, 9 depending on the study population, may secrete excess hormones or be nonfunctioning.", - "tokenCount": 26, - "pageStart": 6, - "pageEnd": 6, - "hash": "cf2d88644e12a66a29bcf8f020257a343254aa0d943a5e0d378238872742617c" - }, - { - "text": "Up to 21% of adrenal incidentalomas in patients with a history of or known current primary cancer indicate adrenal metastasis.", - "tokenCount": 26, - "pageStart": 6, - "pageEnd": 6, - "hash": "e46b91b4e6895400f0dfadeedc1d7f2315bdc1f512be88e9df799d1da82c82de" - }, - { - "text": "9,33 Cancers that are most likely to spread to the adrenal glands are lung cancer, gastrointestinal cancer, melanoma, and renalcell carcinoma.", - "tokenCount": 32, - "pageStart": 6, - "pageEnd": 6, - "hash": "cdb88d691f3f4616d59d5cc9de3b95ea248abd63c8e5beb6d30c899a7509eb86" - }, - { - "text": "33 Tumor size and imaging features are key to determining the likelihood of cancer and guiding treatment (Table 2 and Figs.", - "tokenCount": 26, - "pageStart": 6, - "pageEnd": 6, - "hash": "c08e19f702e8345f32c900fb806342d5b96ccfbd6301960ae3547b3d3a814f3b" - }, - { - "text": "Tumor Size Although many studies of the risks of cancer associated with tumor size are limited by small samples, retrospective design, and selection bias, data consistently support associations between tumors that are larger than 4 cm in greatest diameter and an increased risk of cancer among patients with a unilateral adrenal mass (Table 2).", - "tokenCount": 62, - "pageStart": 6, - "pageEnd": 6, - "hash": "7d58f2eb2fe68c461066e37b3b3fb60ea6389f76d69c2f073453d9ae424237d4" - }, - { - "text": "35,36 The risk of adrenocortical carcinoma is less than 2% among patients with tumors smaller than 4 cm in diameter, 6% among those with tumors between 4 cm and 6 cm in diameter, and 25% or higher among those with tumors that are at least 6 cm in diameter.", - "tokenCount": 61, - "pageStart": 6, - "pageEnd": 6, - "hash": "2f0f89aaef0e9118976d43bac2754fbf9fe22815e4aeee772eddd628857e3e3e" - }, - { - "text": "35 However, patient age is an important factor in estimating cancer risk; because benign incidentalomas are uncommon in patients younger than 40 years of age, cancer is a concern even with smaller tumors (<4 cm in diameter) in this age group.", - "tokenCount": 48, - "pageStart": 6, - "pageEnd": 6, - "hash": "3140bac464019b4db4c3a3b3d15b982741bc1d59198f197736416b62fcfe7984" - }, - { - "text": "It is important to measure the adrenal tumor in three dimensions (the greatest length, width, and height) because twodimensional (crosssectional) measurements often underestimate size.", - "tokenCount": 35, - "pageStart": 6, - "pageEnd": 6, - "hash": "8623168e45e938efcfec3f9f91375804d96f619940b85fc8a6026442c987cf80" - }, - { - "text": "Imaging Features Suggestive of Cancer On CT imaging, features other than tumor size can help to differentiate benign from malignant adrenal incidentalomas, although the ultimate diagnosis is based on histologic findings or clinical followup.", - "tokenCount": 44, - "pageStart": 6, - "pageEnd": 6, - "hash": "33565c69828bc7641933237133e95078138b330e9cb68da54048938bd2e8969b" - }, - { - "text": "34,37 Irregular tumor margins, heterogeneity, necrosis, vascularity, and calcification are features that arouse suspicion for cancer (Table 2).", - "tokenCount": 31, - "pageStart": 6, - "pageEnd": 6, - "hash": "9db7fcf402df44aff57928722748c0eb7ac88de0e35b351922dde17a1aee3249" - }, - { - "text": "An attenuation of 10 Hounsfield units or less on unenhanced CT is consistent with a benign lesion; in a series of 1161 adrenal tumors with an attenuation of 10 Hounsfield units or less, no malignant tumors were observed.", - "tokenCount": 55, - "pageStart": 6, - "pageEnd": 6, - "hash": "9df2cb7ae22bea6753a866498d0766ca2bac77c6dd76ece34e1f14236825a7dd" - }, - { - "text": "38 In patients who have incidentalomas with an attenuation of more than 10 Hounsfield units, followup imaging may include contrastenhanced CT (to measure the percentage of washout of contrast medium at various times), MRI with chemicalshift analysis, or positronemission tomography (PET)CT with 18 Ff luorodeoxyglucose ( 18 FFDG).", - "tokenCount": 80, - "pageStart": 6, - "pageEnd": 6, - "hash": "104e512c72d693ff1ae567a6cef3921d08361c120514c2913cb26efb8ef4e07c" - }, - { - "text": "On contrastenhanced CT, adenomas commonly enhance more rapidly and have faster washout of intravenous contrast medium when .", - "tokenCount": 25, - "pageStart": 6, - "pageEnd": 6, - "hash": "d636990ecf83965bb8dd81393647d86be3eb93e751e22915810a445dacd18866" - }, - { - "text": "Clinical Pr actice measured at 60 to 90 seconds (early enhancement) and at 10 to 15 minutes (delayed enhancement) after the administration of contrast medium than adrenocortical carcinomas.", - "tokenCount": 40, - "pageStart": 8, - "pageEnd": 8, - "hash": "eb584a74724f4b5a3df23716d4c5dc7da1c3e693112e5af3be73c84bcba620c2" - }, - { - "text": "Absolute washout is defined as the attenuation value in Hounsfield units on early enhanced CT minus Hounsfield units on delayed CT, divided by Hounsfield units on early enhanced CT minus Hounsfield units on unenhanced CT, multiplied by 100%, and relative washout is defined as Hounsfield units on early enhanced CT minus Hounsfield units on delayed CT, divided by Hounsfield units on enhanced CT, multiplied by 100%.", - "tokenCount": 99, - "pageStart": 8, - "pageEnd": 8, - "hash": "03c5be6a10e42081da35f455a424460e3f695a62593bb17a8e6fd452a7013cc7" - }, - { - "text": "Absolute washout of more than 60% of the contrast medium and relative washout of more than 40% of the contrast medium are suggestive of an adenoma, but the sensitivities and specificities of these cutoff values vary across studies owing to variations in technique and timing of measurement of washout.", - "tokenCount": 61, - "pageStart": 8, - "pageEnd": 8, - "hash": "c9b825a6ecde711e23d3f001f7759928f0065c635073ae3f062c583a7a1ff8cb" - }, - { - "text": "34 MRI with chemicalshift analysis, which assesses qualitative loss of signal intensity, quantitative loss of signal intensity, or both between inphase and outofphase imaging, is especially useful to avoid radiation exposure in pregnant women and children and in patients who are allergic to iodinated contrast medium.", - "tokenCount": 57, - "pageStart": 8, - "pageEnd": 8, - "hash": "d91981e8c8eedc0f299388cc7da55a752e2b116254053ff23fc5c8231406b661" - }, - { - "text": "In a systematic review, qualitative (visual) analysis of the adrenal signalintensity index and quantitative assessment of the adrenaltospleen ratio (i.", - "tokenCount": 31, - "pageStart": 8, - "pageEnd": 8, - "hash": "8ff2987acb908a139897242183f83ac7fc5898094dba8e6435569bc631c09244" - }, - { - "text": ", the signal intensity of the adrenal mass divided by the signal intensity of the spleen) both had high accuracy (pooled sensitivities and specificities, 94% and 95%, respectively) for identifying adenomas.", - "tokenCount": 45, - "pageStart": 8, - "pageEnd": 8, - "hash": "bc485233a712199916284e5df82db2a431772299d306d9cec836011ae9b646d7" - }, - { - "text": "37 In a metaanalysis of 29 studies, findings on 18 FFDG PETCT adrenal imaging that determined the maximum standardized uptake value and the ratio of the maximum standardized uptake value in the adrenal tumor as compared with the spleen or liver effectively distinguished benign from malignant tumors (pooled sensitivities, 85 to 91%, and pooled specificities, 89 to 91%).", - "tokenCount": 75, - "pageStart": 8, - "pageEnd": 8, - "hash": "39360d97d515ab6f0e0c305d0905796988926ad1d167b4df9d004afba5750b50" - }, - { - "text": "39 Adrenal Biopsy Biopsy of an adrenal incidentaloma is rarely indicated, 33 since it has low accuracy for distinguishing benign from malignant adrenal tumors and may lead to tumor seeding if the mass is an adrenocortical carcinoma.", - "tokenCount": 51, - "pageStart": 8, - "pageEnd": 8, - "hash": "186a1b6e4be991b388de4a4675e0e89455e39a421f2e58cc28f09948846c741d" - }, - { - "text": "An exception is the rare case in which adrenal metastasis is strongly suspected and biopsy confirmation would change the treatment plan; in such cases, biochemical testing to exclude a pheochromocytoma should be performed first to avoid precipitation of a hyperadrenergic crisis by biopsy.", - "tokenCount": 59, - "pageStart": 8, - "pageEnd": 8, - "hash": "3bb6310eff2aeb501d23de42ce58e38fa2e173a306b5f74fc9eace98172c99c4" - }, - { - "text": "Assessment of Bilateral Adrenal Masses Approximately 15% of patients with adrenal incidentaloma have bilateral adrenal masses.", - "tokenCount": 25, - "pageStart": 8, - "pageEnd": 8, - "hash": "b2f1dc4945c74f92b509b0ed8cacd7b6e819e68377fbae39c33415c8e1543161" - }, - { - "text": "40 The differential diagnosis of bilateral adrenal masses includes primary bilateral macronodular adrenal hyperplasia and adenomas, bilateral pheochromocytomas, congenital adrenal hyperplasia, bilateral adrenal hyperplasia due to Cushings disease or ectopic corticotropin secretion, metastases or primary cancers, myelolipomas, infections, hemorrhage, and partial glucocorticoid resistance.", - "tokenCount": 90, - "pageStart": 8, - "pageEnd": 8, - "hash": "1c28cff0ab0610fcea2c8f2179b37eb81dc507855181f65968952741607c15ea" - }, - { - "text": "In addition to the hormonal assessments described for a solitary adrenal incidentaloma, measurement of the serum 17-hydroxyprogesterone level is indicated to rule out congenital adrenal hyperplasia.", - "tokenCount": 41, - "pageStart": 8, - "pageEnd": 8, - "hash": "c79bca7860e28331b58b9907ee42ba21336ba4138518e73c947949947233907e" - }, - { - "text": "41 In addition, if bilateral adrenal masses appear on imaging to be hemorrhagic or infiltrative, the patient should undergo testing for adrenal insufficiency.", - "tokenCount": 32, - "pageStart": 8, - "pageEnd": 8, - "hash": "bfb74c998253acb91cfda0d304c9d8fcefa3804bf0f1acf54f5fd99bcbb8b8a2" - }, - { - "text": "In patients with bilateral adrenal masses, the imaging characteristics of each adrenal lesion should be evaluated independently in determining appropriate management.", - "tokenCount": 26, - "pageStart": 8, - "pageEnd": 8, - "hash": "42f709b7861000a4567f8350465df39d115cc6358f21163b78fb90525ebee87e" - }, - { - "text": "Followup in Patients with Nonfunctioning Lesions Nonfunctioning adrenal incidentalomas with features that are consistent with an adenoma on imaging (10 Hounsfield units) and that are smaller than 4 cm in greatest diameter usually have a benign course and do not warrant additional followup imaging.", - "tokenCount": 61, - "pageStart": 8, - "pageEnd": 8, - "hash": "5f6997a12601f82c5beb80c70528651a00c231787d3554506dffaf3e3bd26907" - }, - { - "text": "In a metaanalysis involving 4121 patients with nonfunctioning adrenal lesions, the mean tumor growth was 2 mm over a median of 52.", - "tokenCount": 29, - "pageStart": 8, - "pageEnd": 8, - "hash": "590622f8cd80427583c3406062610e57e5a0ebcbe6908d1c937c7dbc5885dc69" - }, - { - "text": "5% of the patients had tumor enlargement of 1 cm or more, and adrenocortical carcinoma did not develop in any of the patients.", - "tokenCount": 31, - "pageStart": 8, - "pageEnd": 8, - "hash": "e17758ff8f482ad77f9f6c1d8c9dfa913a3c0245fc7d42a4dcb1962b1e89043e" - }, - { - "text": "15 Followup with imaging and biochemical tests is recommended for patients with nonfunctioning tumors with indeterminate features on imaging.", - "tokenCount": 25, - "pageStart": 8, - "pageEnd": 8, - "hash": "597d8441174fc0e396e8308e4ffb5ba7d6a3d541c456a9e645edcafc88a8aab6" - }, - { - "text": "However, the most appropriate time intervals for reassessment are unclear, and they vary among different guidelines.", - 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"hash": "b4b7bcde91420175dd6b1015e48e353a44e28d37a8442938dbc419e2c9f0da3e" - }, - { - "text": "), Milwaukee, Wisconsin 53226; University of Sheffield (J.", - "tokenCount": 13, - "pageStart": 1, - "pageEnd": 1, - "hash": "7034b35018deb1a73ca8a8304627828114e7d4d5b9bbeea79f6efcf3a157b55d" - }, - { - "text": "), Sheffield S102JF, United Kingdom; William Harvey Research Institute, Queen Mary, University of London (M.", - "tokenCount": 24, - "pageStart": 1, - "pageEnd": 1, - "hash": "06f68da4b53d95fa342794b9555d32e73974c0d005bc8fb031c40e9757e9fabc" - }, - { - "text": "), London EC1M6BQ, United Kingdom; University of Birmingham (P.", - "tokenCount": 18, - "pageStart": 1, - "pageEnd": 1, - "hash": "5a4b38cbc23198cc2e5b07e9ed688d7f42286b33bdc647c80c270e67cb44dbd9" - }, - { - "text": "), Birmingham B15 2TT, United Kingdom; and Mayo Clinic (V.", - "tokenCount": 16, - "pageStart": 1, - "pageEnd": 1, - "hash": "0f85360a49c8ab4143fbd8d8461af46159b23c9d72c12a7f25ca622297cd0553" - }, - { - "text": "), Rochester, Minnesota 55905 Cosponsoring Association: European Society of Endocrinology Objective: The objective of the study was to develop clinical practice guidelines for the diagnosis of Cushings syndrome.", - "tokenCount": 40, - "pageStart": 1, - "pageEnd": 1, - "hash": "aa44d693ed64462099a5250f2e17b7fee6e62776cdf11b1bb673acf3e471fc44" - }, - { - "text": "Participants: The Task Force included a chair, selected by the Clinical Guidelines Subcommittee (CGS) of The Endocrine Society, five additional experts, a methodologist, and a medical writer.", - "tokenCount": 39, - "pageStart": 1, - "pageEnd": 1, - "hash": "58753823dff8fea71c3f06461a93a4400e4eceb333985d512029ba4004244765" - }, - { - "text": "The Task Force received no corporate funding or remuneration.", - "tokenCount": 12, - "pageStart": 1, - "pageEnd": 1, - "hash": "921d3800fba0c99e0265545fdf84f835686fa70bf1e57b07441b59a278376db0" - }, - { - "text": "Consensus Process: Consensus was guided by systematic reviews of evidence and discussions.", - "tokenCount": 16, - "pageStart": 1, - "pageEnd": 1, - "hash": "02ea322beb98b42ed053f30175e7ac4268382fa310544e8f49c0a995d7d60904" - }, - { - "text": "The guidelines were reviewed and approved sequentially by The Endocrine Societys CGS and Clinical AffairsCoreCommittee,membersrespondingtoawebposting,andTheEndocrineSocietyCouncil.", - "tokenCount": 41, - "pageStart": 1, - "pageEnd": 1, - "hash": "caa74c453ccee977bd2e0aae017cf76d1b4a79094e750705b00cc904d7dfa75b" - }, - { - "text": "At each stage the Task Force incorporated needed changes in response to written comments.", - "tokenCount": 15, - "pageStart": 1, - "pageEnd": 1, - "hash": "d484232a42b5b55f4f88d6d16ff4ea3b9d07c2d7968770b8091e398bbe527897" - }, - { - "text": "Conclusions: After excluding exogenous glucocorticoid use, we recommend testing for Cushings syndrome in patients with multiple and progressive features compatible with the syndrome, particularly those with a high discriminatory value, and patients with adrenal incidentaloma.", - "tokenCount": 50, - "pageStart": 1, - "pageEnd": 1, - "hash": "6a957f60ac0116ef051727c865a1cd213df31157654c959e765260099e95b6bf" - }, - { - "text": "We recommend initial use of one test with high diagnostic accuracy (urine cortisol, late night salivary cortisol, 1 mg overnight or 2 mg 48-h dexamethasone suppression test).", - "tokenCount": 40, - "pageStart": 1, - "pageEnd": 1, - "hash": "b64e79ac3cdf3812cf26d4f33334a31cf74b99dca051a011c18d431eb5482024" - }, - { - "text": "We recommend that patients with an abnormal result see an endocrinologist and undergo a second test, either one of the above or, in some cases, a serum midnight cortisol or dexamethasoneCRH test.", - "tokenCount": 44, - "pageStart": 1, - "pageEnd": 1, - "hash": "0acca2c1a91cb174c93b126aadf5158d4bcdf3660d437b0da63bbbee1a8b70f4" - }, - { - "text": "Patients with concordant abnormal results should undergo testing for the cause of Cushings syndrome.", - "tokenCount": 20, - "pageStart": 1, - "pageEnd": 1, - "hash": "640c227dc81b32c260ce38a231c87218bf3da9552f911059140fc054cf0505f4" - }, - { - "text": "Patients withconcordantnormalresultsshouldnotundergofurtherevaluation.", - "tokenCount": 20, - "pageStart": 1, - "pageEnd": 1, - "hash": "eecb916550fbe2a478b54b4faac888b5d50033e8c251c929e02457ca20483f8a" - }, - { - "text": "Werecommendadditional testing in patients with discordant results, normal responses suspected of cyclic hypercortisolism, or initially normal responses who accumulate additional features over time.", - "tokenCount": 36, - "pageStart": 1, - "pageEnd": 1, - "hash": "3788e862b42d7aa08eda521eac7a2acb460d087fe435cac695feb39356814413" - }, - { - "text": "( J Clin Endocrinol Metab 93: 15261540,2008) SUMMARY OF RECOMMENDATIONS 3.", - "tokenCount": 28, - "pageStart": 1, - "pageEnd": 1, - "hash": "67366e782bd8475e51bea7943ba82ccc3d8e3fca535f2cded102108366d8f2b0" - }, - { - "text": "0 Diagnosis of Cushings syndrome Who should be tested 3.", - "tokenCount": 14, - "pageStart": 1, - "pageEnd": 1, - "hash": "9d0a9f3536926e5f04f652e6fe0528b6a0bfe2eb32b0da6fd224d53cadc9e99d" - }, - { - "text": "1Werecommendobtainingathoroughdrughistorytoexclude excessive exogenous glucocorticoid exposure leading to iatrogenicCushingssyndromebeforeconductingbiochemicaltesting (1 QQQQ ).", - "tokenCount": 50, - "pageStart": 1, - "pageEnd": 1, - "hash": "003a85cf12b915cde82dba4295f7f19c2c46725111d4956417e5b04ac377dbb3" - }, - { - "text": "2 We recommend testing for Cushings syndrome in the following groups: Patients with unusual features for age ( e.", - "tokenCount": 24, - "pageStart": 1, - "pageEnd": 1, - "hash": "151922c74dd4eacaefc91a5bee950b8dcd14aed271350feb890ccf42c4bcf900" - }, - { - "text": "osteoporosis, hypertension) (Table 1) (1 QQEE ) 0021-972X/08/$15.", - "tokenCount": 29, - "pageStart": 1, - "pageEnd": 1, - "hash": "59c8275d06a807a64806474949e57a4dfc8bd91eab5989f6aef89a4ccd326c0c" - }, - { - "text": "Copyright 2008 by The Endocrine Society doi: 10.", - "tokenCount": 12, - "pageStart": 1, - "pageEnd": 1, - "hash": "f641b58761c57a63121148b23873c37f1348024047a735a8b5328f37fa717a08" - }, - { - "text": "2008-0125 Received January 18,2008.", - "tokenCount": 10, - "pageStart": 1, - "pageEnd": 1, - "hash": "18e189c36bdf5859084a8ee5a5aaa7cf8b543b69083fadfb528c503506cddc74" - }, - { - "text": "First Published Online March 11,2008 Abbreviations: CBG, Cortisolbinding globulin; DST, dexamethasone suppression test; HPA, hypothalamicpituitaryadrenal; 11 -HSD2,11 -hydroxysteroid dehydrogenase type 2; LCMS/MS, tandem mass spectrometry; LDDST, lowdose DST; 17OHCS, 17- hydroxycorticosteroid; SMR, standard mortality ratio; UFC, urine free cortisol.", - "tokenCount": 111, - "pageStart": 1, - "pageEnd": 1, - "hash": "21fb2ce05ac86ab0f3a8c92f1853027c70d57d5c43e453d4696376ddd9e575f9" - }, - { - "text": "SPECIAL FEATURE Clinical Practice Guideline 1526 jcem.", - "tokenCount": 14, - "pageStart": 1, - "pageEnd": 1, - "hash": "8ee043d615f6698c08cc77bd5b8a23a242cd252202b3a92f6c6b3a3b1b381a90" - }, - { - "text": "May 2008,93(5):15261540 Downloaded from https://academic.", - "tokenCount": 19, - "pageStart": 1, - "pageEnd": 1, - "hash": "1a79920e902be81b306f8eba4275a57768a526b49d502563c669822e7a7a6bc3" - }, - { - "text": "Patientswithmultipleandprogressivefeatures,particularly those who are more predictive of Cushings syndrome (Table 1) (1 QQEE ) Children with decreasing height percentile and increasing weight (1 QEEE ) Patients with adrenal incidentaloma compatible with adenoma (1 QEEE ).", - "tokenCount": 61, - "pageStart": 2, - "pageEnd": 2, - "hash": "3b7a6be00f71a65c62830844afc23bab6efe80d7f741613f3364b0baff152c8b" - }, - { - "text": "3 We recommend against widespread testing for Cushings syndrome in any other patient group (1 QEEE ).", - "tokenCount": 21, - "pageStart": 2, - "pageEnd": 2, - "hash": "5c61abc44200b7e197f4e2a1eb0f43d4367c3b79061d98172159ff1e6e1f9469" - }, - { - "text": "4 For the initial testing for Cushings syndrome, we recommendoneofthefollowingtestsbasedonitssuitabilityforagiven patient (Fig.", - "tokenCount": 32, - "pageStart": 2, - "pageEnd": 2, - "hash": "185627e3767044183162294df30a079a21bda2ab58e64fd0ae092e2d99711966" - }, - { - "text": "1 Urine free cortisol (UFC; at least two measurements) 3.", - "tokenCount": 15, - "pageStart": 2, - "pageEnd": 2, - "hash": "5c4230415f6eb5a1af9aceeff98516779b172465238d369441b2ad1d2b286198" - }, - { - "text": "2 Latenight salivary cortisol (two measurements) 3.", - "tokenCount": 14, - "pageStart": 2, - "pageEnd": 2, - "hash": "8791edc1cfc0cb7c144f5f5a253d044fd4734939721a07ca5565a2d4cad0a1c0" - }, - { - "text": "3 1-mg overnight dexamethasone suppression test (DST) 3.", - "tokenCount": 18, - "pageStart": 2, - "pageEnd": 2, - "hash": "a87aa6e44684411c3d8ede44dd215b63c4e03fce9945e48cb982e17d4a634954" - }, - { - "text": "4 Longer lowdose DST (2 mg/d for 48 h) 3.", - "tokenCount": 18, - "pageStart": 2, - "pageEnd": 2, - "hash": "81a5a5917ff54af8bafce5e684d48d14cb21ff66c8cb408f1e30e85e66a2b9d1" - }, - { - "text": "5 We recommend against the use of the following to test for Cushings syndrome (1 QEEE ): Random serum cortisol or plasma ACTH levels Urinary 17-ketosteroids Insulin tolerance test Loperamide test Tests designed to determine the cause of Cushings syndrome ( e.", - "tokenCount": 63, - "pageStart": 2, - "pageEnd": 2, - "hash": "d7401e73b01f85f1aa8d954249725e4bf0157132b3a5eeec376044eb311a2e42" - }, - { - "text": "pituitary and adrenal imaging, 8 mg DST).", - "tokenCount": 13, - "pageStart": 2, - "pageEnd": 2, - "hash": "548456f2f81cb0c91c6a93b2d5a61583d371e0e3801d9315b5b3758bfa0d7258" - }, - { - "text": "6 In individuals with normal test results in whom the pretest probability is high (patients with clinical features suggestive of Cushings syndrome and adrenal incidentaloma or suspected cyclic hypercortisolism), we recommend further evaluation by an endocrinologist to confirm or exclude the diagnosis (1 QEEE ).", - "tokenCount": 62, - "pageStart": 2, - "pageEnd": 2, - "hash": "8603705cf4fd0cfc170d61bfe0fae88e83bb6ac3c453eac1a0ce9a3135ded002" - }, - { - "text": "7 In other individuals with normal test results (in whom Cushings syndrome is very unlikely), we suggest reevaluation in 6 months if signs or symptoms progress (2 QEEE ).", - "tokenCount": 37, - "pageStart": 2, - "pageEnd": 2, - "hash": "28eda98765a8eaee954e409b295c9904ba064e82554656da0bad399127295991" - }, - { - "text": "8 In individuals with at least one abnormal test result (for whom the results could be falsely positive or indicate Cushings syndrome), we recommend further evaluation by an endocrinologist to confirm or exclude the diagnosis (1 QEEE ).", - "tokenCount": 46, - "pageStart": 2, - "pageEnd": 2, - "hash": "5f70f71e6617f3b64be96a3ffc89675bd0b9db40f40180c08304dd8c11d12406" - }, - { - "text": "9Forthesubsequentevaluationofabnormalinitialtestresults, we recommend performing another recommended test (Fig.", - "tokenCount": 23, - "pageStart": 2, - "pageEnd": 2, - "hash": "64d7e1dde7c605f967c81ab2c53321e52c8626e513132f537b0072b88ef6868d" - }, - { - "text": "1 We suggest the additional use of the dexamethasoneCRHtestorthemidnightserumcortisoltestinspecificsituations (Fig.", - "tokenCount": 36, - "pageStart": 2, - "pageEnd": 2, - "hash": "5d852c5b25e7613ef39d7dbf10a36ec4eea83b53565f0adfc6b61860eecf5a77" - }, - { - "text": "2 We suggest against the use of the desmopressin test, exceptinresearchstudies,untiladditionaldatavalidateitsutility (2 QEEE ).", - "tokenCount": 34, - "pageStart": 2, - "pageEnd": 2, - "hash": "8592db0ac87a272d674b18c8984b3104ab21085fda114b0a2fe450b34699aaf0" - }, - { - "text": "3 We recommend against any further testing for Cushings syndrome in individuals with concordantly negative results on two different tests (except in patients suspected of having the very rare case of cyclical disease) (1 QEEE ).", - "tokenCount": 45, - "pageStart": 2, - "pageEnd": 2, - "hash": "2ac32bf98a4c706f2367364d81c3270e6ea9a0cbdb3eb60ea1d3ce3070f6ff0c" - }, - { - "text": "4 We recommend tests to establish the cause of Cushings syndrome in patients with concordantly positive results from two different tests, provided there is no concern regarding possible nonCushings hypercortisolism (Table 2) (1 QQEE ).", - "tokenCount": 52, - "pageStart": 2, - "pageEnd": 2, - "hash": "48d7a9a976902b6e0e93a478d4259f43a429a7aded532a812635e38433add26c" - }, - { - "text": "5Wesuggestfurtherevaluationandfollowupforthefew patients with concordantly negative results who are suspected of having cyclical disease and also for patients with discordant results, especially if the pretest probability of Cushings syndrome is high (2 QEEE ).", - "tokenCount": 56, - "pageStart": 2, - "pageEnd": 2, - "hash": "a76ccc24a0bc97afe6fbdee62ded3a6fa20bba071fe077ce33ffb09deca76c96" - }, - { - "text": "1 Pregnancy: We recommend the use of UFC and against the useofdexamethasonetestingintheinitialevaluationofpregnant women (1 QQQE ).", - "tokenCount": 39, - "pageStart": 2, - "pageEnd": 2, - "hash": "f6672000876f964756e82e75ac81827304c3b630810c1ec73d270a105f4f5f5c" - }, - { - "text": "2 Epilepsy: We recommend against the use of dexamethasone testing in patients receiving antiepileptic drugs known to enhance dexamethasone clearance and recommend instead measurements of nonsuppressed cortisol in blood, saliva, or urine (1 QQQE ).", - "tokenCount": 58, - "pageStart": 2, - "pageEnd": 2, - "hash": "5d1bca1994fbab30b9d1d23db2633dab9e658275d09638a4092760cccabf7fda" - }, - { - "text": "3 Renal failure: We suggest using the 1-mg overnight DST rather than UFC for initial testing for Cushings syndrome in patients with severe renal failure (2 QEEE ).", - "tokenCount": 37, - "pageStart": 2, - "pageEnd": 2, - "hash": "50a49268ba175e4c6a539c3f8865e82601e570f44820eec93ea35d19ab33ea94" - }, - { - "text": "4 Cyclic Cushings syndrome: We suggest use of UFC or midnight salivary cortisol tests rather than DSTs in patients suspected of having cyclic Cushings syndrome (2 QEEE ).", - "tokenCount": 41, - "pageStart": 2, - "pageEnd": 2, - "hash": "2ca9a969c0d8e4cd590037ee24f54ba4766aabba51156748599048fc5f20c760" - }, - { - "text": "5 Adrenal incidentaloma: We suggest use of the 1-mg DST or latenight cortisol test, rather than UFC, in patients suspected of having mild Cushings syndrome (2 QQEE ).", - "tokenCount": 43, - "pageStart": 2, - "pageEnd": 2, - "hash": "12627ede67b686f8a62b7f425420ee2a8522b9d349df59dadb35b0723b615103" - }, - { - "text": "METHOD OF DEVELOPMENT OF EVIDENCEBASED RECOMMENDATIONS The Clinical Guidelines Subcommittee of The Endocrine Society deemed detection and diagnosis of patients with Cushings syndrome a priority area in need of practice guidelines and appointed a sixmember Task Force to formulate evidencebased recommendations.", - "tokenCount": 58, - "pageStart": 2, - "pageEnd": 2, - "hash": "1b807c8377a56e8701d2c4e3d5dbfb8fa69bbea8565b48981777ace08bb08970" - }, - { - "text": "The Task Force followed the approach recommended by the Grading of Recommendations, Assessment, Development, and Evaluation Group, an international group with expertise in development and implementation of evidencebased guidelines (1).", - "tokenCount": 39, - "pageStart": 2, - "pageEnd": 2, - "hash": "f5a0a1e00dd1dc88e489fb68cfcd87adcb6fa5a7521d8bd2d4730fe9692e5876" - }, - { - "text": "The Task Force used the best available research evidence that members identified and systematic reviews and metaanalyses of test accuracy to inform the recommendations (2).", - "tokenCount": 29, - "pageStart": 2, - "pageEnd": 2, - "hash": "8b94fa71fe343ae6b6becc14613cc7b5761dbc2388e12c51209f67c3a7e02182" - }, - { - "text": "The Task Forcealsousedconsistentlanguageandgraphicaldescriptionsof both the strength of a recommendation and the quality of evidence.", - "tokenCount": 27, - "pageStart": 2, - "pageEnd": 2, - "hash": "93700bd0b3fd33d836500e855a1c7c7d63f764e121de4e359cae28afe6d7906f" - }, - { - "text": "In terms of the strength of the recommendation, strong recommendationsusethephrasewerecommendandthenumber 1, and weak recommendations use the phrase we suggest and the number 2.", - "tokenCount": 37, - "pageStart": 2, - "pageEnd": 2, - "hash": "73515b81a2204cae21db1e785b5cbf5bc6e69ea8df6c6b6c04a39505b4e50c48" - }, - { - "text": "Crossfilled circles indicate the quality of the evidence, such that QEEE denotes very lowquality evidence; QQEE , low quality; QQQE , moderate quality; and QQQQ , high quality.", - "tokenCount": 44, - "pageStart": 2, - "pageEnd": 2, - "hash": "2b3d607fa14d53b955df73607170e885e0d1f7eaa54b23a55eccd2299b5530ec" - }, - { - "text": "A detailed description of this grading scheme has been published elsewhere (3).", - "tokenCount": 14, - "pageStart": 2, - "pageEnd": 2, - "hash": "7ef4582710d6486e12629e00872c06b7ad0cfd4c385c14da3aa88aea236b89c2" - }, - { - "text": "The Task Force has confidence that patients who receive care according to the strong recommendations will derive, on average, more good than harm.", - "tokenCount": 26, - "pageStart": 2, - "pageEnd": 2, - "hash": "e9ad4ef0dc6281974c5175696850c3eb13ff77539bc6ab05b6180f89dd8495ab" - }, - { - "text": "Lowor very lowquality evidence usually leads to weak recommendations because of uncertainty J Clin Endocrinol Metab, May 2008,93(5):15261540 jcem.", - "tokenCount": 37, - "pageStart": 2, - "pageEnd": 2, - "hash": "59cede8bcce36698495dd6a932e8fc81e9ad9cc234e72d6273d88b2cbf565c62" - }, - { - "text": "org 1527 Downloaded from https://academic.", - "tokenCount": 11, - "pageStart": 2, - "pageEnd": 2, - "hash": "262df020b3663a29c7aaa120f25edcf36f71d779fcfeb39f7cd92c1f7f6bc416" - }, - { - "text": "about the balance between risks and benefits; strong recommendations based on lowquality evidence usually indicate the panels strong preference against the alternative course of action but are subject to change with new research.", - "tokenCount": 36, - "pageStart": 3, - "pageEnd": 3, - "hash": "d51275f5ac3ae6ee21ba9dd0c7455627769851a86642fc63c2825d3fc54785b0" - }, - { - "text": "Given a weak recommendation, careful consideration of the patients circumstances, values, and preferences is appropriate to determine the best course of action.", - "tokenCount": 26, - "pageStart": 3, - "pageEnd": 3, - "hash": "6a7d0b6a249854987eb18e3293b838485f093893c0834175a014ba30b2d27399" - }, - { - "text": "Linked to each recommendation is a description of the evidence , values that panelists considered in making the recommendation(whenmakingtheseexplicitwasnecessary),and remarks , asectioninwhichpanelistsoffertechnicalsuggestionsfortesting conditions, dosing, and monitoring.", - "tokenCount": 55, - "pageStart": 3, - "pageEnd": 3, - "hash": "c29902cc1a71722dfab5da70702afa38dc0a0bb7decc31c01067f1d6c93d9128" - }, - { - "text": "These technical comments reflect the best available evidence applied to a typical patient.", - "tokenCount": 14, - "pageStart": 3, - "pageEnd": 3, - "hash": "60681be67b81a30033233ba0e33299594ca7e1f776085347d97d35ac56a99ecf" - }, - { - "text": "Oftenthisevidencecomesfromtheunsystematicobservationsof the panelists and should therefore be considered suggestions.", - "tokenCount": 27, - "pageStart": 3, - "pageEnd": 3, - "hash": "0a1488c9ee969a56b0e090c4c033b1bab722e96feee372464f1949ed02801e43" - }, - { - "text": "0 Definition, pathophysiology, and etiology of hypercortisolism Cushings syndrome comprises a large group of signs and symptomsthatreflectprolongedandinappropriatelyhighexposureof tissue to glucocorticoids (Table 1).", - "tokenCount": 52, - "pageStart": 3, - "pageEnd": 3, - "hash": "b78abc9b198c198b00955f4bf5e37e77620b7c895bac474ececad20d52e270a7" - }, - { - "text": "Whereas the most common cause is iatrogenic from medically prescribed corticosteroids, endogenous Cushings syndrome is an uncommon disorder.", - "tokenCount": 28, - "pageStart": 3, - "pageEnd": 3, - "hash": "6d07b45ba49c84c61f5ee4a0e9d85def99a01390e99832faff1ed1a0c54ba72a" - }, - { - "text": "European populationbased studies reported an incidence of two to three cases per 1 million inhabitants per year (4,5).", - "tokenCount": 23, - "pageStart": 3, - "pageEnd": 3, - "hash": "d06a11e549a3a3163d1b6b8c7e746e0f1380b04ca5683988b0ba3a20cca1096c" - }, - { - "text": "Excess cortisol production, the biochemical hallmark of endogenous Cushings syndrome, may be caused by either excess ACTH secretion (from a pituitary or other ectopic tumor) or independent adrenal overproduction of cortisol.", - "tokenCount": 45, - "pageStart": 3, - "pageEnd": 3, - "hash": "d6dacd1e7cee93217b5531b47d3dbde969cd2c315cec21e9a5e8968c4d7bc456" - }, - { - "text": "Although Cushings syndrome is clinically unmistakable when full blown, the spectrum of clinical presentation is broad, and the diagnosis can be challenging in mild cases.", - "tokenCount": 31, - "pageStart": 3, - "pageEnd": 3, - "hash": "418e0d1af66d533154ba964e20bfbe38423e6396fb9bc6aede674ccc69ecadb9" - }, - { - "text": "Few, if any, features of Cushings syndrome are unique, but some are more discriminatory than others, including reddish purple striae, plethora, proximal muscle weakness, bruising with no obvious trauma, and unexplained osteoporosis (68).", - "tokenCount": 51, - "pageStart": 3, - "pageEnd": 3, - "hash": "928f4e9db52c62f6cb6ff4872ab42a3e9d09f2afc2af085f72474e9a60fda657" - }, - { - "text": "More often patientshaveanumberoffeaturesthatarecausedbycortisolexcess but that are also common in the general population, such as obesity, depression, diabetes, hypertension, or menstrual irregularity.", - "tokenCount": 46, - "pageStart": 3, - "pageEnd": 3, - "hash": "98a3f2b0ec1baaa5f67d65e788ddd94d24560cae34d506afdaf419938f533dfb" - }, - { - "text": "As a result, there is an overlap in the clinical presentation of individuals with and without the disorder (Table 1).", - "tokenCount": 23, - "pageStart": 3, - "pageEnd": 3, - "hash": "5e8cfaa61574249cdb286e3ccd71754ee169a2cdef3cb5cc46f5305998e10531" - }, - { - "text": "We encourage caregivers to consider Cushings syndrome as a secondary cause of these conditions, particularly if additional features of the disorder are present.", - "tokenCount": 27, - "pageStart": 3, - "pageEnd": 3, - "hash": "4fc1d90d61475f2f4edc8e16bad33dda6eb6e12463ec172cdb071a60461887c7" - }, - { - "text": ") If Cushings syndrome is not considered, the diagnosis is all too often delayed.", - "tokenCount": 18, - "pageStart": 3, - "pageEnd": 3, - "hash": "85d79441efb585bf194d62a3e8809116e33beb386e446b465bcca3d702ce8b9b" - }, - { - "text": "In addition, overactivity of the hypothalamicpituitaryadrenal (HPA) axis occurs without true Cushings syndrome, so that there is an overlap between physiological and pathophysiological causes of hypercortisolism (Table 2).", - "tokenCount": 51, - "pageStart": 3, - "pageEnd": 3, - "hash": "abcc5c225351fb1a447539dec05e78d9180cd0c17bc209de323ede7bdadaeeac" - }, - { - "text": "Thus, certain psychiatric disorders (depression, anxiety disorder, obsessivecompulsive disorder), poorly controlled diabetes mellitus, and alcoholism can be associated with mild hypercortisolism and may produce test results suggestive of Cushings syndrome, including abnormal dexamethasone suppressibility and mildly elevated UFC (9).", - "tokenCount": 63, - "pageStart": 3, - "pageEnd": 3, - "hash": "9400963a935f9942755ba30533b11dd62582f9a9144f1dcbb98384b815c07ec3" - }, - { - "text": "Circulating cortisol concentrations are usually normal (or slightly reduced) in obesity, but severe obesity can raise UFC.", - "tokenCount": 22, - "pageStart": 3, - "pageEnd": 3, - "hash": "fcad32a2d03ec398e720b5635f44fa477ba11446aef8e55c42b4418e90717bce" - }, - { - "text": "It is thought that higher brain centers stimulate CRH release in these conditions, with subsequent activation of the entireHPAaxis(10).", - "tokenCount": 27, - "pageStart": 3, - "pageEnd": 3, - "hash": "a21095adff909211f8ab5cb5eaacfc00c843321afbc911743348bede329dac99" - }, - { - "text": "Thenegativefeedbackinhibitionofcortisol on CRH and pituitary ACTH release partially restrains the reTABLE 1.", - "tokenCount": 29, - "pageStart": 3, - "pageEnd": 3, - "hash": "3d59c55669292c30d26e7fd45cd66800ebdc3465f3819b092b11e2aa27a002ab" - }, - { - "text": "Overlapping conditions and clinical features of Cushings syndrome a Symptoms Signs Overlapping conditions Features that best discriminate Cushings syndrome; most do not have a high sensitivity Easy bruising Facial plethora Proximal myopathy (or proximal muscle weakness) Striae (especially if reddish purple and 1 cm wide) In children, weight gain with decreasing growth velocity Cushings syndrome features in the general population that are common and/or less discriminatory Depression Dorsocervical fat pad ( buffalo hump ) Hypertension b Fatigue Facial fullness Incidental adrenal mass Weight gain Obesity Vertebral osteoporosis b Back pain Supraclavicular fullness Polycystic ovary syndrome Changes in appetite Thin skin b Type 2 diabetes b Decreased concentration Peripheral edema Hypokalemia Decreased libido Acne Kidney stones Impaired memory (especially short term) Hirsutism or female balding Unusual infections Insomnia Poor skin healing Irritability Menstrual abnormalities In children, slow growth In children, abnormal genital virilization In children, short stature In children, pseudoprecocious puberty or delayed puberty a Features are listed in random order.", - "tokenCount": 246, - "pageStart": 3, - "pageEnd": 3, - "hash": "07885695239ff6581327645efe1ed75d1206e8b0fecc7bc7afa99948653afe83" - }, - { - "text": "b Cushings syndrome is more likely if onset of the feature is at a younger age.", - "tokenCount": 19, - "pageStart": 3, - "pageEnd": 3, - "hash": "df0159b4ace4780445597dc4b4ff7526ea8f18c440df4668267a7ad02c1266f9" - }, - { - "text": "Guidelines for the Diagnosis of Cushings Syndrome J Clin Endocrinol Metab, May 2008,93(5):15261540 Downloaded from https://academic.", - "tokenCount": 38, - "pageStart": 3, - "pageEnd": 3, - "hash": "0dc0ed5ce03121791b08b31f047395b449e9705fc3c4de834e1e3e2fc2d4ddc9" - }, - { - "text": "sulting hypercortisolemia.", - "tokenCount": 10, - "pageStart": 4, - "pageEnd": 4, - "hash": "f96dad00ae05e6527304b0ccc17b31296c6c9eebedc12c3b3c53f2b828c56801" - }, - { - "text": "As a result, the overlap in UFC excretion is limited to values up to about 4-fold normal.", - "tokenCount": 22, - "pageStart": 4, - "pageEnd": 4, - "hash": "7cd63c44d312629f019f6b25fa5ff02c585368bab03fad55573b3b3e7c26f7b0" - }, - { - "text": "0 Morbidity and mortality of Cushings syndrome: rationale for diagnosis and treatment The earliest reports of mortality in Cushings syndrome likely described individuals with severe hypercortisolism, representing one end of the clinical spectrum.", - "tokenCount": 46, - "pageStart": 4, - "pageEnd": 4, - "hash": "71c08018c907a8314dc2113c72762fbbfbf581d4a1516442fd6e76b72b627c13" - }, - { - "text": "These reports documented a mediansurvivalof4.", - "tokenCount": 12, - "pageStart": 4, - "pageEnd": 4, - "hash": "85d0f37f618647d40b45e70f4370e3b9b2edd550c32b29894c68e293a5ec1c88" - }, - { - "text": "6yr,andin1952a5-yrsurvivalofjust50%, with most deaths caused by vascular (myocardial infarction, cerebrovascular accident) or infectious complications (11,12).", - "tokenCount": 45, - "pageStart": 4, - "pageEnd": 4, - "hash": "f2c3958cd1320d296ef7be0bd8682d8bb1e503c4cfe402313204fe212d4baddd" - }, - { - "text": "However, with modernday treatments the standard mortality ratio (SMR) after successful normalization of cortisol was similar to that of an agematched population during 120 yr of followup evaluation in one study (13).", - "tokenCount": 44, - "pageStart": 4, - "pageEnd": 4, - "hash": "f515333baf00f2c24ccba14b9305520206ef07a54bc6144be19062f38bedb58d" - }, - { - "text": "Because markers of cardiovascular risk remain abnormal for up to 5 yr after surgery, further studies are needed to assess longterm SMR (14).", - "tokenCount": 28, - "pageStart": 4, - "pageEnd": 4, - "hash": "f2140df98991aab1599dd3e72cd2b5c34d6eeb08d6334b964f72a89c10d18d83" - }, - { - "text": "In patients who have persistent moderate hypercortisolism despite treatment, SMR is increased 3.", - "tokenCount": 20, - "pageStart": 4, - "pageEnd": 4, - "hash": "41d48463b8ec071feeaded08bb3a1a91ee899d04ea18362a152b6ebf954e5b73" - }, - { - "text": "0-fold, compared with the general population (4,5).", - "tokenCount": 14, - "pageStart": 4, - "pageEnd": 4, - "hash": "340fcd8c438f54cca4e92e23d781f595484bc445ab0d09ee4cc6c642dd994311" - }, - { - "text": "These data are consistent with the increased cardiovascular mortality and morbidity reported in patients with iatrogenic Cushings syndrome secondary to the chronic use of synthetic corticosteroids (15).", - "tokenCount": 38, - "pageStart": 4, - "pageEnd": 4, - "hash": "c31c3323770eec9e8f52e59bea917c7aea2a947f28a2e85df76cebe74fecc42d" - }, - { - "text": "Successful treatment of hypercortisolism reverses, but may not normalize, features of Cushings syndrome.", - "tokenCount": 25, - "pageStart": 4, - "pageEnd": 4, - "hash": "501cb0263bbd34bfa207f89e9f9494ea4ce6e6b4b2f560c4171f82ea7e3dcc6c" - }, - { - "text": "Bone mineral density and cognitive dysfunction improve after successful surgical treatment of Cushings syndrome but do not normalize in all patients (16,17).", - "tokenCount": 29, - "pageStart": 4, - "pageEnd": 4, - "hash": "27a441fbda3ac362c8538703deb53e6620dd93ecb26b78781b712d708572096b" - }, - { - "text": "Additionally, quality of life improves after surgical treatment but remains below that of ageand gendermatched subjects for up to 15 yr (18).", - "tokenCount": 27, - "pageStart": 4, - "pageEnd": 4, - "hash": "f1387b039b3e9a20c81a8c8c7dd2a06bf2d150b84d71a7e2d2930b2f6985bfb3" - }, - { - "text": "Indirect evidence supporting the need for intervention includes the finding that the risk of infection is lower in patients with mild to moderate, compared with severe, hypercortisolism (19).", - "tokenCount": 37, - "pageStart": 4, - "pageEnd": 4, - "hash": "2b4054a401118e32efbb9e977e6b74f640c5dae57f58c0371c277378046f0f55" - }, - { - "text": "There are limited and conflicting data regarding whether surgical treatment of patients with mild hypercortisolism in the settingofanadrenalincidentalomaissuperiortomedicaltreatment of comorbidities alone (2023).", - "tokenCount": 46, - "pageStart": 4, - "pageEnd": 4, - "hash": "e9930935930c8a4df338c330c5be96ee866630716d160024bddf31e43238dd93" - }, - { - "text": "Although there are no formal controlled studies of consequences of cure in pediatric Cushings syndrome, improvements in growth and body composition after treatment are reported in both patients with adrenal and those with pituitary causes (24,25).", - "tokenCount": 46, - "pageStart": 4, - "pageEnd": 4, - "hash": "0c3bfbb4980385fdd0aed60ad57b02602d2d3e2735c27f0bbb2afb7ac60c28ae" - }, - { - "text": "Final stature in patients with endogenous Cushings syndrome was reported to be disappointing (26), but more recent data showed that most patients reach a final height within their predicted parental target range (24).", - "tokenCount": 39, - "pageStart": 4, - "pageEnd": 4, - "hash": "391cd7f99fe76e685b6d29d381907696adc64dd9f1e279b5fd59fdf100e23c2b" - }, - { - "text": "Treatment of patients with moderate to severe Cushings syndrome clearly reduces mortality and morbidity. Because Cushings syndrome tends to progress and severe hypercortisolism is probably associated with a worse outcome, it is likely that early recognition and treatment of mild disease would reduce the risk ofresidualmorbidity.", - "tokenCount": 65, - "pageStart": 4, - "pageEnd": 4, - "hash": "4a32ec4ee6205d8d4833072291c49f9abb4488aa241fc88518459be21955ef97" - }, - { - "text": "However,nodataaddressingthisassumption have been reported.", - "tokenCount": 14, - "pageStart": 4, - "pageEnd": 4, - "hash": "86b39fe7ef9773e5cc29f70ca564316fc594abdf88ee9ee86d63a820cd44a55d" - }, - { - "text": "OurrecommendationsfortestingforCushingssyndromeare based on direct evidence from observational studies indicating a large treatment effect (which we have rated as low to moderate quality evidence) on morbidity and mortality in patients diagnosed with the condition.", - "tokenCount": 50, - "pageStart": 4, - "pageEnd": 4, - "hash": "2223b210816bacde60de9dfc5e21d40d336b95fd2b68ca6e4af8c7c774909b55" - }, - { - "text": "The next section of this document focuses on evidence that bears indirectly on these recommendations.", - "tokenCount": 16, - "pageStart": 4, - "pageEnd": 4, - "hash": "5235f029d51be4616f0274de8c12bcf90e8c541473055ccbb6041d5bba78c8c9" - }, - { - "text": "The research in this area yields data on the likelihood of Cushings syndrome in certain populations and on the accuracy of currently available tests in these populations.", - "tokenCount": 30, - "pageStart": 4, - "pageEnd": 4, - "hash": "72a943aa94dc854c0bdec731274a59136579e365fb6c6ef8484cd47826d188e7" - }, - { - "text": "As a result, the majority of our recommendations are based on very lowto lowquality evidence.", - "tokenCount": 19, - "pageStart": 4, - "pageEnd": 4, - "hash": "819f464865d0c63f85a76e7abc4a59ae556cfddaadf37a1c88a0211224f38222" - }, - { - "text": "Higherquality evidence to support testing should come from studies directly comparing the effect of testing strategies on patientimportant outcomes.", - "tokenCount": 22, - "pageStart": 4, - "pageEnd": 4, - "hash": "59e4c017fce039bfaa014f1f3e68dc5ad754f3910037579f7089b76350d7b680" - }, - { - "text": "To date such evidence is not available in this field.", - "tokenCount": 11, - "pageStart": 4, - "pageEnd": 4, - "hash": "44c54da7e9e2bda3d0014f43f77e2db069e0b0d671e8d42fbeb1e37f0915c553" - }, - { - "text": "These guidelines focus on the more common clinical scenarios, with brief mention of conditions and situations that are rare or more complicated than space limitations allow; we hope that the reader will investigate these further.", - "tokenCount": 38, - "pageStart": 4, - "pageEnd": 4, - "hash": "8d83297e409a7c653d146015d1ff3829e2a1eb3b44609c6efa0767aad58fb7df" - }, - { - "text": "1Werecommendobtainingathoroughdrughistorytoexclude exogenous glucocorticoid exposure leading to iatrogenic Cushings syndrome before conducting biochemical testing (1 QQQQ ).", - "tokenCount": 45, - "pageStart": 4, - "pageEnd": 4, - "hash": "e9d1344d111f07bf9c2a8b4e23e28bab4ffb03282bb53cf8266141802ac6e6ad" - }, - { - "text": "osteoporosis, hypertension) (Table 1) (1 QQEE ) Patientswithmultipleandprogressivefeatures,particularly those that are more predictive of Cushings syndrome (Table 1) (1 QQEE ) Children with decreasing height percentile and increasing weight (1 QEEE ) Patients with adrenal incidentaloma compatible with adenoma (1 QEEE ).", - "tokenCount": 79, - "pageStart": 4, - "pageEnd": 4, - "hash": "3e8936a6026ca08e996d3d6332d66168356a986d30cd8a7c69f2513cd0718b62" - }, - { - "text": "1 Evidence Features of Cushings syndrome may occur as a result of exogenousglucocorticoiduse.", - "tokenCount": 24, - "pageStart": 4, - "pageEnd": 4, - "hash": "2485f37189ee43a193497abac7a1dc29b34b8857acda622f1a2f3e1a3d328fad" - }, - { - "text": "TheseverityoftheCushingoidfeatures TABLE 2.", - "tokenCount": 12, - "pageStart": 4, - "pageEnd": 4, - "hash": "8f116bf1e419fa22b68c84cc1497d238b9d2743f512dfc17760b4d728ed2f155" - }, - { - "text": "Conditions associated with hypercortisolism in the absence of Cushings syndrome a Conditions Some clinical features of Cushings syndrome may be present Pregnancy Depression and other psychiatric conditions Alcohol dependence Glucocorticoid resistance Morbid obesity Poorly controlled diabetes mellitus Unlikely to have any clinical features of Cushings syndrome Physical stress (hospitalization, surgery, pain) Malnutrition, anorexia nervosa Intense chronic exercise Hypothalamic amenorrhea CBG excess (increased serum but not urine cortisol) a Whereas Cushings syndrome is unlikely in these conditions, it may rarely be present.", - "tokenCount": 125, - "pageStart": 4, - "pageEnd": 4, - "hash": "96302104de80bdec39b9310278f3e1608f0336ba6005df305bdac36668162f74" - }, - { - "text": "If there is a high clinical index of suspicion, the patient should undergo testing, particularly those within the first group.", - "tokenCount": 23, - "pageStart": 4, - "pageEnd": 4, - "hash": "55a697e9bf5dac5a7a5fa225e9dcd46384a2219f5e8db9668feabc973c3290f9" - }, - { - "text": "J Clin Endocrinol Metab, May 2008,93(5):15261540 jcem.", - "tokenCount": 23, - "pageStart": 4, - "pageEnd": 4, - "hash": "482245b4113d18b1f240399b2ff9e2ebbeb94073d1e96534f06589742a58bd98" - }, - { - "text": "org 1529 Downloaded from https://academic.", - "tokenCount": 11, - "pageStart": 4, - "pageEnd": 4, - "hash": "2ab2bdc439dc217571b286f41949f0f387eded5fb4b7b5a484b58491bb9d70a7" - }, - { - "text": "depends on the potency of the preparation used, its dose, the route and duration of its administration, and whether concomitant medications prolong its halflife (27).", - "tokenCount": 34, - "pageStart": 5, - "pageEnd": 5, - "hash": "b68fcd436752447be9d1435eb8a44bd74d5bf8084db22026babea6816a85b442" - }, - { - "text": "A thorough drug history noting current or recent use of these medications, oral, rectal, inhaled, topical, or injected, should be obtained before embarking on any biochemical testing (28).", - "tokenCount": 39, - "pageStart": 5, - "pageEnd": 5, - "hash": "a48c11616a4adf6dec1dd08555caf9711e9e65f5775240259820ffd489ed00da" - }, - { - "text": "In particular, glucocorticoid components of skin creams (including bleaching agents), herbal medications, tonics, and joint or nerve injections may be overlooked.", - "tokenCount": 34, - "pageStart": 5, - "pageEnd": 5, - "hash": "4014fcb6bc6d8b5e54a15b97fec4ccc4d8f818695708987da934dacf98d338d5" - }, - { - "text": "Megestrol acetate (medroxyprogesterone acetate) is a synthetic progesterone derivative that has glucocorticoid activity and in high doses may cause Cushings syndrome (29).", - "tokenCount": 43, - "pageStart": 5, - "pageEnd": 5, - "hash": "50c54504f66f4fbe9784135d583f01648186c0048dbc0d1b5967f0d245614f5e" - }, - { - "text": "Our recommendation is based on highquality evidence because it derives from the common observation that pursuing the alternative, testing to establish the diagnosis of Cushings syndrome without first excluding exogenous glucocorticoiduse,isassociatedwithaverylargeriskofundesirable effects (including unnecessary testing and the associated consequences) without expectation of benefit.", - "tokenCount": 68, - "pageStart": 5, - "pageEnd": 5, - "hash": "20c5280c0351436f2bc241ae2a7388148caff59bedffeee40a4438a901c6d6b9" - }, - { - "text": "2 Evidence Cushings syndrome is more likely to be present when a large number of signs and symptoms, especially those with high discriminatory index ( e.", - "tokenCount": 30, - "pageStart": 5, - "pageEnd": 5, - "hash": "5f22c5fe8a2fbf5428196ea9af4a98eb2d4aa15edfea7ae9db1ded1b8f0ee769" - }, - { - "text": "myopathy, plethora, red striae, easy bruising, and thin skin in the young) are present (6,8).", - "tokenCount": 26, - "pageStart": 5, - "pageEnd": 5, - "hash": "27526102a47c9423f0c217a7eb6b7df3310b454f45085e3ea222b11397cabc9f" - }, - { - "text": "However, there is a wide spectrum of clinical manifestations at any given level of hypercortisolism.", - "tokenCount": 21, - "pageStart": 5, - "pageEnd": 5, - "hash": "c6f33148aff5d033e71026cbea7b3d79b768fa2edd06ebf1580a6bbd5079d3df" - }, - { - "text": "Because Cushings syndrome tends to progress, accumulation of new features increases the probability that the syndrome is present.", - "tokenCount": 22, - "pageStart": 5, - "pageEnd": 5, - "hash": "237b4ec472a72d504b8f0b60448632988b39da5286643ca858e70b852f89ee9c" - }, - { - "text": "A review of old photographs of the patient may help the clinician better appreciate whether physical changes have occurred over time.", - "tokenCount": 23, - "pageStart": 5, - "pageEnd": 5, - "hash": "60b2f65b5771b346645416d4d809dd11553e0aafecb31a478e98578e2268955f" - }, - { - "text": "In children, the sensitivity of combined reduced linear growth and increased weight is quite high.", - "tokenCount": 17, - "pageStart": 5, - "pageEnd": 5, - "hash": "facf980f8e6c875257e5e550552302dd99ed1b217f73ac9198df678c7a2982a1" - }, - { - "text": "Although the probability of Cushings syndrome has not been evaluated in a large number of children, clinical experience suggests that the specificity of these clinical features for the diagnosis is also very high (30).", - "tokenCount": 39, - "pageStart": 5, - "pageEnd": 5, - "hash": "2355ca0e2eda307235dadbf2ab36b3349dcb347b0f23e44ec507ba8503bf67fc" - }, - { - "text": "As a result, tests for Cushings syndrome are not indicated in obese children unless their statural growth rate has slowed.", - "tokenCount": 25, - "pageStart": 5, - "pageEnd": 5, - "hash": "bbb31c68cc3100e6437342243997ecfc4a95519a71938aa6c57e09d58645f682" - }, - { - "text": "Clinicians often evaluate patients with an incidentally found adrenal nodule for autonomous adrenal cortisol excess.", - "tokenCount": 21, - "pageStart": 5, - "pageEnd": 5, - "hash": "7c335c9aa6916da948ead7ea8d97730c25c8c23efda92aff17aca85ef1056eb7" - }, - { - "text": "Such patients usually do not present with overt clinical features of Cushings syndrome, but biochemical hypercortisolism is presentinalargefraction(upto10%).", - "tokenCount": 34, - "pageStart": 5, - "pageEnd": 5, - "hash": "bb2ca091fb64cc32dbc2b1e9a87b3998d2080503e3cc148b3d61cf4aecddcfee" - }, - { - "text": "(31)reported 2% prevalence of Cushings syndrome; Libe et al.", - "tokenCount": 18, - "pageStart": 5, - "pageEnd": 5, - "hash": "fcaf15134e5da1726b0e39d14ea23a5868f3d70080d41a875d7cd9c996f834c8" - }, - { - "text": "(32) reported 18%; Terzolo et al.", - "tokenCount": 12, - "pageStart": 5, - "pageEnd": 5, - "hash": "15b2b4cdd649732ef39a95921613b1fad797c5d81e84696353aa0ce63bf7dd42" - }, - { - "text": "(21) quoted 520%, depending on referral bias and diagnostic tests and criteria.", - "tokenCount": 16, - "pageStart": 5, - "pageEnd": 5, - "hash": "ad295688edc981a5bce023230b38acf10bc7494a5c648a68907565df0d843060" - }, - { - "text": "3 Evidence Testing for Cushings syndrome in certain highrisk populations has shown an unexpectedly high incidence of unrecognized Cushings syndrome as compared with the general population.", - "tokenCount": 33, - "pageStart": 5, - "pageEnd": 5, - "hash": "f0e40be7cfcd140cf727d26cfd8ff72db037e07ec5e139c22fd34b6fa3fbcce3" - }, - { - "text": "Although there are limited data on the prevalence of the syndrome in these disorders, the diagnosis should be considered.", - "tokenCount": 21, - "pageStart": 5, - "pageEnd": 5, - "hash": "8091f530f32f1c809a37cb3039be9a04b4fb65375d2d3cf7d56b4570079817d3" - }, - { - "text": "3% of patients with poorly controlled diabetes mellitus had surgically confirmed Cushings syndrome or mild hypercortisolism.", - "tokenCount": 26, - "pageStart": 5, - "pageEnd": 5, - "hash": "afea3a2a784112edf24ee966e5be3229e7b9acee01934faef52b926cd00d2088" - }, - { - "text": "Most of these patients had unilateral adrenal adenomas (33).", - "tokenCount": 14, - "pageStart": 5, - "pageEnd": 5, - "hash": "957b7fbf232f9b446721d9efde05ede657e76dbf73e7e51799c6528a6f979eac" - }, - { - "text": "In another recent report, one of 99 patients with newly diagnosed diabetes mellitus had surgically proven Cushings disease (34).", - "tokenCount": 26, - "pageStart": 5, - "pageEnd": 5, - "hash": "29fe5e97d422853a2857d7d6daa4f83c48b7b67525072a02f12508dff91389e0" - }, - { - "text": "Another study of 86 consecutive obese subjects referred to an endocrine clinic with diabetes mellitus, hypertension, and/or the polycystic ovary syndrome found a 5.", - "tokenCount": 34, - "pageStart": 5, - "pageEnd": 5, - "hash": "abc40e798f2c49fae47806d594b9f42c13009cbc55368adf3e1d0e0c74e49f07" - }, - { - "text": "8% incidence of Cushings syndrome (35).", - "tokenCount": 11, - "pageStart": 5, - "pageEnd": 5, - "hash": "7179f503f1938c454b79c07ccdf6648b969dd589e53335b1a3bc9ae530612958" - }, - { - "text": "Screening studies of patients with hypertension reported a 0.", - "tokenCount": 11, - "pageStart": 5, - "pageEnd": 5, - "hash": "657869788606c18a30e862cc21ba6901c8c0e99809d776f776e572c51f271f83" - }, - { - "text": "51% prevalence of Cushings syndrome (36,37).", - "tokenCount": 13, - "pageStart": 5, - "pageEnd": 5, - "hash": "554aebe450966fc6e54c30248ed5b4670ab06da3ec8448981ce4be5a6d084ae9" - }, - { - "text": "Unsuspected Cushings syndrome also was found in as many as 10.", - "tokenCount": 17, - "pageStart": 5, - "pageEnd": 5, - "hash": "728f7af60213339681332be21097fae1a12f3e6e19d5fd3eac2a0e4d7c573906" - }, - { - "text": "8% of older patients with osteoporosis and vertebral fracture in whom comprehensive testing was done for secondary causes (38).", - "tokenCount": 26, - "pageStart": 5, - "pageEnd": 5, - "hash": "c4faf51b90bcd79c689f7fde7e4b257769d9d4636a2dddb5e94252d095f49409" - }, - { - "text": "Unfortunately, there is little information on additional comorbidities and risk factors in these studies.", - "tokenCount": 19, - "pageStart": 5, - "pageEnd": 5, - "hash": "21089fdce48114cd586b6147ba1672fd2e3364aee6147e2b86c637f3e61a3ebf" - }, - { - "text": "The few data on the outcome, after surgical remission of hypercortisolism, in patients with unsuspected Cushings syndrome are mixed; hypertension and diabetes did not improve in all individuals (2023).", - "tokenCount": 42, - "pageStart": 5, - "pageEnd": 5, - "hash": "888c071bd7f083c53cbc8e8bcec050177164da03a631b42c0f9a31c234db5217" - }, - { - "text": "Patients with familial disease that puts them at risk of Cushings syndrome ( e.", - "tokenCount": 18, - "pageStart": 5, - "pageEnd": 5, - "hash": "7397b7876b82ace33e670639a18dd03ec6ac34d833aea304f9a2bf5378ea03ce" - }, - { - "text": "Carney complex, multiple endocrine neoplasia-1) should be evaluated by an endocrinologist as part of a surveillance screening program.", - "tokenCount": 29, - "pageStart": 5, - "pageEnd": 5, - "hash": "892234082c56c982e054b20013df7dde5325009f5f8fc1f572a4f9bef47c7e60" - }, - { - "text": "3 Values Because of the rarity of Cushings syndrome, the high prevalence of conditions such as diabetes mellitus, obesity, and depression, andthelimitationsofthescreeningtests,theriskoffalsepositive test results is high.", - "tokenCount": 48, - "pageStart": 5, - "pageEnd": 5, - "hash": "f1b0a0cf6b9f2cb25d54fa72ecc1add0400e615bfafcd4ed844879745d4791a2" - }, - { - "text": "Falsepositive results, with their attendant costs, are reduced if case detection is limited to individuals with an increased pretest probability of having the disorder.", - "tokenCount": 29, - "pageStart": 5, - "pageEnd": 5, - "hash": "d0916d0f3227e1abf8a6080b8a4549bc7cf20d9da456457f143c43ffbd964f87" - }, - { - "text": "The subsequent testing, labeling, and treatment may harm individuals with falsepositive results and distract attention from the treatment of the conditions that prompted testing.", - "tokenCount": 28, - "pageStart": 5, - "pageEnd": 5, - "hash": "30f63ab75fe35d45ad5340e47c2e8e229cd680fc47138742c3f9b86252746160" - }, - { - "text": "The proposed testing strategy places higher value on reducing the number of falsepositive test results, particularly in patients with very mild disease in whom the benefits of intervention are unproven.", - "tokenCount": 34, - "pageStart": 5, - "pageEnd": 5, - "hash": "08bfb0ecd538987291e55b9a90a491559292ec237da7a8a2a6ddbee5657bc749" - }, - { - "text": "Conversely, once the clinical scenario suggests a high pretest probability of the disorder, sensitivity needs to be high so that cases are not missed.", - "tokenCount": 29, - "pageStart": 5, - "pageEnd": 5, - "hash": "448313e49052b58e9d5dc3f42f591e10ed079b6b3593af2d1bf25c26eb441c98" - }, - { - "text": "This approach also seeks to use more convenient and less expensive tests.", - "tokenCount": 13, - "pageStart": 5, - "pageEnd": 5, - "hash": "cafac0cfcd27d1e3cf5232b392cc79d96201ca1c5c55adea4e46741da1e86777" - }, - { - "text": "1 UFC (at least two measurements) 3.", - "tokenCount": 10, - "pageStart": 5, - "pageEnd": 5, - "hash": "befd030c52b9881550584e1f2ac91965c10b25e4bd230ad2b197b459fc8583c6" - }, - { - "text": "6 In individuals with normal test results in whom the pretest probability is high (patients with clinical features suggestive of 1530 Nieman et al.", - "tokenCount": 30, - "pageStart": 5, - "pageEnd": 5, - "hash": "0c84d70c8c6d9aacb5b1fc66a7b809f77b9a547eaa5b4ceb2018615a3ed9715a" - }, - { - "text": "Cushings syndrome and adrenal incidentaloma or suspected cyclic hypercortisolism), we recommend further evaluation by an endocrinologist to confirm or exclude the diagnosis (1 QEEE ).", - "tokenCount": 39, - "pageStart": 6, - "pageEnd": 6, - "hash": "7c59e397bec8390b4f787e6ac10d7653a3316156d34a9e77a7ad7d08090b2a9b" - }, - { - "text": "4 Evidence In this section, we first discuss the testing strategies and then provide evidence for and remarks about each of the recommended tests that can be used to identify patients with Cushings syndrome.", - "tokenCount": 38, - "pageStart": 6, - "pageEnd": 6, - "hash": "5e01582d8ad18789e58196997c0c4dd9cad45cb2fa63088fbbefe40c41e2b252" - }, - { - "text": "Nonendocrinologist clinicians may perform the initial evaluation for Cushings syndrome (or refer to an endocrinologist).", - "tokenCount": 24, - "pageStart": 6, - "pageEnd": 6, - "hash": "8f3ff7c6b2e8e9afac69164d5b58d79192c412c0844a64f709ff26b60c27551b" - }, - { - "text": "In this setting, the goal is to choose a test with a high sensitivity for the disorder; unfortunately, no test has optimally high specificity, so that falsepositive results may occur.", - "tokenCount": 37, - "pageStart": 6, - "pageEnd": 6, - "hash": "33ad4d3c17813cde0f2c1af95e1e11d27b28c6411c701ae012f83b14263a6771" - }, - { - "text": "The four recommended tests have acceptable diagnostic accuracy when the suggested cutoff points are used (2,30).", - "tokenCount": 20, - "pageStart": 6, - "pageEnd": 6, - "hash": "965baedc966860ad96a7f145e091cf9f1578cc34ae2269ef60513d365b81ee80" - }, - { - "text": "If the initial testing results arenormal,assumingthatthereisnoreasontomistrusttheresult (see remarks below), then the patient is very unlikely to have Cushings syndrome.", - "tokenCount": 40, - "pageStart": 6, - "pageEnd": 6, - "hash": "3df6ab6b6bcdbfa9480f758987a1fc6cf3ffae5519334131d4ed91ae60fea426" - }, - { - "text": "Thus, the patient can be reassured and no further testing need be done; a recommendation to return in 6 months if symptoms progress ensures that evolving symptoms or new features will not be ignored.", - "tokenCount": 37, - "pageStart": 6, - "pageEnd": 6, - "hash": "38257411deb8a4d621d7c6aa99a9c4885c37bd11c9ad545bec1d7d3d8419ebd6" - }, - { - "text": "Inpatientswithahighpretestprobability of Cushings syndrome, to expedite diagnosis, the physician may elect to perform two tests simultaneously.", - "tokenCount": 32, - "pageStart": 6, - "pageEnd": 6, - "hash": "159cf0df33c8b9372be8a8d34b4a8a00adeb0bdc90bdd269b1c39512e3f26c77" - }, - { - "text": "4 Remarks for all tests Measurement of cortisol (urine, serum, or salivary) is the end point for each of the recommended tests.", - "tokenCount": 32, - "pageStart": 6, - "pageEnd": 6, - "hash": "844558308b67de827cfaa9dff3d56ed80a620559ddc62090e10aeb3fa247d574" - }, - { - "text": "As with all hormone assays, the physician must be aware that several collection and assay methods are available for the measurement of cortisol, and results for a single sample measured in various assays may be quite different (39).", - "tokenCount": 44, - "pageStart": 6, - "pageEnd": 6, - "hash": "0d3fd01349d26ce791036f1d026371b7093b115726f059bd694c7b89b7cf1df4" - }, - { - "text": "Assays differ widely in their accuracy; results near the cutoff value on a single measurement often can be explained by assay variability.", - "tokenCount": 25, - "pageStart": 6, - "pageEnd": 6, - "hash": "df3784b47793a66ca5c512328e7244d0939148d1408cbd0f77ba0dc23aae8041" - }, - { - "text": "In particular, the expected salivary and serum concentrations in these tests are close to the functional limit of detection of the assays.", - "tokenCount": 27, - "pageStart": 6, - "pageEnd": 6, - "hash": "42ede1b4d24b234864fbcbf79b7c2fcc41335e7c62c0520831f30ddffc8f5622" - }, - { - "text": "Because precision deteriorates at these levels, assays should be chosen on the basis of their performance at this low range.", - "tokenCount": 24, - "pageStart": 6, - "pageEnd": 6, - "hash": "fe82248f406b1fd8cd0d22869635a2780cc9d79ecce9858bc11d299ca1001c6c" - }, - { - "text": "Normal ranges vary substantially, dependingonthemethodused,soitisessential to interpret test results in the context of the appropriate normal range.", - "tokenCount": 27, - "pageStart": 6, - "pageEnd": 6, - "hash": "675c2c2f1762c9ccc7f2a6feaa2507441a0d1a8d17cd2aec2368e7d11aaf52e0" - }, - { - "text": "Antibodybased immunoassays such asunextractedRIAandELISAcanbeaffectedbycrossreactivity with cortisol metabolites and synthetic glucocorticoids.", - "tokenCount": 36, - "pageStart": 6, - "pageEnd": 6, - "hash": "c235c9d2e7965bcfa473965f066489e352ef699c2eb37f90bc8fb994a4600a48" - }, - { - "text": "In contrast, structurally based assays such as HPLC and tandem mass spectrometry (LCMS/MS) do not pose this problem and are being used with increasing frequency.", - "tokenCount": 37, - "pageStart": 6, - "pageEnd": 6, - "hash": "9cd96b8f17ff809e3a7e65b2395506d704fffc89bb064057e5d206d7a3cd34f8" - }, - { - "text": "However, there are also drugs (carbamazepine and fenofibrate) that may interfere with someofthesechromatographicmethods(Table3),therebycausing falsely elevated values (40,41).", - "tokenCount": 47, - "pageStart": 6, - "pageEnd": 6, - "hash": "33982a4bb63a744a7ab61aa4a4b49a781bbd08dd4208509a21a81bc80e611d10" - }, - { - "text": "Upper limits of normal are much lower with HPLC or LCMS/MS than in antibodybased assays.", - "tokenCount": 23, - "pageStart": 6, - "pageEnd": 6, - "hash": "664535bac8e9cfa5ed40749e3d40ed3a359247aee3531dc64c2125b1e008a4e0" - }, - { - "text": "For example, urine cortisol values obtained using HPLC may be as low as 40% of the value measured by RIA (42,43).", - "tokenCount": 29, - "pageStart": 6, - "pageEnd": 6, - "hash": "6076a46f32d11eb234f15a9a6d664c8b2247d3cdfeea0db91776b11e06398ee5" - }, - { - "text": "Estrogens increase the cortisolbinding globulin (CBG) concentration in the circulation.", - "tokenCount": 17, - "pageStart": 6, - "pageEnd": 6, - "hash": "6c8d162f4f760200fd0efcd1cb0408b75ed686a013639d0f240168540123ee2d" - }, - { - "text": "Because serum assays measure total cortisol, falsepositive rates for the overnight DST are seen in 50% of women taking the oral contraceptive pill (44).", - "tokenCount": 31, - "pageStart": 6, - "pageEnd": 6, - "hash": "698260760dfeef2a3b3a827d8954de17ed6866fabd71997b0ced351da445fb8f" - }, - { - "text": "Wherever possible, estrogencontaining drugs should be withdrawn for 6 wkbeforetestingorretesting(45).", - "tokenCount": 22, - "pageStart": 6, - "pageEnd": 6, - "hash": "342d6786554c6c08336595319402bac22fa424c5e97bbeccb377fc5b458ef14c" - }, - { - "text": "Conversely,decreasesinCBG or albumin, which occur in the critically ill or nephrotic patient, are associated with decreased serum cortisol values (39,46).", - "tokenCount": 38, - "pageStart": 6, - "pageEnd": 6, - "hash": "e4627cad67ab5a07680515c4d7fd74329909ebfbbd38c1a884330cb6b3a43b1c" - }, - { - "text": "Because the hypercortisolism of Cushings syndrome can be variable, we recommend that at least two measurements of urine or salivary cortisol be obtained.", - "tokenCount": 33, - "pageStart": 6, - "pageEnd": 6, - "hash": "7c8db38cd22aba7613a8bc69c87321517c8f87835d2f5152363dbb77c45e6dda" - }, - { - "text": "This strategy increases confidenceinthetestresultsifconsistentlynormalorabnormalresults are obtained.", - "tokenCount": 20, - "pageStart": 6, - "pageEnd": 6, - "hash": "79bb486d7d85eadfcce717c98f067369a11a50a7257c0227907892061ee217d1" - }, - { - "text": "Cushings syndrome suspected Perform one of the following tests ANY ABNORMAL RESULT Normal (CS unlikely) Consult endocrinologist Discrepant (Suggest additional evaluation) Normal (CS unlikely) ABNORMAL Cushings syndrome Exclude exogenous glucocorticoid exposure (consider endocrinologist consultation) 24-h UFC (> 2 tests) Overnight Late night salivary 1-mg DST cortisol (> 2 tests) Consider caveats for each test (see text) Use 48-h, 2-mg DST in certain populations (see text) Perform 1 or 2 other studies shown above Suggest consider or repeating the abnormal study Suggest DexCRH or midnight serum cortisol in certain populations (see text) Exclude physiologic causes of hypercortisolism (Table 2) FIG.", - "tokenCount": 161, - "pageStart": 6, - "pageEnd": 6, - "hash": "a8de40cc782702cf373b0083b92ccfb7b328c54928070c5c820a1b55bdb9a97c" - }, - { - "text": "Algorithm for testing patients suspected of having Cushings syndrome (CS).", - "tokenCount": 15, - "pageStart": 6, - "pageEnd": 6, - "hash": "927720cb9d9b9271fe6b90180549af4c5781e9a139ab389788da69e5918bf545" - }, - { - "text": "All statements are recommendations except for those prefaced by suggest.", - "tokenCount": 12, - "pageStart": 6, - "pageEnd": 6, - "hash": "9576fa055e0f3096239cb92ec65d6964671f205be4da639e541c16199b66371c" - }, - { - "text": "Diagnostic criteria that suggest Cushings syndrome are UFC greater than the normal range for the assay, serum cortisol greater than 1.", - "tokenCount": 27, - "pageStart": 6, - "pageEnd": 6, - "hash": "51354bfd88c526ba07962db2c55e52b15d677a97271af099d9ecfc8abb48ac06" - }, - { - "text": "8 g/dl (50 nmol/liter) after 1 mg dexamethasone (1-mg DST), and latenight salivary cortisol greater than 145 ng/dl (4 nmol/liter).", - "tokenCount": 48, - "pageStart": 6, - "pageEnd": 6, - "hash": "5fd6afeb9b96b2feb5cd0a3ad773b2acdeee9e1383852de63380c2c5895059d0" - }, - { - "text": "org 1531 Downloaded from https://academic.", - "tokenCount": 11, - "pageStart": 6, - "pageEnd": 6, - "hash": "2c06ba812fe90c3bc44f863a3b3225651da7a09d85bfb983e08ae968a3c1095d" - }, - { - "text": "Remarks for dexamethasone tests Variable absorption and metabolism of dexamethasone may influence the result of both the overnight 1-mg DST and the 48-h, 2 mg/d test.", - "tokenCount": 44, - "pageStart": 7, - "pageEnd": 7, - "hash": "ca4cace3b0cd55a9a9387edde13eb65751eff549cc68fecb5adf009a0a2ac451" - }, - { - "text": "Drugs such as phenytoin, phenobarbitone, carbamazepine, rifampicin, and alcohol induce hepatic enzymatic clearance of dexamethasone, mediated through CYP 3A4, thereby reducing the plasma dexamethasone concentrations (Table 3) (47).", - "tokenCount": 66, - "pageStart": 7, - "pageEnd": 7, - "hash": "689591f014669b4295a5991f63422c377c892ba4ea0a97c91041a6450328d96d" - }, - { - "text": "Conversely, dexamethasone clearance may be reduced in patients with liver and/or renal failure.", - "tokenCount": 22, - "pageStart": 7, - "pageEnd": 7, - "hash": "36612575cdbf450154daf2382c8748d15a94e48d426d5a15346dd8bffc4bf3a9" - }, - { - "text": "Dexamethasone levels show interindividual variation, however, even in healthy individuals on no medication.", - "tokenCount": 21, - "pageStart": 7, - "pageEnd": 7, - "hash": "4c008ae1983d2614a7e0a95cfe2f66ac330d0a15f1d986027321892ffb7cefb3" - }, - { - "text": "To evaluate for falsepositive and negative responses, some experts have advocated simultaneous measurement of both cortisol and dexamethasone for these tests to ensure adequate plasma dexamethasone concentrations [ 5.", - "tokenCount": 41, - "pageStart": 7, - "pageEnd": 7, - "hash": "83993d3efe9b8e0190937f489a7b19c08aa11ffac936e38c402a13d9e0c6cdb5" - }, - { - "text": "However, given the limited availability outside the United States and cost of the dexamethasone assay, this otherwise desirable approach may not be feasible.", - "tokenCount": 30, - "pageStart": 7, - "pageEnd": 7, - "hash": "05ee89a3b860f3db95eb778bc20e5fce3001acc3096df204ed9b68f259e035ed" - }, - { - "text": "As noted above, falsepositive rates for the overnight DST are seen in 50% of women taking the oral contraceptive pill because of increased CBG levels (44).", - "tokenCount": 33, - "pageStart": 7, - "pageEnd": 7, - "hash": "0d5d44ad109edcccc9d55965e6a37d347afb22d9df908d2b169a97ec4a297350" - }, - { - "text": "1 Evidence for use of UFC The introduction of UFC represented a major advance over measurement of 17-hydroxycorticosteroids (17OHCS), which reflects both urine metabolites and cortisol.", - "tokenCount": 39, - "pageStart": 7, - "pageEnd": 7, - "hash": "9bc6cb029b972932f5c598c201b9e888de390f255670e9289dbc53f853ae7874" - }, - { - "text": "Because 17OHCS has high rates of falsepositive and negative results, it is now rarely used.", - "tokenCount": 20, - "pageStart": 7, - "pageEnd": 7, - "hash": "7241aff8b3322d6749a38f82c8978a3aa5081a397a483fac3d46e2b21a972534" - }, - { - "text": "Since the 1970s, experts have advocated the use of UFC for making the diagnosis of Cushings syndrome (49,50).", - "tokenCount": 26, - "pageStart": 7, - "pageEnd": 7, - "hash": "ca92a1ca54980627d6b4b68ad5fda420d1696b4521b92bd3015868cc66b4ce88" - }, - { - "text": "UFC provides an integrated assessment of cortisol secretion over a 24-h period.", - "tokenCount": 15, - "pageStart": 7, - "pageEnd": 7, - "hash": "8b0ccc81659801c66720f463423b2548d0d4b9025896b023df9bd766501c5ab9" - }, - { - "text": "It measures the cortisol that is not bound to CBG, which is filtered by the kidney unchanged.", - "tokenCount": 20, - "pageStart": 7, - "pageEnd": 7, - "hash": "5219d8a26c4e2bb2a9bc42a7e902892df7ec5a8f6dbf077e7671eb420840cc7c" - }, - { - "text": "Therefore, unlike serum cortisol, which measures both CBGbound and free hormone, UFC is not affected by conditions and medications that alter CBG.", - "tokenCount": 29, - "pageStart": 7, - "pageEnd": 7, - "hash": "2a9456a0c6e6934a9f595f6447a89fb951dc3e0a23b300689a95eb8233f266ef" - }, - { - "text": "For example, healthy women taking oral estrogen may have increased CBG, and therefore high serum cortisol concentration, but their UFC remains normal.", - "tokenCount": 27, - "pageStart": 7, - "pageEnd": 7, - "hash": "1de8a33100e2aebe06e3c13b29a374e392080623e2381b9dac3f577f9cd75e6c" - }, - { - "text": "Because cortisol production is increased in Cushings syndrome, the amount of unbound hormone is higher, resulting in elevated UFC values.", - "tokenCount": 26, - "pageStart": 7, - "pageEnd": 7, - "hash": "6450581346ead3b95f43ead6a5573fc3dd4811d84475d6447d6cc42aa9868e6e" - }, - { - "text": "As with any other test, sensitivity and specificity of UFC are subject to the cutoffs selected.", - "tokenCount": 19, - "pageStart": 7, - "pageEnd": 7, - "hash": "cb4edf119e63c5c6893a4c7e8fa75756a851a7deed5182c11036250af8c4dcdd" - }, - { - "text": "When the assay upper limit of normal is used as a criterion, the overall evidence supports the diagnostic accuracy of UFC in adults suspected of having Cushings syndrome (2,51).", - "tokenCount": 36, - "pageStart": 7, - "pageEnd": 7, - "hash": "f73360c17fc0849ccc77907fc47c271d6a0ae45c09bf93c8b91b606f328e3c45" - }, - { - "text": "Sensitivity for Cushings syndrome in pediatric patients is high ( 89%) (30).", - "tokenCount": 19, - "pageStart": 7, - "pageEnd": 7, - "hash": "8d429b638424f904872b365096840955c60caa7fbb4fc7f2832fccad739626ed" - }, - { - "text": "Thus, to achieve the goal of high sensitivity, we recommend using the upper limit of normal for the particular assay as the criterion for a positive test, provided the creatinine shows that the collection is complete and there is not excessive volume.", - "tokenCount": 48, - "pageStart": 7, - "pageEnd": 7, - "hash": "0c1eae71e0476ada2dc2ed9766421814d03c9e97f73084f2e3d88cb90f110bb3" - }, - { - "text": "For pediatric patients, the adult normal ranges may be used because most pediatric patients are of adult weight ( i.", - "tokenCount": 22, - "pageStart": 7, - "pageEnd": 7, - "hash": "1078c97a928b692ea7bbf899e4a85781bdc50b4cfe136bcf16a5cef9e051e25b" - }, - { - "text": "At the recommended cutoff point, falsepositive elevations of UFC may be seen in several conditions.", - "tokenCount": 19, - "pageStart": 7, - "pageEnd": 7, - "hash": "040593a5257cfcfa91c5eecb8e497e7aac9cc7c820324e023d9a2d35978b804e" - }, - { - "text": "High fluid intake ( 5 liters/d) significantly increases UFC (52).", - "tokenCount": 17, - "pageStart": 7, - "pageEnd": 7, - "hash": "acf5bed4b6d1fa6a150c99478d6aa96ed4d160dea6d6fe9420b07af845e47fb6" - }, - { - "text": "Any physiological or pathological condition that increases cortisol production raises UFC (Table 2).", - "tokenCount": 15, - "pageStart": 7, - "pageEnd": 7, - "hash": "613d67cc1147efb3a5ca9034f4523f0cf9ed203e019c65e27785cc0b15441bae" - }, - { - "text": "Therefore, in these conditions a normal result is more reliable than an abnormal one.", - "tokenCount": 16, - "pageStart": 7, - "pageEnd": 7, - "hash": "bd649401d0517dc32d0e60f24d1e5fe55470992aabca05f1436fd63d9a7a7943" - }, - { - "text": "At the recommended cutoff point, falsenegative results of urine cortisol collections also may occur.", - "tokenCount": 18, - "pageStart": 7, - "pageEnd": 7, - "hash": "90e42b89efa18ece19ea048b721e79c91721cc618d4e881fe3cde15cd1a9c71a" - }, - { - "text": "Because UFC reflects renal filtration, values are significantly lower in patients with moderate to severe renal impairment.", - "tokenCount": 21, - "pageStart": 7, - "pageEnd": 7, - "hash": "8246e22d1bd2a8ac86cd39b2b49d4578a29156ba627f6d24d3739ad74deaa48b" - }, - { - "text": "A falsely low UFC can occur when creatinine clearance falls less than 60 ml/min, and UFC levels fall linearly with more severe renal failure (53).", - "tokenCount": 33, - "pageStart": 7, - "pageEnd": 7, - "hash": "c3e11ba82fd8e0e4afc333f68b05b258e16bb572b9458f2b65add4af65793006" - }, - { - "text": "UFC can be normal if a patient has cyclic disease and collects urine when the disease is inactive.", - "tokenCount": 20, - "pageStart": 7, - "pageEnd": 7, - "hash": "95207d5e94fb1f12c933ece960a156e37a9ba64ae87ac8b3a5e5113ff7a3cd59" - }, - { - "text": "Finally, it may be normal in some patients with mild Cushings syndrome, in whom salivary cortisol may be more useful (54).", - "tokenCount": 29, - "pageStart": 7, - "pageEnd": 7, - "hash": "2e1d202b26107010dc8b62f15068d399739d10f0433fd85e83c0d4463aa9a821" - }, - { - "text": "1 Remarks for UFC Sample collection and instructions It is important to ensure that patients provide a complete 24-h urine collection with appropriate total volume and urinary creatininelevels.", - "tokenCount": 35, - "pageStart": 7, - "pageEnd": 7, - "hash": "04ef78b26850c5ecb6b6272a6455a3ceacb78ebf069cbf462e8a62d8b6c0eb06" - }, - { - "text": "Thismayrequirepatienteducationusingbothoral and written instructions.", - "tokenCount": 13, - "pageStart": 7, - "pageEnd": 7, - "hash": "46dcd1b8709b9621a64ee1b1be55bd168b0c5fd67ebe2480297d17e55ec916e9" - }, - { - "text": "The first morning void is discarded so that the collection begins with an empty bladder.", - "tokenCount": 16, - "pageStart": 7, - "pageEnd": 7, - "hash": "d3ac5826f5911e8f3256b16c90a2f53bb6a92600ff3e5972024a26c86808a1d6" - }, - { - "text": "All subsequent voids throughout the day and night should be included in the collection, which is kept refrigerated (but not frozen), up to and including the first morning void on the second day.", - "tokenCount": 39, - "pageStart": 7, - "pageEnd": 7, - "hash": "097ae21ef7a674f51754ad6200b7d4adcc4eafd9d06f3134c2684245f7fb2b8f" - }, - { - "text": "Once the bladderhasbeenemptiedintothecollectiononthesecondmorning, the sample is complete.", - "tokenCount": 20, - "pageStart": 7, - "pageEnd": 7, - "hash": "d43f7c8aa13a29c7d04f3d95efb9b671fca3cf725d517a8c5f2ed1c4c7645e3b" - }, - { - "text": "Patients should be instructed not to drink excessive amounts of fluid and to avoid the use of any glucocorticoid preparations, including steroidcontaining skin or hemorrhoid creams, during TABLE 3.", - "tokenCount": 40, - "pageStart": 7, - "pageEnd": 7, - "hash": "ab742de50298bd58cf4e520dd7dafc4d4fa256008f004a89b2afca5f2e26df43" - }, - { - "text": "Selected drugs that may interfere with the evaluation of tests for the diagnosis of Cushings syndrome a Drugs Drugs that accelerate dexamethasone metabolism by induction of CYP 3A4 Phenobarbital Phenytoin Carbamazepine Primidone Rifampin Rifapentine Ethosuximide Pioglitazone Drugs that impair dexamethasone metabolism by inhibition of CYP 3A4 Aprepitant/fosaprepitant Itraconazole Ritonavir Fluoxetine Diltiazem Cimetidine Drugs that increase CBG and may falsely elevate cortisol results Estrogens Mitotane Drugs that increase UFC results Carbamazepine (increase) Fenofibrate (increase if measured by HPLC) Some synthetic glucocorticoids (immunoassays) Drugs that inhibit 11 -HSD2 (licorice, carbenoxolone) a This should not be considered a complete list of potential drug interactions.", - "tokenCount": 209, - "pageStart": 7, - "pageEnd": 7, - "hash": "6555940d0027f59a3dd151751bfcd7a4abfafcbcf62b142c5146beedf22965c4" - }, - { - "text": "Data regarding CYP3A4 obtained from http://medicine.", - "tokenCount": 15, - "pageStart": 7, - "pageEnd": 7, - "hash": "2de5bd6d4a845a558cc93cb30a3961db44ef1884e492744eea8b2c41a6b1cbf0" - }, - { - "text": "Because UFC levels in a patient with Cushings syndrome are variable, at least two collections should be performed, particularly in children in whom reproducibility can be low.", - "tokenCount": 34, - "pageStart": 8, - "pageEnd": 8, - "hash": "702c46ca3e37bac9a3713bfdbff69eb36ffde2bdc11501e50602a8111174a726" - }, - { - "text": "2 Evidence for latenight salivary cortisol In healthy individuals with stable conventional sleepwake cycles, the level of serum cortisol begins to rise at 03000400 h, reaches a peak at 07000900 h, and then falls for the rest of the day to very low levels when the person is unstressed and asleep at midnight (55).", - "tokenCount": 69, - "pageStart": 8, - "pageEnd": 8, - "hash": "d4c3869004ac82d0455d60c5a19d8a1166803907a51bff1a3a9b57532bef3de0" - }, - { - "text": "The loss of circadian rhythm with absence of a latenight cortisol nadir is a consistent biochemical abnormality in patients with Cushings syndrome (56,57).", - "tokenCount": 34, - "pageStart": 8, - "pageEnd": 8, - "hash": "33aad509f62e339d228fbba5a40983174757f428550c24cc0feae9af13338a57" - }, - { - "text": "This difference in physiology forms the basis for measurement of a midnight serum or latenight salivary cortisol.", - "tokenCount": 22, - "pageStart": 8, - "pageEnd": 8, - "hash": "c0abcb34e74581485f57c5b9acc08cd562fac9cce10238ef1819c7b58f0676f3" - }, - { - "text": "Biologically active free cortisol in the blood is in equilibrium with cortisol in the saliva, and the concentration of salivary cortisol does not appear to be affected by the rate of saliva production.", - "tokenCount": 38, - "pageStart": 8, - "pageEnd": 8, - "hash": "6a76c53ef9713fda68e639dd966d72b551f773ba42805ca573d235506dfb5955" - }, - { - "text": "Furthermore, an increase in blood cortisol is reflected by a change in the salivary cortisol concentration within a few minutes (58).", - "tokenCount": 26, - "pageStart": 8, - "pageEnd": 8, - "hash": "135a0a773107e156f981f97bef12d70f02258d54f56f5a0a9f83faa479524358" - }, - { - "text": "Various methods have been used to measure cortisol in the saliva, resulting in different reference ranges and yielding differences in sensitivity and specificity (5967).", - "tokenCount": 28, - "pageStart": 8, - "pageEnd": 8, - "hash": "cc5ace9288e374176fef8862128b16da3be93f250abd265581ef72dbcb5e621b" - }, - { - "text": "The bestvalidatedassaysusedintheUnitedStatestomeasuresalivarycortisol are an ELISA and an assay performed by LCMS/MS (28).", - "tokenCount": 36, - "pageStart": 8, - "pageEnd": 8, - "hash": "aa263666b3a31a8a78d9e73b5edaf1cdb6058b0ffa63c735f9f3d1e1b207b4f0" - }, - { - "text": "When these two assay techniques are used, normal subjects usually have salivary cortisol levels at bedtime, or between 2300 and 2400 h, of less than 145 ng/dl (4 nmol/liter).", - "tokenCount": 43, - "pageStart": 8, - "pageEnd": 8, - "hash": "89c89082655f0e2aabec96367fa0ae0f66315b050b60b9376d499ebaece68e22" - }, - { - "text": "Using a variety of assays and diagnostic criteria, investigators from different countries have reported that latenight salivary cortisol levels yield a 92100%sensitivityanda93100%specificityforthediagnosis of Cushings syndrome (5967).", - "tokenCount": 53, - "pageStart": 8, - "pageEnd": 8, - "hash": "f30d9ccee1148c1afb18f9b85fa8f418e1853f5f18cafd056474303b265c2383" - }, - { - "text": "Overall, the evidence in adults suggeststhattheaccuracyofthistestissimilartothatofUFC(2).", - "tokenCount": 26, - "pageStart": 8, - "pageEnd": 8, - "hash": "2a3ec5bbc5778722f5375702c6e10228b01ed5e3377a9afac1eda836c101d8ce" - }, - { - "text": "This easily performed, noninvasive test has been used in children to differentiate patients with Cushings syndrome from those with simple obesity.", - "tokenCount": 27, - "pageStart": 8, - "pageEnd": 8, - "hash": "e6428710e35a5a1aa88782b3cbc3ff2971871e74be849ba04026107ef050ec53" - }, - { - "text": "Investigators have reported high sensitivity (100%) and specificity (95.", - "tokenCount": 13, - "pageStart": 8, - "pageEnd": 8, - "hash": "e9453f104dd6a5ca9c467e9485067e405c3f145f30a040d31372bc448500836c" - }, - { - "text": "2%) for Cushings syndrome in this setting (68).", - "tokenCount": 13, - "pageStart": 8, - "pageEnd": 8, - "hash": "de90e990a315a87810c6de374538164a95bdfa255462f8f30bef8b0a35283015" - }, - { - "text": "The influence of gender, age, and coexisting medical conditions on the latenight salivary cortisol concentrations has not beenfullycharacterized.", - "tokenCount": 29, - "pageStart": 8, - "pageEnd": 8, - "hash": "d76a256414e67d8db18af8ed19d7d9a1c326c9ffaae36e19af68d711495c0e34" - }, - { - "text": "Itisimportanttonotethatthecircadian rhythm is blunted in many patients with depressive illness and in shift workers (69,70) and may be absent in the critically ill (71).", - "tokenCount": 41, - "pageStart": 8, - "pageEnd": 8, - "hash": "c9d277e6378697577471a2741945c73e52aa26d8f6102aec4e3eb1104842d7f4" - }, - { - "text": "Other populations may have a high percentage of falsepositive results.", - "tokenCount": 12, - "pageStart": 8, - "pageEnd": 8, - "hash": "110f7bdde44b42f59e20af7485bb49f152e731c35e5cd49a7840d4e87ca92adb" - }, - { - "text": "For example, in a study of men aged 60 yr or older, Liu et al.", - "tokenCount": 18, - "pageStart": 8, - "pageEnd": 8, - "hash": "c1e79a3c88e1b75a5c5eb3b7f6ccd10a189efe05b4e809bd41b0a3ab40bc589f" - }, - { - "text": "(72) reported that 20% of all participants and 40% of diabetichypertensivesubjectshadatleastoneelevatedlatenight salivary cortisol measurement.", - "tokenCount": 41, - "pageStart": 8, - "pageEnd": 8, - "hash": "5528a001f53072308f93a35d16ed1dbf69f93a30ba215945dd6d97469bd41b5b" - }, - { - "text": "Using the upper reference range of each assay as the cutoff point, Baid et al.", - "tokenCount": 18, - "pageStart": 8, - "pageEnd": 8, - "hash": "dd56852d5951f889fcfa95a647af86a9de335ffbcf771f78a1ea325cebc7295f" - }, - { - "text": "(28) measured bedtime salivary cortisol levels in a large number of obese subjects and found a specificity of only 85% when they used a RIA technique, but a better specificity of 92% when tandem mass spectrometry was used.", - "tokenCount": 50, - "pageStart": 8, - "pageEnd": 8, - "hash": "be7f4ac35c9168697ac6fbb00ef33cc7d8313d7cffc505f820ba6794dac6ad97" - }, - { - "text": "2 Remarks for latenight salivary cortisol Most clinicians using the latenight salivary cortisol test ask patientstocollectasalivasampleontwoseparateeveningsbetween 2300 and 2400 h.", - "tokenCount": 46, - "pageStart": 8, - "pageEnd": 8, - "hash": "f3a4ec9713d34c469f61a18e4fb654be8a4febef31e7e546338e3a5b70398b0e" - }, - { - "text": "Saliva is collected either by passive drooling into a plastic tube or by placing a cotton pledget (salivette) in the mouth and chewing for 12 min.", - "tokenCount": 35, - "pageStart": 8, - "pageEnd": 8, - "hash": "49ea9b5fba5d244675ac3ab9db61cdb21ea55402ef83ec94f847f8397efd8606" - }, - { - "text": "The sample is stable at room or refrigerator temperature for several weeks and can be mailed to a reference laboratory.", - "tokenCount": 21, - "pageStart": 8, - "pageEnd": 8, - "hash": "5c11d65fee3b8bda5358c65bccde3629685c830c220229693565d6edb221c008" - }, - { - "text": "Reports show good correlation between salivary and simultaneous serum cortisol values in healthy volunteers(73,74).", - "tokenCount": 21, - "pageStart": 8, - "pageEnd": 8, - "hash": "40992147f013c7c8f77f2b5b3d86d3bcab6d2d2cab9d2a09e44db1fcbf61ff8d" - }, - { - "text": "Whensampleswereobtainedatthesamesitting, those collected using the salivette device had lower cortisol concentrations than those collected from passive drooling, but they correlated better with total and free serum cortisol levels (74).", - "tokenCount": 46, - "pageStart": 8, - "pageEnd": 8, - "hash": "c0e8bd630dd7c01c584c461c3233318ebae95d193b6c4781bff76184a8bd24d3" - }, - { - "text": "Several factors that affect the salivary cortisol test should be considered when evaluating the results.", - "tokenCount": 18, - "pageStart": 8, - "pageEnd": 8, - "hash": "54d690821ed4862f9a627f7db8095601f394e05542d2a60d8e52e9df3a6dbd5f" - }, - { - "text": "The salivary glands express 11 -hydroxysteroid dehydrogenase type 2 (11 -HSD2), which converts the biologically active cortisol to inactive cortisone (75).", - "tokenCount": 40, - "pageStart": 8, - "pageEnd": 8, - "hash": "b4174f9e96dae859d8e1db4d7a46cd34776265583918cbdcd726035c6bd6210b" - }, - { - "text": "It is theoretically possible that individuals using licorice or chewing tobacco (both of which contain the 11 -hydroxysteroid dehydrogenase type 2 inhibitor glycyrrhizic acid) may have a falsely elevated latenight salivary cortisol.", - "tokenCount": 53, - "pageStart": 8, - "pageEnd": 8, - "hash": "feba0bf4486ab9de66bb0f13630133299aec0d636b9e6c6052d9c042f13690f6" - }, - { - "text": "Patients who smoke cigarettes also have been shown to have higher latenight salivary cortisol measurements than do nonsmokers (76).", - "tokenCount": 28, - "pageStart": 8, - "pageEnd": 8, - "hash": "5e79679e23ac91f340cfdf6b6796deb0e19c811e05547f8bd4967cff7cb920d9" - }, - { - "text": "Although the duration of this effect is not known, it seems prudent to avoid cigarette smoking on the day of collection.", - "tokenCount": 23, - "pageStart": 8, - "pageEnd": 8, - "hash": "6994f8d27060adadf743aa1dbd72438cd3febf7974aa399db4ec6ca78eaf4407" - }, - { - "text": "Direct contamination of the salivette by steroidcontaining lotion or oral gels also may result in falsepositive results.", - "tokenCount": 25, - "pageStart": 8, - "pageEnd": 8, - "hash": "daae22069ae9a06cece3afef1211bb7d4e992f820a12ad7ad5a9de45ec1f2462" - }, - { - "text": "Because the test assumes a nadir of cortisol in the late evening, it may not be appropriate for shift workers or those with variable bedtimes, and the timing of the collection should be adjusted to the time of sleepingforthosewithbedtimesconsistentlylongaftermidnight.", - "tokenCount": 57, - "pageStart": 8, - "pageEnd": 8, - "hash": "2213497603693c314dd57a3e34c1e2a0305564b28c2de77c8de1340c1826e201" - }, - { - "text": "Similarly, nocturnal salivary cortisols may be transiently abnormal in individuals crossing widely different time zones.", - "tokenCount": 24, - "pageStart": 8, - "pageEnd": 8, - "hash": "34df64471fa0174ed709f4d828f3a2f79052b6df107d08d0df596ca69ee6ce65" - }, - { - "text": "Finally, stress immediately before the collection also may increase salivary cortisol physiologically; therefore, ideally, samples should be collected on a quiet evening at home (64).", - "tokenCount": 34, - "pageStart": 8, - "pageEnd": 8, - "hash": "c00fd5f8d06f58871005e3ad34ebe97cb78b4dd1620612900ebb4b376ea3398e" - }, - { - "text": "Theoretically, contamination with blood might increase salivary cortisol levels.", - "tokenCount": 15, - "pageStart": 8, - "pageEnd": 8, - "hash": "436692aa6cfe7c76e29c847543c503b466b7505d7993362132813ffd334b6c5e" - }, - { - "text": "(77) reported that minor to moderate blood leakage as a result of vigorous tooth brushing had no effect on salivary cortisol values, the possible effect of gingivitis or oral sores or injury is not known.", - "tokenCount": 45, - "pageStart": 8, - "pageEnd": 8, - "hash": "c87277d136270f238e9caa9a3668f12da823ca1860c212a863e0de910ffc99a7" - }, - { - "text": "3 Evidence for the 1-mg DST In normal subjects, the administration of a supraphysiological dose of glucocorticoid results in suppression of ACTH and cortisol secretion.", - "tokenCount": 38, - "pageStart": 8, - "pageEnd": 8, - "hash": "42063c60bcb9866db67724f3a53b22d7cd399e508c9d3335f52928373cddadcc" - }, - { - "text": "In endogenous Cushings syndrome of any cause, there is a failure of this suppression when low doses of the synthetic glucocorticoid dexamethasone are given (78).", - "tokenCount": 38, - "pageStart": 8, - "pageEnd": 8, - "hash": "1cda9233209c94a57bbb40231ff57c52ae4a944f42d3bfac809e6c43ce512183" - }, - { - "text": "Theovernighttestisasimpleoutpatienttest.", - "tokenCount": 12, - "pageStart": 8, - "pageEnd": 8, - "hash": "68cd3da240a8550b66fbcc285e20d3217d9eac4bc954f7b6f936794fc4c34ed7" - }, - { - "text": "Variousdosesof dexamethasone have been used, but 1 mg dexamethasone is usually given between 2300 and 2400 h, and cortisol is measured between 0800 and 0900 h the following morning.", - "tokenCount": 46, - "pageStart": 8, - "pageEnd": 8, - "hash": "ce3b840bf910397bd3b8a6ad0181a4a142a6097c5b8ef08d46646da5855f0cec" - }, - { - "text": "5or2mg)donotsignificantlyimprovetheaccuracyofthetest (49).", - "tokenCount": 19, - "pageStart": 8, - "pageEnd": 8, - "hash": "4a8fc22c076de4d5b893a44e26c7a1db25fa8eafd15ac9d1ecce9745041c4f62" - }, - { - "text": "Researchers have used cutoff values for the suppression of serum cortisol from 3.", - "tokenCount": 14, - "pageStart": 8, - "pageEnd": 8, - "hash": "c2b71bf6d9162a0e34ead9e583a1f8b078013d58bc26ba3fe6f58abe80344904" - }, - { - "text": "2 g/dl (100200 nmol/liter) when measured by modern RIA (79).", - "tokenCount": 22, - "pageStart": 8, - "pageEnd": 8, - "hash": "528af6a965c25d288433c5ae1609f10df8a572b11440c847c52ce6fc59788890" - }, - { - "text": "A widely cited normal response is a serum cortisol less than 5 g/dl ( 140 nmol/liter) (7,80).", - "tokenCount": 29, - "pageStart": 8, - "pageEnd": 8, - "hash": "f42b8f247b5e79e83e617b67086fc83b8d02c06e44901c84ca00e7a8143fc76c" - }, - { - "text": "Because some patients with Cushings disease demonstrate suppressibility to dexamethasone, use of this diagnostic criterion J Clin Endocrinol Metab, May 2008,93(5):15261540 jcem.", - "tokenCount": 46, - "pageStart": 8, - "pageEnd": 8, - "hash": "8f04efa2003bce6d1f70a71d2d3ea4dca2a9e5bc2af4fa745351c67c2794988a" - }, - { - "text": "org 1533 Downloaded from https://academic.", - "tokenCount": 11, - "pageStart": 8, - "pageEnd": 8, - "hash": "36dd0298c6da4100aa6466801b4036c5f8c8c89510c8a8fbc3980e63370073a5" - }, - { - "text": "misclassified up to 15% of such patients as negative (81,82).", - "tokenCount": 16, - "pageStart": 9, - "pageEnd": 9, - "hash": "a7736e18d0d24489944033902a9086a8a59379de307eac12d9f5da52fe0a9b2b" - }, - { - "text": "Therefore,toenhancesensitivity,expertshaveadvocatedrequiring a lower cutoff for suppression of the postdexamethasone serum cortisol to less than 1.", - "tokenCount": 35, - "pageStart": 9, - "pageEnd": 9, - "hash": "f6c99b7aa2a7cda0df9337a893b7c63d17718f3e8904516b5c16c97c37679563" - }, - { - "text": "8 g/dl (50 nmol/liter) to achieve sensitivityratesofgreaterthan95%(83).", - "tokenCount": 25, - "pageStart": 9, - "pageEnd": 9, - "hash": "63604ca2af4ef6e30a3980daab959846fda6cd8e354dee496f90e44b2e8fe9c0" - }, - { - "text": "8 g/dlcutoff, the sensitivity is high with specificity rates of 80%; specificity increasestogreaterthan95%ifthediagnosticthresholdisraised to 5 g/dl (140 nmol/liter) (7).", - "tokenCount": 53, - "pageStart": 9, - "pageEnd": 9, - "hash": "17d4e29f9c125b080ebb8472fd771a9803eacf02db9e3c8c9abf94d991cc2b8a" - }, - { - "text": "Given our objective of using tests with high sensitivity at this stage, we recommend use of the more stringent cutoff of 1.", - "tokenCount": 24, - "pageStart": 9, - "pageEnd": 9, - "hash": "3973ac3d6b2f0e61d737dfc4a44bc1fff9ce0bddcd09c6dc255132f10db2b47a" - }, - { - "text": "Overall, the evidence in adults indicates that in studies with low prevalence of Cushings syndrome this test has similar performance as the others recommended for initial testing (2).", - "tokenCount": 33, - "pageStart": 9, - "pageEnd": 9, - "hash": "3fccdcc5a98aceac1585221b8177bd7ee5548ff5971fc0cd9d0932ba60faccc1" - }, - { - "text": "Although the 1-mg overnight test is used as a screening test for pediatric patients, there are no specific data regarding its interpretation or performance in this population.", - "tokenCount": 31, - "pageStart": 9, - "pageEnd": 9, - "hash": "747fc5d169177b49d752faeff763075d00c546c7baaee80949e5b74e7a8c0bb1" - }, - { - "text": "3 Remarks for the 1-mg DST See the earlier comments under 3.", - "tokenCount": 17, - "pageStart": 9, - "pageEnd": 9, - "hash": "339888c45ad05e9d64b6a591870a0cacb8615cfa9fc6b532b38e9f1459881d2e" - }, - { - "text": "4 Remarks for dexamethasone tests .", - "tokenCount": 11, - "pageStart": 9, - "pageEnd": 9, - "hash": "79729b59b9667a08e844f296f63d058090d3fe5585440c74eba57b3024801b99" - }, - { - "text": "4 Evidence for the 48-h, 2 mg/d DST Some endocrinologists prefer to use the 48-h, 2 mg/d lowdose DST(LDDST)asaninitialtestbecauseofitsimprovedspecificity as compared with the 1-mg test.", - "tokenCount": 59, - "pageStart": 9, - "pageEnd": 9, - "hash": "cf21adf504ab81f81010309f6a453f2d7b551a9f7307395f71406f5f12ea333e" - }, - { - "text": "With adequate written instructions for the patient, the LDDST is easily performed in the outpatient setting.", - "tokenCount": 20, - "pageStart": 9, - "pageEnd": 9, - "hash": "203ac243e827c4c1598dc5228f8588e4664811c869ed0a06e95215e70b32f1ab" - }, - { - "text": "0 ), certain psychiatric conditions (depression, anxiety, obsessive compulsive disorder), morbid obesity, alcoholism, and diabetes mellitus can be characterized by overactivation of the HPA axis but without true Cushings syndrome, i.", - "tokenCount": 46, - "pageStart": 9, - "pageEnd": 9, - "hash": "fec212f53c6b367027be2e748f9e19f69571352538b3d9403c01b547fc15b514" - }, - { - "text": "In these conditions, UFC measurements are less useful as an initial test.", - "tokenCount": 14, - "pageStart": 9, - "pageEnd": 9, - "hash": "50acf78e25c54c91ba45e543af1e59dd359e7d77a4c15beccc37d33f20a79cc9" - }, - { - "text": "Previous studies using various doses of dexamethasone and differing criteria for suppression suggest that at least 2 wk of abstinence from alcohol are needed to reduce the falsepositive rate (84).", - "tokenCount": 38, - "pageStart": 9, - "pageEnd": 9, - "hash": "6af525b3af0575a17c5c55073d326031ca917c49e22ac8f2ef7c322fff0dc833" - }, - { - "text": "First described by Liddle (85) in 1960, the LDDST initially evaluated urinary 17OHCS as an indicator of cortisol suppression.", - "tokenCount": 28, - "pageStart": 9, - "pageEnd": 9, - "hash": "026d0c0c4c79816dc4b419206e63a102e8fd4acaaed6cd01ad4750f2c4a1b00a" - }, - { - "text": "However, using 17OHCS or UFC, sensitivity and specificity rates are less than 7080%.", - "tokenCount": 19, - "pageStart": 9, - "pageEnd": 9, - "hash": "22356559ab2db24abe76a732f2ef6821e8789747cc04a3fa5a63ddd8177293bb" - }, - { - "text": "Use of a serum cortisol end point is simpler and has higher diagnostic accuracy (78).", - "tokenCount": 17, - "pageStart": 9, - "pageEnd": 9, - "hash": "cc4599e537bfa8d6eae174adf58812ebebddba8d2b3aca46c93b64864fefdc04" - }, - { - "text": "With a cutoff value for suppression of 50 nmol/liter (1.", - "tokenCount": 15, - "pageStart": 9, - "pageEnd": 9, - "hash": "3cb471f8a26c16a10cbc1901574cbb54f73f60466c052f377bff43b3b97ce480" - }, - { - "text": "8 g/ dl), the initially reported sensitivity was greater than 95% for adultpatients(86).", - "tokenCount": 23, - "pageStart": 9, - "pageEnd": 9, - "hash": "3dc73de7eba641a6c745628555abf93ceb9ec68d44ff31dd7adf4d905d39b8ce" - }, - { - "text": "Withthisapproach,thesensitivityforCushings syndrome in 36 pediatric patients was 94% (87).", - "tokenCount": 23, - "pageStart": 9, - "pageEnd": 9, - "hash": "24f29a371e6775f6e99943167c2d5d97a431960a2f30d9c6840e9b14a5ab3d8e" - }, - { - "text": "With a slightly different protocol and a lower cortisol criterion [38 nmol/liter (1.", - "tokenCount": 19, - "pageStart": 9, - "pageEnd": 9, - "hash": "dbf4317e55a2d16f3e8a6997f962ed3dc57806aaf3f8e6362332d8445c9f5bc9" - }, - { - "text": "4 g/dl)], the sensitivity was 90% in another study (9).", - "tokenCount": 18, - "pageStart": 9, - "pageEnd": 9, - "hash": "33b1ad173c57832c3214a29e386056189e39efcbdd5a0008980d3bb1909f6b5c" - }, - { - "text": "Subsequent reports showed lower diagnostic accuracy of the LDDST (7,8890).", - "tokenCount": 18, - "pageStart": 9, - "pageEnd": 9, - "hash": "72d749c27ac0cebc6daf08fa23f65a688412a717b95cfe721b0bbb7bdc433489" - }, - { - "text": "Overall, in 92 patients without Cushings syndrome, the specificity of the LDDST was 70% (95% confidence interval 6987%). In 59 patients with Cushings syndrome, sensitivity was 96% for the LDDST (91).", - "tokenCount": 50, - "pageStart": 9, - "pageEnd": 9, - "hash": "2cf61d5cd3c42ef205bcccc04363adf330e53a55851e92467c5c6900b2836aa4" - }, - { - "text": "The reasons for this apparent decrease in specificity are unknown.", - "tokenCount": 11, - "pageStart": 9, - "pageEnd": 9, - "hash": "9cc39d868e389b6bafac78580cc36bf0a55aa99f7c1a2ac4d063eaea765424fc" - }, - { - "text": "Serum dexamethasone levels were not evaluated; in healthy volunteers, dexamethasone levels 2 h after the last dose were 13.", - "tokenCount": 31, - "pageStart": 9, - "pageEnd": 9, - "hash": "288c54447b3ba46713866bbdf78a94d9f0ae4a965665af402e9cd06b7ec02d7a" - }, - { - "text": "Consequently, the overall evidence in adults indicates that this test has similar or slightly less diagnostic accuracy than the other tests recommended here for initial testing (2).", - "tokenCount": 32, - "pageStart": 9, - "pageEnd": 9, - "hash": "dd2bdd6d2c0682c2648f67a4c95e52a413e4c1f81163402e7ba307d56e262813" - }, - { - "text": "4 Remarks for the 48-h, 2 mg/d DST In addition to the general remarks on dexamethasone tests presented in the Initial testing section, there are further considerationsfortheLDDST.", - "tokenCount": 45, - "pageStart": 9, - "pageEnd": 9, - "hash": "d564c79899231a376e169681d4ca11bbac8eab554e827cb5c7311b7a2f5c8ce8" - }, - { - "text": "Dexamethasoneisgivenindosesof0.", - "tokenCount": 12, - "pageStart": 9, - "pageEnd": 9, - "hash": "dfb3aae19819908c8d762fc80ab5bf4d3565613aaebcf6c5a7271f2e2bc9cb63" - }, - { - "text": "5mg for 48 h, beginning at 0900 h on d 1, at 6-h intervals, i.", - "tokenCount": 23, - "pageStart": 9, - "pageEnd": 9, - "hash": "6f9813fbaab39b513036b16bcc5ac062ffa14119dfc6886afc777f60e9c97c52" - }, - { - "text": "at 0900,1500, 2100, and 0300 h.", - "tokenCount": 13, - "pageStart": 9, - "pageEnd": 9, - "hash": "af0c8a6640483eeace7d75e0d0171c541b7e6c9222de1421448106923231932e" - }, - { - "text": "Serum cortisol is measured at 0900 h, 6 h after the last dose of dexamethasone.", - "tokenCount": 23, - "pageStart": 9, - "pageEnd": 9, - "hash": "9232b6dcdc671700c050229976d90ecf919ecf36f81aa77f175ac1d168cb2c78" - }, - { - "text": "(9) proposed a different protocol: administering 48 h of dexamethasone at 6-h intervals but beginning at 1200 h and obtaining serum cortisol at 0800 h, exactl y 2 h (rather than 6 h as in the usual protocol) after the last dexamethasone dose.", - "tokenCount": 62, - "pageStart": 9, - "pageEnd": 9, - "hash": "799577b285de7cf81ccf63605eb757fb29a61967ec5a98c671e62b6ae80d0e88" - }, - { - "text": "For pediatric patients weighing more than 40 kg, the initial adult protocol described above and the adult threshold for normal suppression [ 50 nmol/liter (1.", - "tokenCount": 32, - "pageStart": 9, - "pageEnd": 9, - "hash": "398bea073d9f38aed893f975c10bc2a4b878bc86e7107834f4842715ec7d08c2" - }, - { - "text": "For patients weighing less than 40 kg, the dose is adjusted to 30 g/kg d (in divided doses) (87).", - "tokenCount": 28, - "pageStart": 9, - "pageEnd": 9, - "hash": "e73c07bfee58b20ea16e394fc568a549f090496eab64daafeb72742df57dc888" - }, - { - "text": "5 Evidence The diagnostic accuracy of various other tests previously advocated for the diagnosis of Cushings syndrome (urinary 17-ketosteroids,1600horotherrandomcortisollevels,andtheinsulin tolerance test) is too low to recommend them for testing (49).", - "tokenCount": 55, - "pageStart": 9, - "pageEnd": 9, - "hash": "a22994a9461acb3b1557fdebcb62ae0d98aa5099c7f12f38beab00796643769d" - }, - { - "text": "Other tests, such as the loperamide test, have insufficient evidence for their diagnostic accuracy.", - "tokenCount": 19, - "pageStart": 9, - "pageEnd": 9, - "hash": "1b04a580a985a498211d3a4a203fbb66b273af6357eeb9b34d46b50dd07fb553" - }, - { - "text": "The response to those tests used specifically to establish the cause of Cushings syndrome ( e.", - "tokenCount": 19, - "pageStart": 9, - "pageEnd": 9, - "hash": "c51f14e7cb037842051851d49a7f27b3dcce7c27e0c6ee99524efcc4de1bd3f5" - }, - { - "text": "pituitary, adrenal or thoracic imaging, plasma ACTH concentration, CRH stimulation test, 8 mg dexamethasone suppression test) may be both abnormal in healthy people and normal in patients with Cushings syndrome and therefore are not helpful in establishing the diagnosis (78).", - "tokenCount": 60, - "pageStart": 9, - "pageEnd": 9, - "hash": "429aa0dfe9d48fb4b065d21f9435b990ea9be2d56519e003dcb5791f1d7feb34" - }, - { - "text": "8 Evidence Our recommendations for retesting patients with initially normal test results who develop new or progressive signs or symptoms of Cushings syndrome comes from the panels clinical observations and relate to the recognition that the patients pretest probability of Cushings syndrome would be higher on retesting and that hypercortisolism may have evolved concomitantly with the progression of the clinical syndrome, enhancing the likelihood that repeat tests would be positive. Similarly, the recommendation to retest patients with suspected cyclic Cushings syndrome comes from the recognition that these individuals may have normal test results when the disorder is quiescent (93).", - "tokenCount": 124, - "pageStart": 9, - "pageEnd": 9, - "hash": "d37350552bbc9370bfe9ce30ab7809ff3fa25ff266255939cd4797af1e2917fd" - }, - { - "text": "The performance and interpretation of subsequent testing for Cushings syndrome requires considerable expertise (both in the clinic and in the laboratory) and may be followed by either complex testing to establish its cause and surgical treatments or expert reassurance of patients that they do not have this condition.", - "tokenCount": 54, - "pageStart": 9, - "pageEnd": 9, - "hash": "67e79d0f0d05604eced26f82a797da65c75d6978701e36df895b6c3b96a74a2f" - }, - { - "text": "Because of this, it is the panels observation that referral to endocrinology centers with expertise and interest in Cushings syndrome in patients with abnormal initial testing is likely to be associated with better patient outcomes.", - "tokenCount": 41, - "pageStart": 9, - "pageEnd": 9, - "hash": "78678e2d3bd0e744fd71a7a9d8636eaac0f12c0f50625b9004ddbb98dab579b9" - }, - { - "text": "The recommendation to perform additional testing in patients with discordant results derives from the knowledge that some patients with Cushings syndrome, usually those with mild or cyclic disease, may have discordant results.", - "tokenCount": 40, - "pageStart": 10, - "pageEnd": 10, - "hash": "99929d524bee59075e6c83611d1ff3c069766af29731b11437b25a1d98917e0e" - }, - { - "text": "Also, some patients without Cushings syndrome may have only a minimally abnormal but discordant result.", - "tokenCount": 21, - "pageStart": 10, - "pageEnd": 10, - "hash": "09ce400c096234766ed24df4fa24813e4f6aea2e39e5659b0d7d3c846fc411b7" - }, - { - "text": "The distinction between these groupsisdifficult,andthereisnoonecorrectdiagnosticstrategy.", - "tokenCount": 20, - "pageStart": 10, - "pageEnd": 10, - "hash": "72196357c977962a515a1915280eb636e89bf66a134e1aa752ced56e51d09783" - }, - { - "text": "The test results validity should be evaluated in light of the caveats mentioned for specific patient situations and for each test and assay.", - "tokenCount": 24, - "pageStart": 10, - "pageEnd": 10, - "hash": "4527d246d288f9541247699e1a9a0240dc6f64aa9a0d802d992d520d0b0452b7" - }, - { - "text": "For example, an abnormal UFC may not be accepted if the specimen volume and creatinine suggest overcollection.", - "tokenCount": 22, - "pageStart": 10, - "pageEnd": 10, - "hash": "361443753a2cd20481755f57dbc12e9812fa4941795bcbf4a1297e480111727f" - }, - { - "text": "Underlying disorders that may cause mild hypercortisolism (Table 2) should be considered and testing repeated when these are treated or resolved.", - "tokenCount": 29, - "pageStart": 10, - "pageEnd": 10, - "hash": "6d1215619e807f1783b09c9d76a609353f8362b702f92d9d95f232d36b2b9965" - }, - { - "text": "Postponing additional testing to allow progression of clinical and biochemical features may be useful.", - "tokenCount": 17, - "pageStart": 10, - "pageEnd": 10, - "hash": "4bc30fadfd3fe735e4e9992dd2271864cde29d5ec20b63944777d4d0ea8b72dd" - }, - { - "text": "The patient should be reassured that this poses minimal risk in the setting of mild hypercortisolism.", - "tokenCount": 21, - "pageStart": 10, - "pageEnd": 10, - "hash": "64a5b3b36b710cbc997a34e9a7e074b2aa2ee11885a6938c8443c0a76880a067" - }, - { - "text": "8 For the subsequent evaluation of abnormal test results from one of the highsensitivity tests, we recommend performing another recommended test (Fig.", - "tokenCount": 26, - "pageStart": 10, - "pageEnd": 10, - "hash": "e7881404a1c4f7eab06f10d661c1284426f3f0ce268282d999c58dd6309272a3" - }, - { - "text": "8 Remarks If the initial test result is abnormal, further evaluation by an endocrinologist will ensure that the disorder is confirmed or refuted and that the possibility of a falsepositive result will be considered.", - "tokenCount": 40, - "pageStart": 10, - "pageEnd": 10, - "hash": "01ba5fe55700670d1fdb90cfbc86dae8c1d88c5e4ce62ccb0647cc5b7f840abb" - }, - { - "text": "Conversely, in cases in which there is a high pretest probability of Cushings syndrome but a normal initial test, use of an additional alternative test has the potential benefit of disclosing those with milder disease.", - "tokenCount": 43, - "pageStart": 10, - "pageEnd": 10, - "hash": "0137f56b4c648185b0f71f5dab5ac07ca1afe596a64bd1c83533ca9f9b194320" - }, - { - "text": "1 Evidence for the 48-h, 2 mg/d LDDST with CRH In an effort to improve the sensitivity of the 48-h, 2 mg/d test, researchers developed a combined CRH stimulation test.", - "tokenCount": 46, - "pageStart": 10, - "pageEnd": 10, - "hash": "173d785ff78abe7c1065e24a24437b19eea6578ace6bbaedd2f67b678d13d220" - }, - { - "text": "In theory, dexamethasone suppresses serum cortisol levels in individuals without Cushings syndrome as well as a small number of those with Cushings disease, but if given CRH, patients with Cushings disease should respond with an increase in ACTH and cortisol.", - "tokenCount": 57, - "pageStart": 10, - "pageEnd": 10, - "hash": "c95e43c03e72f2bbbdad0829b561bb2bca42ed8de442bc9217e6df8a23fe6f4a" - }, - { - "text": "The test is done by administering the 48-h 2 mg/d DST, followedbyadministrationofCRH(1 g/kg,iv )2hafterthelast dose of dexamethasone.", - "tokenCount": 46, - "pageStart": 10, - "pageEnd": 10, - "hash": "8c23ea814376e6ad2d3a0dbc1b050adc6d3fffaeec8f80fd1d2aa39685514e34" - }, - { - "text": "The initial report of this strategy showed high diagnostic accuracy (92,94).", - "tokenCount": 15, - "pageStart": 10, - "pageEnd": 10, - "hash": "74a388c99125d593a389cd19892a9d664d064f083dda8e99000f4ce56a6ae273" - }, - { - "text": "All eight of 59 patients with proven Cushings disease who suppressed preCRH cortisol to less than 1.", - "tokenCount": 22, - "pageStart": 10, - "pageEnd": 10, - "hash": "0daa412bc93ba00fb51982004bce4285f8999da9bc884fa932bf5dd5d9055336" - }, - { - "text": "4 g/dl ( 38 nmol/liter; sensitivity 86%) were properly characterized after CRH administration.", - "tokenCount": 24, - "pageStart": 10, - "pageEnd": 10, - "hash": "6cca6e687a367afa2e11667e729a2b0f85fce093d4986d550f710a030c7c1809" - }, - { - "text": "Subsequent reports showed lower diagnostic accuracy of both the DST and the combined test (7,8890).", - "tokenCount": 22, - "pageStart": 10, - "pageEnd": 10, - "hash": "d69104f0616d247700576f840b5c34682034f714eb0605b6d67b1034343835a0" - }, - { - "text": "Overall, in 92 patients without Cushings syndrome, the specificity of the LDDST was 70% (95% confidence interval 6987%), compared with a 60% specificity for the dexamethasoneCRH test (95% confidence interval 5979%). In 59 patients with Cushingssyndrome,sensitivitywas96%fortheLDDSTand98%for the dexamethasoneCRH test.", - "tokenCount": 88, - "pageStart": 10, - "pageEnd": 10, - "hash": "e635e7cf5415b683039c71eaf361c7e31e386fb1288082dd97db221514c9b97a" - }, - { - "text": "The reasons for the differences in the responses to the LDDST and the combined test are not clear.", - "tokenCount": 21, - "pageStart": 10, - "pageEnd": 10, - "hash": "696b803facefd14582ef6b93f86091e355311fbe7b575f75612bacf51095874e" - }, - { - "text": "As discussed above, any dexamethasone test may give either falsepositive or falsenegativeresultsinconditionsthatalterthemetabolicclearanceofthe agent; additionally, differences in the performance of cortisol assays may contribute.", - "tokenCount": 49, - "pageStart": 10, - "pageEnd": 10, - "hash": "06463b5e9313d94e8899f124b857dfd38ac398db230132f635bfb05085b414cb" - }, - { - "text": "1 Remarks for the dexamethasoneCRH test The dexamethasoneCRH test can be useful in patients with equivocal results for UFC.", - "tokenCount": 35, - "pageStart": 10, - "pageEnd": 10, - "hash": "d2bfef3cfda25223bd8fb821132f062471552fe7d400d700c7d7b02574893418" - }, - { - "text": "A dexamethasone level should be measured at the time of CRH administration to exclude a falsepositive result, and the serum cortisol assay must be accurate at these low levels of detection.", - "tokenCount": 39, - "pageStart": 10, - "pageEnd": 10, - "hash": "cb89b1eaa3a3b479dc0d5975e421b946bb9cb0f69b69ffd74bafd8194a50ea60" - }, - { - "text": "Additionally, it is possible that the 2-h time interval between dexamethasone and CRH administration is critical so that compliance must be assured.", - "tokenCount": 31, - "pageStart": 10, - "pageEnd": 10, - "hash": "65da130de2a1e8fbf3fc0a7b45d336acbf71abe25004b0e5710ec88306fad5f9" - }, - { - "text": "In the United States, ovinesequence CRH is available commercially (ACTHREL; Ferring Corp.", - "tokenCount": 23, - "pageStart": 10, - "pageEnd": 10, - "hash": "c714d1e526da6279d8ebe26f5307f27c9a74e7800bd629ab91f3f548898c7825" - }, - { - "text": ", Malmo, Sweden) with Food and Drug Administrationapproved labeling for the differential diagnosis of Cushings syndrome.", - "tokenCount": 23, - "pageStart": 10, - "pageEnd": 10, - "hash": "4b73c541fac1dbc0e92c224bfd1bba508f97f4f22393f497a61b9c10dea89897" - }, - { - "text": "In Europe, the humansequence peptide is in widespread use (Ferring) but has lower stimulatory effect than the ovinesequence CRH (95).", - "tokenCount": 33, - "pageStart": 10, - "pageEnd": 10, - "hash": "b21e639a85c1ab69ab882236c0e5cc910a2786a9e87d9f2a12725a0f534eb775" - }, - { - "text": "1 Evidence for the midnight serum cortisol test As noted above, the nocturnal nadir of serum cortisol values is lost in patients with Cushings syndrome, forming the basis of this test.", - "tokenCount": 40, - "pageStart": 10, - "pageEnd": 10, - "hash": "32e9d2ae6572a248cadde63bfe2f4053ab9594b1e7bf23e6d302f821a05bdd45" - }, - { - "text": "Because the test is cumbersome to perform, we do not suggest its use in initial testing for Cushings syndrome.", - "tokenCount": 23, - "pageStart": 10, - "pageEnd": 10, - "hash": "2a772091c9f62f1a30baeb5cfc50f3b6dd0205e297c3268d733b11e5e7f5a5f0" - }, - { - "text": "However, the test may be useful in specific situations detailed below.", - "tokenCount": 13, - "pageStart": 10, - "pageEnd": 10, - "hash": "65bf37011696650aa9f963b0790d814a70d30eb8dba322ed7305b0a15d771786" - }, - { - "text": "Midnightserumcortisolmaybeassessedinthesleepingorawake state, using different diagnostic criteria.", - "tokenCount": 25, - "pageStart": 10, - "pageEnd": 10, - "hash": "ffda42ccb46fd007143bec4d07ae7b2bd3615bd40d5537ba07a7f05cc885ec46" - }, - { - "text": "As with all tests, use of a higher diagnostic criterion is associated with reduced sensitivity but increased specificity.", - "tokenCount": 20, - "pageStart": 10, - "pageEnd": 10, - "hash": "52bb0d1085363ac5ccf61f0d17e23ce77e086e7c13a5b260b70b86e50f453128" - }, - { - "text": "Sleeping midnight serum cortisol In one study, a single sleeping serum cortisol greater than 1.", - "tokenCount": 19, - "pageStart": 10, - "pageEnd": 10, - "hash": "985c4cdb399429aa7159c081d7d786223d1a6f36100c29dfeb0498b490e36915" - }, - { - "text": "8 g/dl ( 50 nmol/liter) had high sensitivity (100%) for the diagnosis of Cushings syndrome (96).", - "tokenCount": 30, - "pageStart": 10, - "pageEnd": 10, - "hash": "7049919aab3657e1df946898c717f35ba04ae36f7221bd50ffeefd4de41deb46" - }, - { - "text": "More recent larger studies confirm the poor specificity for this criterion (20.", - "tokenCount": 14, - "pageStart": 10, - "pageEnd": 10, - "hash": "c24d6ac45f495cf836c433fd1fe5df56971c3daf93470f15cb75699d572db4f9" - }, - { - "text": "5 g/dl having higher specificity (87%) (7).", - "tokenCount": 14, - "pageStart": 10, - "pageEnd": 10, - "hash": "3d254152c55a5a105e959f8160f056fb4e4ba80a7a1d0680bd7a25171d7671a1" - }, - { - "text": "org 1535 Downloaded from https://academic.", - "tokenCount": 11, - "pageStart": 10, - "pageEnd": 10, - "hash": "b7e442f7e75ea1cb75da5ea9f5201d21138a14966f497122ecc8cf65ad1c3741" - }, - { - "text": "In 105 children with Cushings syndrome, measurement of sleepingmidnightcortisolhadhighersensitivitythanUFC(99 vs.", - "tokenCount": 27, - "pageStart": 11, - "pageEnd": 11, - "hash": "440eb694dbe34634ab11ab549b45edf06ea8be0944b8e18660b44e4435b75e52" - }, - { - "text": "When used in patients with a high clinical index of suspicion of Cushings syndrome and who had normal UFC and full suppression on dexamethasone testing, a sleeping midnight serum cortisol of greater than 1.", - "tokenCount": 42, - "pageStart": 11, - "pageEnd": 11, - "hash": "26188fe5857799248afe6f0e1f7656129a6802edac0962ae00642169ba1a15bf" - }, - { - "text": "8 g/dl or an awake value of greater than 7.", - "tokenCount": 14, - "pageStart": 11, - "pageEnd": 11, - "hash": "7c9dd5ca57949a8e27ce735f36a1ca817c06884b1c0f46253805d68e20e86e40" - }, - { - "text": "5 g/dl increases the probability of Cushings syndrome (96).", - "tokenCount": 16, - "pageStart": 11, - "pageEnd": 11, - "hash": "23a7207000bb8fc6340117ac26f09ded6ed6b012e9ca87c0a979f25b64159181" - }, - { - "text": "Conversely, where there is a low clinical index of suspicion, such as in simple obesity, but lack of suppression on dexamethasone testing and mildly elevated UFC, a sleeping midnight serum cortisol less than 1.", - "tokenCount": 44, - "pageStart": 11, - "pageEnd": 11, - "hash": "603b92f1703d5d8f549401b1a2b48fb5c28ae2b3b41c32d0480fcf5b77276d42" - }, - { - "text": "8 g/dl effectively excludes Cushings syndrome at the time of assessment (7).", - "tokenCount": 19, - "pageStart": 11, - "pageEnd": 11, - "hash": "ac9a6ef1a8a3bb5fd978409ca593c4f15340df93ae2a36f89cef3e5faf5a72c5" - }, - { - "text": "The midnight serum cortisoltestalsohasutilityinthecontextoffailureofsuppression on dexamethasone testing due to anticonvulsant medication, in which a sleeping midnight serum cortisol less than 1.", - "tokenCount": 47, - "pageStart": 11, - "pageEnd": 11, - "hash": "276888c59d8f075b5b2fea7076d89e4be133393e1f316823b4955e954c760b69" - }, - { - "text": "8 g/dl has been used to exclude Cushings syndrome (97).", - "tokenCount": 17, - "pageStart": 11, - "pageEnd": 11, - "hash": "837470db82fe0e1e3b527248256fd755472448e126181fd767345c7cc217c911" - }, - { - "text": "It is likely that similar values for awake measurements would have similar utility, but this has not been tested directly.", - "tokenCount": 22, - "pageStart": 11, - "pageEnd": 11, - "hash": "c931d3bb071235d4656713274bbcc7072c354a9748eb9d4bc40209082e8202e9" - }, - { - "text": "Overall, the evidence in adult patients for the midnight serum cortisol accuracy is limited and inconsistent across studies, with at least one study showing that this test can enhance the accuracy of the UFC and 1-mg dexamethasone tests (2).", - "tokenCount": 49, - "pageStart": 11, - "pageEnd": 11, - "hash": "6e3b35df66d5e43e553965f2c990d3f1c1862f9ee724e5f395b9942962839efd" - }, - { - "text": "Awake midnight serum cortisol Sampling for midnight serum cortisol when the patient is awake is far easier.", - "tokenCount": 20, - "pageStart": 11, - "pageEnd": 11, - "hash": "6be3d0c7c5ab330a5f1d2a339fa50fbe164e4e48436a5b668d9aa6071c8d3b0c" - }, - { - "text": "Initial studies suggested that an awake midnight serum cortisol greater than 7.", - "tokenCount": 13, - "pageStart": 11, - "pageEnd": 11, - "hash": "245847aa5090da6f6478e021a7d3909a94093ebb30b44e37df6fd209e2f455c5" - }, - { - "text": "5 g/dl ( 207 nmol/liter) had a sensitivity and specificity greater than 96% (98,99).", - "tokenCount": 27, - "pageStart": 11, - "pageEnd": 11, - "hash": "0cc55238e85bdbf357f909a653f4c5e663cd140f4afa9c4c9a02488ea585aaef" - }, - { - "text": "However, when applied to an obese cohort, the specificity was only 83% (100).", - "tokenCount": 18, - "pageStart": 11, - "pageEnd": 11, - "hash": "856093b3cfa2b3b47c8a3fe03e22804703a99d74951e569f56981a538dcdcb14" - }, - { - "text": "In an effort to improve on specificity, higher cutoff points have been advocated, inevitably at the cost of sensitivity: values of serum midnight cortisol greater than 8.", - "tokenCount": 31, - "pageStart": 11, - "pageEnd": 11, - "hash": "967732ec982fb5950d0459f2c30774e281a4482d279079126a01b68539049ea6" - }, - { - "text": "312 g/dl had 90 92% sensitivity with specificity of 96% (63,101).", - "tokenCount": 20, - "pageStart": 11, - "pageEnd": 11, - "hash": "6d6db86f4e91248e40b499613be4d8a6284f11769e8510e1ca845d4a1e08f24e" - }, - { - "text": "1 Remarks for the midnight serum cortisol test The sleeping midnight cortisol requires inpatient admission for a period of 48 h or longer to avoid falsepositive responses due tothestressofhospitalization;thisapproachmaynotbepossible in some practice settings.", - "tokenCount": 52, - "pageStart": 11, - "pageEnd": 11, - "hash": "31d11345c45f9491b029a31d2551e4f64fa2d1eb97c8dd6e81d509ea5973df8f" - }, - { - "text": "If a sleeping value is desired, the blood sample must be drawn within 510 min of waking the patient, or through an indwelling line, to avoid falsepositive results (96).", - "tokenCount": 37, - "pageStart": 11, - "pageEnd": 11, - "hash": "c5ae25e701ad448827b07f1c2d584626eac47db0f28661fe1eb2f7b77cf246eb" - }, - { - "text": "Young children may have their cortisol nadir earlier than midnight.", - "tokenCount": 13, - "pageStart": 11, - "pageEnd": 11, - "hash": "29f533e0c37dc8c53e4f66b900afbc93a7c73718cb3290611a6d8e02e6a563c4" - }, - { - "text": "In children, precatheterization is essential so that a sleeping sample for serum cortisol can be obtained.", - "tokenCount": 21, - "pageStart": 11, - "pageEnd": 11, - "hash": "f3c874634d11953986d578bd9ba268d930028f7bbd61030035b7df6d22128fdd" - }, - { - "text": "2 Remarks for the desmopressin stimulation test The desmopressin stimulation test involves measurement of plasma ACTH just before and 10,20, and 30 min after iv administration of 10 g 1-desamino-8- Darginine vasopressin.", - "tokenCount": 58, - "pageStart": 11, - "pageEnd": 11, - "hash": "634c7a3f4604e229300377c971631404d47479d548ec782ff5c37edd4f7ad2a4" - }, - { - "text": "In general, patients with Cushings disease show an increase in ACTH, but those with other causes of Cushings syndrome or those without Cushings syndrome do not respond (7,22, 102).", - "tokenCount": 43, - "pageStart": 11, - "pageEnd": 11, - "hash": "684b522093bfa10003bd8a2923c75c92c63fedc8739345a8589712c9c6b3d89e" - }, - { - "text": "The sensitivity for patients with Cushings disease was 8287%; whenotherpatientswithCushingssyndromewereincluded,the sensitivity was 6375%.", - "tokenCount": 35, - "pageStart": 11, - "pageEnd": 11, - "hash": "84708821ed295f603747752c5c6d32964435a64d409d9f50241313f0381d5e55" - }, - { - "text": "Until additional data validate the utility of the test in a larger population of patients with all causes of Cushings syndrome, it seems prudent to restrict this test to research studies.", - "tokenCount": 35, - "pageStart": 11, - "pageEnd": 11, - "hash": "49ddd51af519977719d557f1e842457dc3c787d05c51886dd4b201a661de693f" - }, - { - "text": "5 Adrenal incidentaloma: We suggest use of the 1-mg DST or latenight cortisol test, rather than UFC in patients suspected of having mild Cushings syndrome (2 QQEE ).", - "tokenCount": 42, - "pageStart": 11, - "pageEnd": 11, - "hash": "e5e194c2e6fe8cb4cbb3fee9de8111989ddf134895a3588afc4f990403b4d73e" - }, - { - "text": "1 Evidence for choice of tests in pregnant women Screening for hypercortisolism is more difficult in pregnancy, particularly in the second and third trimesters.", - "tokenCount": 33, - "pageStart": 11, - "pageEnd": 11, - "hash": "91b09e9e75998ab8490b172335217c69516f60e6c294c269bf1d6c38a6e0548b" - }, - { - "text": "UFC excretion is normal in the first trimester; however, it increases up to 3-fold by term to overlap values seen in women with Cushings syndrome (103). Thus, only UFC values in the second or third trimester greater than 3 times the upper limit of normal can be taken to indicate Cushings syndrome.", - "tokenCount": 67, - "pageStart": 11, - "pageEnd": 11, - "hash": "c6271bcf4dc0a575f0693eba4373c633b47ffeab7ba9aa5d651b29cb67817d02" - }, - { - "text": "Serum cortisol circadian variation is preserved in normal pregnancy, albeit with a higher midnight nadir.", - "tokenCount": 20, - "pageStart": 11, - "pageEnd": 11, - "hash": "e60ce694955ba9e2bfc53bd68d9bc9c062dd5d0be305941b06b1b9ae999cd7b1" - }, - { - "text": "Whereas loss of circadian variation is characteristic of Cushings syndrome, diagnostic thresholds for evening serum or salivary cortisol in pregnant patients are not known (103,104).", - "tokenCount": 34, - "pageStart": 11, - "pageEnd": 11, - "hash": "dacabaa2ecc14a10cb488ddd383164aaac38743ca08703a8260ce901ca6cdba4" - }, - { - "text": "Furthermore,suppressionofserumandurinarycortisolbydexamethasone is blunted in pregnancy (105).", - "tokenCount": 29, - "pageStart": 11, - "pageEnd": 11, - "hash": "31c2a9a79699a48a88fd26a5909ec82b0d34d7406cd3d258f881686a6ec0675b" - }, - { - "text": "Thus, dexamethasone testing has an increased potential for falsepositive results in pregnancy.", - "tokenCount": 19, - "pageStart": 11, - "pageEnd": 11, - "hash": "0d2c6c6815b6cc33d9df2ae0d2bd29be8056e82ac46f2db5e01129d54fa95cdb" - }, - { - "text": "2 Evidence for choice of tests in patients receiving anticonvulsants As discussed above (see 3.", - "tokenCount": 21, - "pageStart": 11, - "pageEnd": 11, - "hash": "70fe7e0028330c49fb0bb7451872b043eaed8252135eef0805c8fa8a6032e276" - }, - { - "text": "4 Remarks for dexamethasone tests ), commonly used anticonvulsant medications, including phenytoin, phenobarbitone, and carbamazepine, induce hepatic enzymatic clearance of dexamethasone, mediated through CYP 3A4, and may cause falsepositive responses on testing.", - "tokenCount": 68, - "pageStart": 11, - "pageEnd": 11, - "hash": "75d97ef8dc739073a031f9cfedb0c22eab19b6eca5098f264fc02ed0e8f5ce65" - }, - { - "text": "There are, however, no data to guide the length of time needed after withdrawal of such medication to allow dexamethasone metabolism to return to normal, and such a medication change may not be clinically possible.", - "tokenCount": 43, - "pageStart": 11, - "pageEnd": 11, - "hash": "13725fd6295e1b987fb0f95b1da7265e2f715227d14d7cb565cf554b6fb524f3" - }, - { - "text": "Switching to nonenzymeinducing medication may correct this situation, but an alternative and more practical approach is to use another test, such as assessment of midnight salivary or serum cortisol, to exclude Cushings syndrome in these patients (97).", - "tokenCount": 50, - "pageStart": 11, - "pageEnd": 11, - "hash": "fd87778e584b7c268b43d8a8ed87f0ff4dbb55793255cca5bbdfbd31f166e214" - }, - { - "text": "3 Evidence for choice of tests in chronic renal failure As noted above (see 3.", - "tokenCount": 17, - "pageStart": 11, - "pageEnd": 11, - "hash": "f3d4bd21cd8e635f4e6eafce2d21c07fca85cfcd2f9ea08f611458cb7cb02582" - }, - { - "text": "1), excreted urine cortisol values decreasebelowcreatinineclearanceof60ml/minandarequitelow, 1536 Nieman et al.", - "tokenCount": 33, - "pageStart": 11, - "pageEnd": 11, - "hash": "1e9c20b8db8d7fd1a5fe969335fafd803be821a6fb11f9b3aeed4d933b35c28d" - }, - { - "text": "Although the cortisol circadian rhythm was present in one study, neither serum nor salivary midnight cortisol concentrations have been reported in this population (106).", - "tokenCount": 29, - "pageStart": 12, - "pageEnd": 12, - "hash": "ca28fd6e1991cc23c9fb2d6cc3f9698173c07b53e0c8532726b6344a3181a1f2" - }, - { - "text": "However, serum free cortisol values measured over a 24-h period were reported to be elevated (106).", - "tokenCount": 21, - "pageStart": 12, - "pageEnd": 12, - "hash": "c6034fff09dd87973e80a8a0cdae2d61f5e6f0acb6b74e006521477095dc25d0" - }, - { - "text": "As a result, a normal (low) midnight cortisol value probably excludes Cushings syndrome, but the diagnostic threshold for either serum or salivary cortisol is not known.", - "tokenCount": 35, - "pageStart": 12, - "pageEnd": 12, - "hash": "bf2199dc9af61da37e7083602fda3c3634f17d8828236f58bd1ab31b1ab4b8a0" - }, - { - "text": "The absorption and metabolism of 1 mg dexamethasone, as well as the cortisol response, have been reported to be both normal and abnormal (107109). Responses to administration of 3 and 8 mg dexamethasone were normal in some but not all patients (106,108).", - "tokenCount": 60, - "pageStart": 12, - "pageEnd": 12, - "hash": "9f9c9c6e25122163364bd24a63bd91970bff73c0f3686848898816d98227426b" - }, - { - "text": "In the absence of additional data, a normal response to 1 mg dexamethasone is likely to exclude Cushings syndrome, but an abnormal response is not diagnostic.", - "tokenCount": 35, - "pageStart": 12, - "pageEnd": 12, - "hash": "0c5595157bc358da1bab101a6b947c8a1e141e44b3da8e34b3d40b633aec7c70" - }, - { - "text": "4 Evidence for choice of tests in cyclic Cushings syndrome Rarely patients have been described with episodic secretion of cortisol excess in a cyclical pattern with peaks occurring at intervals of several days to many months (93).", - "tokenCount": 45, - "pageStart": 12, - "pageEnd": 12, - "hash": "8dc48c5a941c40d0abb6199aef55821719c8f5e13f824cce897a18fd7248d33f" - }, - { - "text": "Because the DST results may be normal in patients who are cycling out of hypercortisolism, these tests are not recommended for patients suspected of having cyclic disease.", - "tokenCount": 35, - "pageStart": 12, - "pageEnd": 12, - "hash": "c8838652f4b3781c9a00dcec93437f65fb171dd88ee74a7750301526f510414b" - }, - { - "text": "Instead, measurement of UFC or salivary cortisol may best demonstrate cyclicity.", - "tokenCount": 16, - "pageStart": 12, - "pageEnd": 12, - "hash": "0d8149cfebb3e4bce3ee9253f067e380d98c368ee13a837da14c3c0b261d4091" - }, - { - "text": "In patients for whom clinical suspicion is high but initial tests are normal, followup is recommended with repeat testing, if possible to coincide with clinical symptoms.", - "tokenCount": 30, - "pageStart": 12, - "pageEnd": 12, - "hash": "8758442486fbb16c53969e5f416318eee1e8cbbb2758025c8a9c077e52264451" - }, - { - "text": "5 Evidence for choice of tests in adrenal incidentaloma UFC appears to be less sensitive than the 1-mg DST or latenight cortisol for the identification of Cushings syndrome in this population (2023).", - "tokenCount": 44, - "pageStart": 12, - "pageEnd": 12, - "hash": "fcbc7b0e581d1ecc1b8be5879191f40a456b2f42eee5dadda847a4a736c603f8" - }, - { - "text": "There is no consensus on the best algorithm or the best diagnostic criterion for the 1-mg DST.", - "tokenCount": 21, - "pageStart": 12, - "pageEnd": 12, - "hash": "e9a159cd365cd0c1ac3c7ed76a361389fb88e282bd8eddf7820ce9954651afe6" - }, - { - "text": "A suppressed ACTH or dehydroepiandrosterone sulfate concentration supports the diagnosis of Cushings syndrome in patients with adrenal masses (2023). Measurement of ACTH or dehydroepiandrosteronesulfateisnotpartofinitialdiagnosticevaluationof a patient presenting with clinical features of Cushings syndrome, but it may indicate subtle adrenal hyperfunction in this specific population.", - "tokenCount": 85, - "pageStart": 12, - "pageEnd": 12, - "hash": "7ee3227f948fc6a883fbac0f483c132bfc6ecba160f2379528c4f09e789b736d" - }, - { - "text": "Future directions and recommended research The evidence on which many of these recommendations have been made is of low to very low quality because there are limited data linking diagnostic strategies to patient outcomes as much of theworkhasfocusedondeveloping,validating,andascertaining diagnostic test performance.", - "tokenCount": 56, - "pageStart": 12, - "pageEnd": 12, - "hash": "a2b5dd13d17391680c0db3616e7110525dec5e8bd294ff61bc6c703bf1235cd4" - }, - { - "text": "This focus may be due to the rarity of the disease and the availability of diverse diagnostic methods.", - "tokenCount": 19, - "pageStart": 12, - "pageEnd": 12, - "hash": "408f68c8757623a50abc108edb4166166e29de74902de97c46f062cb26db5c04" - }, - { - "text": "In addition, published data, which are often from larger tertiary referral centers, might be biased toward more diagnostically challenging cases, higher pretest probability, and greater disease severity.", - "tokenCount": 37, - "pageStart": 12, - "pageEnd": 12, - "hash": "12543dcd4f2a1a2698b81ac41dfa6446a45911af2e42263b2ed4199b939abd2d" - }, - { - "text": "Such bias may result in an overly sanguine view of the diagnostic performance of these tests, particularly compared with their expected performance in unselected populations in usual clinical practice.", - "tokenCount": 34, - "pageStart": 12, - "pageEnd": 12, - "hash": "214538eb83bfc3b2e412a4dd6c2a09f9885f7660c23e893b278faf9cb6ffd023" - }, - { - "text": "These issues highlight the need for further research and for improvements in the research methods used to determine whether testing will lead to improved patient outcomes.", - "tokenCount": 27, - "pageStart": 12, - "pageEnd": 12, - "hash": "74741faeec6c5237b2cb6911df7334fb05c07285d67ad0452239f8e076de3ee9" - }, - { - "text": "Investigation in the following areas would significantly improve the future care of patients with hypercortisolism: 1.", - "tokenCount": 23, - "pageStart": 12, - "pageEnd": 12, - "hash": "dde94f7eff0191476a4204e721c3c789c9691d5ba65c1150400b3c01e03ba361" - }, - { - "text": "A commitment from endocrinologists supported by national and international endocrine organizations and funding agencies to establish databases of consecutive patients tested for Cushings syndrome allowing for prospective pooling of the diagnostic test information.", - "tokenCount": 40, - "pageStart": 12, - "pageEnd": 12, - "hash": "78df9958d5693a3bb5f1b616190dedef38c3e676faa841f295f2ddfb11f6ed94" - }, - { - "text": "This pooled information would help to define discriminatory symptoms and signs and provide data on the most accurate testing strategies.", - "tokenCount": 21, - "pageStart": 12, - "pageEnd": 12, - "hash": "4f541b0f2dc02b0f30a51c61f2455d6fa2b8151c5364c3d44ed0a3d6adf130ec" - }, - { - "text": "The diagnosis of Cushings syndrome is critically dependent on the quality and performance of cortisolassays,betheyfromserum,saliva,orurineandmeasured by RIA, ELISA, or LCMS/MS.", - "tokenCount": 49, - "pageStart": 12, - "pageEnd": 12, - "hash": "d9b0de20c798384725b73cc2eacf8fed6535ad60f7c04516e5440d5cc49f573c" - }, - { - "text": "Clinicians need a greater appreciation of the robustness (or otherwise) of their particular assay and its variance from published cutoff data.", - "tokenCount": 27, - "pageStart": 12, - "pageEnd": 12, - "hash": "c89578a72376af24b32190a63970111febd8cc6f4ac22cdb256e0106a005e565" - }, - { - "text": "National laboratories of excellence might be used as referral centers in difficult cases; approval by the health authorities/insurance companies for such use would be important.", - "tokenCount": 30, - "pageStart": 12, - "pageEnd": 12, - "hash": "843808cb5ba5ba628ed411129bcd9a4945695ee0d1ccfaf43a383e56999b2fcf" - }, - { - "text": "Initial testing for hypercortisolism may be desirable to the extent that its results will favorably affect outcomes that matter to patients.", - "tokenCount": 26, - "pageStart": 12, - "pageEnd": 12, - "hash": "c348490921294ef2e9af59abcc0232f86bd0bc912322e897914fa3d5355a7cd0" - }, - { - "text": "Thereisapressingneedtoinvestigateoutcomesinpatients cured of Cushings syndrome with modernday practice.", - "tokenCount": 25, - "pageStart": 12, - "pageEnd": 12, - "hash": "b181fb860cceebf46ae4f9a717b3670139d37e28fa563347a459be0c60cb08e4" - }, - { - "text": "In particular, there are conflicting data on the need to treat mild or socalled subclinical Cushings syndrome, notably in patients with adrenal incidentalomas.", - "tokenCount": 32, - "pageStart": 12, - "pageEnd": 12, - "hash": "0cb1761cfd1ae11e29d9eb8c22e2ad1a8e0abd0de7ab8dbdd8427bf3a4b5b615" - }, - { - "text": "Appropriately powered and rigorously designed randomized clinical trials to compare diagnostictreatment strategies should be established to inform clinicians and patients on optimal management.", - "tokenCount": 30, - "pageStart": 12, - "pageEnd": 12, - "hash": "a8ff6ee5972da9d72cc5369052aa8fb97505a48d6592cd791d123e7ddbc69873" - }, - { - "text": "Acknowledgments The members of the Task Force thank Dr.", - "tokenCount": 11, - "pageStart": 12, - "pageEnd": 12, - "hash": "245c3dabb3ac1aea4be4231dd14177c4a97cb1b2429e488f88966416f73d10d1" - }, - { - "text": "Robert Vigersky, the members of the Clinical Guidelines Subcommittee, the Clinical Affairs Core Committee, and The Endocrine Society Council for their careful review of earlier versions of this manuscript and their helpful suggestions.", - "tokenCount": 40, - "pageStart": 12, - "pageEnd": 12, - "hash": "86ff221ac2d13d98934a5c8a27c6b4dd7cdfd22f9482f5c6bc0b3cbbbb351e35" - }, - { - "text": ", medical writer on this guideline, who meticulously checked the references and formatted the guideline into its currentform.", - "tokenCount": 21, - "pageStart": 12, - "pageEnd": 12, - "hash": "997a8c62565fb6d55d6c67d97855fcb180b135f25a7e6ad00214968e1c5a89d2" - }, - { - "text": "Inaddition,wethankthemanymembersofTheEndocrine Society who reviewed the draft version of this guideline when it was posted on the The Endocrine Society Web site and who sent a great number of comments, most of which were incorporated into the final version of the manuscript.", - "tokenCount": 59, - "pageStart": 12, - "pageEnd": 12, - "hash": "7b3d571f1aad5c97ff7a4f9f13fc38e3893cffa7eea504c5dd4688a8e55e0a71" - }, - { - "text": "We thank the European Society of Endocrinology for their cosponsorship of this guideline. Finally, we thank the staff at The Endocrine Society office for their helpful support during the development of this guideline.", - "tokenCount": 41, - "pageStart": 12, - "pageEnd": 12, - "hash": "41588df6381082bc59ad11e7983be93d8368ffecbc16e9c0759262aa97b2bbd8" - }, - { - "text": "Address all correspondence to: The Endocrine Society, 8401 Connecticut Avenue, Suite 900, Chevy Chase, Maryland 20815.", - "tokenCount": 25, - "pageStart": 12, - "pageEnd": 12, - "hash": "515fa0069b8536178b138e17f505f695217987a29eb9710478cc4a17bf242cfd" - }, - { - "text": "Address all reprint requests for orders of 101 and more to: Heather Edwards, Reprint Sales Specialist, Cadmus Professional Communications, 8621 Robert Fulton Drive, Columbia, Maryland 21046.", - "tokenCount": 37, - "pageStart": 12, - "pageEnd": 12, - "hash": "ad48324b4f3575df4e54580ea1e4178626444061a232485b408a7d1ad8e79b0b" - }, - { - "text": "Email: endoreprints@cadmus.", - "tokenCount": 10, - "pageStart": 12, - "pageEnd": 12, - "hash": "4537757bd24d96516e4e019e7f9492eb055cba25cee53395bd9a45504b667617" - }, - { - "text": "Address all reprint requests for orders of 100 or less to Society Services.", - "tokenCount": 14, - "pageStart": 12, - "pageEnd": 12, - "hash": "e53ee97647cae6320cbcb1a540cefc7852375dd0dd4cc1ac0796e6d9f38cfca3" - }, - { - "text": "Email: societyservices@endosociety.", - "tokenCount": 13, - "pageStart": 12, - "pageEnd": 12, - "hash": "6d42816f9c9a9c6bf41c967420af0c2aec21dad790a5e09efa573a3a5dc4b26d" - }, - { - "text": "org 1537 Downloaded from https://academic.", - "tokenCount": 11, - "pageStart": 12, - "pageEnd": 12, - "hash": "f9ed6a5dc7dd4ad0c254feb9e8e8425d3279d4ee4f4f77c82f043c96e9a1ca31" - }, - { - "text": "Disclaimer Statement Clinical practice guidelines are developed to be of assistance to physicians by providing guidance and recommendations for particular areas of practice.", - "tokenCount": 24, - "pageStart": 13, - "pageEnd": 13, - "hash": "195689cdad9ee336c0ebe96cb679717fa37a7259234021befb21c46e47242451" - }, - { - "text": "The guidelines should not be considered inclusive of all proper approaches or methods, or exclusive of others.", - "tokenCount": 19, - "pageStart": 13, - "pageEnd": 13, - "hash": "345000f6c12effb387455e8d3251d4cafb205435ed647a966da80a0e0b824d07" - }, - { - "text": "The guidelines cannot guarantee any specific outcome, nor do they establish a standard of care.", - "tokenCount": 17, - "pageStart": 13, - "pageEnd": 13, - "hash": "0dd6b40a52c7a93038b849711aaa0ca1d72e9cdc3ea8757e08d3f9ddaaae1c47" - }, - { - "text": "The guidelines are not intended to dictate the treatment of a particular patient.", - "tokenCount": 14, - "pageStart": 13, - "pageEnd": 13, - "hash": "69243b311852632221800aad0e971b73a8db4dfaa4e9bae93a9734ae67c57df6" - }, - { - "text": "Treatment decisions must be made based on the independent judgment of health care providers and each patients individual circumstances.", - "tokenCount": 21, - "pageStart": 13, - "pageEnd": 13, - "hash": "8eb6e4a9c419994f6de1a3e669e900ca045603caaee6162c59258a5add165b40" - }, - { - "text": "The Endocrine Society makes no warranty, express or implied, regarding the guidelines and specifically excludes any warranties of merchantability and fitness for a particular use or purpose. The Endocrine Society shall not be liable for direct, indirect, special, incidental, or consequential damages related to the use of the information contained herein.", - "tokenCount": 62, - "pageStart": 13, - "pageEnd": 13, - "hash": "50cfae6370c4de2c0aaae6b6a6690a06b9a8cedbbc5b02ea748a2f6636fa89b9" - }, - { - "text": "(chair)Financial or Business/Organizational Interests: UpToDate, HRA Pharma, Significant Financial Interest or Leadership Position: none declared; Beverly M.", - "tokenCount": 33, - "pageStart": 13, - "pageEnd": 13, - "hash": "93366869fb1ef645672cc3ccf2ba54bcfdcf7d9bee58a0e87c01648b237a2203" - }, - { - "text": "Financial or Business/Organizational Interests: Novartis, consultant, Significant Financial or Leadership Position: none declared; James W.", - "tokenCount": 27, - "pageStart": 13, - "pageEnd": 13, - "hash": "ee1cd638466b9968c24674a50f63952adf9908b8b2a22859549ff0a0017d02ed" - }, - { - "text": "Financial or Business/Organizational Interests: Novartis, Corcept, Significant Financial or Leadership Position: none declared; John D.", - 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}, - { - "text": "J Clin Endocrinol Metab 63:741746 1540 Nieman et al.", - "tokenCount": 19, - "pageStart": 15, - "pageEnd": 15, - "hash": "733ded2e6748c87acbcdd5288c993075b3ddf95b7c574a3c6106bfeb8162e90a" - } -] \ No newline at end of file diff --git a/Capstone Course Adrenal Nodule information/FINAL Adrenal Nodual Workflow Flyer copy.pdf_semantic.json b/Capstone Course Adrenal Nodule information/FINAL Adrenal Nodual Workflow Flyer copy.pdf_semantic.json deleted file mode 100644 index eb52fa27c3a62b40f40be9b8d4ad0bed820a63e0..0000000000000000000000000000000000000000 --- a/Capstone Course Adrenal Nodule information/FINAL Adrenal Nodual Workflow Flyer copy.pdf_semantic.json +++ /dev/null @@ -1,79 +0,0 @@ -[ - { - "text": "Evaluating adrenal nodules *See next page for hormonal workup reference Incidental adrenal nodule > 1 cm Found on noncontrast (noncon) CT? DO NOT BIOPSY adrenal mass without hormone workup and consulation Assess imaging characteristics Obtain adrenal protocol CT Suspicious appearance Hormonal workup* Abnormal DST or metanephrines or aldosterone : renin Normal hormonal workup Refer to Endocrine Surgery Adrenal Nodules Clinic Benign appearance Hormonal workup* Size 4 cm in diameter >10 Hounsfield units (HU) on noncon CT CT contrast washout <4060% On MRI, hyperintense on T2 imaging or no signal loss on chemicalshift analysis On 18FFDG PETCT, SUVmax 5 or adrenaltospleen or adrenalto liver signalintensity ratio 1 Catecholamine Excess Plasma fractionated metanephrines Abnormal: >2x Upper Limit of Normal (ULN) Adrenal hypercortisolism 1mg Dexamethasone suppression test (DST) Abnormal: >1.", - "tokenCount": 246, - "pageStart": 1, - "pageEnd": 1, - "hash": "30e1f1b2f10cbd6afd0d06f17d6279146023ce527cc7469cd639317816d87d69" - }, - { - "text": "8 mcg/dl Adrenal hyperaldosteronism If patient has a history of HTN Plasma aldosterone and renin Abnormal: aldosterone >10 and renin <1.", - "tokenCount": 45, - "pageStart": 1, - "pageEnd": 1, - "hash": "1888b83a2c91430a6483a5dbeb80ac9f929829510ac04ed74ee90eb8e93ca1f2" - }, - { - "text": "0 Size 1-4 cm in diameter 10 Hounsfield units (HU) on noncon CT CT contrast washout 4060% Signal loss on MRI chemicalshift analysis On 18FFDG PETCT, SUVmax <5 or adrenaltospleen or adrenalto liver signalintensity ratio <1 Adrenal hypercortisolism 1mg Dexamethasone suppression test (DST) Abnormal: >1.", - "tokenCount": 98, - "pageStart": 1, - "pageEnd": 1, - "hash": "c0856ceebb215d78fdb6cc48aa989c431b41e64d7b7bedef70a9c1c66705bfbd" - }, - { - "text": "GS-2727550-26 Hormonal workup reference 1.", - "tokenCount": 14, - "pageStart": 2, - "pageEnd": 2, - "hash": "49eb5fab9f931acf8fe0a5d0cb34dde8bf014609308ea0b2ff8b4c7d075b5ab1" - }, - { - "text": "Cortisol evaluation Dexamethasone Suppression Test (DST) Prescribe 1 mg of oral dexamethasone to be taken at 11 pm The next morning at 8 am, a cortisol and dexamethasone level are drawn If the 8 am cortisol is < 1.", - "tokenCount": 64, - "pageStart": 2, - "pageEnd": 2, - "hash": "530bedc3c137603793ac35fc6ae82c23cce814d4f7b2219e6654a434a6d62d86" - }, - { - "text": "8 mcg/dL, cortisol excess is ruled out If the am cortisol after dexamethasone is >1.", - "tokenCount": 26, - "pageStart": 2, - "pageEnd": 2, - "hash": "5cf61a8f6c15ef0875a27a7ab0c479b9ff0023a5e399fddb7ecb69ce1c7cdc62" - }, - { - "text": "8mcg/dL, then screening is POSITIVE or ABNORMAL Cortisol between 1.", - "tokenCount": 22, - "pageStart": 2, - "pageEnd": 2, - "hash": "0c9b32ff332487d924156603b138547204174acf5a019d8a9f6166e155e91020" - }, - { - "text": "0 mcg/dL may represent mild cortisol excess, therefore you need to proceed with confirmatory testing: Morning serum corticotropin and cortisol levels 24-hr urinary cortisol 3 midnight/latenight salivary cortisol Midnight serum cortisol DHEAS (<40 mcg/dL) Failure to suppress below 5. 0 mcg/dL raises concern for cortisol excess 2.", - "tokenCount": 82, - "pageStart": 2, - "pageEnd": 2, - "hash": "343b5524cbce72ce58a9969dada36d2acfa64015a5e487733c5ac5a34a32bae5" - }, - { - "text": "Screen for aldosteronoma Aldosterone level : Plasma Renin Activity (PRA) Perform if patient has a history of hypertension or hypokalemia Obtain midmorning plasma aldosterone concentration and plasma renin activity These must be drawn at the same time and should not be done with the DST Divide the aldosterone level by the PRA to calculate the aldosterone : renin (ARR) If the ARR is > 20, screen is POSITIVE or ABNORMAL for hyperaldosteronism If aldosterone > 10 ng/dL AND renin < 1.", - "tokenCount": 129, - "pageStart": 2, - "pageEnd": 2, - "hash": "a73d5f95cf73dd83e142ccc51b2516ef2b99990db6eb2da134815e0898a25bfa" - }, - { - "text": "0 ng/dL then screen is POSITIVE or ABNORMAL for hyperaldosteronism Proceed to confirmatory testing with oral sodium load test, aldosterone suppression test or seated saline infusion test If aldosterone < 10 ng/dL OR renin > 1. 0 ng/dL, then screen is NEGATIVE or NORMAL for hyperaldosteronism If aldosterone > 10 ng/dL AND renin > 1.", - "tokenCount": 94, - "pageStart": 2, - "pageEnd": 2, - "hash": "a7a708831b846919dd6785148565bee4609c4f511c549dd47152595080691e7f" - }, - { - "text": "0 ng/dL and is on a potentially interfering medication, then hold/replace medications for 4 weeks and repeat 3.", - "tokenCount": 24, - "pageStart": 2, - "pageEnd": 2, - "hash": "c0b020029a7371a6549a8956a4ae856ec5871bdb96f98097cae38973f1bdaea4" - } -] \ No newline at end of file diff --git a/Capstone Course Adrenal Nodule information/JAMA Guidelines for Adrenalectomy.pdf_semantic.json b/Capstone Course Adrenal Nodule information/JAMA Guidelines for Adrenalectomy.pdf_semantic.json deleted file mode 100644 index 8acb8d161faa61fc98453533b1015bfff3021a04..0000000000000000000000000000000000000000 --- a/Capstone Course Adrenal Nodule information/JAMA Guidelines for Adrenalectomy.pdf_semantic.json +++ /dev/null @@ -1,2690 +0,0 @@ -[ - { - "text": "American Association of Endocrine Surgeons Guidelines for Adrenalectomy Executive Summary Linwah Yip, MD; QuanYang Duh, MD; Heather Wachtel, MD; Camilo Jimenez, MD; Cord Sturgeon, MD; Cortney Lee, MD; David VelzquezFernndez, MD, MSc, PhD; Eren Berber, MD; Gary D.", - "tokenCount": 80, - "pageStart": 1, - "pageEnd": 1, - "hash": "31633cac21e69bb22992eb12311ba360d23e8b2570079725c038ba5b8e91c87b" - }, - { - "text": "Hammer, MD, PhD; Irina Bancos, MD; James A.", - "tokenCount": 18, - "pageStart": 1, - "pageEnd": 1, - "hash": "62d9397c55957596ce6b85ecbf1071a265fa4751b446987adcffb349f545c3d3" - }, - { - "text": "Lee, MD; Jamie Marko, MD; Lilah F.", - "tokenCount": 14, - "pageStart": 1, - "pageEnd": 1, - "hash": "eb332623c86b61e5156217475c6dec140b050e55850010ca7c304488c23e0870" - }, - { - "text": "MorrisWiseman, MD; Marybeth S.", - "tokenCount": 13, - "pageStart": 1, - "pageEnd": 1, - "hash": "7436679c8d5920872d0b27c0bee19c47eef06916c50407a6b5ea891c593a5068" - }, - { - "text": "Livhits, MD; MiAh Han, MD; Philip W.", - "tokenCount": 16, - "pageStart": 1, - "pageEnd": 1, - "hash": "38683e47c306abf4b5e037e7e956a1e2bd25af18656f5343f51a4e27826e54f9" - }, - { - "text": "Smith, MD; Scott Wilhelm, MD; Sylvia L.", - "tokenCount": 12, - "pageStart": 1, - "pageEnd": 1, - "hash": "a756ddc03c51839b44daeb932572f9cd26e09ad785d17e247858ece9da695da4" - }, - { - "text": "Asa, MD, PhD; Thomas J.", - "tokenCount": 10, - "pageStart": 1, - "pageEnd": 1, - "hash": "954e92200ec6a452debb49f4e962018c9a9e32db88728f220626caf8e47854c1" - }, - { - "text": "McKenzie, MD; Vivian E.", - "tokenCount": 10, - "pageStart": 1, - "pageEnd": 1, - "hash": "f6b0e6f1a15236a8c78476459137da97645baf8aba9808d087f8695e478a3e00" - }, - { - "text": "Perrier, MD IMPORTANCE Adrenalectomy is the definitive treatment for multiple adrenal abnormalities.", - "tokenCount": 20, - "pageStart": 1, - "pageEnd": 1, - "hash": "7c21c319ae2d3668a8b77587f8246e03d35fd6639e7ed86436cf24d0b93a0324" - }, - { - "text": "Advances in technology and genomics and an improved understanding of adrenal pathophysiology have altered operative techniques and indications.", - "tokenCount": 24, - "pageStart": 1, - "pageEnd": 1, - "hash": "a885fcef91054e698c0fdba5bf394eac9e3416eb957156b930880efeb8cf7acb" - }, - { - "text": "OBJECTIVE To develop evidencebased recommendations to enhance the appropriate, safe, and effective approaches to adrenalectomy.", - "tokenCount": 23, - "pageStart": 1, - "pageEnd": 1, - "hash": "708c81bd09e33aa604ff8133ee6478ed353e6abb55efeb600ada95e609837a30" - }, - { - "text": "EVIDENCE REVIEW A multidisciplinary panel identified and investigated 7 categories of relevant clinical concern to practicing surgeons.", - "tokenCount": 23, - "pageStart": 1, - "pageEnd": 1, - "hash": "70fd576cdf2e33a92f18c63395926d3b28797ac156a20da538a5a8af48fda060" - }, - { - "text": "Questions were structured in the framework Population, Intervention/Exposure, Comparison, and Outcome, and a guided review of medical literature from PubMed and/or Embase from 1980 to 2021 was performed.", - "tokenCount": 40, - "pageStart": 1, - "pageEnd": 1, - "hash": "cae00af565f495ec0fdcf3e67e923d66e97223504f26899048e545d06df6575d" - }, - { - "text": "Recommendations were developed using Grading of Recommendations, Assessment, Development and Evaluation methodology and were discussed until consensus, and patient advocacy representation was included.", - "tokenCount": 30, - "pageStart": 1, - "pageEnd": 1, - "hash": "45ffa48ac774e550f22fa436c07d00d1cd36f2d66e622b1e20f25037a53dff1d" - }, - { - "text": "FINDINGS Patients with an adrenal incidentaloma 1 cm or larger should undergo biochemical testing and further imaging characterization.", - "tokenCount": 23, - "pageStart": 1, - "pageEnd": 1, - "hash": "63351c56c22ae71804d71da700dceca38ecae2973d47a272ce405f8c7e3092ce" - }, - { - "text": "Adrenal protocol computed tomography (CT) should be used to stratify malignancy risk and concern for pheochromocytoma.", - "tokenCount": 31, - "pageStart": 1, - "pageEnd": 1, - "hash": "8c62acab07b66f8e6b2c65b4e09c2a01844fdfa816f01cb76921130f3c51404b" - }, - { - "text": "Routine scheduled followup of a nonfunctional adrenal nodule with benign imaging characteristics and unenhanced CT with Hounsfield units less than 10 is not suggested.", - "tokenCount": 35, - "pageStart": 1, - "pageEnd": 1, - "hash": "c8cc5efc4c417581555386870cef79a86a142d0f19f6fbdaa994473ceb229775" - }, - { - "text": "When unilateral disease is present, laparoscopic adrenalectomy is recommended for patients with primary aldosteronism or autonomous cortisol secretion.", - "tokenCount": 28, - "pageStart": 1, - "pageEnd": 1, - "hash": "299fe04eeb9ea76e76e23c877f19b2bc71a9d18727025e010433c378a25a13be" - }, - { - "text": "Patients with clinical and radiographic findings consistent with adrenocortical carcinoma should be treated at highvolume multidisciplinary centers to optimize outcomes, including, when possible, a complete R0 resection without tumor disruption, which may require en bloc radical resection.", - "tokenCount": 54, - "pageStart": 1, - "pageEnd": 1, - "hash": "d8c33ed8e53d32f7f44d9a03d0da517eb7950b131a2d2b5cf52c30f193f33526" - }, - { - "text": "Selective or nonselective blockade can be used to safely prepare patients for surgical resection of paraganglioma/pheochromocytoma.", - "tokenCount": 33, - "pageStart": 1, - "pageEnd": 1, - "hash": "860c995d14c10216ed2c1ae3c570d11583f6ae3266028401eec4190cf4c0c582" - }, - { - "text": "Empirical perioperative glucocorticoid replacement therapy is indicated for patients with overt Cushing syndrome, but for patients with mild autonomous cortisol secretion, postoperative day 1 morning cortisol or cosyntropin stimulation testing can be used to determine the need for glucocorticoid replacement therapy.", - "tokenCount": 62, - "pageStart": 1, - "pageEnd": 1, - "hash": "f5aeab1e0a8351de897ab062fc0ecf778942bbe4407b9e254b12871fb3b96367" - }, - { - "text": "When patient and tumor variables are appropriate, we recommend minimally invasive adrenalectomy over open adrenalectomy because of improved perioperative morbidity. Minimally invasive adrenalectomy can be achieved either via a retroperitoneal or transperitoneal approach depending on surgeon expertise, as well as tumor and patient characteristics.", - "tokenCount": 66, - "pageStart": 1, - "pageEnd": 1, - "hash": "367d1fda44ab5f9765c06eea5bba3da63b1cf3656dd577939e06daacd8c80225" - }, - { - "text": "CONCLUSIONS AND RELEVANCE Twentysix clinically relevant and evidencebased recommendations are provided to assist surgeons with perioperative adrenal care.", - "tokenCount": 29, - "pageStart": 1, - "pageEnd": 1, - "hash": "292c6215303d9d7245cfeaef36beeeeb79a16bd2a4e34cc363817d6f728e0ea9" - }, - { - "text": "2022;157(10):870-877.", - "tokenCount": 11, - "pageStart": 1, - "pageEnd": 1, - "hash": "8e223e205ac9304f6ecbf7e47b0b9c0521d07f527670abf13b688088d919f59c" - }, - { - "text": "3544 Published online August 17,2022.", - "tokenCount": 10, - "pageStart": 1, - "pageEnd": 1, - "hash": "ddccdbc94816061288a7c77d3ddfb6f38d0a5592bae126366bbbb236cf91ffc8" - }, - { - "text": "Invited Commentary page 877 Multimedia Supplemental content Author Affiliations: Author affiliations are listed at the end of this article.", - "tokenCount": 27, - "pageStart": 1, - "pageEnd": 1, - "hash": "c42231115a53465b8cd0c067176da09adb8aa6be8e966f5cac7cf792f2b9c1e5" - }, - { - "text": "Corresponding Author: Nancy Perrier, MD, Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Unit 1484, Houston, TX 77030 ( nperrier@ mdanderson.", - "tokenCount": 52, - "pageStart": 1, - "pageEnd": 1, - "hash": "f954b26134b59b59961e7b78e9e3695b81dc45cf416cbf677eca3a6dc48a2fd7" - }, - { - "text": "Research JAMA Surgery | Original Investigation 870 (Reprinted) jamasurgery.", - "tokenCount": 19, - "pageStart": 1, - "pageEnd": 1, - "hash": "4a1918fa7794e601b4654dccdbf26ecb7b341ced1fcafa101da961711731cea0" - }, - { - "text": "A drenalectomy is the definitive treatment for multiple adrenal abnormalities.", - "tokenCount": 15, - "pageStart": 2, - "pageEnd": 2, - "hash": "ea42b2b7eae877dbdc3319eb074beb8924d08dc964225bc9f81fa2890f04091b" - }, - { - "text": "To optimize clinical best practices for the integration of current technology and care advances related to adrenalectomy, a multidisciplinary expert group was convened by the American Association of Endocrine Surgeons with the aim of creating guidelines to address perioperative adrenal care.", - "tokenCount": 52, - "pageStart": 2, - "pageEnd": 2, - "hash": "daa995578b43e6ae5a99edcd80e5c9ef5300e07ce1993942f00d41dfb740ac57" - }, - { - "text": "In a structured process, 7 clinically relevant topics were framed with subsequent questions considering technique, outcome, undesirable consequences, cost, and safety.", - "tokenCount": 27, - "pageStart": 2, - "pageEnd": 2, - "hash": "fb37ddedc1ff33f416e1f51d5eaec9124dd1754c5a0d768f8ff3f361b7ae75d5" - }, - { - "text": "Contemporary literature review was used to provide evidencebased recommendations.", - "tokenCount": 12, - "pageStart": 2, - "pageEnd": 2, - "hash": "14db40e362998287088a9e1a174ef94f11c59b0f6df9fdbeb6f5335c5d2819fc" - }, - { - "text": "This guideline may be of use to not only surgeons but endocrinologists, oncologists, radiologists, radiation oncologists, internists, and pathologists and may also be of use to patients with adrenal tumors.", - "tokenCount": 46, - "pageStart": 2, - "pageEnd": 2, - "hash": "7c1aff254358576126d5c6cf5649d3f8b2f97dc2e74915b41e2715c25cc9e7f2" - }, - { - "text": "Methods An expert group of surgeons, endocrinologists, oncologists, pathologists, radiologists, and National Adrenal Diseases Foundation patient advocates composed 7 writing subcommittees.", - "tokenCount": 36, - "pageStart": 2, - "pageEnd": 2, - "hash": "40f969a84487623ee9e87eeea4433d85a7fa744326cc6d0e6d2f728688e56197" - }, - { - "text": "Questions were structured using the framework Population, Intervention/Exposure, Comparison, and Outcome ( Box ) and discussed and edited by the group.", - "tokenCount": 29, - "pageStart": 2, - "pageEnd": 2, - "hash": "28dd0dcd8b5671f4f6e06b101c366bdec76436f139d3c09d0f3ec7397c29df53" - }, - { - "text": "Relevant literature written in English was extracted from PubMed and/or Embase with publication dates from 1980 to 2021.", - "tokenCount": 23, - "pageStart": 2, - "pageEnd": 2, - "hash": "750224266fa2ea806a0f966b8dd5490026d997530a17391eedd80192d21df4d0" - }, - { - "text": "Detailed review of the literature, assessment of study quality, and recommendation construction used the methodology Grading of Recommendations, Assessment, Development, and Evaluation.", - "tokenCount": 30, - "pageStart": 2, - "pageEnd": 2, - "hash": "3b93ee1d29d3cac25a6a74bdb891ef320074d12598ba5a51b105d5e3d98bf633" - }, - { - "text": "Briefly, certainty of evidence was assessed as high, moderate, low, or very low.", - "tokenCount": 20, - "pageStart": 2, - "pageEnd": 2, - "hash": "33fbd7d121a54c03636d3ebd8f9b691428385f2fd70298ee75bf1f6e2ac5bb9d" - }, - { - "text": "1 For therapy, evidence from randomized clinical trials was classified initially as high certainty and observationalstudiesaslow.", - "tokenCount": 22, - "pageStart": 2, - "pageEnd": 2, - "hash": "266e8da28b7ecf11fe50768fafb71e184a68d1e806f3a309e6262168563dedc4" - }, - { - "text": "Forprognosis,evidencefromobservational studies was eligible as high certainty.", - "tokenCount": 17, - "pageStart": 2, - "pageEnd": 2, - "hash": "2ff908d712b6285f75f4d4415518ed6dde81f273584fdffb967421bbd1f839a8" - }, - { - "text": "In addition to certainty of evidence, recommendations were constructed considering resource utilization, practical approaches to the contemporary adrenal management dilemmas, a parsimonious approach to investigation, and measures to reduce morbidity or mortality.", - "tokenCount": 43, - "pageStart": 2, - "pageEnd": 2, - "hash": "cc871aab8ae6c0475453427b39f1cf4402003e18ac172412ac1c4660c807dbcb" - }, - { - "text": "Recommendations were discussed and modified through group consensus and evaluated by a methodological expert (M.", - "tokenCount": 18, - "pageStart": 2, - "pageEnd": 2, - "hash": "eeaacaeace899557c873839c20fcf20bcd2249e9d4147492c0dfa185cb6766eb" - }, - { - "text": ") collaboratively oversaw the process and led the writing.", - "tokenCount": 11, - "pageStart": 2, - "pageEnd": 2, - "hash": "3270a21862c23700d3a576c11502a6c8f0f85d197b05baf3d5c07c108ffedd3e" - }, - { - "text": "Conflicts of interest were disclosed, and there was no industry funding.", - "tokenCount": 14, - "pageStart": 2, - "pageEnd": 2, - "hash": "832c0a8db606b608d432dda4b82f5d78c0697b4e9bb9fbe07c2a7b303cfa1863" - }, - { - "text": "The guidelines do not apply to children, and they may require adaptation in practice settings with barriers to implementation.", - "tokenCount": 21, - "pageStart": 2, - "pageEnd": 2, - "hash": "261caa118a27dafeebfa33171b5c086dfab4595c6db255bef41782bdd16eb37a" - }, - { - "text": "The guidelines do not constitute a legal standard of care.", - "tokenCount": 11, - "pageStart": 2, - "pageEnd": 2, - "hash": "9fcd4d28bfa04d41966f491278cc6030c7225d0100e294b7b2d9d8224458e595" - }, - { - "text": "The process of creating the guidelines was based on current evidence at the time of writing, so they do not represent the only approach to the management of adrenal conditions and are not meant to replace individual physician judgment.", - "tokenCount": 42, - "pageStart": 2, - "pageEnd": 2, - "hash": "012f6120c502539468cc4545d9c87fefec3b9cb54561186bf523fd03a45bc420" - }, - { - "text": "Summary of Recommendations Statements and a summary supporting the recommendations are in the eAppendix in the Supplement .", - "tokenCount": 21, - "pageStart": 2, - "pageEnd": 2, - "hash": "a1622976b5da1cfcf5331b40e487c13d909fa7a66d3a7079444213dc7c8921c8" - }, - { - "text": "Additional details in the Supplement include future directions for research opportunities and technical pearls.", - "tokenCount": 16, - "pageStart": 2, - "pageEnd": 2, - "hash": "c524a61446e0baafb937d77531dec80e8f648d0d709884e6da15e50914e3ea80" - }, - { - "text": "Incidentalomas, Myelolipomas, and Cysts Adrenal lesions are common incidental findings identified on imaging studies not performed for suspected adrenal disease.", - "tokenCount": 32, - "pageStart": 2, - "pageEnd": 2, - "hash": "3a018815a5823312528e137986bdc8e82744c26b8a558e84d7f3c15f0b964dd7" - }, - { - "text": "2 A size cutoff of 1 cm or larger has typically been used to recommend further diagnostic evaluation in the absence of concerning clinical features.", - "tokenCount": 26, - "pageStart": 2, - "pageEnd": 2, - "hash": "7960f870d9c0cd98b164a1f050b60b223d62de0593341fc0d847ae5e81a59182" - }, - { - "text": "2,3 More than 75% of adrenal incidentalomas are benign adenomas and are nonfunctional; however, evaluation for hormone excess and potential malignancy are of critical importance, as these typically require surgical excision (eTable 1 in the Supplement ).", - "tokenCount": 53, - "pageStart": 2, - "pageEnd": 2, - "hash": "37ec9dd3d16622adb32cbe004cc9667b9ff00dc6912bc2c73ea22e639e822aeb" - }, - { - "text": "Adrenal adenomas often contain high lipid content, which can be detected by both computed tomography (CT) and magnetic resonance imaging (MRI).", - "tokenCount": 31, - "pageStart": 2, - "pageEnd": 2, - "hash": "3f4a8801d9499fb01be9c3880c2a9057825d9bf21e45f19d0b305892b416b762" - }, - { - "text": "Tumor density of less than 10 Hounsfield units (HU) on noncontrast CT represents a lipidrich adenoma.", - "tokenCount": 30, - "pageStart": 2, - "pageEnd": 2, - "hash": "2b42afb766c005ab44da6f8d7181ac4fac7aec04c724cd1e424eaeec9aa2f195" - }, - { - "text": "4 An adrenal protocol CT refers to unenhanced images followed by administration of intravenous contrast and repeated imaging at 60 to 75 seconds (venous phase) at 15 minutes (delayed phase).", - "tokenCount": 40, - "pageStart": 2, - "pageEnd": 2, - "hash": "8e06e5f1ec56d34de8fc1eef9aca7ef5cec6edc8a2994ed609d8f3121e813186" - }, - { - "text": "Benign adenomas typically exhibit rapid contrast washout, defined as an absolute percentage washout greater than 60% or relative percentage washout greater than 40% at 15 minutes delay.", - "tokenCount": 37, - "pageStart": 2, - "pageEnd": 2, - "hash": "4a223c3ef7a249e5b0be58129d7d21d538de3b393a9babec64757c80e502a1ee" - }, - { - "text": "We suggest that washout characteristics on an adrenal protocol CT be used to stratify the risk of malignancy for adrenal nodules when noncontrast HU are greater than 10 and other clinical risk factors for malignancy are not present.", - "tokenCount": 51, - "pageStart": 2, - "pageEnd": 2, - "hash": "21493adf10df0997448630e275fee7687913fe9178718ad0c5ab3e7953d3d791" - }, - { - "text": "Adrenal protocol CT does not improve diagnostic accuracy for nodules with noncontrast HU less than 10 nor does it improve evaluation for pheochromocytoma (eFigure in the Supplement ).", - "tokenCount": 42, - "pageStart": 2, - "pageEnd": 2, - "hash": "23818307f83f2b701123375477642d1f35389ccbd57018198183847ffca96c7a" - }, - { - "text": ") Hyperaldosteronism and hypercortisolism are reported in 1% to 4% and 5% to 12% of patients with adrenal incidentalomas, respectively.", - "tokenCount": 36, - "pageStart": 2, - "pageEnd": 2, - "hash": "595d120c247c5251643e876b2a55080301e0212e021af7b98eb18e5f9752a507" - }, - { - "text": "2,5,6 However, approximately 30% to 35% of patients may have mild autonomous cortisol secretion (MACS), which has been increasingly recognized as an important cardiovascular risk factor in patients with adrenal incidentalomas.", - "tokenCount": 44, - "pageStart": 2, - "pageEnd": 2, - "hash": "b1fdaca97506ac6abae919e66504af787c6b8c33c4e009f929b2276a47e0ad17" - }, - { - "text": "6,7 The prevalence of pheochromocytoma has been widely reported as being 0.", - "tokenCount": 21, - "pageStart": 2, - "pageEnd": 2, - "hash": "ccdbbda50ee43bb8cdbb44cef1cd1058f7e41a49bbece231f6df4b1545332cda" - }, - { - "text": "8% to 8% of all adrenal tumors.", - "tokenCount": 11, - "pageStart": 2, - "pageEnd": 2, - "hash": "bf5e1639a2792cdaf9b9ed2a6719d8c42aa046cc0838d56764c3a5b070405d9e" - }, - { - "text": "5,8 The prevalence of adrenocortical carcinoma (ACC) in incidentally discovered adrenal nodules is less than 0.", - "tokenCount": 27, - "pageStart": 2, - "pageEnd": 2, - "hash": "13cc7a580cc9e130ed667aeb53693aba3a1ecc2f62e07aaaa2f6606b44184458" - }, - { - "text": "5% for nodules smaller than 4 cm, 5% for nodules from 4 to 6 cm, and up to 35% for nodules larger than 6 cm at presentation.", - "tokenCount": 36, - "pageStart": 2, - "pageEnd": 2, - "hash": "98eefa8077ee97f4d239354f1e4d3d88ace1f724bb0c2f7bc1c7c2b0b288e5e3" - }, - { - "text": "8-11 Metastatic disease to the adrenal gland can be identified in 1% to Key Points Question What are the evidencebased data to reflect bestpractice decisions for adrenal surgery?", - "tokenCount": 38, - "pageStart": 2, - "pageEnd": 2, - "hash": "103a712ce72aabfb9080e4a0f4463ad89aeaaab7f783896d59cc7a5470cca0dc" - }, - { - "text": "Findings Specific recommendations are available for decisionmaking regarding diagnostic, perioperative, and multidisciplinary followup of adrenal surgical disease.", - "tokenCount": 28, - "pageStart": 2, - "pageEnd": 2, - "hash": "29135c30fa3e5387e9769256f18a75a40be1777bfff47360ed06e8217acd3ddf" - }, - { - "text": "Meaning Important developments and advances have better informed adrenal surgery decisionmaking.", - "tokenCount": 15, - "pageStart": 2, - "pageEnd": 2, - "hash": "eba0e06705b1aa2bf94b1d3a1a8da7668a1e9865a57128229696167d5d05150a" - }, - { - "text": "American Association of Endocrine Surgeons Guidelines for Adrenalectomy Original Investigation Research jamasurgery.", - "tokenCount": 20, - "pageStart": 2, - "pageEnd": 2, - "hash": "ad8ede3639f601a895c0ff2d4a799381e860abd6bf9853fb87d3164ef44b57c8" - }, - { - "text": "com (Reprinted) JAMA Surgery October 2022 Volume 157, Number 10 871 2022 American Medical Association.", - "tokenCount": 24, - "pageStart": 2, - "pageEnd": 2, - "hash": "f0ef605d173fc2f4df8547a3b6684ec2d9d23219a295702e6df44ec007650707" - }, - { - "text": "3% in patients without a history of malignancy and up to 8% in patients with a history of extraadrenal malignancy.", - "tokenCount": 30, - "pageStart": 3, - "pageEnd": 3, - "hash": "e83acaf6f952f8b611868579eccdf7eff46674f79aa384f97257f79fdae4c3b8" - }, - { - "text": "8 Other features in addition to size should be considered when assessing risk of either a primary or secondary malignancy in an adrenal incidentaloma (eTable 2 in the Supplement ).", - "tokenCount": 36, - "pageStart": 3, - "pageEnd": 3, - "hash": "21a29cbde14a3ec031e3c11cbe22cab49f21b115e31d9f80f138784759b48111" - }, - { - "text": "We recommend that all patients with an adrenal incidentaloma 1 cm or larger undergo biochemical testing for autonomous cortisol secretion.", - "tokenCount": 23, - "pageStart": 3, - "pageEnd": 3, - "hash": "806cff59ea59a7104605172c1e6428abba01ace5103d6aaf382b12704a1948df" - }, - { - "text": "Patients with hypertension or hypokalemia also require biochemical evaluation for primary aldosteronism.", - "tokenCount": 21, - "pageStart": 3, - "pageEnd": 3, - "hash": "c39c5a742c5dc06aea4771a50e6b38291016955ec5dc096de6ff50d688797530" - }, - { - "text": "Patients with adrenal imaging findings that have noncontrast CT with HU greater than 10 should undergo evaluation for pheochromocytoma.", - "tokenCount": 31, - "pageStart": 3, - "pageEnd": 3, - "hash": "6c5c69fa31f1e398982573643a9de4f09ef9bb5dad8a06afcc3fc42e8a6c2506" - }, - { - "text": "We recommend that a primary adrenal malignancy be considered in patients with an adrenal incidentaloma larger 4 cm and/or HU greater than 20 on noncontrast CT and in any patient younger than 18 years.", - "tokenCount": 45, - "pageStart": 3, - "pageEnd": 3, - "hash": "1243334035deb4f31c0af3b10f9e58b579e789d716fd4421d0e698ff172e76f8" - }, - { - "text": "We recommend that patients with a history of extraadrenal malignancy be recognized to be at increased risk for adrenal metastases.", - "tokenCount": 28, - "pageStart": 3, - "pageEnd": 3, - "hash": "851a0bdc40a0c961b4177a04b07b6e673de7f78372fd73d5921e6fd72de5d821" - }, - { - "text": ") Most nonfunctional adrenal nodules with benign imaging characteristics remain stable in size 5,7,12 while up to 10% of adrenal incidentalomas will grow 1 cm or more over 2 to 5 years of surveillance.", - "tokenCount": 45, - "pageStart": 3, - "pageEnd": 3, - "hash": "4f58127c154ee2785a7c209280afa057146df985e2c0c8a6e65398a1b29c2ac1" - }, - { - "text": "13-15 Surgical resection may be considered for nodules that are larger than 2 cm at initial presentation and grow more than 1 cm by 12 months, while smaller nodules or those with less growth may undergo repeated shortinterval imaging at 6 to 12 months.", - "tokenCount": 54, - "pageStart": 3, - "pageEnd": 3, - "hash": "10d7ec6005414cfb4118732e34d5e50d9ffa3d046eca79a25c58e3dd70fe80c9" - }, - { - "text": "However, there are insufficient data to recommend specific criteria for nodule growth during surveillance that should prompt adrenalectomy.", - "tokenCount": 23, - "pageStart": 3, - "pageEnd": 3, - "hash": "35885eeab9e7d8773a84f86ae6297e693110b3693375e37ad18913a6762bf73d" - }, - { - "text": "Topics and Questions in the Population, Intervention/Exposure, Comparison, and Outcome (PICO) Framework 1.", - "tokenCount": 24, - "pageStart": 3, - "pageEnd": 3, - "hash": "78202403ab25a7bcca1ac5895c43a7209a6398dd5510d23a6df9b665ee9909fd" - }, - { - "text": "Incidentalomas, myelolipomas, and cysts 1.", - "tokenCount": 15, - "pageStart": 3, - "pageEnd": 3, - "hash": "30da823bb34b04d23f144ef623202b9662ec68c39b1d4979fd3e99bfb2383249" - }, - { - "text": "In patients with an adrenal incidentaloma, does adrenal protocol computed tomography improve diagnostic accuracy for malignancy or pheochromocytoma compared with other imaging modalities?", - "tokenCount": 38, - "pageStart": 3, - "pageEnd": 3, - "hash": "42d72537a2f00bea666b05c6c99a42c38a9efe8a04d7c58f8a36c2a7c28a6253" - }, - { - "text": "In patients with an adrenal incidentaloma, should clinical and imaging characteristics influence the hormonal workup?", - "tokenCount": 20, - "pageStart": 3, - "pageEnd": 3, - "hash": "4a95fcc0993eaf795b57a42f2351bc33c5a25d0e3a453d982a5f1e4b4025538a" - }, - { - "text": "In patients with an adrenal incidentaloma, what clinical and imaging characteristics increase the risk that malignancy is present?", - "tokenCount": 24, - "pageStart": 3, - "pageEnd": 3, - "hash": "e0c8533a5ab13d5797622e4df3b6136a5000e1bc18bea2e36cad7ef60da94925" - }, - { - "text": "In patients with a nonfunctional adrenal incidentaloma, what are the outcomes during surveillance?", - "tokenCount": 18, - "pageStart": 3, - "pageEnd": 3, - "hash": "6c3995a0e6ec401cd6d2c8d376ddd3c9474ca4dd47fe78d6abf0664a07b9c371" - }, - { - "text": "Does resection of a myelolipoma or an adrenal cyst improve quality of life compared with observation alone?", - "tokenCount": 25, - "pageStart": 3, - "pageEnd": 3, - "hash": "bcd90d47de8f8448e6b51cde91db99d3d543a3b07b436b8af697178ff51dce5d" - }, - { - "text": "In patients with primary aldosteronism (PA), does adrenalectomy compared with mineralocorticoid antagonist therapy alone improve related comorbidities and mortality?", - "tokenCount": 35, - "pageStart": 3, - "pageEnd": 3, - "hash": "32a68a4fce8718c7b7aaf219b0650f12128317bf06aee7f2d65f324a30677d4c" - }, - { - "text": "In patients with PA and crosssectional imaging consistent with a unilateral adenoma, does preoperative adrenal venous sampling increase the likelihood of a clinical or biochemical cure?", - "tokenCount": 34, - "pageStart": 3, - "pageEnd": 3, - "hash": "3c6f23abe8c67155b3aeee8ef12e99a7e2f820bdbbe1a207c72a0818c3daeb7e" - }, - { - "text": "In patients with PA due to unilateral disease, does laparoscopic adrenalectomy improve healthrelated quality of life and/or reduce health carerelated costs compared with medical management?", - "tokenCount": 35, - "pageStart": 3, - "pageEnd": 3, - "hash": "450af8421ae00358ceed962809f92c249120153ea67eb28306be2ec3a5c773a7" - }, - { - "text": "Do patients with mild autonomous cortisol secretion (MACS) who undergo laparoscopic adrenalectomy compared with conservative medical management have improvement in cardiometabolic comorbidities without major surgical (30-day) adverse events?", - "tokenCount": 46, - "pageStart": 3, - "pageEnd": 3, - "hash": "992f820ebf42b64ff17b24c60411bf1717e867db7a4431bf54ec8e5e7cb3ae2a" - }, - { - "text": "Do patients with Cushing syndrome and bilateral macronodular hyperplasia who undergo unilateral laparoscopic adrenalectomy achieve biochemical remission of hypercortisolism when compared with patients treated with bilateral adrenalectomy?", - "tokenCount": 44, - "pageStart": 3, - "pageEnd": 3, - "hash": "82e0afb0b650c9baa39eda0b3d698f3e461e1f1af5892176b855deff8ff2e684" - }, - { - "text": "In patients with adrenocorticotropic hormonedependent hypercortisolism, does bilateral laparoscopic adrenalectomy improve diseasefree survival or mortality compared with pharmacologic management?", - "tokenCount": 38, - "pageStart": 3, - "pageEnd": 3, - "hash": "2041643602c5fab03fe8378ef658e6c568e968d74f8191ef0b0beae63ceb6cd5" - }, - { - "text": "Is the incidence of postoperative adrenal insufficiency after unilateral adrenalectomy different between patients with overt Cushing syndrome vs those with MACS?", - "tokenCount": 30, - "pageStart": 3, - "pageEnd": 3, - "hash": "be50c1b2ec84e3b909dad7e6bb3f9afa44e01ecc98a493b90487927cc20f0f14" - }, - { - "text": "In patients with adrenocortical carcinoma (ACC), does treatment at a highvolume multidisciplinary center improve survival outcomes?", - "tokenCount": 26, - "pageStart": 3, - "pageEnd": 3, - "hash": "94d81da4f25c0635942b209a4feedcd9fa35fc49e6ec981b1fbd279a1c178646" - }, - { - "text": "In patients with ACC without evidence of distant metastatic disease at diagnosis, does operative technique affect survival?", - "tokenCount": 20, - "pageStart": 3, - "pageEnd": 3, - "hash": "349ad312f027d3b041429e6cf70675197d4e98a2f7590065c4a9959c5aa99115" - }, - { - "text": "In patients with ACC and systemic disease at diagnosis, does resection of the primary tumor improve survival?", - "tokenCount": 20, - "pageStart": 3, - "pageEnd": 3, - "hash": "5bb563b1f362e7696bc67c9d17b5c6c187da42cee1e856523e033b88f1cac872" - }, - { - "text": "In patients with advanced ACC, what is the role of neoadjuvant therapy followed by resection vs surgery with or without adjuvant therapy?", - "tokenCount": 30, - "pageStart": 3, - "pageEnd": 3, - "hash": "4c3306e5ca0405e61bc16815e93b4d151d8852718be4318acc57e1960be29b6d" - }, - { - "text": "Metastasis to the adrenal gland 1.", - "tokenCount": 10, - "pageStart": 3, - "pageEnd": 3, - "hash": "926314de2bab6e583d53849cf4d19210c23d783d1a4d1d9c9f0f95561b35eda1" - }, - { - "text": "In patients with an adrenal mass, does history of an extraadrenal malignancy influence the hormonal evaluation?", - "tokenCount": 24, - "pageStart": 3, - "pageEnd": 3, - "hash": "f6dbd8b0d45c1072bed4b6247dee66711338e447eb33fc71fa1c3011a53a9db1" - }, - { - "text": "In a patient with a history of an extraadrenal malignancy and an adrenal mass, when is imageguided needle biopsy recommended?", - "tokenCount": 30, - "pageStart": 3, - "pageEnd": 3, - "hash": "6b90ceb8b4a0846e6b0078c2a115e476a32c54bb6dbf7a8ebe5f7a27bf4d5761" - }, - { - "text": "In patients with an adrenal metastasis, does resection improve survival compared with systemic therapy alone?", - "tokenCount": 20, - "pageStart": 3, - "pageEnd": 3, - "hash": "a6a27576cd7805d005e220fa9091997f402f87d4dae895bf7ea84c371960aa0b" - }, - { - "text": "Pheochromocytoma and paraganglioma 1.", - "tokenCount": 15, - "pageStart": 3, - "pageEnd": 3, - "hash": "d5e458f1e1e8afbd3a35a735cb7cbcb90e3e519b97403ceb26ce43bb5a19a52f" - }, - { - "text": "In patients with pheochromocytoma and paraganglioma, how does selective blockade affect perioperative hemodynamic stability when compared with nonselective blockade with phenoxybenzamine?", - "tokenCount": 43, - "pageStart": 3, - "pageEnd": 3, - "hash": "230117a5611f156565dbd2114801bfd3bb22b348150c9f80bed3d4c0437994c6" - }, - { - "text": "In patients with genetic mutations driving longterm development of bilateral pheochromocytomas, what is the impact of corticalsparing adrenalectomy compared with bilateral total adrenalectomy on steroid dependence and disease recurrence?", - "tokenCount": 45, - "pageStart": 3, - "pageEnd": 3, - "hash": "af262b2e3ea43e729b89e16a736fc871a98c202bd5a41e522524f938c74975dc" - }, - { - "text": "In patients with metastatic pheochromocytoma and paraganglioma, does surgical resection of primary disease improve survival compared with nonsurgical treatment?", - "tokenCount": 34, - "pageStart": 3, - "pageEnd": 3, - "hash": "f41301354f0cb3a3eb0aa240e5482c188aed6e2a4dadafb61eba0afb61cabf3d" - }, - { - "text": "In patients undergoing adrenalectomy, what is the benefit of minimally invasive surgery compared with open surgery on perioperative outcomes?", - "tokenCount": 26, - "pageStart": 3, - "pageEnd": 3, - "hash": "c6c18010b6b70f3eb6fd7316aa674649b5b11ebe75d2ead5a25999bf9114dd7d" - }, - { - "text": "In patients who are appropriate candidates for minimally invasive adrenalectomy, does a retroperitoneal compared with a transperitoneal approach change perioperative outcomes?", - "tokenCount": 34, - "pageStart": 3, - "pageEnd": 3, - "hash": "01314de9c2a1625b3d6fcf1a05bc465857001e0ce51d3bc1c9e22b8658f2aa39" - }, - { - "text": "For surgeons performing adrenal surgery, does surgeon volume influence morbidity and mortality?", - "tokenCount": 16, - "pageStart": 3, - "pageEnd": 3, - "hash": "8797096a685cdcd7f66a7ebc3a6965eaad8b0fb58e9487b0148877b3bd3dc679" - }, - { - "text": "In patients with adrenal tumors, what is the efficacy of radiofrequency ablation and stereotactic radiation compared with adrenalectomy?", - "tokenCount": 27, - "pageStart": 3, - "pageEnd": 3, - "hash": "90432158afbdb8c78c1c4ca92af93a65f0ec1fd7b96c8b4bed67c42bbe490845" - }, - { - "text": "Research Original Investigation American Association of Endocrine Surgeons Guidelines for Adrenalectomy 872 JAMA Surgery October 2022 Volume 157, Number 10 (Reprinted) jamasurgery.", - "tokenCount": 37, - "pageStart": 3, - "pageEnd": 3, - "hash": "e51bb6eddce25814edaf9c1476dc6aa5921566009bf2edbc36201553ad451d69" - }, - { - "text": "We do not recommend routine scheduled followup of a nonfunctional adrenal nodule (size <4 cm) with benign imaging characteristics and noncontrast HU less than 10 because the risk of developing malignancy is very low.", - "tokenCount": 47, - "pageStart": 4, - "pageEnd": 4, - "hash": "d522bc46b197c62e59e25d21e89916f58895460bfcadf46ab3d467b6fb172e1b" - }, - { - "text": "Nodules from 1 to 4 cm with indeterminate imaging characteristics (such as noncontrast CT with HU >10) have a slightly increased risk of malignancy and should undergo at least 1 repeated image at 6 to 12 months to confirm stability.", - "tokenCount": 53, - "pageStart": 4, - "pageEnd": 4, - "hash": "efe852b1e11887078d899f112eff22464322197b7c0c8f0381ea657455fef873" - }, - { - "text": "Autonomous cortisol secretion is the most common hormonal excess to develop during surveillance and thus may be reevaluated at a 2- to 5-year interval.", - "tokenCount": 31, - "pageStart": 4, - "pageEnd": 4, - "hash": "bb73a0138c7f191f0b90a2863a353c129f506de9613c0a276c460e4431ff71b3" - }, - { - "text": ") Adrenalmyelolipomasandcystshavecharacteristicimaging features.", - "tokenCount": 19, - "pageStart": 4, - "pageEnd": 4, - "hash": "a7d856edd01c48f3757091fefdffbd200a67169aab39e9a103cdc5b8c49f38e3" - }, - { - "text": "4 Resection may be considered for indeterminate imaging, symptomatic tumors due to mass effect, substantive growth on surveillance, or those that have hemorrhaged.", - "tokenCount": 32, - "pageStart": 4, - "pageEnd": 4, - "hash": "9eb5e37dbecffab94ae611e212e48a30f79173c05a757b6cd7eccf7e3eff11e4" - }, - { - "text": "We do not suggest resecting a myelolipoma or adrenal cyst with pathognomonic imaging features to improve the patients quality of life unless there are symptoms of mass effect.", - "tokenCount": 40, - "pageStart": 4, - "pageEnd": 4, - "hash": "6fb9f612fef8031973669bacd331be7af1d77952ec278360e923d3b6017868fe" - }, - { - "text": "Primary Aldosteronism Primary aldosteronism (PA) has been reported in 3% to 10% of hypertensive patients.", - "tokenCount": 28, - "pageStart": 4, - "pageEnd": 4, - "hash": "83dd268db6227e44d3101bc9a83413609e05e7bd607105985e4c0d0b6275cf88" - }, - { - "text": "16 Once PA is diagnosed, mineralocorticoid antagonists can be used to effectively manage PArelated hypertension and hypokalemia.", - "tokenCount": 27, - "pageStart": 4, - "pageEnd": 4, - "hash": "17ff0cde7107964b562fa36a2bc32ee31c98ddba822c4554c86bed9d1140c0a7" - }, - { - "text": "Primary aldosteronism may be caused by an aldosteronesecreting adenoma, unilateral adrenal hyperplasia, or bilateral adrenal hyperplasia, and adrenal venous sampling (AVS) may be necessary for lateralization (eTable 3 in the Supplement ).", - "tokenCount": 61, - "pageStart": 4, - "pageEnd": 4, - "hash": "1519a2586a7dbe8ad1ea9162973fdb02486750ae2b5b2041bb556cf2399a5860" - }, - { - "text": "After adrenalectomy, the majority of patients with PA have either complete or partial clinical success, with less than 20% requiring the same or higher doses of medication postoperatively.", - "tokenCount": 36, - "pageStart": 4, - "pageEnd": 4, - "hash": "438aad371d4f6920966c7dda22df50b596b35fd0f1b02a1a551558be46556bd5" - }, - { - "text": "Studies to date have assessed cost and qualityoflife outcomes after adrenalectomy via laparoscopy, and whether similar conclusions can be made using other minimally invasive surgical approaches is not yet known.", - "tokenCount": 40, - "pageStart": 4, - "pageEnd": 4, - "hash": "4c71a572d31bb02f114641568e40d18bcfc3008b6e3a1cf09a5e3ea2faae154d" - }, - { - "text": "We recommend that patients undergo laparoscopic adrenalectomy for unilateral PA because they are more likely to use fewer medications with lower defined daily doses to achieve normalization of blood pressure and potassium levels and have lower risks of newonset atrial fibrillation, chronic kidney disease, stroke, and allcause mortality.", - "tokenCount": 63, - "pageStart": 4, - "pageEnd": 4, - "hash": "8cedbbaa410c441cf04cb1fa58b20f42f6a3c0c9d85080169b68950d58b928b4" - }, - { - "text": "We suggest that in patients 35 years and younger with crosssectional imaging demonstrating a unilateral adenoma and a normal contralateral gland, AVS may be deferred because adrenalectomy directed by CT imaging alone has a cure rate similar to adrenalectomy guided by AVS.", - "tokenCount": 55, - "pageStart": 4, - "pageEnd": 4, - "hash": "f12c162010b08e5d38faa853fab304d721dd9c48f5fb306180c6c258a1358343" - }, - { - "text": "However, AVS should still be considered for all patients older than 35 years.", - "tokenCount": 16, - "pageStart": 4, - "pageEnd": 4, - "hash": "d277706263d758b750f2acbb71c1ee0b91fbfae54a8bf3cbbbbd72def171c452" - }, - { - "text": "We recommend laparoscopic adrenalectomy for primary aldosteronism due to unilateral disease because it improves quality of life and reduces health carerelated costs.", - "tokenCount": 32, - "pageStart": 4, - "pageEnd": 4, - "hash": "4b453c36927251e7c422257885f6070787e6933c7d30b0010573bf7af934986c" - }, - { - "text": "Hypercortisolism Previously known as subclinical Cushing syndrome (CS), MACS has been reported in 0.", - "tokenCount": 24, - "pageStart": 4, - "pageEnd": 4, - "hash": "7f0f4db0501306a435ff90f5ea3ed48256fd61c03fe47c7063891ee133b62882" - }, - { - "text": "2% to 2% of the general adult population and in 5% to 30% of patients with an adrenal incidentaloma (eTable 3 in the Supplement ).", - "tokenCount": 33, - "pageStart": 4, - "pageEnd": 4, - "hash": "a98240ab7e6d65b7c612acd664cc01d4ff3e5d42cba404c46495499321f08096" - }, - { - "text": "17 Although patients with MACS may lack the classical stigmata of hypercortisolism, they have a high prevalence of associated comorbidities such as obesity, arterial hypertension, type 2 diabetes, vertebral fractures, and cardiovascular morbidity and mortality.", - "tokenCount": 54, - "pageStart": 4, - "pageEnd": 4, - "hash": "667d30209c639ea28aa386c593c98ef8e9f18f193b88de1bec1baaa34f3fe9a0" - }, - { - "text": "We recommend that patients with MACS secondary to a unilateral adenoma undergo laparoscopic adrenalectomy because of anticipated significant improvements in cardiometabolic comorbidities.", - "tokenCount": 36, - "pageStart": 4, - "pageEnd": 4, - "hash": "48e3407e7dc7ea167cf3abe12bdde9bd2e158bbba9f7f86c3482d793eabca888" - }, - { - "text": ") Bilateraladrenocorticotropichormone(ACTH)independent CS can be due to either macronodular or micronodular adrenal hyperplasia.", - "tokenCount": 38, - "pageStart": 4, - "pageEnd": 4, - "hash": "113357fd2af1dcf5b8bc3b309b63a5f57acc0732fc3045e891c74bf75e77257d" - }, - { - "text": "20,21 There has been growing interest in whether unilateral adrenalectomy of the larger gland may produce biochemical normalization of hypercortisolism in select patients.", - "tokenCount": 33, - "pageStart": 4, - "pageEnd": 4, - "hash": "dff9d9c4b56b6949ef915c308b71f0c943bb3e24079806613bb7bf65be90ed0c" - }, - { - "text": "While surgical morbidity and mortality are minimal 17 and resolution of hypercortisolism occurs in 84% to 100% of patients, recurrence can be seen in 13.", - "tokenCount": 35, - "pageStart": 4, - "pageEnd": 4, - "hash": "39c5e127253fbdd9ecbba9f65e8229e08086bf008ae43a43292bac8d2f25fba6" - }, - { - "text": "3% to 68% of patients at 4 years.", - "tokenCount": 11, - "pageStart": 4, - "pageEnd": 4, - "hash": "e07d4f9bab64a298647b56848ddb90c445772470b4f0a5d30b2c33cbb2dc87b7" - }, - { - "text": "In patients with bilateral macronodular hyperplasia, we suggest consideration of unilateral laparoscopic adrenalectomy in patients with CS as an attempt to achieve biochemical remission of hypercortisolism without causing permanent adrenal insufficiency.", - "tokenCount": 49, - "pageStart": 4, - "pageEnd": 4, - "hash": "07bdd0a76fc62cd3529af5d0f9e7a5c53a0535d2b0f8705b2134bd5adf865366" - }, - { - "text": ") ACTHdependent CS results from pituitary Cushing disease or an ectopic ACTH source.", - "tokenCount": 21, - "pageStart": 4, - "pageEnd": 4, - "hash": "b7cf3a567af618d35eb6d73cabbbf5d76f3101a4e98bc14464bcc1da26249004" - }, - { - "text": "Although CS can be resolved in most patients with treatment of the primary source, a subset of patients experience persistent, symptomatic CS from incurable pituitary disease or metastatic or occult ectopic ACTH production.", - "tokenCount": 43, - "pageStart": 4, - "pageEnd": 4, - "hash": "85a15f7afd009c615643333d4289a188efb925518edfbe16a4e371a841a8bc97" - }, - { - "text": "Modern surgical techniques permit most patients who require bilateral adrenalectomy to be managed with laparoscopic surgery, and operative morbidity in these patients is approximately 10% with surgical mortality at 3%.", - "tokenCount": 38, - "pageStart": 4, - "pageEnd": 4, - "hash": "6e9472d70c01329472ffc7589d290d3b6613e88eb1a2173e180a529d33a37861" - }, - { - "text": "We suggest that patients with moderate to severe ACTHdependent hypercortisolism refractory to source control undergo bilateral laparoscopic adrenalectomy to ameliorate cortisol excess and improve diseasefree survival and mortality.", - "tokenCount": 45, - "pageStart": 4, - "pageEnd": 4, - "hash": "99a386ea11849cc1e371b86451e2b2bbdf032b0c1759ffe5c54a05b2ad1676a4" - }, - { - "text": "Postoperative adrenal insufficiency is a lifethreatening condition that should be prevented and promptly managed in patients undergoing adrenalectomy.", - "tokenCount": 28, - "pageStart": 4, - "pageEnd": 4, - "hash": "458fd15905b493780b8d84bf5e654b8551ef645953fd2b2f1b96d5c618d722c6" - }, - { - "text": "Symptoms include fatigue, hypotension, anorexia, abdominal pain, weakness, syncope, back pain, nausea, vomiting, fever, and confusion.", - "tokenCount": 32, - "pageStart": 4, - "pageEnd": 4, - "hash": "e961195aa06c7f91f245f987859d36be83bb81cc1002f922dd4b57751c844bab" - }, - { - "text": "The incidence of adrenal insufficiency after unilateral adrenalectomy is nearly 100% in patients with overt CS and about 60% in patients with MACS.", - "tokenCount": 32, - "pageStart": 4, - "pageEnd": 4, - "hash": "fb43c7fe42e52cae53f0fc0ef706da69d1403284ab4acb6d81e2fc253e57d994" - }, - { - "text": "We recommend empirical postoperative glucocorticoid replacement therapy for all patients with overt CS after undergoing unilateral adrenalectomy.", - "tokenCount": 25, - "pageStart": 4, - "pageEnd": 4, - "hash": "7ab6518731bae805d9a225b12d5a1c72b19e7adcb61af771b43a1ae1722cf7d6" - }, - { - "text": "However, we r ecommend that in patients with MACS, postoperative day 1 morning cortisol or corticotropin stimulation testing could be used to determine the need for glucocorticoid replacement therapy (eTable 4 American Association of Endocrine Surgeons Guidelines for Adrenalectomy Original Investigation Research jamasurgery.", - "tokenCount": 66, - "pageStart": 4, - "pageEnd": 4, - "hash": "4b8af42e585eca3692fd8d085dd7eb7d4df846ebddca8ea9a516a0549094dfed" - }, - { - "text": "com (Reprinted) JAMA Surgery October 2022 Volume 157, Number 10 873 2022 American Medical Association.", - "tokenCount": 24, - "pageStart": 4, - "pageEnd": 4, - "hash": "d4ace8c7347f74a3e82898e4b2fcf2135c737c47cf305176ceb5bc382c402c33" - }, - { - "text": "Adrenocortical Carcinoma Adrenocortical carcinoma is a rare cancer and complete surgical resection is the only potential curative therapy (eTable 3 in the Supplement ).", - "tokenCount": 38, - "pageStart": 5, - "pageEnd": 5, - "hash": "f07260ef6843bc44e0a740e3e915ffff9ed29f803d0d38454851fbb52df95a72" - }, - { - "text": "28 Given limited adjuvant therapies and the overall poor prognosis associated with recurrent ACC, complete resection to negative margins at the index operation is a key tenet of ACC management.", - "tokenCount": 37, - "pageStart": 5, - "pageEnd": 5, - "hash": "240d2be3755df33bfe1db9d7fefcc8a347a9dfe6eefa2133274155f59c06760f" - }, - { - "text": "29 While radical surgery with en bloc resection and preservation of an intact tumor capsule is the standard of care for locoregionally invasive disease, the operative technique hinges on skill and experience.", - "tokenCount": 39, - "pageStart": 5, - "pageEnd": 5, - "hash": "954f31e572ea8249d872d524490e6196c6c638f290955f17dce8fd2f33bc97ee" - }, - { - "text": "We recommend that patients with clinical and radiographic findings consistent with ACC should be treated at highvolume multidisciplinary centers to improve recurrence outcomes; data on overall survival are inconclusive.", - "tokenCount": 37, - "pageStart": 5, - "pageEnd": 5, - "hash": "823b6ddb02e1369eaf322bda0dcc413a41fc20fcc9305044bd1d4dfa10c04642" - }, - { - "text": "Regardless of operative approach, we recommend an en bloc radical resection with an intact capsule to microscopically negative (R0) margins because of improved survival.", - "tokenCount": 32, - "pageStart": 5, - "pageEnd": 5, - "hash": "fadf36b9aa7e15a81174532e4a6a9140d1e9ec83030cc4135bcbe65344cfa4b3" - }, - { - "text": "Although open resection is preferred when ACC is suspected, the choice of operative approach should be based on the certainty of a complete R0 resection without tumor disruption.", - "tokenCount": 33, - "pageStart": 5, - "pageEnd": 5, - "hash": "db8f3cf78f27c6af9c59be76570df26c7cdc1cf2fe227329d008a4959d893020" - }, - { - "text": ") Approximately 22% to 35% of patients with ACC have evidence of distant metastatic disease at initial presentation.", - "tokenCount": 22, - "pageStart": 5, - "pageEnd": 5, - "hash": "0e57f144b2ae8896bd706ff8099843ef32e884b628ad51c2877e16462b911506" - }, - { - "text": "29,30 Cases with oligometastatic but potentially resectable ACC present a challenge, as the benefits of primary resection and/or metastasectomy are incompletely understood.", - "tokenCount": 37, - "pageStart": 5, - "pageEnd": 5, - "hash": "f48f196a6ca8d392332b8bd8717c083a1eb664cabe48251e4266f854bb27053d" - }, - { - "text": "Careful patient selection and clinical judgment should be integrated with the patients goals of care.", - "tokenCount": 17, - "pageStart": 5, - "pageEnd": 5, - "hash": "a3bc7b3a3a4829544467bb9f9ba3ed39a68a4460345a24dd75807f530af50213" - }, - { - "text": "We suggest that patients with systemic disease be offered resection of the primary tumor if all sites of disease are reasonably amenable to resection or local treatment and if performance status allows.", - "tokenCount": 36, - "pageStart": 5, - "pageEnd": 5, - "hash": "2612d25ab72e7b5767941f9270c9aa255b49741104cf0792bfef631123908019" - }, - { - "text": "Surgery may also be considered in patients with hormone excess medically refractory to steroidogenic inhibition.", - "tokenCount": 20, - "pageStart": 5, - "pageEnd": 5, - "hash": "6ed35937fb85fb159e242045c196c4881b9ebd818e1dcdfdc5de55ed37c36a7f" - }, - { - "text": ") In ACC, the goal of systemic neoadjuvant therapy is primarily to reduce the burden of disease to facilitate later potential complete resection. Although neoadjuvant therapy for advanced ACC has not been systemically evaluated, the rationale for neoadjuvant treatment is extrapolated from the data on adjuvant therapy.", - "tokenCount": 65, - "pageStart": 5, - "pageEnd": 5, - "hash": "f89e9b4939d0f480f297f128701d3936e892c5b74ecae43498f3e0a73a32bd47" - }, - { - "text": "We recommend that neoadjuvant systemic therapy be administered for advanced ACC when R0 surgical resection is not initially feasible.", - "tokenCount": 25, - "pageStart": 5, - "pageEnd": 5, - "hash": "4dca13cdd5df6918d038b6f46de3406e2e459b4e584423255b2b6d9ccbd55888" - }, - { - "text": "We recommend upfront surgical intervention when R0 resection is possible.", - "tokenCount": 13, - "pageStart": 5, - "pageEnd": 5, - "hash": "6a915eb85552da1ebd336b6266345518d532f16fd23a10bc12ab4fd003e4346c" - }, - { - "text": "Metastasis to the Adrenal Gland Adrenal metastases may have imaging features that make them potentially indistinguishable from other pathologies.", - "tokenCount": 27, - "pageStart": 5, - "pageEnd": 5, - "hash": "b3e616cc22b8424864cfadad6f676ba79059b09cd53412dfeaad5532ba8edcc2" - }, - { - "text": "Functional evaluation is imperative prior to biopsy, ablation, or resection and should aim, at a minimum, to exclude excess hormone production.", - "tokenCount": 30, - "pageStart": 5, - "pageEnd": 5, - "hash": "74be9eccaa8d224eaccc6a7fc49aa8bc1ad5b7ce8609c8e25c372195ab30bf57" - }, - { - "text": "If the indeterminate adrenal mass is the only site of potential metastatic disease and appears resectable in an otherwise fit operative candidate, surgical resection rather than biopsy may be considered for both diagnostic purposes and potential therapeutic benefit.", - "tokenCount": 48, - "pageStart": 5, - "pageEnd": 5, - "hash": "70d7e0d95d5c2f0006bd950b6c35229153b4014ee6ab4fbe26a574f8aac7c5f3" - }, - { - "text": "We recommend that a directed hormonal evaluation should be performed in patients with an adrenal mass regardless of history of extraadrenal malignancy.", - "tokenCount": 29, - "pageStart": 5, - "pageEnd": 5, - "hash": "373291e251e683a1a6f7b82e97f17cc06f2bcda30d39397094913ebc4397af7f" - }, - { - "text": "We suggest that in the setting of a radiographically indeterminate mass, imageguided biopsy be rarely performed and reserved for patients in whom results would change overall disease management and that it be performed only after confirming lack of hormone excess.", - "tokenCount": 47, - "pageStart": 5, - "pageEnd": 5, - "hash": "76670011c77adffa01cbe14e622531bf7897558ad46f9f8d379ca27619c41ad4" - }, - { - "text": ") Adrenal metastasis commonly occurs in patients with malignancy from the lung, kidney, breast, melanoma, and colon but may occur from many other primary sites.", - "tokenCount": 35, - "pageStart": 5, - "pageEnd": 5, - "hash": "87d4cfbca031dbb3b90a1f524ba21be7240ed3ab95a7fcbd2cf5b3bdb21284a9" - }, - { - "text": "While there are currently no established criteria guiding patient selection for adrenal metastasectomy, consideration should be given to pathology, synchronous vs metachronous presentation, diseasefree interval, and tumor size to help select appropriate surgical candidates.", - "tokenCount": 47, - "pageStart": 5, - "pageEnd": 5, - "hash": "b9881a491235b0e8e612f6e9722b8107491d1055ed35fc694a0cf8ddeea7eb21" - }, - { - "text": "Adrenal metastasectomy may be more difficult because of reaction from systemic treatment but can be performed either open or minimally invasive with equivalent oncologic outcomes.", - "tokenCount": 33, - "pageStart": 5, - "pageEnd": 5, - "hash": "463c67d319b54be9998eae6d4b4a9d6e2955c731b9969b2c974f9ea8eb2547aa" - }, - { - "text": "We suggest that after multidisciplinary review, resection may be offered to highly selected patients to improve survival compared with systemic therapy alone.", - "tokenCount": 27, - "pageStart": 5, - "pageEnd": 5, - "hash": "2c07b253838c81e2b7a79c7a2316371d91db7e2d68ee84518b6de7b7c3fb89c4" - }, - { - "text": "Pheochromocytoma and Paraganglioma As recommended in the Endocrine Society clinic practice guideline for pheochromocytoma and paraganglioma (PPGL), initial biochemical testing for PPGLs should include measurement of plasmafree or urinary fractionated metanephrines and are typically more than 2 to 3 times the upper limit of normal in functional PPGLs.", - "tokenCount": 88, - "pageStart": 5, - "pageEnd": 5, - "hash": "09ca003e506bd68b9bd1bcb592d63f9b85145820ffa0fd932f0b95646b3e4d25" - }, - { - "text": "31,32 Following the diagnosis, preoperative blockade for at least 7 days is routinely recommended to prevent dangerous perioperative hemodynamic instability.", - "tokenCount": 28, - "pageStart": 5, - "pageEnd": 5, - "hash": "a3aec26c4622b4ada0903671c1aec1a7e1fc362dde3b3b49eae65bda8a6b9223" - }, - { - "text": "We recommend either selective or nonselective blockade to safely prepare patients for surgical resection of PPGL, depending on the drug availability/cost, experience, and preference of the care team.", - "tokenCount": 40, - "pageStart": 5, - "pageEnd": 5, - "hash": "6e2baa5b8f887fb850d325b5c0d0f5847eb5cd06c065340183342a534648bf4b" - }, - { - "text": "While there is no significant difference in morbidity or mortality between selective and nonselective blockade, selective blockade (doxazosin, prazosin, terazosin) is associated with more intraoperative hemodynamic instability while nonselective blockade (phenoxybenzamine) results in more postoperative hypotension.", - "tokenCount": 68, - "pageStart": 5, - "pageEnd": 5, - "hash": "a1e3da91baae9e89f41820454b597e1e70e9a3f4e411cc6ff4554c427fa9bce7" - }, - { - "text": ") Pheochromocytomas (PCCs) and paragangliomas (PGLs) have the highest heritability of all adrenal tumors (about 40% are due to germline mutations), 33,34 and genetic testing is recommended (eTable 3 in the Supplement ).", - "tokenCount": 61, - "pageStart": 5, - "pageEnd": 5, - "hash": "ed0e3c303ae7c73eddf318e42f2f97f56500b87d95d36b7b6a8f8bb957b4e238" - }, - { - "text": "In the presence of bilateral or familial PCC, corticalsparing adrenalectomy has been successfully used to preserve adrenal cortical tissue, preventing lifelong adrenal insufficiency.", - "tokenCount": 35, - "pageStart": 5, - "pageEnd": 5, - "hash": "e154af74b2306b603cf3f438eac9c99a5c68c22d21089aefd3a9c672fea7e569" - }, - { - "text": "Studies report steroid dependency rates between 9% and 30% with recurrence rates from 9% to 30%.", - "tokenCount": 21, - "pageStart": 5, - "pageEnd": 5, - "hash": "537e387097679494c95e5be07eae320eef5201761558f93dd4c9b7a558f6bf67" - }, - { - "text": "35,36 While there are benefits to corticalResearch Original Investigation American Association of Endocrine Surgeons Guidelines for Adrenalectomy 874 JAMA Surgery October 2022 Volume 157, Number 10 (Reprinted) jamasurgery.", - "tokenCount": 46, - "pageStart": 5, - "pageEnd": 5, - "hash": "7317f576698b056e3e35c5d415d612a2578394f21562e851868ee92d4f1234c0" - }, - { - "text": "sparing adrenalectomy, considerations must include the increased technical difficulty and risk of recurrence in the adrenal remnant, which could necessitate a reoperative adrenalectomy.", - "tokenCount": 35, - "pageStart": 6, - "pageEnd": 6, - "hash": "e735a6e9b042760b37d976bdf59e228bff0f3992acde46ecebe0f16dff9401a4" - }, - { - "text": "If an attempt at corticalsparing adrenalectomy increases concern for tumor disruption or incomplete resection, it may not be appropriate.", - "tokenCount": 26, - "pageStart": 6, - "pageEnd": 6, - "hash": "5709ca2ec71e4f42677c448a86383088e2313663b686305e02b3a6c4d66d33e1" - }, - { - "text": "Because of the decreased rate of steroid dependence, we recommend consideration of corticalsparing adrenalectomy in patients with bilateral PCCs if technically feasible.", - "tokenCount": 30, - "pageStart": 6, - "pageEnd": 6, - "hash": "cb2f2725268639658f1d8c68405a3f1ed63853892786742849bbf6069b1ab038" - }, - { - "text": "However, the pa tients goals of care and a higher risk of recurrent pheochromocytoma should also be considered.", - "tokenCount": 27, - "pageStart": 6, - "pageEnd": 6, - "hash": "0f09271a0360acdfcc047c1bd750257e4f5a38ae1185a03230f1024a524a9d46" - }, - { - "text": ") Approximately 2% to 25% of PCCs are metastatic, as compared with 2% to 60% of PGLs, and several studies suggest a survival benefit associated with resection of the primary tumor in the presence of metastatic disease.", - "tokenCount": 51, - "pageStart": 6, - "pageEnd": 6, - "hash": "820d0f113fdfb74858a2f33db08ebf328add5bb58a54d30d2312fb323f0a561e" - }, - { - "text": "However, more data are needed before potential positive effects of surgery, such as decreasing symptoms of catecholamine excess and improving responsetosystemicradiotherapies,canbeevaluatedandvalidated.", - "tokenCount": 44, - "pageStart": 6, - "pageEnd": 6, - "hash": "1b0771e0381f0e46dceb79d01a74c37ecaee5aac5485a6b32e387031f4df0859" - }, - { - "text": "We suggest that in selected cases of metastatic PPGLs, resection of the primary tumor may be performed to improve overall survival.", - "tokenCount": 28, - "pageStart": 6, - "pageEnd": 6, - "hash": "4b13c3df95d1762860ee6bb898fc045405e5ad4d3429e6a08aaa5f961493944d" - }, - { - "text": "Patients should be carefully evaluated by a multidisciplinary care team to determine if the benefits of resection of the primary tumor outweigh the risks.", - "tokenCount": 29, - "pageStart": 6, - "pageEnd": 6, - "hash": "16764a1a5f91cc1b2486fc4bd007ca46a3211b51cd7843ff774ec73e15112c2b" - }, - { - "text": "Technical Aspects Adrenalectomy may be technically accomplished using either open or minimally invasive techniques via one of several approaches (eTable 5 in the Supplement ).", - "tokenCount": 31, - "pageStart": 6, - "pageEnd": 6, - "hash": "801440b6a2adeae84a21c8a04774747bf5543edae5e8841d287ee486afbf78f5" - }, - { - "text": "Minimally invasive adrenalectomy has become accepted as the goldstandard approach for most small benign adrenal pathology because of multiple studies demonstrating decreased pain, shorter hospitalizations, and more rapid recovery compared with open adrenalectomy.", - "tokenCount": 45, - "pageStart": 6, - "pageEnd": 6, - "hash": "1145e24d5bee684afd6f52b3e288dc8ec47066c3c24f161059f8ebea031e5b3a" - }, - { - "text": "37,38 There have been no prospective randomized trials comparing laparoscopic to open adrenalectomy.", - "tokenCount": 20, - "pageStart": 6, - "pageEnd": 6, - "hash": "6faeeefff4a28700221fd54738582e47a0f82d4ad4b67cd1d3bb2fda93c93035" - }, - { - "text": "Both laparoscopic transabdominal adrenalectomy and posterior retroperitoneal adrenalectomy (PRA) are effective and safe minimally invasive approaches.", - "tokenCount": 33, - "pageStart": 6, - "pageEnd": 6, - "hash": "4cbde7228c979eee582f47d2492e9273351ea8eb0b78a6bacd922e35b07269f7" - }, - { - "text": "Some studies suggest less pain and faster recovery after PRA, and in patients with extensive abdominal surgical history and/or bilateral tumors, PRA offers additional advantages (eTable 6 in the Supplement ).", - "tokenCount": 39, - "pageStart": 6, - "pageEnd": 6, - "hash": "b5731e3e3d13d14108d7986a8e0fde14645fac38c95653a40e3f36761fa3aa48" - }, - { - "text": "When patient and tumor characteristics are appropriate, we recommend minimally invasive adrenalectomy over open adrenalectomy because of improved perioperative morbidity.", - "tokenCount": 30, - "pageStart": 6, - "pageEnd": 6, - "hash": "0849619d45a72a8214cd48407b98ea9df937ea9dcc46bbe3ffda25882415e795" - }, - { - "text": "We recommend either a retroperitoneal or transperitoneal approach because of similar perioperative outcomes.", - "tokenCount": 22, - "pageStart": 6, - "pageEnd": 6, - "hash": "c79bb0392c1693d59a6b7b872b798ac2d1ed74d674bef3db9075c3c547bc62bc" - }, - { - "text": "The choice of approach should be determined by surgeon expertise and guided by tumor and patient characteristics.", - "tokenCount": 18, - "pageStart": 6, - "pageEnd": 6, - "hash": "5cc8c86ff25701eb652565ac66406fab9755a987683651c8f98e27bee76a3241" - }, - { - "text": ") Several definitions of what would be a high volume for an adrenal surgeon have been proposed, ranging from 4 to 7 annual adrenalectomies.", - "tokenCount": 31, - "pageStart": 6, - "pageEnd": 6, - "hash": "f99842338e71d9dcc164b217697796e6e36658cdee11c073cf06742800551745" - }, - { - "text": "A threshold of 6 or more adrenal resections per year was shown in assessment of the National Inpatient Sample to be associated with improved patient outcomes, including lower rates of complications, reduced inhospital mortality, decreased cost of care, and shorter hospital stay.", - "tokenCount": 51, - "pageStart": 6, - "pageEnd": 6, - "hash": "52cb99d96d89868bbbe940b263b6def4097087ef5b0f6c5b432176007881d8b2" - }, - { - "text": "39 Since not all patients have access to highvolume adrenal surgeons, lowervolume surgeons should exercise judgment and careful patient selection to provide safe care at their own center vs seeking referral or consultation with a more experienced adrenal surgeon when appropriate.", - "tokenCount": 49, - "pageStart": 6, - "pageEnd": 6, - "hash": "0cc890e1fc934c9759daa3dd7fc62ba3ac5c41842928e0ffa7843138243160e4" - }, - { - "text": "We recommend that adrenalectomy be preferentially performed by a highvolume adrenal surgeon to optimize outcomes, including lower rates of morbidity and mortality.", - "tokenCount": 31, - "pageStart": 6, - "pageEnd": 6, - "hash": "4054edd058dd5c7e2f1c9343c3f3f108eea6834c9d975f850bb145aceb6333db" - }, - { - "text": ") The utility of percutaneous ablation, mainly with radiofrequency ablation, and stereotactic body radiation therapy for the destruction of hormonally active and inactive tumors and adrenal metastasis has been investigated in small retrospective studies.", - "tokenCount": 48, - "pageStart": 6, - "pageEnd": 6, - "hash": "24dff4236f3991c770e9e7d84a70005e28e7bc7545d70a80f8a716b5b21dfbb3" - }, - { - "text": "The studies suffer from small sample sizes and heterogeneity.", - "tokenCount": 10, - "pageStart": 6, - "pageEnd": 6, - "hash": "c7b14fcc9c19def306b9418ba8a6b44e04c9a6cc99dff090e75af9170bf84bae" - }, - { - "text": "We conditionally suggest ablation and stereotactic radiation not be used as an alternative to adrenalectomy for patients with adrenal lesions because there are inadequate data to support these modalities.", - "tokenCount": 38, - "pageStart": 6, - "pageEnd": 6, - "hash": "104a4c6cda386a7e2ab1927e949041e7acfee6c99b90721946925605307198a8" - }, - { - "text": "Surgeons should be involved in the decisionmaking early in the treatment algorithm.", - "tokenCount": 15, - "pageStart": 6, - "pageEnd": 6, - "hash": "c7bd5ab3293c93f3893f76116bb6258eada9abcce5931020d1d9d7851de9a758" - }, - { - "text": ") Strengths and Limitations The study is limited in some sections by the paucity of strong evidencebased data available in the English literature.", - "tokenCount": 30, - "pageStart": 6, - "pageEnd": 6, - "hash": "316d98fd4d4ace393d351c6f0b1e6bec0896c07e138cc7b49b229b2468d3571b" - }, - { - "text": "In addition, the PICO format (Population, Intervention/Exposure, Comparison, and Outcome) for comparing outcomes limited the sample size for which recommendations were crafted.", - "tokenCount": 34, - "pageStart": 6, - "pageEnd": 6, - "hash": "a0a1091b33aa486fe79a9fb8b875f0c08771577d7416a641320cf21d45428a6d" - }, - { - "text": "However, the strength of the article lies in the extensive review and rigorous attention to bias, strength of the literature that was reviewed, and the comprehensive considerations made by a diverse group of experts in the field.", - "tokenCount": 41, - "pageStart": 6, - "pageEnd": 6, - "hash": "73d216d6e23a25ee633c4942e5060c8d70ac4a3a08f5f88eb42041b9f3c1f2c0" - }, - { - "text": "Conclusions We provide 26 evidencebased recommendations with clinically meaningful data to primarily assist surgeons with perioperative adrenal care.", - "tokenCount": 24, - "pageStart": 6, - "pageEnd": 6, - "hash": "6fd2885ef80d6d563d01af91bb951d936bce6cf7eba94f884c71bf12422ba9a9" - }, - { - "text": "Clinicians from multiple disciplines and patients may also find these recommendations useful.", - "tokenCount": 15, - "pageStart": 6, - "pageEnd": 6, - "hash": "7c5432598becc491d78b2c39fe572a8c82a3d5aa66774ecaa6b0eadb7fea0939" - }, - { - "text": "We highlight topics that have lowquality data or little evidence available and propose these topics as opportunities for further research.", - "tokenCount": 22, - "pageStart": 6, - "pageEnd": 6, - "hash": "1f0d3937354b5f1d33ce024346bf52c9e04bf03cd6666b40ed1101681bc398ab" - }, - { - "text": "ARTICLE INFORMATION Accepted for Publication: April 30,2022.", - "tokenCount": 14, - "pageStart": 6, - "pageEnd": 6, - "hash": "cdc496ded8bff71c5a6d46aa708ba64f0c2e92d9e6e18fdede9ace94e6378cdc" - }, - { - "text": "3544 Author Affiliations: Division of Endocrine Surgery, University of Pittsburgh, Pennsylvania (Yip); Department of Surgery, University of California, San Francisco (Duh); Department of Surgery, Hospital of the University of Pennsylvania, University of Pennsylvania, Philadelphia (Wachtel); Division of Internal Medicine, Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, Houston (Jimenez); Department of Surgery, American Association of Endocrine Surgeons Guidelines for Adrenalectomy Original Investigation Research jamasurgery.", - "tokenCount": 112, - "pageStart": 6, - "pageEnd": 6, - "hash": "768ab62df37b9e4b04b858f7d609e34d96363d87eddea08c826b4192ca7abb64" - }, - { - "text": "com (Reprinted) JAMA Surgery October 2022 Volume 157, Number 10 875 2022 American Medical Association.", - "tokenCount": 24, - "pageStart": 6, - "pageEnd": 6, - "hash": "61d8a2c25ef461e46cdb074547a636fd165a73419c3bb36caca2257abd8efbf8" - }, - { - "text": "Section of Endocrine Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois (Sturgeon); Department of Surgery, University of Kentucky College of Medicine, Lexington (C.", - "tokenCount": 37, - "pageStart": 7, - "pageEnd": 7, - "hash": "4679e2c6c259f746470233f7424e82de351330f908aa5cb3944035e10fd1a7ed" - }, - { - "text": "Lee); National Institute for Medical Sciences and Nutrition Salvador Zubirn, Mexico City, Mexico (VelzquezFernndez); Center for Endocrine Surgery, Cleveland Clinic, Cleveland, Ohio (Berber); Department of Internal Medicine, University of Michigan, Ann Arbor (Hammer); Department of Cell & Developmental Biology, University of Michigan, Ann Arbor (Hammer); Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor (Hammer); Division of Endocrinology, Metabolism and Nutrition, Mayo Clinic, Rochester, Minnesota (Bancos); Department of Surgery, Department of Internal Medicine, Columbia University College of Physicians and Surgeons, New York, New York (J.", - "tokenCount": 144, - "pageStart": 7, - "pageEnd": 7, - "hash": "1e109daf6d032a1d29e6329389d3a981e361ec6009060abb1e6ceada130b0562" - }, - { - "text": "Lee); Department of Radiology and Imaging Sciences, National Institutes of Health Clinical Center, Bethesda, Maryland (Marko); Division of Endocrine Surgery, Johns Hopkins Medicine, Baltimore, Maryland (MorrisWiseman); Division of Surgical Oncology, Department of Surgery, Eastern Virginia Medical School, Norfolk (Hughes); Department of General Surgery, UCLA David Geffen School of Medicine, Los Angeles, California (Livhits); Department of Preventive Medicine, College of Medicine, Chosun University, Gwangju, Korea (Han); Department of Surgery, University of Virginia, Charlottesville (Smith); Department of Surgery, University Hospitals Cleveland Medical Center, Cleveland, Ohio (Wilhelm); Department of Pathology, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, Ohio (Asa); Division of Endocrine & Minimally Invasive Surgery, Department of Surgery, Weill Cornell Medical College, New York Presbyterian Hospital, New York (Fahey); Division of Endocrine and Metabolic Surgery, Department of Surgery, Mayo Clinic, Rochester, Minnesota (McKenzie); Department of Surgery, Gastric and Mixed Tumor Service, Memorial Sloan Kettering Cancer Center, New York, New York (Strong); Section of Surgical Endocrinology, Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston (Perrier).", - "tokenCount": 281, - "pageStart": 7, - "pageEnd": 7, - "hash": "ea71ade0243f59dc0bec111dd613a0a11553686e4ec6ed1c6e997de2aa78b43d" - }, - { - "text": "Author Contributions : Drs Yip and Perrier had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.", - "tokenCount": 38, - "pageStart": 7, - "pageEnd": 7, - "hash": "4eed9405ac9b68a6fc9c4ce48abe7563db8e2650fc842a25019fa5524e2c083d" - }, - { - "text": "Concept and design: Yip, Jimenez, C.", - "tokenCount": 13, - "pageStart": 7, - "pageEnd": 7, - "hash": "e918e9f16f2ebc4a05350836485b1467d41c884dfab11a707539dd04f33cf9cc" - }, - { - "text": "Lee, VelzquezFernndez, Berber, Bancos, J.", - "tokenCount": 19, - "pageStart": 7, - "pageEnd": 7, - "hash": "d35338be1dc7f391434d0edc0575490286a8b165ddaa54bd4dcb4065615fb548" - }, - { - "text": "Lee, Hughes, Han, Smith, Wilhelm, Fahey, McKenzie, Perrier.", - "tokenCount": 18, - "pageStart": 7, - "pageEnd": 7, - "hash": "7bffa5c0999e4912d3566c4a8abfe34a6e4cfde1a6a4410b04b92e76f959787f" - }, - { - "text": "Acquisition, analysis, or interpretation of data: Duh, Wachtel, Jimenez, Sturgeon, C.", - "tokenCount": 25, - "pageStart": 7, - "pageEnd": 7, - "hash": "4c524eaa77a4ce6a6a733ff4978db100b23d69b909290cb7016b528fb19d9ca8" - }, - { - "text": "Lee, VelzquezFernndez, Hammer, Bancos, J.", - "tokenCount": 18, - "pageStart": 7, - "pageEnd": 7, - "hash": "aee0aca814f54adc759bedd7268efb953768eb0ef7f9899f7864bcd722db72ed" - }, - { - "text": "Lee, Marko, MorrisWiseman, Hughes, Livhits, Han, Smith, Asa, Fahey, McKenzie, Strong, Perrier.", - "tokenCount": 33, - "pageStart": 7, - "pageEnd": 7, - "hash": "70c85dceca47432cc71ef0f1e9d7e1a5e04a377043b02c13b5ddc3ca8ec422eb" - }, - { - "text": "Drafting of the manuscript: Yip, Duh, Wachtel, Jimenez, Sturgeon, C.", - "tokenCount": 23, - "pageStart": 7, - "pageEnd": 7, - "hash": "dd3804523b446d1f11835caecc88d61b456efcde01a36325e8ccf2c708768c91" - }, - { - "text": "Lee, MorrisWiseman, Hughes, Livhits, Han, Smith, Fahey, McKenzie, Strong, Perrier.", - 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}, - { - "text": "Administrative, technical, or material support: Yip, Jimenez, VelzquezFernndez, Marko, Hughes, Han, Wilhelm, Fahey, McKenzie, Perrier.", - "tokenCount": 40, - "pageStart": 7, - "pageEnd": 7, - "hash": "45da63b12e8da01ce7ffb87c68f603d2d0b3da8958caac74bce4d9705186c6ba" - }, - { - "text": "Supervision: Duh, Jimenez, Sturgeon, VelzquezFernndez, Berber, Hammer, Hughes, Fahey, McKenzie, Strong, Perrier.", - "tokenCount": 36, - "pageStart": 7, - "pageEnd": 7, - "hash": "134f4409281f977b0bc714d49037e4db4684177d32673c25cd48752057181a83" - }, - { - "text": "Conflict of Interest Disclosures: Dr Wachtel reported grants from the National Institutes of Health (NIH), National Center for Advancing Translational Sciences (KL2 TR001879), during the conduct of the study.", - "tokenCount": 49, - "pageStart": 7, - "pageEnd": 7, - "hash": "2977d23e7380128648f99ecadc8d5a18deda4c6d3639fa1c90ae0a8631645f69" - }, - { - "text": "Dr Jimenez reported research support from Lantheus Pharmaceuticals, Progenics, Exelixis, MSD, and Pfizer and serving on an advisory board for HRA Pharma and Pfizer during the conduct of the study.", - 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"hash": "5552305b3a7d351233e49b399863349055e23762aee9356355f00a3fa90ef481" - }, - { - "text": "Dr Asa reported serving as an advisor for Leica Biosystems, Ibex Medical Analytics, and Iron Mountain outside the submitted work.", - "tokenCount": 28, - "pageStart": 7, - "pageEnd": 7, - "hash": "212f169a38069290211a6b1f66edb244e0206e521835ac59db5440b37163598c" - }, - { - "text": "Dr Fahey reported being a consultant and investor in Mediflix Inc.", - "tokenCount": 16, - "pageStart": 7, - "pageEnd": 7, - "hash": "05fcda35dca96224007618d0017a1b8e67edd3516a901c6899c466b75fa9c984" - }, - { - "text": "Additional Contributions: The Adrenalectomy Guidelines Committee acknowledges the support and dedication of all contributors for the voluntary time and diligence of acquiring the detailed data and constructing the manuscript.", - "tokenCount": 33, - "pageStart": 7, - "pageEnd": 7, - "hash": "9099336e5f7a66cee46908400097aa0c1ac2f19e8657c8c15d0d5d647ec9375b" - }, - { - "text": "In addition, we thank the American Association of Endocrine Surgeons (AAES) membership for their careful review of the manuscript and insightful feedback.", - 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}, - { - "text": "2018; 163(1):157-164.", - "tokenCount": 10, - "pageStart": 8, - "pageEnd": 8, - "hash": "0d4cd9fe314fb61b970c0387b1a4fc4cc5b080d041a2203ca3a30b2a53c4e27a" - }, - { - "text": "028 Invited Commentary Importance of a Multidisciplinary and Comprehensive Approach to Management of Adrenal Tumors Tracy S.", - "tokenCount": 25, - "pageStart": 8, - "pageEnd": 8, - "hash": "2f8785d3bbbd6819c92d537351b0919f24f2f13b0b398afcf8c14c476dbd87b9" - }, - { - "text": "Wang, MD, MPH; Carmen C.", - "tokenCount": 10, - "pageStart": 8, - "pageEnd": 8, - "hash": "3793201c32440d56961cde2cbffbfc4f78b14a4bccce4e23753c7bf2cd272844" - }, - { - "text": "Solrzano, MD The American Association of Endocrine Surgeons Guidelines for Adrenalectomy, published in this issue of JAMA Surgery , represent a series of 26 carefully composed recommendations on the surgical management of patients with adrenal disease.", - "tokenCount": 48, - "pageStart": 8, - "pageEnd": 8, - "hash": "59ccc0a8dd7d0970a4533993008345e3aa4d71172973447345168fb4aa2b29ff" - }, - { - "text": "1 The authors are to be congratulated for this comprehensive update, which focuses on 7 areas of clinical concern to the practicing adrenal surgeon.", - "tokenCount": 27, - "pageStart": 8, - "pageEnd": 8, - "hash": "56b10d73ea7074554e5aeb034b09ea24cd78621051821a51981765cf27d704ec" - }, - { - "text": "We would like to highlight the recommendations for a comprehensive biochemical evaluation of patients with incidentally identified adrenal nodules more than 1 cm on crosssectional imaging (recommendations 1.", - "tokenCount": 35, - "pageStart": 8, - "pageEnd": 8, - "hash": "4b5d5f82a49e0e02b805565753175943dc27aec48bc8d9086d2ae19c807c125f" - }, - { - "text": "3) and emphasize the need for a multidisciplinary approach to adrenal tumors.", - "tokenCount": 17, - "pageStart": 8, - "pageEnd": 8, - "hash": "867127bdfbbedfff9aa1e38866ad18d62779ce41bee8ce1e685ae18998ae7cba" - }, - { - "text": "A systemwide algorithm for adrenal incidentalomas, including standardized terminology in the radiological assessment for evaluation and referral to a multidisciplinary clinic (staffed by endocrinology and adrenal surgeons) at our institution(s), has resulted in an increase in the number of patients who have appropriate evaluation of adrenal incidentalomas; this anecdotal experience is supported by others.", - "tokenCount": 74, - "pageStart": 8, - "pageEnd": 8, - "hash": "c23e505d21dbc4c44388275898347809617f75a9ef1981c2c1b8a297cb2c62b2" - }, - { - "text": "2-4 We encourage adrenal surgeons to lead the implementation of similar processes and the multidisciplinary discussion of patients with adrenal tumors including those being considered for unconventional treatments (recommendation 7.", - "tokenCount": 40, - "pageStart": 8, - "pageEnd": 8, - "hash": "409c6de7b874f6401d16485561d3a58108b9045eeeefaab366b6511d4e335e57" - }, - { - "text": "4), a point emphasized by the authors throughout these guidelines.", - "tokenCount": 12, - "pageStart": 8, - "pageEnd": 8, - "hash": "99b817d030d26d8cebaf7380c74d04034eec2802d5d7711ebb6fae099e0abab0" - }, - { - "text": "Multidisciplinary care is particularly important in determining the appropriate followup, both radiographic and biochemical, in patients who have nonfunctional adrenal tumors with benign imaging characteristics.", - "tokenCount": 34, - "pageStart": 8, - "pageEnd": 8, - "hash": "2b2a6122186ab87ca4dbcc8df27ccb6535ddc044d1403585a14fae1090f43e69" - }, - { - "text": "While the authors do not recommend routine scheduled followup in these patients (recommendation 1.", - "tokenCount": 19, - "pageStart": 8, - "pageEnd": 8, - "hash": "3f452c0f13d7cfcbae07416e4f684d71f6b18aa3e831a6ca53bbe60088e61a1c" - }, - { - "text": "4), due to the low risk of malignancy and low incidence of developing hormonal excess, the level of evidence is low quality and the followup remains Related article page 870 American Association of Endocrine Surgeons Guidelines for Adrenalectomy Original Investigation Research jamasurgery.", - "tokenCount": 56, - "pageStart": 8, - "pageEnd": 8, - "hash": "49fb6bb3d599e3a7ecfa73b7eca70b5e232651f8ff9933db3910ac64bcace240" - }, - { - "text": "com (Reprinted) JAMA Surgery October 2022 Volume 157, Number 10 877 2022 American Medical Association.", - "tokenCount": 24, - "pageStart": 8, - "pageEnd": 8, - "hash": "2c763feca554c44e70eb42f39e94216a7030ffe3f39282fbdc510f02c86f7b36" - } -] \ No newline at end of file diff --git a/Capstone Course Adrenal Nodule information/Primary Aldosteronism- An Endocrine Society Clinical Practice Guideline.pdf_semantic.json b/Capstone Course Adrenal Nodule information/Primary Aldosteronism- An Endocrine Society Clinical Practice Guideline.pdf_semantic.json deleted file mode 100644 index b43b8db854d5400fe4025638a1a10cbbf160d377..0000000000000000000000000000000000000000 --- a/Capstone Course Adrenal Nodule information/Primary Aldosteronism- An Endocrine Society Clinical Practice Guideline.pdf_semantic.json +++ /dev/null @@ -1,11993 +0,0 @@ -[ - { - "text": "Primary Aldosteronism: An Endocrine Society Clinical Practice Guideline Gail K.", - "tokenCount": 18, - "pageStart": 1, - "pageEnd": 1, - "hash": "6e886e66a04e3246b6b7554445be0e0459c1231ab29fa78ff282be0f30490f26" - }, - { - "text": "Adler, 1 Michael Stowasser, 2 Ricardo R.", - "tokenCount": 13, - "pageStart": 1, - "pageEnd": 1, - "hash": "9625596fd98f85780b691a1b75783b0c773f237a40988146d51a6cb1944b450e" - }, - { - "text": "Correa, 3 Nadia Khan, 4 Gregory Kline, 5 Michael J.", - "tokenCount": 17, - "pageStart": 1, - "pageEnd": 1, - "hash": "89215c1e9ac3b702006b607a413fc14d4b3858eb8700a514cc1724755202cc37" - }, - { - "text": "McGowan, 6 Paolo Mulatero, 7 M.", - "tokenCount": 14, - "pageStart": 1, - "pageEnd": 1, - "hash": "14f0f6a46c4782d02228502b9bd2f20c868fa764d0f262ad3a186ab26c05e335" - }, - { - "text": "Hassan Murad, 8 Rhian M.", - "tokenCount": 11, - "pageStart": 1, - "pageEnd": 1, - "hash": "94e2d525ba3251d37e705e24e46a591b5d1c14f661677fbdd412d1d7bec4d8a0" - }, - { - "text": "Touyz, 9 Anand Vaidya, 1 Tracy A.", - "tokenCount": 15, - "pageStart": 1, - "pageEnd": 1, - "hash": "31c4dec8c6da1e8ce6504b93c071c2d870082107e3e1727c8494db803a476ff8" - }, - { - "text": "Williams, 10 Jun Yang, 11,12 William F.", - "tokenCount": 12, - "pageStart": 1, - "pageEnd": 1, - "hash": "07ec33b96620b32194532a73a52a8996f6b27c0ab1f0671e078785256601b387" - }, - { - "text": "Young, 8 MariaChristina Zennaro, 13,14 and Juan P.", - "tokenCount": 17, - "pageStart": 1, - "pageEnd": 1, - "hash": "f2c1bd6dc7da8b07847d78fdfe3e399598454f2ce520923028351c4c75d67c73" - }, - { - "text": "Brito 8,15 1 Brigham and Womens Hospital, Harvard Medical School, Boston, MA 02115, USA 2 Endocrine Hypertension Research Centre, University of Queensland, Princess Alexandra Hospital, QLD 4102, Brisbane, Australia 3 The Cleveland Clinic, Lerner College of Medicine, OH 44195, USA 4 Department of Medicine, The University of British Columbia, Vancouver, T2T 5C7 Canada 5 Department of Medicine, University of Calgary, Calgary, T2T 5C7 Canada 6 Primary Aldosteronism Foundation, 3533 E Ahwatukee Ct, Phoenix, AZ 85044, USA 7 Division of Internal Medicine and Hypertension, Department of Medical Sciences, University of Torino, Torino 10126, Italy 8 Division of Endocrinology, Diabetes, Metabolism and Nutrition, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA 9 Research Institute of McGill University Health Centre, McGill University, Montreal, H4A 3J1 Canada 10 Department of Medicine IV, Ludwig Maximilian University of Munich, Munich 80336, Germany 11 Centre for Endocrinology and Reproductive Health, Hudson Institute of Medical Research, Victoria 3168, Australia 12 Department of Medicine, Monash University, Victoria 3168, Australia 13 Universit Paris Cit, Inserm, PARCC, Paris F-75015, France 14 Assistance PubliqueHpitaux de Paris, Hpital Europen Georges Pompidou, Service de Gntique, Paris F-75015, France 15 Knowledge and Evaluation Research Unit, Division of Endocrinology, Diabetes, Metabolism and Nutrition, Department of Medicine, Mayo Clinic, Rochester, MN 55905, USA Correspondence: Gail K.", - "tokenCount": 356, - "pageStart": 1, - "pageEnd": 1, - "hash": "5ad65f8c7fd3c984aac76506124dc38457503f222a67e324b9336cc9526dd5b6" - }, - { - "text": "Adler, MD, PhD, Brigham and Womens Hospital, 221 Longwood Ave, Richardson Fuller Building 295, Boston, MA 02115, USA.", - "tokenCount": 32, - "pageStart": 1, - "pageEnd": 1, - "hash": "127b3718af5724bc26b4884cf9f399ebc2b3fa3599d65972154f230e8bec28d8" - }, - { - "text": "CoSponsoring Organizations: American Association of Clinical Endocrinology (AACE), American Heart Association (AHA), European Society of Endocrinology (ESE), European Society of Hypertension (ESH), International Society of Hypertension (ISH), Primary Aldosteronism Foundation (PAF).", - "tokenCount": 60, - "pageStart": 1, - "pageEnd": 1, - "hash": "15a3578ba93a2fe2add6ad158f45f41daa9366e4cb52b6d673bf188b77e4b726" - }, - { - "text": "Abstract Background: Primary aldosteronism (PA), a primary adrenal disorder leading to excessive aldosterone production by one or both adrenal glands, is a common cause of hypertension.", - "tokenCount": 39, - "pageStart": 1, - "pageEnd": 1, - "hash": "27f178990894ab1cb9c25aec032683a84d8137ce0d9c4a61d4502e997a781031" - }, - { - "text": "It is associated with an increased risk of cardiovascular complications compared with primary hypertension.", - "tokenCount": 15, - "pageStart": 1, - "pageEnd": 1, - "hash": "4a4eff817709650c72f5e9db834febeec589bc420fcdc0290e3ce93efb44d350" - }, - { - "text": "Despite effective methods for diagnosing and treating PA, it remains markedly underdiagnosed and undertreated.", - "tokenCount": 20, - "pageStart": 1, - "pageEnd": 1, - "hash": "a8391bfaa2ff14e19e3e84e00270ae0a8f5c2a137bdc9c2af0165c80ab44e3b4" - }, - { - "text": "Objective: To develop an updated guideline that provides a practical, clinical approach to identifying and managing PA to improve diagnosis rates and encourage targeted treatment.", - "tokenCount": 29, - "pageStart": 1, - "pageEnd": 1, - "hash": "8abc477c1fbad69c4ef5134d82d0b52cd36ceec241b34f914fb3058d9f540f22" - }, - { - "text": "Methods: The Guideline Development Panel (GDP), composed of a multidisciplinary panel of clinical experts and experts in systemic review methodology, used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to define 10 questions related to the diagnosis and treatment of PA.", - "tokenCount": 60, - "pageStart": 1, - "pageEnd": 1, - "hash": "d89bf4f21cfc6c9deaf753ac170e998e7a421fdbeaf71fff187e8ea7584a29d5" - }, - { - "text": "The GDP used the GRADE Evidence to Decision (EtD) framework to consider contextual factors, such as stakeholder values and preferences, costs and required resources, costeffectiveness, acceptability, feasibility, and the potential impact on health equity.", - "tokenCount": 50, - "pageStart": 1, - "pageEnd": 1, - "hash": "3e86817d836ddc64e6135bb8d522d472fad9f94be5a94d3e75fd1152417a7095" - }, - { - "text": "Results: We suggest that all individuals with hypertension be screened for PA by measuring aldosterone and renin and determining the aldosterone to renin ratio, and that subsequent clinical care be guided by the results.", - "tokenCount": 43, - "pageStart": 1, - "pageEnd": 1, - "hash": "ee4004fc476eb5eaa8679f539c6e710a17f66227d0619b34db513a3e4b78b135" - }, - { - "text": "We suggest that individuals with PA receive PAspecific therapy, either medical or surgical.", - "tokenCount": 18, - "pageStart": 1, - "pageEnd": 1, - "hash": "07fa655dc112f0166939c1fbdf5e3d2b85e8ab164cc03a2ca5795068810b47dc" - }, - { - "text": "In individuals who screen positive for PA, we suggest (1) commencement of PAspecific medical therapy in individuals who do not desire or are not candidates for surgery and in situations where the probability of lateralizing PA (excess aldosterone produced by one adrenal) is low based on screening results; and (2) aldosterone suppression testing in situations when screening results indicate an intermediate probability for lateralizing PA and individualized decision making confirms a desire to pursue eligibility for surgical therapy. In those who test positive by aldosterone suppression testing, and in those in whom screening results show a high probability of lateralizing PA (obviating the need for aldosterone suppression testing), we suggest adrenal lateralization with computed tomography scanning and adrenal venous sampling prior to deciding the treatment approach (medical vs surgical).", - "tokenCount": 167, - "pageStart": 1, - "pageEnd": 1, - "hash": "bef1d8a72ae426a565b6567be88b91f1ae60040ad74d432360091444d3eecbee" - }, - { - "text": "In all individuals with PA and an adrenal adenoma, we suggest performing a 1-mg overnight dexamethasone suppression test.", - "tokenCount": 29, - "pageStart": 1, - "pageEnd": 1, - "hash": "ffdf783f013c44bbfc7d22d859446fdf6a39fe0c6a737b416bbdb90e1236a0ff" - }, - { - "text": "We suggest the use of mineralocorticoid receptor antagonists (MRAs) over epithelial sodiumchannel (ENaC) inhibitors in the medical treatment of PA.", - "tokenCount": 34, - "pageStart": 1, - "pageEnd": 1, - "hash": "2accf28fe862e8a6aa49ec1293e160fd1f97ecee38cf2417f54ce77c5b460596" - }, - { - "text": "We suggest the use of spironolactone over other MRAs, given its lower cost and greater availability; however, all MRAs, when titrated to equivalent potencies, are anticipated to have similar efficacy in treating PA.", - "tokenCount": 47, - "pageStart": 1, - "pageEnd": 1, - "hash": "1e6df85491706550f24bcfac66e92fca1aeeb8aa70a7e72ac8de11eaf9dfc71f" - }, - { - "text": "Thus, MRAs with greater mineralocorticoid receptor specificity and fewer androgen/progesterone receptormediated side effects may be preferred in some situations.", - "tokenCount": 35, - "pageStart": 1, - "pageEnd": 1, - "hash": "2f4cb62f261bed566d10876b619149b96d6013ea867a2abe74169465ce1ab635" - }, - { - "text": "In individuals receiving MRA therapy, we suggest monitoring renin and, in those whose hypertension remains uncontrolled and renin is suppressed, titrating the MRA to increase renin.", - "tokenCount": 36, - "pageStart": 1, - "pageEnd": 1, - "hash": "d077b598a76abddb44c31e558f84e64813ca2acd8556e992276eafa72adf2380" - }, - { - "text": "Corrected and Typeset: 14 July 2025 The Endocrine Society 2025.", - "tokenCount": 16, - "pageStart": 1, - "pageEnd": 1, - "hash": "e920f011e28502e0bf6fad535ac5841f06351064cafe7409d8e3043d7d4f6b85" - }, - { - "text": "Published by Oxford University Press on behalf of the Endocrine Society.", - "tokenCount": 13, - "pageStart": 1, - "pageEnd": 1, - "hash": "934ef611570bfdbe99f21a52f45773971796aebd9e3514e82d4593876c54c3d9" - }, - { - "text": "For commercial reuse, please contact reprints@oup.", - "tokenCount": 11, - "pageStart": 1, - "pageEnd": 1, - "hash": "5a1e4291ce15a2f0ba297596de7eeec894d7fd90b55542dbf1a72940852f9c83" - }, - { - "text": "com for reprints and translation rights for reprints.", - "tokenCount": 11, - "pageStart": 1, - "pageEnd": 1, - "hash": "42c370f768c8b44461cd5cc4146c26b0b5052e6867ee7efe97e9585f1bc6b7f7" - }, - { - "text": "All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our sitefor further information please contact journals.", - "tokenCount": 30, - "pageStart": 1, - "pageEnd": 1, - "hash": "6305f7c2a9f396ab6247762e093c0f5d9e2c82a5f54e98d3baa45b82b0eda1e1" - }, - { - "text": "The Journal of Clinical Endocrinology & Metabolism , 2025,110 , 24532495 https://doi.", - "tokenCount": 24, - "pageStart": 1, - "pageEnd": 1, - "hash": "53255ff3d23e941051acae99a1c335abbdbb6f1e634c51ba3c7f43d948038657" - }, - { - "text": "1210/clinem/dgaf284 Advance access publication 14 July 2025 Clinical Practice Guideline Downloaded from https://academic.", - "tokenCount": 28, - "pageStart": 1, - "pageEnd": 1, - "hash": "5cb86acffc377520b959f76121857096848fc44baacae5440acf8c1b45a7bd19" - }, - { - "text": "Conclusion: These recommendations provide a practical framework for the diagnosis and treatment of PA.", - "tokenCount": 16, - "pageStart": 2, - "pageEnd": 2, - "hash": "10de3298ebb7a6147b9757066abbab8b2d0678f2b6a92acae04f34047cc1bae9" - }, - { - "text": "They are based on currently available literature and take into consideration outcomes that are important to key stakeholders.", - "tokenCount": 19, - "pageStart": 2, - "pageEnd": 2, - "hash": "de999773df460b54c4ffb60a4245b7f792e2bd7384155c0af9788f7a5b23c362" - }, - { - "text": "The goal is to increase identification of individuals with PA and, by initiating PAspecific medical or surgical therapy, improve blood pressure control and reduce PAassociated adverse cardiovascular events.", - "tokenCount": 35, - "pageStart": 2, - "pageEnd": 2, - "hash": "f3eca6841afdb3de089784969f6bf07539073d98d7265af93e0607fc1a002709" - }, - { - "text": "The guidelines also highlight important knowledge gaps in PA diagnosis and management.", - "tokenCount": 13, - "pageStart": 2, - "pageEnd": 2, - "hash": "494ba56cd7c11ed228b48f03713c696c16fdb95ef8547ab0fa4287c5e8a10096" - }, - { - "text": "Key Words: Primary aldosteronism, secondary hypertension, clinical practice guideline, aldosterone Abbreviations: ACE, angiotensinconverting enzyme ; ACS, autonomous cortisol secretion ; APA, aldosteroneproducing adenoma ; ARB, angiotensin receptor blocker ; ARR, aldosterone to renin ratio ; AVS, adrenal venous sampling ; BP, blood pressure ; CKD, chronic kidney disease ; CT, computed tomography ; DRC, direct renin concentration ; ENaC, epithelial sodiumchannel ; EtD, Evidence to Decision ; GDP, Guideline Development Panel ; GRADE, Grading of Recommendations, Assessment, Development, and Evaluation ; IVC, inferior vena cava ; LCMS/MS, liquid chromatographytandem mass spectrometry ; MACE, major adverse cardiovascular event ; MD, mean difference ; MR, mineralocorticoid receptor ; MRA, mineralocorticoid receptor antagonist ; MRI, magnetic resonance imaging ; OR, odds ratio ; PA, primary aldosteronism ; PET, positron emission tomography ; PRA, plasma renin activity ; RAAS, renin angiotensinaldosterone system ; RCT, randomized controlled trial ; QOL, quality of life ; SBP, systolic blood pressure .", - "tokenCount": 276, - "pageStart": 2, - "pageEnd": 2, - "hash": "794c2166577c0654d1c03c1735828be5f3ae64bdb9bd02a304c643f6eb86911d" - }, - { - "text": "Primary aldosteronism (PA) is an adrenal disorder, either unilateral or bilateral, resulting in excess adrenal production of aldosterone.", - "tokenCount": 31, - "pageStart": 2, - "pageEnd": 2, - "hash": "fa240b043e6039b9fa9019d3d90a32e22d7629c18f3202390869cc813ea92bca" - }, - { - "text": "In PA, aldosterone production is at least partially autonomous of its normal major regulator, the renin angiotensin system, circulating levels of which are suppressed.", - "tokenCount": 35, - "pageStart": 2, - "pageEnd": 2, - "hash": "8261fa36d0761ef92939c1ea5c41c6658d7aa7c537bbfbb44ee70e5b0cf87d5a" - }, - { - "text": "The excess aldosterone leads to renal sodium retention, volume expansion, elevated blood pressure (BP), and, in more severe forms, hypokalemia.", - "tokenCount": 32, - "pageStart": 2, - "pageEnd": 2, - "hash": "a2d1eb99af3ea311da707cf61ca4cc36b09e2800e87c3f4286a05315e721de3a" - }, - { - "text": "Compared with those with primary hypertension, individuals with PA face significantly higher health risks ( 1,2 ).", - "tokenCount": 20, - "pageStart": 2, - "pageEnd": 2, - "hash": "1450ecb4c0d1e9ad1cb628a5cfeda7b2bbd3980c2404a3953b97bcd1382b4e6d" - }, - { - "text": "A metaanalysis of 31 studies (3838 individuals with PA, 9284 with primary hypertension) demonstrated that individuals with PA have increased risk of stroke (odds ratio 2.", - "tokenCount": 35, - "pageStart": 2, - "pageEnd": 2, - "hash": "05bed2f976489b3341ea3bbb2297d6b0cec0d3a4edd5b1e1cecdb6e6bc769e9a" - }, - { - "text": "45), coronary artery disease (odds ratio 1.", - "tokenCount": 11, - "pageStart": 2, - "pageEnd": 2, - "hash": "d2607cc72d12b76fa9bd4b8e2b9cda7dd8a49d9bc282846268b8ab6f9c451e9c" - }, - { - "text": "83), atrial fibrillation (odds ratio 3.", - "tokenCount": 13, - "pageStart": 2, - "pageEnd": 2, - "hash": "080639bc93815337333c558ee57135b87a51e9cbdc5097d99079fbfbc1967a8b" - }, - { - "text": "99), and heart failure (odds ratio 2.", - "tokenCount": 11, - "pageStart": 2, - "pageEnd": 2, - "hash": "e43e6b2706023b0151b295f756ef1aefb070cdd8f7dd4f6065a1c5269c864eee" - }, - { - "text": "8 years after the diagnosis of hypertension ( 2 ).", - "tokenCount": 10, - "pageStart": 2, - "pageEnd": 2, - "hash": "50005813d82365ec065cd09780993277922d681e09193e3dcac66f8817d4a23d" - }, - { - "text": "Another metaanalysis of 46 studies (6056 individuals with PA, 9733 with primary hypertension) found an increased risk of renal disease as evidenced by albuminuria (odds ratio 2.", - "tokenCount": 38, - "pageStart": 2, - "pageEnd": 2, - "hash": "79e7046d739bf3613e16b0664b76e143d576b39984653b034d186ca998503377" - }, - { - "text": "12) and proteinuria (odds ratio 2.", - "tokenCount": 11, - "pageStart": 2, - "pageEnd": 2, - "hash": "ff5fbdd7d433c9c78fc3b328f8049e35ee261ebc43708593ef2987fcea40eae3" - }, - { - "text": "Furthermore, individuals with PA often report reduced psychological wellbeing and quality of life ( 3-5 ).", - "tokenCount": 19, - "pageStart": 2, - "pageEnd": 2, - "hash": "75f54d873e44d3591a86d85953346dcfbde05395ec2d91de8bde3c91775f80e5" - }, - { - "text": "Despite its prevalence and the serious health risks it poses, PA remains largely underdiagnosed and undertreated.", - "tokenCount": 21, - "pageStart": 2, - "pageEnd": 2, - "hash": "69e6bc6a15b282c185371c3ccb0b232360ba5ae4024a35303de09e0ba8276df0" - }, - { - "text": "This underrecognition contributes significantly to the health care costs associated with hypertension, including the management of complications and related productivity losses.", - "tokenCount": 25, - "pageStart": 2, - "pageEnd": 2, - "hash": "5085c4640a1d6e799c769910c89c9553f225b95e855a96caf026a47b4e675243" - }, - { - "text": "Screening for PA is critically low, often delayed until years after hypertension has been diagnosed, typically following the emergence of severe complications.", - "tokenCount": 26, - "pageStart": 2, - "pageEnd": 2, - "hash": "c640012547974d175656941c17fa46ed1b8007b71a91a42203127275d49c0233" - }, - { - "text": "This may in part be due to misconceptions that PA is only present in the setting of hypokalemia, adrenal macronodules, frankly elevated aldosterone levels, or severe hypertension.", - "tokenCount": 40, - "pageStart": 2, - "pageEnd": 2, - "hash": "5a04e73a651b6ff0e0057ffe894e9e2b72f623755fa86ba151fe14f13d20e8c4" - }, - { - "text": "As a result, many individuals continue to be treated for primary hypertension, thus missing out on targeted treatments or potential cures, and enduring suboptimally managed BP and increased risks of cardiovascular and renal disease.", - "tokenCount": 40, - "pageStart": 2, - "pageEnd": 2, - "hash": "7ce04b727c554526564fc50f4f1106c776fbe74833ede7bedb1ec8f9e5b1cf59" - }, - { - "text": "The importance of this is emphasized in the latest major clinical guidelines on hypertension: The 2024 European Society of Cardiology (ESC) guidelines for the management of elevated BP and hypertension suggest screening for PA in all adults with diagnosed hypertension ( 6 ).", - "tokenCount": 48, - "pageStart": 2, - "pageEnd": 2, - "hash": "9f3c8ca8e54a3a9a46af3e87b061a1de78a95e4ad5d3d1acbbf3c860c19d9487" - }, - { - "text": "The morbidity and mortality associated with PA are largely preventable.", - "tokenCount": 13, - "pageStart": 2, - "pageEnd": 2, - "hash": "1b8257a3c9bdce6adf1987c1925695a7e193079c48f71b6d27275f1fa5c5d9fa" - }, - { - "text": "Individuals with lateralizing PA can often be cured through unilateral adrenalectomy.", - "tokenCount": 16, - "pageStart": 2, - "pageEnd": 2, - "hash": "a0226013c53791b5f037d980bb4a5b4cff50cf8b6182fd458b307da764198f42" - }, - { - "text": "Those with bilateral PA typically benefit from treatment with mineralocorticoid receptor antagonists (MRAs), such as spironolactone or eplerenone, which effectively control BP, alleviate hypokalemia, and mitigate excess cardiovascular risk associated with PA ( 7-9 ).", - "tokenCount": 57, - "pageStart": 2, - "pageEnd": 2, - "hash": "51dccb9b2bb6e1330799cfeef7b68639703735bc6049e6ac974fae44462592fa" - }, - { - "text": "Despite these advantages, MRAs are not routinely used as firstline treatments for hypertension, resulting in missed diagnostic and therapeutic opportunities for those with undiagnosed PA.", - "tokenCount": 33, - "pageStart": 2, - "pageEnd": 2, - "hash": "0ae6e3c226b69665998551f59a22b5dd18796e208c7c1e85f10609aa5afb6bd2" - }, - { - "text": "The Guideline Development Panel (GDP) s primary objective for the updated guideline was to support the clinical approach to screening and managing PA, thereby replacing the previous guideline of the Endocrine Society.", - "tokenCount": 40, - "pageStart": 2, - "pageEnd": 2, - "hash": "5cd3c52a7257cd6b4852eedbd85c851f8bc5814c8cf146ae9997f4704db20515" - }, - { - "text": "This revision underscores the urgent need to assist clinicians in navigating key clinical practice questions related to PA.", - "tokenCount": 19, - "pageStart": 2, - "pageEnd": 2, - "hash": "e6074cba1afd29d4456a2e686a23bbec1bd6b001142d1090234c450e4064c1cc" - }, - { - "text": "Specifically, the panel asked 10 critical questions, starting with whether all individuals with hypertension should be screened for PA and whether PAspecific therapy leads to superior clinical outcomes as compared to nonspecific antihypertensive therapy.", - "tokenCount": 45, - "pageStart": 2, - "pageEnd": 2, - "hash": "3e13a27939d14f248c28950c8b8e126add1c95a8f28a927e20bafe7cce65af46" - }, - { - "text": "These first 2 questions demonstrate the critical need to diagnose and specifically treat PA by demonstrating that PA is a common cause of secondary hypertension, that it is associated with increased cardiovascular risk compared with primary hypertension, and that PAspecific therapy reduces these risks.", - "tokenCount": 50, - "pageStart": 2, - "pageEnd": 2, - "hash": "4341a0dc5f1675ff1e77c55bf556162ac4b47271f3b67dc622622261433bea1f" - }, - { - "text": "Subsequent questions concern the selection of appropriate tests to screen for PA, the need for aldosterone suppression testing, dexamethasone suppression testing and adrenal venous sampling, and options for medical and surgical management.", - "tokenCount": 45, - "pageStart": 2, - "pageEnd": 2, - "hash": "3d46b1e15f6cbd54d463a7843d8a3f4bc2906da491f8b0c2d40dfa0983669187" - }, - { - "text": "To develop these recommendations, we employed the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach.", - "tokenCount": 26, - "pageStart": 2, - "pageEnd": 2, - "hash": "4398b1d532b857eddce388f224d1c62b6cc0bb581d3c0f7cad0b3f4f133064a9" - }, - { - "text": "A systematic review was conducted for each question, revealing a general scarcity of randomized clinical trials and leaving the panel to rely on observational studies.", - "tokenCount": 27, - "pageStart": 2, - "pageEnd": 2, - "hash": "f1df3594bbac6e4001064c9f8f1da503a466efe1106d28310900a02800b3d74a" - }, - { - "text": "The panel sought evidence relevant to all elements of the GRADE Evidence to Decision (EtD) framework, including stakeholder values and preferences (drawing on input from clinical experts and a patient representative), costs and other resources required, costeffectiveness, acceptability, feasibility, and potential impact on health equity.", - "tokenCount": 63, - "pageStart": 2, - "pageEnd": 2, - "hash": "55663872de19d5fc3df5eb9e7e898c0ebc02bd3ea0b543b9415852cad7759265" - }, - { - "text": "However, the panel did not identify robust evidence addressing these EtD considerations for most clinical questions To enhance the practical application of these recommendations, the panel developed a series of tools aimed at increasing their usefulness.", - "tokenCount": 40, - "pageStart": 2, - "pageEnd": 2, - "hash": "4f726bb3c76e1e8a788279034e51eb09cd0ff2390ae0e95733230880b1367b10" - }, - { - "text": "These tools include algorithms to guide clinicians through the screening and management of PA, detailed steps for the medical management of PA, and a decision aid for making informed choices about the use of MRAs for individuals with PA.", - "tokenCount": 43, - "pageStart": 2, - "pageEnd": 2, - "hash": "c7e6937e860b11cce422b04dcebaecc5e4f1eb755633de75637dbda57d3a99ec" - }, - { - "text": "Additionally, the panel included suggestions for future research studies in each recommendation.", - "tokenCount": 14, - "pageStart": 2, - "pageEnd": 2, - "hash": "ed9020cba4e785011e9cc66ecaf47960d078db55c163a6b5ca8a8119bc76d93d" - }, - { - "text": "These suggestions aim to address existing gaps in evidence for critical clinical questions, thereby fostering a deeper understanding and improving the management of PA.", - "tokenCount": 26, - "pageStart": 2, - "pageEnd": 2, - "hash": "3fb0f147929a586a6aceea8108746cc60046ea97fd194be1f3fef7db196977c5" - }, - { - "text": "Methods of Development of EvidenceBased Clinical Practice Guidelines This guideline was developed using the process detailed on the Endocrine Society website located here: https:/ /www.", - "tokenCount": 31, - "pageStart": 2, - "pageEnd": 2, - "hash": "c1d78e8d787ad3a66a3604b197d02bf9200543736881d383f3ad2bcafaf72c3d" - }, - { - "text": "2454 The Journal of Clinical Endocrinology & Metabolism , 2025, Vol.", - "tokenCount": 18, - "pageStart": 2, - "pageEnd": 2, - "hash": "d99b8b6c51f37b2114277654a0d978c3bbf1b3179c7bdb374458c3f0fe59dffb" - }, - { - "text": "org/clinicalpracticeguidelines/methodology ( 10 ).", - "tokenCount": 12, - "pageStart": 3, - "pageEnd": 3, - "hash": "1e4b556e44fa905d13b368d6ab45f4b985e464e6d8b1f89d55b253977a843533" - }, - { - "text": "The Endocrine Society follows the GRADE approach ( 11 ) ( Tables 1 and 2 ), which includes EtD frameworks to ensure all important criteria are considered when making recommendations ( 14 ).", - "tokenCount": 36, - "pageStart": 3, - "pageEnd": 3, - "hash": "5f9ef9f922476488f224f9dc0f41c27098fc9691f8755bc6d9fb0d13b8520bed" - }, - { - "text": "The process was facilitated by the GRADEpro Guideline Development Tool (GRADEpro GDT) ( 15 ).", - "tokenCount": 23, - "pageStart": 3, - "pageEnd": 3, - "hash": "95c74ea93bfb46474a4ecb99e83f164e34a7ad43ad6284148a7d2f6159aef71f" - }, - { - "text": "The GDP consisted of content experts representing the following clinical specialties: endocrinology, general internal medicine, genetics, hypertension specialists, epidemiology, and a patient representative.", - "tokenCount": 34, - "pageStart": 3, - "pageEnd": 3, - "hash": "e2d383ee372ac77a796a1d3d0af1ba3070a94ce9f23026fdb9e55d3f28c67f99" - }, - { - "text": "Members were identified by the Endocrine Society Board of Directors and the Clinical Guidelines Committee and were vetted according to the Endocrine Society s conflictofinterest policy, which was followed throughout the guideline process to manage and mitigate conflicts of interest.", - "tokenCount": 48, - "pageStart": 3, - "pageEnd": 3, - "hash": "027ba900697f27db71c41c5939ca2c84c1a4ec739eaafd0aff0c51cf45a25f79" - }, - { - "text": "Detailed disclosures of panel members and the management strategies implemented during the development process can be found in Appendix A .", - "tokenCount": 21, - "pageStart": 3, - "pageEnd": 3, - "hash": "e807d414303872a7d2c0fb7407aa8a405e576ef44d76b0862f489bf62a24a2b9" - }, - { - "text": "In addition, the group included a clinical practice guideline methodologist from the Mayo EvidenceBased Practice Center, who led the team that conducted the systematic reviews, and a methodologist from the Endocrine Society, who advised on methodology and moderated the application of the EtD framework and development of the recommendations.", - "tokenCount": 60, - "pageStart": 3, - "pageEnd": 3, - "hash": "862e26f87a548f1f6c864ee3f9b6de5b0a7a78b32c0c46a3d7fb995838871d3b" - }, - { - "text": "A group of 2 to 3 GDP members were assigned to lead each guideline question.", - "tokenCount": 16, - "pageStart": 3, - "pageEnd": 3, - "hash": "06dbdff97ba05eeee958bcc94b18f1a19d39b4445c9b49f1fe0d2080dad826d3" - }, - { - "text": "The 10 clinical questions addressed in this guideline were prioritized from an extensive list of potential questions through a survey of the panel members and discussion.", - "tokenCount": 28, - "pageStart": 3, - "pageEnd": 3, - "hash": "f90859951f49919e7e8c07efa0c3a27add83a234f0e5591e782400dd3e188131" - }, - { - "text": "The Mayo EvidenceBased Practice Center conducted a systematic review for each question and, when available, produced GRADE evidence profiles that summarized the body of evidence for each question and the certainty of the evidence (Murad in press).", - "tokenCount": 44, - "pageStart": 3, - "pageEnd": 3, - "hash": "67400da3c4027ba53b33ed4b11c5d7e2a1433080a19d87c4c48b0fc2cb666b94" - }, - { - "text": "The systematic searches for evidence were conducted in February 2022 and updated in October 2024.", - "tokenCount": 16, - "pageStart": 3, - "pageEnd": 3, - "hash": "f35befeaf06e6a57fdb194e67fc520af3655f068a55e02e364faf4c3a9e5aeff" - }, - { - "text": "In parallel with the development of the evidence summaries, the GDP members searched and summarized research evidence related to each question (generally observational studies) and to other EtD criteria, such as individuals values and preferences, cost and resources required, costeffectiveness, feasibility, acceptability, and the potential impact on health equity.", - "tokenCount": 66, - "pageStart": 3, - "pageEnd": 3, - "hash": "525da09a48f1de34388b6b00b317299f3d5a153a05e7a6f02a8a7e990aa79fda" - }, - { - "text": "Research evidence summaries noted in the EtD frameworks were compiled using standardized terminology templates for clarity and consistency ( 16 ).", - "tokenCount": 23, - "pageStart": 3, - "pageEnd": 3, - "hash": "8ce33010c241e4c8ba45c5d2fc31a588e23cc00ddfc6a32ed3918684e1d5a1a7" - }, - { - "text": "During 2 inperson panel meetings and a series of video conferences, the GDP judged the balance of benefits and harms, in addition to the other EtD criteria, to determine the direction and strength of each recommendation ( 16-18 ) ( Tables 1 and 2 ).", - "tokenCount": 52, - "pageStart": 3, - "pageEnd": 3, - "hash": "e6c5a451c0ace40696feb4f8c758b53794746027dbc764cc47b150f324e5ed65" - }, - { - "text": "The draft recommendations were posted publicly for external peer review and internally for Endocrine Society members, and the draft guideline manuscript was reviewed by the Society s Clinical Guidelines Committee, representatives of any cosponsoring organizations, a representative of the Society s Board of Directors, and an Expert Reviewer.", - "tokenCount": 59, - "pageStart": 3, - "pageEnd": 3, - "hash": "0c43904a21e3f52c89e9365a80b692c01ceeb588c26cf169285541cae76ca24c" - }, - { - "text": "Revisions to the guideline were made based on submitted comments and approved by the Clinical Guidelines Committee, the Expert Reviewer, and the Board of Directors.", - "tokenCount": 30, - "pageStart": 3, - "pageEnd": 3, - "hash": "4414c4e04cf08c83e3ea2406134253c1df90964cfd81b937ac551e4b8a27ba5b" - }, - { - "text": "GRADE certainty of evidence classifications Certainty of evidence Interpretation High There is high confidence that the true value of the estimate of interest is on one side of a threshold of interest or within a specific range.", - 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"text": "The true value of the estimate may deviate from the target of the certainty rating (i.", - "tokenCount": 19, - "pageStart": 3, - "pageEnd": 3, - "hash": "4340c7345fcae58d90d105d69e1e4bfcea32b5571fc39f01166452c08f69bb93" - }, - { - "text": "Very Low OOO There is verylow confidence that the true value of the estimate of interest is on one side of a threshold of interest or within a certain range.", - "tokenCount": 34, - "pageStart": 3, - "pageEnd": 3, - "hash": "3d6d8ca7239c9e9be0370504716fa481ad8a2f6a72a3a65b345af2f9cb8e959a" - }, - { - "text": "The true value of the estimate may deviate significantly from target of the certainty rating (i.", - "tokenCount": 19, - "pageStart": 3, - "pageEnd": 3, - "hash": "e6cddd47b0489cb36a60db90c6bb1f3d0492e46a1c19a5a1052ee3f2ad33c0f3" - }, - { - "text": "Reprinted with permission from Schnemann HJ, Broek J, Guyatt GH, Oxman AD.", - "tokenCount": 24, - "pageStart": 3, - "pageEnd": 3, - "hash": "e75244582628c107fa8dbcb4565bacec2da0bdc5e0852facd09059393f150467" - }, - { - "text": "Handbook for grading the quality of evidence and the strength of recommendations using the GRADE approach.", - "tokenCount": 19, - "pageStart": 3, - "pageEnd": 3, - "hash": "ad2061158e4693891f41738f0e69bdc3fb6b0b9e562270ad755c8d009573b77a" - }, - { - "text": "Adapted with permission from Neumann I, Schnemann H (Editors).", - "tokenCount": 17, - "pageStart": 3, - "pageEnd": 3, - "hash": "145ee3df1bad3109cad71f800c3bbdb4a59335884470ffff8e0d346e4a3524a3" - }, - { - "text": "GRADE strength of recommendation classifications and interpretation Strength of recommendation Criteria Interpretation by individuals Interpretation by health care clinicians Interpretation by policy makers 1: Strong recommendation for or against Desirable consequences CLEARLY OUTWEIGH the undesirable consequences in most settings (or vice versa).", - "tokenCount": 56, - "pageStart": 3, - "pageEnd": 3, - "hash": "063eede5728ba63d983ae364a45fbf2535bbb815e3caf250c9ed9a6419f9048e" - }, - { - "text": "Most individuals in this situation would want the recommended course of action, and only a small proportion would not.", - "tokenCount": 21, - "pageStart": 3, - "pageEnd": 3, - "hash": "1135b108a05ac36ff39f23a46284979e1bb97bf741e3384c4ebff507074951a4" - }, - { - "text": "Most individuals should follow the recommended course of action.", - "tokenCount": 10, - "pageStart": 3, - "pageEnd": 3, - "hash": "76e05e0af0582cf500512458a2084bc95606b12e64377711cf4050c2b97584ff" - }, - { - "text": "Formal decision aids are not likely to be needed to help individuals make decisions consistent with their values and preferences.", - "tokenCount": 22, - "pageStart": 3, - "pageEnd": 3, - "hash": "104abc5d69811ad0f64c3093807c0f4968a1450e868145345269fc3ffb1efe6f" - }, - { - "text": "The recommendation can be adopted as policy in most situations.", - "tokenCount": 11, - "pageStart": 3, - "pageEnd": 3, - "hash": "b2ac3ecdaa07d4e3b806f697322394813d317778b90a14c5766708f6d4a2d521" - }, - { - "text": "Adherence to this recommendation according to the guideline could be used as a quality criterion or performance indicator.", - "tokenCount": 20, - "pageStart": 3, - "pageEnd": 3, - "hash": "c2e883a35a0d08cab84aa72d875fb13aeddf004c00cfa0f4386f6c98f194507d" - }, - { - "text": "2: Conditional recommendation for or against Desirable consequences PROBABLY OUTWEIGH undesirable consequences in most settings (or vice versa).", - "tokenCount": 28, - "pageStart": 3, - "pageEnd": 3, - "hash": "8331e79265241bb36c7d151bc1987d79496236b1995a1c7075b0e1ec91545aa6" - }, - { - "text": "The majority of individuals in this situation would want the suggested course of action, but many would not.", - "tokenCount": 20, - "pageStart": 3, - "pageEnd": 3, - "hash": "304ea78bef46cf5c2449571c3e05c570b440cdb164fce3209e711a985dcebce6" - }, - { - "text": "Decision aids may be useful in helping individuals make decisions consistent with their individual risks, values, and preferences.", - "tokenCount": 22, - "pageStart": 3, - "pageEnd": 3, - "hash": "309135d29cc554d7188f42b58a073f033fb4a700ff1bb74190b4d92931d99611" - }, - { - "text": "Clinicians should recognize that different choices will be appropriate for each individual and that clinicians must help each individual arrive at a management decision consistent with the individuals values and preferences.", - "tokenCount": 34, - "pageStart": 3, - "pageEnd": 3, - "hash": "f06492a3a2ea24cb02977f3c99cc7847d5ff2157f70cfe16d7202c94e920c762" - }, - { - "text": "Policymaking will require substantial debate and involvement of various stakeholders.", - "tokenCount": 14, - "pageStart": 3, - "pageEnd": 3, - "hash": "c9a81592a5150167e0795422299594167837616584b4246f3782de994aff5934" - }, - { - "text": "Performance measures should assess whether decision making is appropriate.", - "tokenCount": 10, - "pageStart": 3, - "pageEnd": 3, - "hash": "6cc921f38754b4c7a367b9a5d7781fbffb0c112d39e808e2c775229582f8d2a3" - }, - { - "text": "Adapted from Schnemann HJ et al Blood Adv, 2018; 2(22):3198-3225.", - "tokenCount": 25, - "pageStart": 3, - "pageEnd": 3, - "hash": "024b1abeb3dd17cd8051902364e0dacb5c4266a6e45be27117db273e304a1b35" - }, - { - "text": "The American Society of Hematology, published by Elsevier ( 13 ).", - "tokenCount": 15, - "pageStart": 3, - "pageEnd": 3, - "hash": "2a4f3682b47218470004019742a87dd75690b7b815c70fbb005fa965d75e7e3e" - }, - { - "text": "The Journal of Clinical Endocrinology & Metabolism , 2025, Vol.", - "tokenCount": 16, - "pageStart": 3, - "pageEnd": 3, - "hash": "0c787169302a2905c2110c7c26b2e91a7529ce93135159f1a93fb55c06b8a0eb" - }, - { - "text": "9 2455 Downloaded from https://academic.", - "tokenCount": 11, - "pageStart": 3, - "pageEnd": 3, - "hash": "7b4be586930db5e760e4d7ecca062bd83dc6412853d0928a8f278000192e3cc4" - }, - { - "text": "manuscript was reviewed before publication by the Journal of Clinical Endocrinology and Metabolisms publisher s reviewers.", - "tokenCount": 23, - "pageStart": 4, - "pageEnd": 4, - "hash": "fdef5f13adaa943d7c5dee06f788382bdcff56ceb93f864f3343fb517b6737a9" - }, - { - "text": "This guideline will be reviewed annually to assess the state of the evidence and determine if any developments warrant an update to the guideline.", - "tokenCount": 25, - "pageStart": 4, - "pageEnd": 4, - "hash": "344caf1573328ab87e4d408912123c833016fb0cdb1843320e1bcc450e4f595d" - }, - { - "text": "Should care that includes primary aldosteronism screening be applied to all individuals with hypertension, compared with care without screening?", - "tokenCount": 25, - "pageStart": 4, - "pageEnd": 4, - "hash": "c56273fe8dd1b60cadf461089ceeca81827f9467da27c15d2bca35ca80a924bf" - }, - { - "text": "Recommendation 1 In all individuals with hypertension, we suggest screening for primary aldosteronism (PA) (2 | OO).", - "tokenCount": 29, - "pageStart": 4, - "pageEnd": 4, - "hash": "5de29b8ef038546c1d401265a5917e29044a81dec23565c1a00c6beee55c412c" - }, - { - "text": "Technical remarks: This is a conditional recommendation, with implementation depending on contextual factors such as available resources, local expertise, and healthcare system capacity, which may affect feasibility and prioritization.", - "tokenCount": 37, - "pageStart": 4, - "pageEnd": 4, - "hash": "86c9cbd481467c2f2ced50f3154b358219c38ac2b78dbad953efb2a134accac4" - }, - { - "text": "This recommendation emphasizes care that is informed and guided by screening, with a positive screening result serving as the critical first step in the care process for individuals with PA.", - "tokenCount": 32, - "pageStart": 4, - "pageEnd": 4, - "hash": "9bfb5bed62d5983b6fae4ea9fba5804cdf33168344ff61f376f0d6c459f1eb20" - }, - { - "text": "PA screening includes measurement of serum/plasma aldosterone concentration and plasma renin (concentration or activity) with determination of the aldosterone to renin ratio (ARR).", - "tokenCount": 38, - "pageStart": 4, - "pageEnd": 4, - "hash": "4022e82518689ea13bfb4fcc1819818e4e9417f1984bc1536b084c7a5ea0d3ad" - }, - { - "text": "Potassium is also assessednot for screening itselfbut to aid in the accurate interpretation of aldosterone (refer to Question 3).", - "tokenCount": 27, - "pageStart": 4, - "pageEnd": 4, - "hash": "0c347e72a6eff55f52937a784f869ab279a9ad474679cf7ff3db1a3d08f453d2" - }, - { - "text": "Should primary aldosteronismspecific therapy (medical or surgical) vs nonspecific antihypertensive therapy be used in individuals with primary aldosteronism?", - "tokenCount": 36, - "pageStart": 4, - "pageEnd": 4, - "hash": "82a371d4add82b6f909ac327ed727dfbcc3c27403d5b5e1f37cd083c4d40c380" - }, - { - "text": "Recommendation 2 In individuals with hypertension and primary aldosteronism (PA), we suggest PAspecific therapy (medical or surgical) (2 | OO).", - "tokenCount": 36, - "pageStart": 4, - "pageEnd": 4, - "hash": "89c6fedcbfc6a63a811ba3d94918590052280ad5ac8cb5e19e75352ed5201c36" - }, - { - "text": "Technical remarks: In individuals with lateralizing PA who are not surgical candidates or do not desire surgery and in individuals with bilateral PA, medical treatment with mineralocorticoid receptor antagonists (MRAs) should be considered preferable over nonspecific antihypertensive therapy.", - "tokenCount": 55, - "pageStart": 4, - "pageEnd": 4, - "hash": "7af5a8de17da5697da32bb949f9d2e1f71860cf58d931970ef09b27b39793566" - }, - { - "text": "In individuals with lateralizing PA who are surgical candidates and desire surgery, unilateral adrenalectomy should be considered preferable over nonspecific antihypertensive therapy.", - "tokenCount": 32, - "pageStart": 4, - "pageEnd": 4, - "hash": "f83c4db8b3228d9a62cb7c74cb62c9b8074bc7c63f102aa0488322c269bc1218" - }, - { - "text": "Should aldosterone (serum/plasma, or urine), renin (concentration or activity), and the aldosterone to renin ratio vs hypokalemia (unprovoked or diureticinduced) be used for screening for primary aldosteronism in individuals with hypertension?", - "tokenCount": 63, - "pageStart": 4, - "pageEnd": 4, - "hash": "b6d7fa78af925683ce91e1f398d3eef798a1428e3028d521da2ce404dd4e6cc6" - }, - { - "text": "Recommendation 3 In individuals with hypertension, we suggest primary aldosteronism (PA) screening with serum/plasma aldosterone concentration and plasma renin (concentration or activity) (2 | OO).", - "tokenCount": 47, - "pageStart": 4, - "pageEnd": 4, - "hash": "73d769e5199bf5315fbca4a36cbd5b31de3fa98f5b9da41afa473bcd183f25dd" - }, - { - "text": "Technical remarks: Screen for PA by measuring serum/plasma aldosterone and plasma renin (concentration or activity) in the morning with individuals seated and avoiding dietary sodium restriction during the few days prior to screening.", - "tokenCount": 46, - "pageStart": 4, - "pageEnd": 4, - "hash": "a76267d07804244b4d7ff615a10304156fa1689edd8664319016f71461be0e1e" - }, - { - "text": "Potassium should be measured alongside renin and aldosteronenot for screening itself but to aid in the accurate interpretation of aldosteroneas low potassium may lead to a falsely low aldosterone.", - "tokenCount": 41, - "pageStart": 4, - "pageEnd": 4, - "hash": "e3460da4de574124358515b602da28d1895caaf8086fbae55281ce764d6f023d" - }, - { - "text": "If screening results are negative and the patient has hypokalemia, potassium should be corrected to within the laboratory reference range and screening should be repeated.", - "tokenCount": 30, - "pageStart": 4, - "pageEnd": 4, - "hash": "735481d375d23596c348f0e36a0963c544495084d9c8c963f62d5df73ba7f53a" - }, - { - "text": "Manage interfering medications depending on individual safety and feasibility.", - "tokenCount": 11, - "pageStart": 4, - "pageEnd": 4, - "hash": "5f767589b6c3092ef8944d593f65d53baf5b814d85f7dee130f416f7274253d0" - }, - { - "text": "The Guideline Development Panel outlined both minimalwithdrawal and nowithdrawal strategies of interfering medications before screening ( Tables 6 and 7 , Fig.", - "tokenCount": 30, - "pageStart": 4, - "pageEnd": 4, - "hash": "733bb4bc74f2a6a243b48b191ed241ca9281c17f4a756e829a60b2d52ca7b87d" - }, - { - "text": "A positive screen meets both of the following conditions in most circumstances: 1.", - "tokenCount": 15, - "pageStart": 4, - "pageEnd": 4, - "hash": "21e1866eab6851bb13ea1e945821e2c02290d32e53e63c2570f9a9c265371913" - }, - { - "text": "Renin is low/suppressed (hallmark of diagnosis) and aldosterone is inappropriately high relative to renin: indicative of PA if plasma renin activity (PRA) is 1 ng/mL/h or direct renin concentration (DRC) is 8.", - "tokenCount": 58, - "pageStart": 4, - "pageEnd": 4, - "hash": "ecb5c59a52b3a09a216c5b767e30f3e20e5df20b5123a5b643d2bc39c46d4adf" - }, - { - "text": "2 mU/L AND serum/plasma aldosterone concentration is 10 ng/dL ( 277 pmol/L) when measured by immunoassay or 7.", - "tokenCount": 39, - "pageStart": 4, - "pageEnd": 4, - "hash": "a7e0f6f8a8ffc1d4e24264ad7050af985feefbc98a4c50de32cd2a54383efb75" - }, - { - "text": "5 ng/dL ( 208 pmol/L) when measured by liquid chromatographytandem mass spectrometry (LCMS/MS) 2.", - "tokenCount": 32, - "pageStart": 4, - "pageEnd": 4, - "hash": "67b9be3b60dd241a2d4bda7d4fc716544d75199823929d926b0643d98438c194" - }, - { - "text": "Elevated aldosterone to renin ratio (ARR): indicative of PA if the aldosterone [ng/dL] to PRA [ng/ mL/h] ratio is > 20 or aldosterone [pmol/L] to DRC [mU/L] ratio is > 70 when aldosterone is measured by immunoassay; the ARR indicative of PA is about 25% lower when aldosterone is measured by LCMS/MS).", - "tokenCount": 98, - "pageStart": 4, - "pageEnd": 4, - "hash": "02498930907f87fc6daa8eded722233d83ce9a8a8edd0d391f06f52f92c7b593" - }, - { - "text": "1 and Table 5 for ARR cut points for differing assays and units).", - "tokenCount": 16, - "pageStart": 4, - "pageEnd": 4, - "hash": "df62527dc5b9d403dd2cff08282820d2d2507b93efe9b6bce65a43b58cd2e610" - }, - { - "text": "The aldosterone, renin, and ARR values above are provided for guidance.", - "tokenCount": 18, - "pageStart": 4, - "pageEnd": 4, - "hash": "4ebde2770f1cd9180b2bbb1d7224e6a850ede772d16230762170db54aa5d2662" - }, - { - "text": "However, as with many diagnostic tests based on continuous variables, the sensitivity and specificity depend on the selected threshold.", - "tokenCount": 22, - "pageStart": 4, - "pageEnd": 4, - "hash": "d9c53cfc70d224deb16839d7dde872b6046dafcc1d56fc440f715c3da08460ea" - }, - { - "text": "Aldosterone and renin levels are further influenced by individual variability, local 2456 The Journal of Clinical Endocrinology & Metabolism , 2025, Vol.", - "tokenCount": 33, - "pageStart": 4, - "pageEnd": 4, - "hash": "147ca3fcbfeb9e76d9c6f5bb926390a96416656feca6fa58ee936e6d9067f447" - }, - { - "text": "laboratory assays, and other factors.", - "tokenCount": 10, - "pageStart": 5, - "pageEnd": 5, - "hash": "733db0ab82c654a1821ff08c1ac25d6d0d10f6c3f4248a8d0b6c27228c7f4043" - }, - { - "text": "Where possible, clinicians should rely on local laboratory cut points, as assays may vary.", - "tokenCount": 18, - "pageStart": 5, - "pageEnd": 5, - "hash": "0b8d96bc4b2a8675c7a6e1ac0d1fd6b64efaa41acf21f27f143c490f75d68ca6" - }, - { - "text": "No cut point is perfecteach carries a tradeoff between false positives and false negatives.", - "tokenCount": 17, - "pageStart": 5, - "pageEnd": 5, - "hash": "4d98a9217ddd05be3141421ca5d82ddd29041f39fdab04851cc327f036003f43" - }, - { - "text": "Therefore, results should be interpreted within the context of the patients pretest probability for PA, along with potential interfering medications and conditions.", - "tokenCount": 26, - "pageStart": 5, - "pageEnd": 5, - "hash": "88e050c3d3de4bc5051bc1b56fe9039ee0ddf460920e2ec87d695d1c3d2f0632" - }, - { - "text": "If the individuals initial screen is negative and factors are present that could have led to a falsenegative result (eg, hypokalemia or medications), the test should be repeated on a different day, preferably after correcting hypokalemia (where present) and withdrawing interfering medications if safe and feasible (for 4 weeks for mineralocorticoid receptor antagonists [MRAs], epithelial Figure 1.", - "tokenCount": 81, - "pageStart": 5, - "pageEnd": 5, - "hash": "a09edcf555a989295b77cc25055bf64a1e534959c4bbcf5bdb9fdb201862de2c" - }, - { - "text": "How to screen for PA in individuals with hypertension. This figure diagrams the process of screening for PA in individuals with hypertension.", - "tokenCount": 24, - "pageStart": 5, - "pageEnd": 5, - "hash": "17ea9c5aa6ebd858dd704b81ac5b70ace8e01763371de80c833ba2e9bb5e41b5" - }, - { - "text": "For individuals whose screening indicates likely PA, the next steps are diagrammed in Fig.", - "tokenCount": 17, - "pageStart": 5, - "pageEnd": 5, - "hash": "b696476ccba73d9508dc04e25f99ddfa155c48b98cbef2f6f7cc69c0a870e57e" - }, - { - "text": "2 , Algorithm for the Management of Adults with Hypertension in Whom PA is Likely Based on Aldosterone, Renin, and ARR.", - "tokenCount": 31, - "pageStart": 5, - "pageEnd": 5, - "hash": "584e886bf4a73f2e68dabbaf3a5255e777f2adf4d010fd38e4c9727a47424d1d" - }, - { - "text": "*Blood is obtained in seated position in the morning; ideally without venous stasis (release tourniquet after venipuncture and wait at least 5 seconds before withdrawing blood) to avoid factitious rises in potassium.", - "tokenCount": 45, - "pageStart": 5, - "pageEnd": 5, - "hash": "dabc791c10d298e284fac34c8bdbf7366b61084d20de826eb5b8f9298f7ff728" - }, - { - "text": "**The aldosterone, renin, and ARR values provided in this figure and in greater detail in Table 5 are for guidance.", - "tokenCount": 28, - "pageStart": 5, - "pageEnd": 5, - "hash": "f9e1f850ab2afc23203da1d22bab8c3e5e0ffd9b9d6a314970950fb4dd2f6701" - }, - { - "text": "Aldosterone and renin levels are further influenced by individual variability, local laboratory assays, and other factors.", - "tokenCount": 23, - "pageStart": 5, - "pageEnd": 5, - "hash": "69a199d724c18881dadeb592e2492c392fe936f4756590967eb498c3b7de4c8e" - }, - { - "text": "***Consider potential false positive induced by -adrenergic blockers when aldosterone < 15 ng/dL ( < 415 pmol/L) by immunoassay, < 10 ng/dL ( < 277 pmol/L) by LCMS/MS.", - "tokenCount": 55, - "pageStart": 5, - "pageEnd": 5, - "hash": "fe6a0e918db2a044a553e48d0889abb788295dccdfffb7544b8293b843f465cb" - }, - { - "text": "# Drospirenone in OCPs is an MRA.", - "tokenCount": 14, - "pageStart": 5, - "pageEnd": 5, - "hash": "6073ab1ab19150e56b298b90fef8d97a52874241e27474bbba1968edfd751bf5" - }, - { - "text": "## Amiloride and triamterene are ENaC inhibitors.", - "tokenCount": 17, - "pageStart": 5, - "pageEnd": 5, - "hash": "5056858c93ed0a460f252e879144ea7df30b41341bbd8123547c50a69de4ddf1" - }, - { - "text": "Abbreviations: ACEi, angiotensinconverting enzyme inhibitor; ARB, angiotensin II receptor blocker; CCB, calciumchannel blocker; DRC, direct renin concentration; ENaC, epithelial sodiumchannel; HRT, hormonereplacement therapy; LCMS/MS: liquid chromatography tandem mass spectrometry; MRA, mineralocorticoid antagonist; OCP, oral contraceptive; PRA, plasma renin activity; SGLT2, sodiumglucose cotransporter 2.", - "tokenCount": 115, - "pageStart": 5, - "pageEnd": 5, - "hash": "fa872523961c35e8a7903d4f00beb048b3b54ffa698ed3dd95793a6e469cf122" - }, - { - "text": "9 2457 Downloaded from https://academic.", - "tokenCount": 11, - "pageStart": 5, - "pageEnd": 5, - "hash": "3ea0f8bb707e2270cba1211765cd2afaa8b707c9c3621bc3eb9744f6a2e241e4" - }, - { - "text": "sodiumchannel [ENaC] inhibitors [eg, amiloride, triamterene], and other diuretics; and 2 weeks for angiotensinconverting enzyme [ACE] inhibitors and angiotensin receptor blockers [ARBs]), which raise renin or lower aldosterone.", - "tokenCount": 65, - "pageStart": 6, - "pageEnd": 6, - "hash": "4411dcfa8e391f7532e6cbfb1eb8ed85527d23fbb1df539b8b67dd94977c792f" - }, - { - "text": "For the most accurate determination of potassium, measure plasma potassium in blood collected slowly with a syringe and needle (preferably not using a vacuumsealed blood collection tube to minimize the risk of spuriously raising potassium).", - "tokenCount": 44, - "pageStart": 6, - "pageEnd": 6, - "hash": "f5bb2d58c01f19b03e1b2ea8121e18ba44055750cdc3217e97e22ec75aedbed2" - }, - { - "text": "During collection, avoid fist clenching, wait at least 5 seconds after tourniquet release (if used) to achieve insertion of needle, and ensure separation of plasma from cells within 30 minutes of collection.", - "tokenCount": 42, - "pageStart": 6, - "pageEnd": 6, - "hash": "97a049f5a9a9eabfb28a294922e4a3419462b1325f2c153c4b73d133b0646566" - }, - { - "text": "If the individuals initial screen is negative and the pretest probability of PA is moderate to high (eg, hypokalemia and/or resistant hypertension) or renin is suppressed with aldosterone of 5 to 10 ng/ dL (138 to 277 pmol/L) by immunoassay, the test should be repeated on a different day.", - "tokenCount": 73, - "pageStart": 6, - "pageEnd": 6, - "hash": "4763bc16fc297b5e1ebfd77217af2f26a57e69252ec49faf786a38bebb178174" - }, - { - "text": "If the individuals initial screen is positive, but they are receiving medications (eg, -adrenergic blockers and centrally acting 2 -agonists [eg, clonidine, -methyldopa]) that can lower renin and thereby cause falsepositive results, the test should be repeated after withdrawing those medications for 2 weeks if it is safe and feasible.", - "tokenCount": 74, - "pageStart": 6, - "pageEnd": 6, - "hash": "aa634aa664be9a6327e3d4b1c6ebdc85f00d162450c81b20577f6411019a694b" - }, - { - "text": "Consider potential false positives induced by -adrenergic blockers when aldosterone is 10 to 15 ng/dL (277-416 pmol/L) by immunoassay or 7. 5 to 10 ng/dL (208-277 pmol/L) by LCMS/MS; if aldosterone is above these concentrations, PA is likely despite being on -adrenergic blockers.", - "tokenCount": 83, - "pageStart": 6, - "pageEnd": 6, - "hash": "92c26c540262041cfccb4ea70f26085e89d99363fe6264a538626b6f0ac905b2" - }, - { - "text": "If screening hypertensive patients with chronic kidney disease, renin decreases proportionately to nephron loss, except in cases where there is renal ischemia from renal artery stenosis where renin will be elevated.", - "tokenCount": 43, - "pageStart": 6, - "pageEnd": 6, - "hash": "fa423af0b1ad137832b9fa758ec6e832f2eb345235af6b41da45c1243a1d7e14" - }, - { - "text": "Aldosterone can also be elevated in chronic kidney disease, leading to overall increases in falsepositive testing.", - "tokenCount": 21, - "pageStart": 6, - "pageEnd": 6, - "hash": "bc0d7821c660ee98ebd07180a9f87600a8847bb5ec3f81d02670c839670fb696" - }, - { - "text": "If all initial screening is negative, consider rescreening in the future if a patient develops: Unexplained worsening of hypertension or resistant hypertension New spontaneous or diureticinduced hypokalemia Atrial fibrillation in the absence of structural heart disease or hyperthyroidism Question 4.", - "tokenCount": 63, - "pageStart": 6, - "pageEnd": 6, - "hash": "5b80e25d90e02bb176a765a6da48295f901306525076102c174c8cee2fa3b5c7" - }, - { - "text": "Should care guided by aldosterone suppression testing vs no aldosterone suppression testing be used in individuals with positive primary aldosteronism screen before initiating primary aldosteronismspecific therapy (medical or surgical)? Recommendation 4 In individuals who screen positive for primary aldosteronism (PA), we suggest aldosterone suppression testing in situations when screening results suggest an intermediate probability for lateralizing PA and individualized decision making confirms a desire to pursue eligibility for surgical therapy (2 | OOO). Technical remarks: Situations in which aldosterone suppression testing may be helpful include: In individuals with an intermediate probability of having lateralizing PA who are willing and able to undergo surgical adrenalectomy ( Fig.", - "tokenCount": 147, - "pageStart": 6, - "pageEnd": 6, - "hash": "9e97df57c2b705641ecd14db1106fe7984d4b81b96a8d938734e57152e510b99" - }, - { - "text": "Situations in which aldosterone suppression testing is not required prior to initiating PAspecific therapy include ( Fig.", - "tokenCount": 24, - "pageStart": 6, - "pageEnd": 6, - "hash": "ce3aeaea5bd04d3d345bf273daabfe44e1a1695a9da56310b74b4d0c8588302a" - }, - { - "text": "2 ): In individuals with resistant hypertension or hypertension with hypokalemia and overt biochemical evidence of reninindependent aldosterone production (plasma renin activity [PRA] < 0.", - "tokenCount": 40, - "pageStart": 6, - "pageEnd": 6, - "hash": "effd9c556094ffd4e2df2e5946230b7da065ed819c03cfc8290136acb5283573" - }, - { - "text": "2 ng/mL/h or direct renin concentration [DRC] < 2 mU/L and plasma aldosterone concentration > 15 ng/dL [ > 416 pmol/L] via liquid chromatographytandem mass spectrometry [LCMS/MS] assay or > 20 ng/dL [ > 554 pmol/L] via immunoassay), aldosterone suppression testing is not recommended due to the risk of falsenegative results, which may exceed the risk of falsepositive screening results.", - "tokenCount": 107, - "pageStart": 6, - "pageEnd": 6, - "hash": "19f310abfd2f1b1c36a6f714d9b150be48109b28e4bb6d614665fe818199057d" - }, - { - "text": "Individuals unwilling or unable to pursue adrenal venous sampling and adrenalectomy can be empirically treated with mineralocorticoid receptor antagonists (MRAs) based on screening results, without aldosterone suppression testing.", - "tokenCount": 45, - "pageStart": 6, - "pageEnd": 6, - "hash": "252fa6d03f0b631be272518cf85b603e5f4836502fdd460be78e61738ebed1b2" - }, - { - "text": "Aldosterone suppression testing may still provide value in some cases for further documenting the diagnosis.", - "tokenCount": 18, - "pageStart": 6, - "pageEnd": 6, - "hash": "2beb447743b0283c86a65835304fecbd8998ebc59f9639afa153deac3f7d1639" - }, - { - "text": "Aldosterone suppression testing is unnecessary in individuals from families with germline mutations associated with familial hyperaldosteronism.", - "tokenCount": 24, - "pageStart": 6, - "pageEnd": 6, - "hash": "15788c8089cc5277d840eff41193c04635bf4b6e06e2d8673ed7096f3aa685e6" - }, - { - "text": "Genetic screening is recommended for all firstdegree relatives of individuals with familial hyperaldosteronism and for individuals with youngonset PA ( < 20 years) to enable early diagnosis and treatment.", - "tokenCount": 39, - "pageStart": 6, - "pageEnd": 6, - "hash": "b280a33136dd188c55720430a89fd4adad76563deca8d5d46c3da0cb30016b17" - }, - { - "text": "Aldosterone suppression testing can also be avoided if the likelihood of lateralizing PA is so low that pursuing a formal diagnosis of PA is not justifiable (eg, normokalemia + plasma/serum aldosterone < 11ng/dL [ < 305 pmol/L] [immunoassay] or < 8 ng/dL [ < 222 pmol/L] [LCMS/MS]).", - "tokenCount": 85, - "pageStart": 6, - "pageEnd": 6, - "hash": "1798adb07793ed431be895d7692259eb08b37e6a1a0faee66ed148ce97deb49c" - }, - { - "text": "Should primary aldosteronismspecific medical therapy vs surgical therapy be used in individuals with diagnosed primary aldosteronism?", - "tokenCount": 27, - "pageStart": 6, - "pageEnd": 6, - "hash": "614f14b59de0e0f42bea3773c33abf785eedc1e4d0c533984e763d2287010042" - }, - { - "text": "Recommendation 5 In individuals with primary aldosteronism (PA), we suggest medical therapy or surgical therapy with the choice of therapy based on lateralization of aldosterone hypersecretion and candidacy for surgery (2 | OOO).", - "tokenCount": 49, - "pageStart": 6, - "pageEnd": 6, - "hash": "9f6b3a989222bbb620309623f5c7623f211683a96fb57c59001f4d1207217b3f" - }, - { - "text": "2458 The Journal of Clinical Endocrinology & Metabolism , 2025, Vol.", - "tokenCount": 18, - "pageStart": 6, - "pageEnd": 6, - "hash": "3b170002a914d385be0003f6ae85d9d3dca9ba6a3c51840b12a5f61ccedae85c" - }, - { - "text": "Technical remarks: Surgical therapy by total unilateral adrenalectomy, usually by the laparoscopic approach, is mainly offered to individuals with lateralizing PA who choose to pursue the surgical option ( Fig.", - "tokenCount": 41, - "pageStart": 7, - "pageEnd": 7, - "hash": "f53eaa2eb9c8fdf9e2d931cf20ba00c531ea7b7aa0295c76cd90eb062c0696ab" - }, - { - "text": "Lifelong medical therapy that includes a mineralocorticoid receptor antagonist (MRA) is usually offered to individuals with bilateral PA or lateralization status unknown (refer to Question 6 for definition of lateralization) and to those who are not surgical candidates or who decline the surgical option ( Fig.", - "tokenCount": 61, - "pageStart": 7, - "pageEnd": 7, - "hash": "c3a5f85cc72b7c313ca4855dff4ee267fc31297d4f5a485b15793292b0f47d88" - }, - { - "text": "Individuals with mild PA typically have bilateral disease and may bypass adrenal venous sampling (AVS), proceeding directly to medical management, as outlined in the diagnostic algorithm ( Fig.", - "tokenCount": 36, - "pageStart": 7, - "pageEnd": 7, - "hash": "65cf832a47c729cb535365bf03a7b49d75b6c79478caac3027cb988b041d1078" - }, - { - "text": "Individuals with multiple comorbidities who may not be good surgical candidates may also proceed directly to medical therapy ( Fig.", - "tokenCount": 25, - "pageStart": 7, - "pageEnd": 7, - "hash": "6409d11db8fb19c7114411cba64ad5da5256d876c06aeb582383334aa8f5c1a1" - }, - { - "text": "Should care guided by adrenal lateralization with computed tomography scanning and adrenal venous sampling vs computed tomography scanning alone be used for deciding treatment approach in individuals with primary aldosteronism? Recommendation 6 In individuals with primary aldosteronism (PA) considering surgery, we suggest adrenal lateralization with computed tomography (CT) scanning and adrenal venous sampling (AVS) prior to deciding the treatment approach (medical or surgical) (2 | OO). Technical remarks: Individuals with PA who desire and are candidates for adrenalectomy should undergo AVS in order to reliably differentiate lateralizing from bilateral forms.", - "tokenCount": 132, - "pageStart": 7, - "pageEnd": 7, - "hash": "298ea6ec37571d1edaaca04de28629967a5b5347289acbc37468087ed8ab786a" - }, - { - "text": "Algorithm for the management of adults with hypertension in whom PA is likely based on aldosterone, renin, and ARR.", - "tokenCount": 27, - "pageStart": 7, - "pageEnd": 7, - "hash": "106f1bcb5493d9f9acd7d16e56d64cacf289993e5393dee0ecc543c5c98c5dd4" - }, - { - "text": "Patients who are likely to have PA, but have no desire for surgical adrenalectomy, or have contraindications to undergoing surgery, can be offered MRA therapy without further testing.", - "tokenCount": 39, - "pageStart": 7, - "pageEnd": 7, - "hash": "43ef16e87b2d89533cc1face5ffeb2b967025305c880edb707284ef0ed125bb7" - }, - { - "text": "In addition, in studies of hypertensive individuals, MRAs have been consistently shown to be superior to alternative medication classes at lowering BP when renin is low or when the ARR is high ( 19 - 22 ).", - "tokenCount": 43, - "pageStart": 7, - "pageEnd": 7, - "hash": "ed4c1c736ec75acfd600b2c7c8586fc5e237909d4b4cda277cb97b24b9cd5a7c" - }, - { - "text": "For patients who are interested in the possibility of, and capable of undergoing, unilateral adrenalectomy, probabilistic and shared decision making should be pursued.", - "tokenCount": 31, - "pageStart": 7, - "pageEnd": 7, - "hash": "4f6a17691a926712afe67206c968aa47c3bcea93a7aa160424542897dfb275bc" - }, - { - "text": "When the probability of lateralizing PA is low, patients can be offered MRA therapy without further testing.", - "tokenCount": 21, - "pageStart": 7, - "pageEnd": 7, - "hash": "ecde309b871185527a2f5abffb07306a39f0a8c6190b97c5816251bb55c15217" - }, - { - "text": "When the probability of lateralizing PA is high, crosssectional adrenal imaging with CT and AVS can be pursued to adjudicate the possibility of lateralizing PA.", - "tokenCount": 33, - "pageStart": 7, - "pageEnd": 7, - "hash": "189007f7faf59d65eaa5aa45b90ad6a833c1f5d4eb00aa08860f18abe7e95f0d" - }, - { - "text": "When the probability of lateralizing PA is intermediate, or uncertain, shared decision making is advised.", - "tokenCount": 19, - "pageStart": 7, - "pageEnd": 7, - "hash": "9ee242a2b6845d7e09439a7b448b434c93b3c48c2d5c23ea0af0171592daff34" - }, - { - "text": "When possible, aldosterone suppression testing may be considered to steer the direction of management in individuals willing and able to undergo testing.", - "tokenCount": 26, - "pageStart": 7, - "pageEnd": 7, - "hash": "bbba5b2b5f357bc9d44d8b90031713e8a5e9fd38bc49cce96a41b41adfcd59e7" - }, - { - "text": "In interpreting the aldosterone suppression test one should consider the possibility of false negatives ( 23 - 27 ).", - "tokenCount": 21, - "pageStart": 7, - "pageEnd": 7, - "hash": "5535aa9def84f14a7c4e012af5ab1a7f5776641929ffa28771e3710b1f6dc48b" - }, - { - "text": "When aldosterone suppression testing is not available or desired, MRA therapy can be initiated.", - "tokenCount": 19, - "pageStart": 7, - "pageEnd": 7, - "hash": "9b1191064b30a49c0a9fda3f919bcf52822b43ec2ff6a6cc434720121b0cca33" - }, - { - "text": "Approximate values for aldosterone and renin are provided for guidance.", - "tokenCount": 16, - "pageStart": 7, - "pageEnd": 7, - "hash": "f74d6ed07a750e6b0cff0e29fb6a2383e289802ca5c02287b2c6ba8f0eeb8edd" - }, - { - "text": "# False negatives may occur, may be impacted by local study conditions, and should be considered when deciding on whether to proceed to AVS testing.", - "tokenCount": 29, - "pageStart": 7, - "pageEnd": 7, - "hash": "1abccc791c61b163d8ac051ca3f8e62b8f0e1ccef0fefd27b2caf6ab52f82e07" - }, - { - "text": "Abbreviations: HTN, hypertension; CVA, cerebrovascular accident; MRA, mineralocorticoid antagonist.", - "tokenCount": 29, - "pageStart": 7, - "pageEnd": 7, - "hash": "98cd5d7aeee9305fcdf1b02695b2a1a61aed5a3915e7d489c33e4a37dd616962" - }, - { - "text": "9 2459 Downloaded from https://academic.", - "tokenCount": 11, - "pageStart": 7, - "pageEnd": 7, - "hash": "7fa62ac4440a8e9ebcb09213f7bbe22b913b634898277b3c60e3a6a5af6403b6" - }, - { - "text": "A potential exception is when the diagnosis of unilateral aldosteroneproducing adenoma (APA) is so likely that AVS could be considered unnecessary (eg, individual age < 35 years with marked PA with hypokalemia and a > 1.", - "tokenCount": 51, - "pageStart": 8, - "pageEnd": 8, - "hash": "c3c2672566e88150f11160fc58ab8756d78fda1cd6c46a9f0a710d5452610f78" - }, - { - "text": "0-cm unilateral adrenal adenoma on CT scanning).", - "tokenCount": 13, - "pageStart": 8, - "pageEnd": 8, - "hash": "025ee9846d410cab5e5a7d1b1a68487bc0aba430412fede54141f1c12f685411" - }, - { - "text": "Should suppressed renin vs unsuppressed renin be used in individuals with primary aldosteronism receiving primary aldosteronismspecific medical therapy?", - "tokenCount": 33, - "pageStart": 8, - "pageEnd": 8, - "hash": "f3f8f6b2e5e490722d8169238815a38ab7222c33e9f5ea2d590f0558915a6236" - }, - { - "text": "Recommendation 7 In individuals with primary aldosteronism (PA) receiving PAspecific medical therapy whose hypertension is not controlled and renin is suppressed, we suggest increasing PAspecific medical therapy to raise renin (2 | OOO). Technical remarks: This recommendation applies to individuals with PA receiving aldosteronedirected medical therapy whose blood pressure (BP) remains high.", - "tokenCount": 82, - "pageStart": 8, - "pageEnd": 8, - "hash": "dd65718c681969634d68cf91c941d942f1e4ff598e3f087b3827d20d102019d6" - }, - { - "text": "Uncertainty remains as to whether titrating aldosteronedirected medical therapy to raise renin when BP is controlled is efficacious.", - "tokenCount": 29, - "pageStart": 8, - "pageEnd": 8, - "hash": "f40b263ef7eb608ecd04e4c969b4929ac33ef9637ec86c11713eae94588fa798" - }, - { - "text": "The panel does not specify a renin level to target but rather advises titration of aldosteronedirected medical therapy to a rise in renin from pretreatment baseline.", - "tokenCount": 36, - "pageStart": 8, - "pageEnd": 8, - "hash": "d2e04d343256dd65d4168da414dba84eace4857029dd7eaa86ab135441468861" - }, - { - "text": "Should a dexamethasone suppression test vs no dexamethasone suppression test be used in individuals with primary aldosteronism and adrenal adenoma?", - "tokenCount": 36, - "pageStart": 8, - "pageEnd": 8, - "hash": "59ea916acd2299a8cc52372580533c296cb4d094085b81272b14cba0f0fea394" - }, - { - "text": "Recommendation 8 In individuals with primary aldosteronism (PA) and adrenal adenoma, we suggest a dexamethasone suppression test (2 | OOO).", - "tokenCount": 39, - "pageStart": 8, - "pageEnd": 8, - "hash": "23e6da2ac413d632b9c12a041d64f95e2164b2abcf73d3793429e6c741600d90" - }, - { - "text": "Technical remarks: A dexamethasone suppression test should be performed, and a positive test should prompt further evaluation for Cushing syndrome as detailed in the Endocrine Society Clinical Practice Guidelines.", - "tokenCount": 39, - "pageStart": 8, - "pageEnd": 8, - "hash": "ab9efae97ef618e4b437e7bb4eba175f273a19a33d99fb14aa863ed451d4e1d2" - }, - { - "text": "For the 1-mg overnight dexamethasone suppression test, 1 mg dexamethasone is taken orally at 23:00 to 24:00 with serum cortisol measured at 08:00 to 09:00 the next morning.", - "tokenCount": 48, - "pageStart": 8, - "pageEnd": 8, - "hash": "636873ca2bdf997865a19dabe0818b45d6aef6cb6383df8d162a4658e8d6e79f" - }, - { - "text": "8 g/dL (50 nmol/L) suggests autonomous cortisol secretion (ACS).", - "tokenCount": 20, - "pageStart": 8, - "pageEnd": 8, - "hash": "760fc7ce1aad58e56271416d84f95611aeee9c80be9838b59bf0c6098c043b85" - }, - { - "text": "For individuals with mild autonomous cortisol secretion, measuring plasma metanephrine during adrenal venous sampling may help lateralize both aldosterone and cortisol secretion, although further research is needed.", - "tokenCount": 38, - "pageStart": 8, - "pageEnd": 8, - "hash": "56a9e4d28946adbd1cee4388dace585eb3bb630ef295c795fd532d28c02717b9" - }, - { - "text": "It will also be important to measure early morning cortisol following adrenal surgery and prepare for a period of possible glucocorticoid insufficiency.", - "tokenCount": 30, - "pageStart": 8, - "pageEnd": 8, - "hash": "7ab0a634b86e82c203eef7678d908f5bbbcd079613f07e7acc011e140d42dde4" - }, - { - "text": "Should spironolactone vs other mineralocorticoid receptor antagonists be used for primary aldosteronism specific medical therapy?", - "tokenCount": 28, - "pageStart": 8, - "pageEnd": 8, - "hash": "b0956c00d2f1b1091f1c88401880f9aad4a9c59860fc4e823243378d13bc5425" - }, - { - "text": "Recommendation 9 In individuals with primary aldosteronism (PA) receiving PAspecific medical therapy, we suggest spironolactone over other mineralocorticoid receptor antagonists (MRAs) due to its low cost and widespread availability (2 | OOO).", - "tokenCount": 58, - "pageStart": 8, - "pageEnd": 8, - "hash": "30476acbf570f3e9a79917f7151e319441b144774d2a6d91e3c121856903ce20" - }, - { - "text": "Technical remarks: The recommendation is driven by the availability and low cost of spironolactone vs other MRAs; however, all MRAs, when titrated to equivalent potencies, are anticipated to have similar efficacy in treating PA.", - "tokenCount": 49, - "pageStart": 8, - "pageEnd": 8, - "hash": "4da641ded0564989b1f37507de3c1688d6cd9f8b6d51b164ebd56df7db4d247e" - }, - { - "text": "MRAs with greater mineralocorticoid receptor specificity and fewer androgen/progesterone receptormediated side effects may be preferred.", - "tokenCount": 30, - "pageStart": 8, - "pageEnd": 8, - "hash": "bfb17720b1d9dd5d3e5b4a837bf3035a8b3393f2fbc1164dd6f19e62b9a85618" - }, - { - "text": "When initiating an MRA, consider hypertension severity for dosing and potential discontinuation of other antihypertensive medications ( Fig.", - "tokenCount": 26, - "pageStart": 8, - "pageEnd": 8, - "hash": "760edfad044eb2a8d684613009834d4dd0a8c8d2e131141a1fc7aa651d01a210" - }, - { - "text": "Monitor potassium, renal function, renin (concentration or activity), and blood pressure response during followup to guide MRA dose titration.", - "tokenCount": 30, - "pageStart": 8, - "pageEnd": 8, - "hash": "8fcffd8d9deb4c978f67a2ae127dc1c259569fc4f83c8d083f281482d8471299" - }, - { - "text": "Should epithelial sodiumchannel inhibitors vs mineralocorticoid receptor antagonists (steroidal and nonsteroidal) be used for medical treatment of primary aldosteronism?", - "tokenCount": 35, - "pageStart": 8, - "pageEnd": 8, - "hash": "f02c1da1f7a84cd6415bbcbb20c57732f32f604355609b74d09b47153069cc32" - }, - { - "text": "Recommendation 10 For individuals with primary aldosteronism (PA) receiving PAspecific medical therapy, we suggest using mineralocorticoid receptor antagonists (MRAs) rather than epithelial sodiumchannel (ENaC) inhibitors (amiloride, triamterene) (2 | OOO).", - "tokenCount": 68, - "pageStart": 8, - "pageEnd": 8, - "hash": "db784a25f570fd10310c807d7148bb50de24c11a76424ab755615ef364bc413f" - }, - { - "text": "Technical remark: The recommendation (see Fig.", - "tokenCount": 10, - "pageStart": 8, - "pageEnd": 8, - "hash": "748cc7615e93e731fc74abd486a9e82e116f52e0887cc1ed36328cedced22c1e" - }, - { - "text": "3 ) does not apply to clinical conditions in which spironolactone is contraindicated (eg, hyperkalemia, advanced renal impairment, or pregnancy) or if a nonspironolactone MRA were indicated for other nonPA indications (eg, heart failure).", - "tokenCount": 59, - "pageStart": 8, - "pageEnd": 8, - "hash": "fbc0fe9daea1160563b7b723a01885b3dba11d1903afbccb12d84700899571c9" - }, - { - "text": "2460 The Journal of Clinical Endocrinology & Metabolism , 2025, Vol.", - "tokenCount": 18, - "pageStart": 8, - "pageEnd": 8, - "hash": "bc9698aee1c2ee2bf280d1dab3716afbfa6f47645bb4f73df11b91b79bdd21d0" - }, - { - "text": "This is a general guide and there is a wide range of interpatient responsiveness to varying doses of MRA.", - "tokenCount": 22, - "pageStart": 9, - "pageEnd": 9, - "hash": "de32aaddbe6428f3ed40369e1c5fde973c4b5d1adf03d258c41fcd80ba927ab2" - }, - { - "text": "The process of MRA initiation and titration is expected to be multistep for many patients; each MRA adjustment is followed by an assessment of both BP and biochemical response, then reentering the treatment algorithm as appropriate.", - "tokenCount": 46, - "pageStart": 9, - "pageEnd": 9, - "hash": "eeebbdbd90b34fcd7fd5b008eb10756928ef315966664c2b15d34b99fe186140" - }, - { - "text": "The primary goal of therapy is control of BP.", - "tokenCount": 10, - "pageStart": 9, - "pageEnd": 9, - "hash": "94e1945d445c0a8541cd3639abc6d9d743871a5c92b1dc921a75b36ade90a19c" - }, - { - "text": "The secondary goal of therapy is achievement of normokalemia.", - "tokenCount": 13, - "pageStart": 9, - "pageEnd": 9, - "hash": "5d87bdb184c5c907685490a1aea89df582b02d9b48389d6a7e912465cf1f0a17" - }, - { - "text": "Measurement of renin (as a marker of MR blockade) may assist in the process of MRA dose titration for achieving these goals and possibly reducing other nonMRA antihypertensive drugs.", - "tokenCount": 41, - "pageStart": 9, - "pageEnd": 9, - "hash": "f748fe11dc30ced996246cb8bda2f5bb49d6df97c735eac510af6b2f4c53715a" - }, - { - "text": "Clinicians may start at a relatively low dose MRA (spironolactone 12.", - "tokenCount": 20, - "pageStart": 9, - "pageEnd": 9, - "hash": "4ec3ed6a3f9f9b92dbac81c4d715c0b6a1c528f1456e03135dacc42967d4bf04" - }, - { - "text": "5-25 mg/d or eplerenone 25 mg daily or twice daily).", - "tokenCount": 18, - "pageStart": 9, - "pageEnd": 9, - "hash": "77ae7e8d188d774456557afeb1622d4a8c1c62673c67c851704ed03db784f176" - }, - { - "text": "Medically complex or frail individuals and those in whom MRAdrug interactions (eg, with an ACE inhibitor or ARB) are possible may need careful monitoring.", - "tokenCount": 32, - "pageStart": 9, - "pageEnd": 9, - "hash": "f0fee1d3fb959e15b141b3aa902b78f918d700895e3869fae0ef05e157e7eea8" - }, - { - "text": "For individuals with more severe PA, especially if profound hypokalemia is present, a higher initial dose could be considered (spironolactone 50 mg/d or eplerenone 50 mg twice daily).", - "tokenCount": 44, - "pageStart": 9, - "pageEnd": 9, - "hash": "9e9de7a3c4f3e3ea8865db6e34d0f50a6589bf0ced364e218620219d9a5f6fbf" - }, - { - "text": "All individuals should get routine measurement of serum electrolytes, renal function, and renin within 2 to 3 months of starting MRA therapy; more frequent serial measurements may be needed in those with prior severe hypokalemia or renal impairment.", - "tokenCount": 48, - "pageStart": 9, - "pageEnd": 9, - "hash": "efd33b77e165c7ac76027f17b48fbbfcd777e79340511e8f39f93192cf4dfe21" - }, - { - "text": "Some panelists recommend enquiring about dietary sodium or measuring 24-hour urine sodium at baseline and periodically throughout followup as a means of tracking dietary salt restriction; a target of < 85.", - "tokenCount": 38, - "pageStart": 9, - "pageEnd": 9, - "hash": "bb4904f4b8b1fbfd4112cbd2a526c249b6585aee63fa328298750a08a0685fb4" - }, - { - "text": "5 mmol/d sodium is recommended (representing < 5 g/d salt intake) ( 6 ).", - "tokenCount": 21, - "pageStart": 9, - "pageEnd": 9, - "hash": "17b34d0d428a21a4e7da2ba3515dec08655d386c6d1eba4d830d68094e06fa4f" - }, - { - "text": "MRA dose changes to target BP control should occur at 8- to 12-week intervals, and the full drug effect may take up to 3 months in more severe PA forms ( 28 ).", - "tokenCount": 38, - "pageStart": 9, - "pageEnd": 9, - "hash": "a8b4555fbfb8dc27cb9b6a31b8733c792f96951acfbf1280e0414c85e75bc27e" - }, - { - "text": "Typical doses required to desuppress renin are variable and likely higher than doses used as empiric addon for resistant hypertension ( 29 ) ( 30 ); most individuals will achieve renin desuppression with spironolactone doses (or spironolactone dose equivalents) between 50 and 100 mg/day.", - "tokenCount": 65, - "pageStart": 9, - "pageEnd": 9, - "hash": "6b68ed1bbaa7eea9a269c49310607dcac9debf279b0ac3fcf88a9a78d34eba47" - }, - { - "text": "Spironolactone may be increased in 25- to 50-mg increments, and eplerenone in 25- to 100-mg increments.", - "tokenCount": 31, - "pageStart": 9, - "pageEnd": 9, - "hash": "26cf6328aa5ecbd960dd383564085069b62381b2698fa11165c72fe4fb5f0126" - }, - { - "text": "With each MRA dose change, repeat electrolytes, renal function, and renin 2 to 3 months later is recommended.", - "tokenCount": 25, - "pageStart": 9, - "pageEnd": 9, - "hash": "dd3348fca9547cc3ec6ab95bfd7b1c821eb01e4d695ea9cd2fa62390c02d2975" - }, - { - "text": "When possible, consider offtitration of other antihypertensives.", - "tokenCount": 16, - "pageStart": 9, - "pageEnd": 9, - "hash": "be990f1d6d0237fbb981115aacb13a32af010e1b1fc51978e5dfee7f7764be57" - }, - { - "text": "Once renin is desuppressed, and if further BP reduction is required, other nonMRA antihypertensives should be added or uptitrated.", - "tokenCount": 33, - "pageStart": 9, - "pageEnd": 9, - "hash": "7712d11f60a6daee3183111177b5dc4d5a6a785fb72a25d092a27e2f4d2463db" - }, - { - "text": "If blood pressure is controlled on MRA monotherapy, there is insufficient evidence to suggest further MRA dose increases in response to low renin levels alone.", - "tokenCount": 31, - "pageStart": 9, - "pageEnd": 9, - "hash": "793f26f607d779e7672f32dd71fbc9093bd39bd37cad850658711d9d5e549bd5" - }, - { - "text": "Normalization of serum potassium usually occurs, even with lowerdose MRAs, in the first 3 to 5 days, so it is reasonable to reduce or discontinue any potassium supplements at day 2 to 4 of MRA initiation in all but the most severe hypokalemic cases.", - "tokenCount": 56, - "pageStart": 9, - "pageEnd": 9, - "hash": "fbd6d044225e74d89e74b2a1f2ed08f65f5e3a3c51e2b5a5456aebb160b2e2c2" - }, - { - "text": "Individuals who do require ongoing potassium supplementation require frequent careful monitoring of potassium.", - "tokenCount": 15, - "pageStart": 9, - "pageEnd": 9, - "hash": "896753f47735cf76e24840f2956c8fd3995d658bc2c8a0a79353904eb38f8233" - }, - { - "text": "Dietary salt restriction is a critical part of determining response to MRA therapy ( 31 ); individuals should be explicitly instructed on and assisted with dietary salt reduction strategies. An ongoing highsalt diet is a very common reason for apparent nonresponse to MRA therapy.", - "tokenCount": 52, - "pageStart": 9, - "pageEnd": 9, - "hash": "99c121ede07b078cecdd3bad7d67a0ea7d6ce4dba222f841af460c5ab995e8b9" - }, - { - "text": "The glomerular filtration rate (GFR) may decrease in individuals with PA on introduction of PAtargeted medical therapy or with successive titration of MRA ( 32,33 ).", - "tokenCount": 40, - "pageStart": 9, - "pageEnd": 9, - "hash": "f8ac33492ebcd595375baaa9a0d7587cc1c2cd022ebbb931513b28f5d60a33d7" - }, - { - "text": "The time course of change may be over days to weeks and, in most cases, represents a marker of treatment efficacy as opposed to adverse effect.", - "tokenCount": 29, - "pageStart": 9, - "pageEnd": 9, - "hash": "308703a5a261f5ac60baf95aa3d0204bef1d7a7048e0cc35e2a40ccd89659dc2" - }, - { - "text": "The natural history of an appropriate treatmentinduced decrease in GFR is usually one of eventual longterm stability, anticipating a renalsparing effect of effective MRA therapy ( 32,33 ).", - "tokenCount": 38, - "pageStart": 9, - "pageEnd": 9, - "hash": "a4093f5f470fab21dc45b5d32696cd6cbe81843d01377e8dade50b4e48c5dc60" - }, - { - "text": "If renal function progressively declines, consider referring to nephrology and discontinuing ACE inhibitors or ARBs.", - "tokenCount": 21, - "pageStart": 9, - "pageEnd": 9, - "hash": "449a43b8d342fc38a1afd3a02ddd7372ddb3e2cc1dc9681b1ac38f86b1f86351" - }, - { - "text": "Gynecomastia from spironolactone is doserelated and may appear as early as 1 to 2 months into therapy but more commonly after 6 months of treatment.", - "tokenCount": 36, - "pageStart": 9, - "pageEnd": 9, - "hash": "7a9f02b9d7fbdc3ba0e15012dfe6e0f818005e84b047ef80a8d16e804b7b8f11" - }, - { - "text": "In some cases (especially in younger males) a dose reduction to 50 mg per day resolves gynecomastia.", - "tokenCount": 25, - "pageStart": 9, - "pageEnd": 9, - "hash": "392640f35cd87e30baee7d5a57e51fc091ae1d96ec9575b08c295aa9c3790be0" - }, - { - "text": "Some men may request a switch to a more selective MRA such as eplerenone or other new MRA agents; amiloride is an alternative option (see Question 10).", - "tokenCount": 38, - "pageStart": 9, - "pageEnd": 9, - "hash": "69d7e4457f360084bf0f85be842808a2643db4e7816e47d73fb5f240c0e1b1f8" - }, - { - "text": "This almost always allows complete resolution of the gynecomastia if it has not already progressed to advanced size.", - "tokenCount": 23, - "pageStart": 9, - "pageEnd": 9, - "hash": "7c442085af293a565e80fb211583d0c32998d058ec89f7d41cb871a2805e9e4b" - }, - { - "text": "Routine followup after MRA dose optimization should generally consist of blood pressure monitoring, along with annual measures of potassium and kidney function.", - "tokenCount": 27, - "pageStart": 9, - "pageEnd": 9, - "hash": "1a8911ffa210fdf5411d5ca6c83881547a6570e1986f1af0ef748193ea3f2d45" - }, - { - "text": "Patients with chronic kidney disease or other risk factors for impaired renal function/electrolyte disorders (eg, combination MRA and ACE inhibitor/ARB drugs) should undergo biochemical monitoring more frequently.", - "tokenCount": 40, - "pageStart": 9, - "pageEnd": 9, - "hash": "7e7274adc2df10986445523de074975a3d30d615b3c7b74a30100a305b6a4c22" - }, - { - "text": "Routine repeat renin measures are not necessary unless reentering the MRA titration algorithm due to incomplete BP/potassium control.", - "tokenCount": 28, - "pageStart": 9, - "pageEnd": 9, - "hash": "f39b45c82547bf597c70f2e2cec64342b8a50446f67bf8fa9c7585fa031353c5" - }, - { - "text": "9 2461 Downloaded from https://academic.", - "tokenCount": 11, - "pageStart": 9, - "pageEnd": 9, - "hash": "4476b7a8c16874b3d01189702372e83b86f6540b5a8fe940fb374bf8f1204c89" - }, - { - "text": "Who Should be Screened for Primary Aldosteronism?", - "tokenCount": 12, - "pageStart": 10, - "pageEnd": 10, - "hash": "eb073aa122992775992414bbc573037d9442f23148a4f2a986c6fe266ff0e3d1" - }, - { - "text": "Background Primary aldosteronism (PA) is the most common endocrine cause of secondary hypertension with an estimated prevalence of 5% to 14% of individuals with hypertension seen in primary care ( 34-36 ) and up to 30% in referral centers ( 37-39 ).", - "tokenCount": 56, - "pageStart": 10, - "pageEnd": 10, - "hash": "dc73a81dfa0657ddfee02af09b7b411b5ec7298437a89c051b9d93813942a537" - }, - { - "text": "PA is particularly prevalent in individuals with specific clinical characteristics or comorbid conditions ( Table 3 ).", - "tokenCount": 19, - "pageStart": 10, - "pageEnd": 10, - "hash": "089356916bcb00dfdeacffdfde19b10b6b34f5b148204b7298937df163a1f495" - }, - { - "text": "PA is characterized by excessive production of aldosterone ( 49 ), leading to higher blood pressure (BP), renal injury, and an elevated risk of stroke, atrial fibrillation, and other cardiovascular diseases ( 1,2 ).", - "tokenCount": 46, - "pageStart": 10, - "pageEnd": 10, - "hash": "410e231553b5e08c939afa32274e5a6416aff4b6c9b8bab150a6747deb029938" - }, - { - "text": "Detection of PA allows the use of specific treatmentssuch as mineralocorticoid receptor antagonists (MRAs), or adrenalectomy for those with lateralizing diseasethat can effectively control BP, correct hypokalemia, and reduce cardiovascular risk ( 7-9 ) Despite the potential benefits of treatment, PA remains underdiagnosed, in part due to limited screening in routine clinical practice ( 50,51 ).", - "tokenCount": 85, - "pageStart": 10, - "pageEnd": 10, - "hash": "43c668a2f3dcd97158deb1ff082ef943a5a5f47b3114ad5d01b5c4f6c41214e3" - }, - { - "text": "Many individuals with PA, even those with highrisk features, such as resistant hypertension and hypokalemia ( 52 ), are never identified, leading to suboptimal management of their hypertension and cardiovascular risk.", - "tokenCount": 41, - "pageStart": 10, - "pageEnd": 10, - "hash": "0c0f7d161bd7ba89c8d2088982dccd950cc3602c250ec505d155751964e61dec" - }, - { - "text": "Expanding PA screening to all hypertensive individuals could increase the detection rate, allowing more individuals to benefit from targeted therapies and potentially reducing longterm cardiovascular risks.", - "tokenCount": 31, - "pageStart": 10, - "pageEnd": 10, - "hash": "74efb1c5118fe4151d461b8161584f29d1541a3f0aef1f852b623c99ef434606" - }, - { - "text": "However, the benefits of widespread screening must be weighed against certain challenges.", - "tokenCount": 14, - "pageStart": 10, - "pageEnd": 10, - "hash": "eba14c3a7310bb4818e3f4e2fc353544bb9bd7416d21b1070951b8e9688223e6" - }, - { - "text": "The accuracy of screening tests, such as aldosterone concentration, renin concentration or activity, and the aldosterone to renin ratio (ARR), is influenced by various factors, including medication use, dietary sodium intake, and test conditions.", - "tokenCount": 49, - "pageStart": 10, - "pageEnd": 10, - "hash": "ad33b24f3476d48f875f6e52278b8f939c6efb5ddd45cdea94f0fcfb26512a9e" - }, - { - "text": "False positives can occur, resulting in unnecessary aldosterone suppression testing or even inappropriate PA treatment in individuals without the condition.", - "tokenCount": 24, - "pageStart": 10, - "pageEnd": 10, - "hash": "d2953e530da56a49a60e06183c837ec97412d70f5aa09b85b5e3789feedf7afd" - }, - { - "text": "Access to diagnostic and subtyping tests and the availability of specialized treatments may also undermine the feasibility of universal screening unless alternative strategies are proposed.", - "tokenCount": 28, - "pageStart": 10, - "pageEnd": 10, - "hash": "c419c8e31c0d78550cb49d902bc47904f46ed1d9b6b9a94185b33a284154e4d4" - }, - { - "text": "Therefore, the guideline addresses the question of whether care with PA screening should be implemented for all individuals with hypertension.", - "tokenCount": 22, - "pageStart": 10, - "pageEnd": 10, - "hash": "5c87b6cd3cbcb7946c24689b09307b2f1764fc58e4a4ea91e40982da3ff5b006" - }, - { - "text": "Summary of the Evidence The metaanalysis results, a detailed summary of the evidence and Evidence to Decision (EtD) tables can be found online at: https:/ /guidelines.", - "tokenCount": 37, - "pageStart": 10, - "pageEnd": 10, - "hash": "27e69ea265ab326c8810071406480f118523ef70ca9eae202f0ff59a6823fbe9" - }, - { - "text": "org/profile/goKsLjFSyDQ .", - "tokenCount": 14, - "pageStart": 10, - "pageEnd": 10, - "hash": "a4e3eda7a9188ef9c926ffcbd1ed9bba085d055cdcbcd799d968dc16d4a26e87" - }, - { - "text": "Prevalence of primary aldosteronism in different subgroups Setting Prevalence Reference Hypertension in Primary Care 5.", - "tokenCount": 27, - "pageStart": 10, - "pageEnd": 10, - "hash": "52643d683dbb3a59197029b620692c59843678d6c78e8443658d19ef905829bb" - }, - { - "text": "0) ( 34 - 36,39 ) Hypertension in referral centers 7.", - "tokenCount": 17, - "pageStart": 10, - "pageEnd": 10, - "hash": "ef7839427110437f1fa51f66aa5f3480b85921d0a4622328d3b16af2c64c7d14" - }, - { - "text": "9) ( 39 ) Hypertension in young adults (ages 18-40 years) 16.", - "tokenCount": 20, - "pageStart": 10, - "pageEnd": 10, - "hash": "e70a1fa1891dbe232416f3f8f206a37d06accabb02a2da184b7f9601f371da35" - }, - { - "text": "2% ( 39 ) a Grade 1 hypertension 3.", - "tokenCount": 11, - "pageStart": 10, - "pageEnd": 10, - "hash": "6165254b0078569ad4f8b29d340448c21fc0c99af9008ae6ff755288c10f36d3" - }, - { - "text": "7% ( 23,34 ) a Grade 2 hypertension 9.", - "tokenCount": 13, - "pageStart": 10, - "pageEnd": 10, - "hash": "8b7b8fb2e046f26f4e87efd20a5d554993351c1c4fb5ada99c2cd5881d23606c" - }, - { - "text": "6% ( 23,34 , 37 ) a Grade 3 hypertension 11. 9%-19% ( 34,37 ) Resistant hypertension 11.", - "tokenCount": 29, - "pageStart": 10, - "pageEnd": 10, - "hash": "27ee7b579fd6fc839f96d41fdfb6102509b8d06d934607e3ccc00910e09e135c" - }, - { - "text": "1% ( 23,40 - 42 ) Hypertension and hypokalemia 28.", - "tokenCount": 19, - "pageStart": 10, - "pageEnd": 10, - "hash": "051a62ed6724f3f3c52e8eb7b417c5d8994904e22a6548d7b3bc6b547b871ac6" - }, - { - "text": "1% ( 43 ) Hypertension and adrenal incidentaloma 4.", - "tokenCount": 15, - "pageStart": 10, - "pageEnd": 10, - "hash": "53af87e57249d17bbcf77abdc73030b58cb61edc88f6590ee9ad99c81373dacd" - }, - { - "text": "6%) ( 44 ) Hypertension and atrial fibrillation b 42.", - "tokenCount": 17, - "pageStart": 10, - "pageEnd": 10, - "hash": "b98032ef0bb7cb9b14f2bb1082baeb867801503cfa1e0204527da0f5464c3849" - }, - { - "text": "5% ( 45 ) Hypertension and type 2 diabetes mellitus 11.", - "tokenCount": 16, - "pageStart": 10, - "pageEnd": 10, - "hash": "06f06b0c83f87ed044f9faeaedbd4434db0f5c628568b88f2b43fbdab12fefe6" - }, - { - "text": "1% ( 46,47 ) Abbreviations: DBP, diastolic blood pressure; SBP, systolic blood pressure.", - "tokenCount": 30, - "pageStart": 10, - "pageEnd": 10, - "hash": "654f496a7d5100284b20f2dcb7c9ab1ba8badb37b9f82d29080d3914b848206f" - }, - { - "text": "a Grades 1,2, and 3 hypertension refer to the classification of the 2023 European Society of Hypertension guideline ( 48 ).", - "tokenCount": 28, - "pageStart": 10, - "pageEnd": 10, - "hash": "7514ea950d87821982f6bd24229c132f26a32faf107747b7ed2b50c6fbd59a23" - }, - { - "text": "Grade 1, SBP 140-159 mmHg and/or DBP 90-99 mmHg; grade 2,160-179 mmHg and/or DBP 100-109 mmHg; grade 3, SBP 180 mmHg and/or DBP 110 mmHg.", - "tokenCount": 65, - "pageStart": 10, - "pageEnd": 10, - "hash": "24be8c2a559d90ab3686bdb69c9a2962bc90e59610a86928f1b65a9a17bcad34" - }, - { - "text": "b If unexplained by structural heart disease and other conditions like hyperthyroidism.", - "tokenCount": 16, - "pageStart": 10, - "pageEnd": 10, - "hash": "f70d00684353096988da05aea82e7ce02cb8d0106a354d23c3adf21aebe3a258" - }, - { - "text": "2462 The Journal of Clinical Endocrinology & Metabolism , 2025, Vol.", - "tokenCount": 18, - "pageStart": 10, - "pageEnd": 10, - "hash": "2fbb7383849788fa8051c56e227f4071861ecb98d6293ff160f00ad57751023a" - }, - { - "text": "Benefits and Harms The panel voted for the following patientimportant outcomes for Question 1 decision making: 1) percent of individuals achieving BP control, 2) number of antihypertensive agents, 3) dosage of antihypertensive agents, 4) systolic BP (SBP) level, 5) major adverse cardiovascular events (MACEs), 6) atrial fibrillation, 7) stroke, 8) ischemic heart disease, 9) heart failure, 10) cardiovascular mortality, 11) allcause mortality, and 12) adverse events.", - "tokenCount": 114, - "pageStart": 11, - "pageEnd": 11, - "hash": "3c5b56b2dbc66e60a7ec4aa99a7874ca1f602e509dd77dc8a646d928eadd182a" - }, - { - "text": "The commissioned systematic review ( 53 ) identified a single retrospective observational study ( 51 ) that showed that screening for PA was associated with a significantly lower SBP over time.", - "tokenCount": 33, - "pageStart": 11, - "pageEnd": 11, - "hash": "74feeb38eba37f271bd00f96162f8d449132e663efe6791790fe6ee5519484e2" - }, - { - "text": "The authors reported that of 269 010 US veterans with apparent treatmentresistant hypertension, only 1.", - "tokenCount": 19, - "pageStart": 11, - "pageEnd": 11, - "hash": "63b8a46002d52e92562c51dd28c56d7140d8cbc5991e7abc175349d76fb0e346" - }, - { - "text": "6% were tested for PA with a concomitant measurement of blood aldosterone concentration and either plasma renin activity (PRA) or direct renin concentration (DRC).", - "tokenCount": 37, - "pageStart": 11, - "pageEnd": 11, - "hash": "e0d7ee0e749fef0b2a036aac3aa98829bab329396bc04b322f298494c02c0dab" - }, - { - "text": "Testing for PA was associated with a 4-fold higher likelihood of initiating treatment with an MRA.", - "tokenCount": 20, - "pageStart": 11, - "pageEnd": 11, - "hash": "674e43986291719c31083248377445dbe9e87053c5294d55011bcd552005a61f" - }, - { - "text": "Individuals who underwent PA testing also had an average 1.", - "tokenCount": 12, - "pageStart": 11, - "pageEnd": 11, - "hash": "4689c28b482ce39ac048d04d20bdc0f14a7ba5ff4cb10b75c30213047e690d93" - }, - { - "text": "47-mmHg lower SBP over time compared with those not tested.", - "tokenCount": 16, - "pageStart": 11, - "pageEnd": 11, - "hash": "1d3c57468ac7027fd373d6e34988863b139949dae6a68fc7a986d0022b7e3c2c" - }, - { - "text": "Certainty of evidence for the outcome of BP control is low due to the nonrandomized nature of the study and indirectness.", - "tokenCount": 26, - "pageStart": 11, - "pageEnd": 11, - "hash": "3daedfd73eca541620169277d4c6822e8462d3d6ecb46138e247eb89801c7b59" - }, - { - "text": "The panel did not identify any headtohead studies comparing screening vs no screening for the outcomes of interest.", - "tokenCount": 21, - "pageStart": 11, - "pageEnd": 11, - "hash": "449c32b3e4677dd345103e87faa5fc47afe1916ab8e0c587c28ac8f4fa8b0eda" - }, - { - "text": "Due to the limited availability of studies directly evaluating the comparative effectiveness and potential harms of screening, this recommendation relies on indirect evidence.", - "tokenCount": 25, - "pageStart": 11, - "pageEnd": 11, - "hash": "bff7cd831336aec32efe56dd67a65b0c79a91f20258b7a7d271781fd8470c64d" - }, - { - "text": "The panel used a guideline screening framework that considers multiple factors required to justify screening ( 54 ).", - "tokenCount": 18, - "pageStart": 11, - "pageEnd": 11, - "hash": "8fde6353ba6d13348006a0d414ff00cf56a3541c413c3354f6559cc1d8d1dd9d" - }, - { - "text": "The panel also adopted a framework based on Wilson and Jungner s principles of screening ( 55 ).", - "tokenCount": 20, - "pageStart": 11, - "pageEnd": 11, - "hash": "dd9e3e3fece1f1c67d95c0e54888465132305b72e37c0e714829f1e991e816d0" - }, - { - "text": "This framework, as relevant to screening for PA, is detailed in Table 4 .", - "tokenCount": 16, - "pageStart": 11, - "pageEnd": 11, - "hash": "6273478e3d01dc8091ff4d84bbe0fe8a693e11546ae7f6c426bfdeb3b41f943b" - }, - { - "text": "It is common, affecting 5% to 14% of hypertensive individuals in the primary care population and up to 30% in referral centers ( 34,38 , 35,36 ).", - "tokenCount": 36, - "pageStart": 11, - "pageEnd": 11, - "hash": "c5e6db026c9c3d41119317490f575d523b5ee22d5784a05b94e4b2c4dbfc6d27" - }, - { - "text": "Untreated PA confers a higher risk of cardiovascular complications, with a metaanalysis of 31 studies showing an increased risk of stroke, coronary artery disease, atrial fibrillation, and heart failure for individuals with PA compared with BPmatched primary hypertension ( 2 ).", - "tokenCount": 52, - "pageStart": 11, - "pageEnd": 11, - "hash": "6c36d1b8647f0d019c955fc8d49d66f9096ab44e4ec2decd45d421a75e65af2a" - }, - { - "text": "While the natural history of PA is not fully understood, due to the general lack of screening from a young age, multiple studies provide evidence that elevated aldosterone concentration, especially in the presence of low renin concentration or activity, is associated with increased risk of hypertension and cardiovascular events over time.", - "tokenCount": 59, - "pageStart": 11, - "pageEnd": 11, - "hash": "35bb046e8ac30c492d256d5a5d73719cda2d6fc6c40e08b171aaa30893f4d48b" - }, - { - "text": "For example, data from the Framingham Heart Study demonstrate that individuals with aldosterone levels in the higher quartiles of the normal distribution are more prone to develop hypertension or to have an increase in BP during the followup period than individuals with lower aldosterone levels ( 56 ).", - "tokenCount": 56, - "pageStart": 11, - "pageEnd": 11, - "hash": "d495497d7a17e9e1aaefdedd97d80d4ae34445d97383ca53b8b3ee1c282d7fd4" - }, - { - "text": "Furthermore, higher aldosterone levels predict the development of chronic kidney disease and microalbuminuria ( 57 ).", - "tokenCount": 22, - "pageStart": 11, - "pageEnd": 11, - "hash": "50249ea254d40483fe0bdc62559c017a04fe881dfa09d3369e9abc35e4bd1091" - }, - { - "text": "The effect of aldosterone on hypertension development is more evident in individuals with low renin (ie, those with a higher ARR) ( 58,59 ), with the ratio being associated with incident hypertension in different population studies ( 58,60 , 61 ).", - "tokenCount": 52, - "pageStart": 11, - "pageEnd": 11, - "hash": "082e6ea01c43791b66dd8bf4af7ebfd2ee63825f14a141c8a0eee6fb904f9cbf" - }, - { - "text": "Reninindependent aldosteronism (with low renin), in contrast to renindependent aldosteronism, is associated with higher cardiovascular risk ( 62 ).", - "tokenCount": 34, - "pageStart": 11, - "pageEnd": 11, - "hash": "9f3c3396cdbc5ac254afd5e6f32b0070c3c1086be41eaeef72bf3dadcd773c1d" - }, - { - "text": "The ARR in healthy individuals also correlates with vascular stiffness ( 63 ).", - "tokenCount": 14, - "pageStart": 11, - "pageEnd": 11, - "hash": "410ed3520ab5801b6a0b2ab02d0169403c7cd7044e8a91b368e3c704dba45c28" - }, - { - "text": "These data were replicated in a Canadian population ( 64 ), which showed that, independent of BP, a biochemical phenotype of subclinical PA is negatively associated with cardiovascular health, including greater arterial stiffness, Table 4.", - "tokenCount": 42, - "pageStart": 11, - "pageEnd": 11, - "hash": "d246bfeb757aedd2ad997bfb909f68352ce55043b8c2cf270a7ef1aedf035b9a" - }, - { - "text": "Evidence for the recommendation of primary aldosteronism screening Importance The condition should be an important health problem.", - "tokenCount": 23, - "pageStart": 11, - "pageEnd": 11, - "hash": "1441f1c2586c01ecd10eff21c058b0f400b25a05032afeca83e545a49b8da333" - }, - { - "text": "PA, independent of blood pressure, is associated with increased mortality and morbidity if untreated.", - "tokenCount": 18, - "pageStart": 11, - "pageEnd": 11, - "hash": "30aa55de0329ce8acd7c5e5c4dafe4c1ff3933549f6f5ddd82983a086b76cbb3" - }, - { - "text": "Natural History The condition being screened for should have a natural history that is understood and a recognized latent period.", - "tokenCount": 21, - "pageStart": 11, - "pageEnd": 11, - "hash": "fb57ad3f0935d053e52d40db859eb55a2d20319059d17da54b5892311a7d1edc" - }, - { - "text": "Individuals with PA develop organ damage and cardiovascular events if left untreated.", - "tokenCount": 14, - "pageStart": 11, - "pageEnd": 11, - "hash": "7f82c06e03dd934896a55756364f71e921d8d206c4fc43d943967dd85e9077fc" - }, - { - "text": "Difference in Management Individuals with a positive screening test would receive different care than those with a negative test.", - "tokenCount": 21, - "pageStart": 11, - "pageEnd": 11, - "hash": "b61b560fabad86444156f813924a240b7a5ab423484be6b251ec2d24a6cd2f6c" - }, - { - "text": "Individuals with a positive screening test are candidates for PAtargeted therapy.", - "tokenCount": 16, - "pageStart": 11, - "pageEnd": 11, - "hash": "e5c41f813d74edb189dfa4c1b37a21376b790357f111e05360fe610a0c2f8030" - }, - { - "text": "Available Treatment Effective treatment should be available for the condition that improves outcomes if administered earlier than when the condition is clinically apparent.", - "tokenCount": 24, - "pageStart": 11, - "pageEnd": 11, - "hash": "5ef86580a663364ba3c9ab695d77625f5da450d24ed6472afaf9ca83ba5a698c" - }, - { - "text": "Also, adrenalectomy for lateralizing subtypes of PA is effective.", - "tokenCount": 15, - "pageStart": 11, - "pageEnd": 11, - "hash": "6c9848d73c731b42b6a20355fb9f732f204e65bb519185e609935e1ba8ab0228" - }, - { - "text": "PAspecific therapies reduce the rate of cardiovascular complications.", - "tokenCount": 12, - "pageStart": 11, - "pageEnd": 11, - "hash": "85cb6e33f907af303fa710784710a899dd117958016bbfdf50dd1ae980237a02" - }, - { - "text": "Difference in Outcomes Improvement in outcomes based on management according to screening results outweighs harms of screening.", - "tokenCount": 21, - "pageStart": 11, - "pageEnd": 11, - "hash": "e1b4a7dc55a905132b8e48d88d2f32c3186573be21d63aa32e82c2f9f654d9aa" - }, - { - "text": "Individuals with PA display a significant benefit from targeted treatment, with the possibility of cure in those with surgically resectable lateralizing adrenal disease.", - "tokenCount": 31, - "pageStart": 11, - "pageEnd": 11, - "hash": "d7821dc5e507c9e31da16f178fadb95be6328639d18099c2206baa3cc018ddba" - }, - { - "text": "Individuals with potentially falsepositive results are not exposed to harm if treated with aldosteroneblocking drugs since they also proved effective in individuals with primary hypertension.", - "tokenCount": 31, - "pageStart": 11, - "pageEnd": 11, - "hash": "7ce93bf358a1d4206b019f60592b2009f816042c016c7616608683af95687dc4" - }, - { - "text": "Careful selection for individuals undergoing AVS should be made to avoid unnecessary invasive procedures.", - "tokenCount": 17, - "pageStart": 11, - "pageEnd": 11, - "hash": "01341eb4db15d7fb6068ca11042a8251cadafd3601d23e8ad13956128829f9e3" - }, - { - "text": "Harms associated with screening are minimal as we provide pathways for screening that involve no or minimal withdrawal of current antihypertensive medications.", - "tokenCount": 27, - "pageStart": 11, - "pageEnd": 11, - "hash": "eca378eaff659137cff338c516f0b1714caf6dbd81ed04db147312e13cb9720a" - }, - { - "text": "Accuracy Certainty of evidence for a sufficient accuracy of the test is high or moderate.", - "tokenCount": 18, - "pageStart": 11, - "pageEnd": 11, - "hash": "c2d43419ac7e30ab55353e2b11a546d373c286306b6bd0757323ccdcbabbd22a" - }, - { - "text": "Falsenegative results may be observed in mild forms or may be caused by variability in aldosterone concentration; aldosterone suppression testing can help to confirm PA.", - "tokenCount": 34, - "pageStart": 11, - "pageEnd": 11, - "hash": "31b60dc3c1aec958a917a14f07c50cae7916325b97fc75222f1dc5f2111ff279" - }, - { - "text": "Other Considerations Screening should be costeffective, acceptable to individuals, and feasible to implement.", - "tokenCount": 19, - "pageStart": 11, - "pageEnd": 11, - "hash": "d18b9061643c0029620da89d8ca6748ced9181cef5c5b16d9d2e1b45e67b4cba" - }, - { - "text": "Screening for PA is costeffective, convenient, and accepted by the individuals.", - "tokenCount": 16, - "pageStart": 11, - "pageEnd": 11, - "hash": "607559481d439e3614f1b79b3793a140dfd04a17e4b854db536f70ac950fa710" - }, - { - "text": "Feasibility depends on collaboration between general practitioners, specialists, laboratories, and referral centers.", - "tokenCount": 18, - "pageStart": 11, - "pageEnd": 11, - "hash": "a26862abc5e630317980319e61c1b6c9eca8cf2361b25f1624a0c23657c3adb4" - }, - { - "text": "9 2463 Downloaded from https://academic.", - "tokenCount": 11, - "pageStart": 11, - "pageEnd": 11, - "hash": "cd51400cd5c2aa111e9409fd3cb9bd9f4b4600bd8d8fc130ac5d335587f5d482" - }, - { - "text": "adverse cardiac remodeling, and incident hypertension.", - "tokenCount": 10, - "pageStart": 12, - "pageEnd": 12, - "hash": "be5eac236ba75a5dd1b2091f8c01b0805a24cec05902fdf207d9567d90696cbd" - }, - { - "text": "In the ARIC study ( 65 ), low renin and high aldosterone levels are associated with cardiac structural and functional alterations.", - "tokenCount": 26, - "pageStart": 12, - "pageEnd": 12, - "hash": "507bee15230aafde90297bbc711f3a238e9722d8da24d472e690b90befb67dc7" - }, - { - "text": "Even in adults as young as 27 years of age, aldosterone concentrations or the ARR have been found to correlate with left ventricular mass index ( 66 ).", - "tokenCount": 33, - "pageStart": 12, - "pageEnd": 12, - "hash": "9e63180bc9ba73468a4446bc685e85dffd7f62d8dbdff6f5fdc7679d3fd637f0" - }, - { - "text": "Management is different if PA screening is incorporated, or not, into the care of individuals with hypertension.", - "tokenCount": 20, - "pageStart": 12, - "pageEnd": 12, - "hash": "dd71376f2a04a08bcc7755e07dcbb7ce2aad4d17eec5b759e9b2347e49e0f011" - }, - { - "text": "In the absence of specific recommendations for PA screening with measurement of aldosterone and renin in all individuals with hypertension, this blood test is rarely done ( 50,51 ).", - "tokenCount": 35, - "pageStart": 12, - "pageEnd": 12, - "hash": "b1e26744f7e776e97fc72d5c27192aa9d0dee47bb86deff14ed230f31d87a38d" - }, - { - "text": "In a Canadian population of 1 million hypertensive individuals, fewer than 1% had been screened for PA ( 67 ), and an Australian primary care study reported that aldosterone was only measured 66 times over 1.", - "tokenCount": 42, - "pageStart": 12, - "pageEnd": 12, - "hash": "c8715f02938c17f633ad956c1fce9b13db754f05883bc88ccd3d05ad8db81295" - }, - { - "text": "5 million primary care patient encounters during a 16-year period ( 68 ).", - "tokenCount": 15, - "pageStart": 12, - "pageEnd": 12, - "hash": "1726bd297031f18ab6bc72ce602b6ca685e0ace5fab0137363e1ccc9f3ab9ccc" - }, - { - "text": "Similar rates of low detection have been observed in the United States and Europe ( 50,51 ).", - "tokenCount": 19, - "pageStart": 12, - "pageEnd": 12, - "hash": "7af062d2de4bb5be38f83e2d6c6a407d875ba2a88b2acf264fab90a79523fe53" - }, - { - "text": "Without the screening blood test, PA is almost impossible to diagnose due to the absence of specific symptoms and signs other than high BP.", - "tokenCount": 26, - "pageStart": 12, - "pageEnd": 12, - "hash": "1aeb7c8f5e694e51ecf20a38463b5ee6a23785abfd5ea66c63f45a08ff16b37f" - }, - { - "text": "PA screening: ARR cut points according to aldosterone and renin assay and unit measurements Renin Aldosterone concentration measured by immunoassay Aldosterone concentration measured by LCMS/MS 10 ng/dL 277 pmol/L 7.", - "tokenCount": 53, - "pageStart": 12, - "pageEnd": 12, - "hash": "d9c6928bdd990b410bd5446fa16aad484590026a9383b5d02af327079bae9e92" - }, - { - "text": "5 ng/dL 208 pmol/L Plasma renin activity 1 ng/mL/h > 20 > 555 > 15 > 416 12.", - "tokenCount": 32, - "pageStart": 12, - "pageEnd": 12, - "hash": "2af0e66917dd6e24aff5957493d828516f30963b315ec77f73401d54b9143974" - }, - { - "text": "9 pmol/L/min > 1.", - "tokenCount": 10, - "pageStart": 12, - "pageEnd": 12, - "hash": "8aa669743db34ab934b6516db5bb435d096e2f2d6bff7e3e21b46f2c49d0c393" - }, - { - "text": "28 ng/L/s > 71 > 2000 > 53 > 1500 DRC 5.", - "tokenCount": 19, - "pageStart": 12, - "pageEnd": 12, - "hash": "b668ee38a3f6e960023aae8236bab9b379aa32ad8f952841b4dca2fab4087952" - }, - { - "text": "8 > 52 The aldosterone, renin, and aldosterone to renin ratio (ARR) values above are provided for guidance.", - "tokenCount": 29, - "pageStart": 12, - "pageEnd": 12, - "hash": "c006bf8f248b2f13e61d05223646778481c0eba19c27c04945837900b7c5e470" - }, - { - "text": "Therefore, results should be interpreted within the context of the patients pretest probability for primary aldosteronism (PA), along with potential interfering medications and conditions.", - "tokenCount": 33, - "pageStart": 12, - "pageEnd": 12, - "hash": "7d0a46c7121f80560a9761ab3ebf638a5dd3acfacbf974d4d884909c1025e708" - }, - { - "text": "Abbreviations: DRC, direct renin concentration; LCMS/MS, liquid chromatographytandem mass spectrometry.", - "tokenCount": 28, - "pageStart": 12, - "pageEnd": 12, - "hash": "8c9b53db5f9a224ffcdce6472c78d5183f6202a6927f5d4203b1c77d889975b4" - }, - { - "text": "Managing interfering antihypertensive medications during PA screening and interpretation of aldosterone, renin, and ARR Management strategy Medication to withdraw Timeline of withdrawal Replacement antihypertensive agents Interpretation of negative screen Interpretation of positive screen No medication withdrawal None Possible false negative if moderate to high pretest probability Repeat screen on different day with minimalor fullmedication withdrawal strategy Possible false positive if individual taking -adrenergic blockers or centrally acting 2 -agonists (clonidine, -methyldopa) Repeat screen after withdrawing these medications Minimal medication withdrawal Stop MRAs and ENaC inhibitors (amiloride, triamterene) 4 weeks before testing Hydralazine a 1 -adrenergic blockers Nondihydropyridine CCBs Moxonidine Possible false negative if moderate to high pretest probability Repeat screen on different day with full withdrawal strategy If pretest probability is low, then likely true negative Likely true positive Proceed to algorithm ( Fig. 2 ) Stop -adrenergic blockers and centrally acting 2 -agonists (clonidine, -methyldopa) 2 weeks before testing Ideal full medication withdrawal Stop MRAs, ENaC inhibitors (amiloride, triamterene), and other diuretics 4 weeks before testing Hydralazine a 1 -adrenergic blockers Nondihydropyridine CCBs Moxonidine Possible false negative if moderate to high pretest probability Repeat screen on different day.", - "tokenCount": 311, - "pageStart": 12, - "pageEnd": 12, - "hash": "b56848fd5a965db923d9f44ea9c73ba9dc0930b5620f562a701dcf5e23be36b4" - }, - { - "text": "If repeat is negative, then likely true negative If pretest probability is low, then likely true negative Likely true positive Proceed to algorithm ( Fig.", - "tokenCount": 29, - "pageStart": 12, - "pageEnd": 12, - "hash": "efd64f17ed3afe00b581faf785c549ca4acba42bd79f9228ee50627823283560" - }, - { - "text": "2 ) -adrenergic blockers ACE inhibitors ARBs Dihydropyridine CCBs Centrally acting 2 -agonists (clonidine, -methyldopa) SGLT2 inhibitors 2 weeks before testing Abbreviations: ACE, angiotensinconverting enzyme; ARB, angiotensin IIreceptor blocker; CCB, calciumchannel blocker; ENaC, epithelial sodiumchannel, MRA, mineralocorticoid antagonist; SGLT2, sodiumglucose cotransporter 2.", - "tokenCount": 117, - "pageStart": 12, - "pageEnd": 12, - "hash": "8d6b02bac7cc46c43942ee62fd302980767fc84922182cba3f66d0753f93fece" - }, - { - "text": "a Ideally individuals receiving hydralazine should also be administered a negative chronotropic agent such as verapamil slow release to avoid reflex tachycardia.", - "tokenCount": 32, - "pageStart": 12, - "pageEnd": 12, - "hash": "309f2a4508457dea5ecb524a6fb500765fc7b98be81caf765d66b691f232a3f7" - }, - { - "text": "2464 The Journal of Clinical Endocrinology & Metabolism , 2025, Vol.", - "tokenCount": 18, - "pageStart": 12, - "pageEnd": 12, - "hash": "72f38822288fdedb56c107baaa965457d9d97955d4d41ea02de2e063178e7481" - }, - { - "text": "diagnosis of PA is associated with poor BP control, high burden of symptoms, and poor quality of life (QOL) ( 3,4 ) and results in increased morbidity and mortality ( 1,2 , 7,69 ).", - "tokenCount": 47, - "pageStart": 13, - "pageEnd": 13, - "hash": "4f8492b4cc8883bfd9c32bd29061d8281f34c772485d3642a9d1f328d8e01216" - }, - { - "text": "Once diagnosed, PA has specific treatment that differs from that of primary hypertension.", - "tokenCount": 15, - "pageStart": 13, - "pageEnd": 13, - "hash": "ec0d60bb58777a4e6e52899bb3730f4c5168772a10b2614c613a5debab0e43ba" - }, - { - "text": "The source of excess aldosterone from a unilateral adrenal adenoma can be removed surgically, leading to a potential cure of hyperaldosteronism, or the actions of aldosterone can be specifically blocked by MRAs.", - "tokenCount": 48, - "pageStart": 13, - "pageEnd": 13, - "hash": "be88532e05b759fe0e50e793331b6a914970defd3c0be88265fa9dafb38b04fb" - }, - { - "text": "The elevated risk of cardiovascular events is ameliorated in individuals with PA treated with unilateral adrenalectomy or sufficient dose of an MRA ( 7 ).", - "tokenCount": 31, - "pageStart": 13, - "pageEnd": 13, - "hash": "1f6134558f0034916b33d14deed3fc92ce9eff982cd7b71ebd4cd51c8f3f217a" - }, - { - "text": "Numerous studies demonstrate that specific treatment is able to improve cardiovascular and renal outcomes in individuals with PA (see Question 2 ( 7-9,32 ).", - "tokenCount": 30, - "pageStart": 13, - "pageEnd": 13, - "hash": "6b40cb8fe865c3d3350eb3740abfbba202cf2f32e7344c4981ed5e9b9d15624b" - }, - { - "text": "This highlights the importance of early detection of individuals with PA who can benefit from targeted medical or surgical treatment that would not be applied if individuals remained undiagnosed and instead treated as having primary hypertension.", - "tokenCount": 40, - "pageStart": 13, - "pageEnd": 13, - "hash": "93b1fdad170dd62cd848f3bc2375cd50367dfa3d1a8ea603e6da3e8c11303b10" - }, - { - "text": "Early screening for PA has also been demonstrated to be costeffective in studies from Japan, China, and Australia ( 70-72 ).", - "tokenCount": 26, - "pageStart": 13, - "pageEnd": 13, - "hash": "9f41ef6ea5f8316b89da1e8c26213717815e897f74e47d9c269d543810718e05" - }, - { - "text": "It is also favored by primary care clinicians ( 73 ) and desired by patients ( 74 ).", - "tokenCount": 18, - "pageStart": 13, - "pageEnd": 13, - "hash": "8c4917747a3f7addacde6337521f51bafcdcab3cc001b241a3683b35b3791775" - }, - { - "text": "The screening test for PA has varying diagnostic accuracy, depending on the decision threshold adopted by individual centers.", - "tokenCount": 20, - "pageStart": 13, - "pageEnd": 13, - "hash": "e9997ed292c59c667ad8c86c00b298b048982b65d588659dbc256827c6208024" - }, - { - "text": "By the nature of screening, the threshold is usually set lower to permit high sensitivity at the expense of lower specificity (ie, more falsepositive results) ( 75 ).", - "tokenCount": 33, - "pageStart": 13, - "pageEnd": 13, - "hash": "877f2eccb4d24404056a7718f1927afa1347778f3d012300d55232f694488114" - }, - { - "text": "A falsepositive screening blood test could lead to a cascade of unnecessary investigations, but PA can generally be excluded by the next diagnostic step with aldosterone suppression testing.", - "tokenCount": 33, - "pageStart": 13, - "pageEnd": 13, - "hash": "6daf0836216f48c19300dc3a404bf7c6415dcdbd1efdab8a6f44640b872386b7" - }, - { - "text": "However, even if the individual is initiated on an MRA on the basis of a falsepositive screening test, MRA treatment may still benefit individuals with an elevated ARR (typically due to a low or suppressed renin) for a few reasons.", - "tokenCount": 50, - "pageStart": 13, - "pageEnd": 13, - "hash": "6a6357bb1355dbd3802454f27e1213c81950a4bb78f5027d3d5a549cff390b48" - }, - { - "text": "First, a systematic review and metaanalysis demonstrated that MRAs are superior to routine antihypertensive therapy (eg, angiotensinconverting enzyme [ACE] inhibitors, angiotensin receptor blockers [ARBs]) in treating lowrenin hypertension, which is the typical diagnosis given to individuals with suspected PA who do not meet current diagnostic criteria for PA ( 76 ).", - "tokenCount": 76, - "pageStart": 13, - "pageEnd": 13, - "hash": "c786cd5d182d9293bbd2a5d54d4c506a5818d6cf9a79b942723e1de0721ce7c1" - }, - { - "text": "Second, 20% of individuals with a positive ARR screening test but a negative aldosterone suppression test (ie, falsepositive screening test) may develop PA over time ( 77 ).", - "tokenCount": 37, - "pageStart": 13, - "pageEnd": 13, - "hash": "9bbd32f7ea6afdcc9063a7a434bd960ee313b41a237e3792e406ecec75529bc7" - }, - { - "text": "Third, low renin levels and high ARRs are predictors of BP response to MRA treatment, even in individuals without a formal diagnosis of PA ( 19 ).", - "tokenCount": 33, - "pageStart": 13, - "pageEnd": 13, - "hash": "a601779329a52af2e66fa7ab499af1e3070c051cbe7c99d69666636d94502b0f" - }, - { - "text": "Evidence to Decision Factors As described in the Introduction, the panel also used the Evidence to Decision (EtD) framework for this and all subsequent Questions, to consider broader factors such as stakeholder values and preferences (including insights from clinical experts and patient representatives), costs and resources required, costeffectiveness, acceptability, feasibility, and the potential impact on health equity.", - "tokenCount": 74, - "pageStart": 13, - "pageEnd": 13, - "hash": "b32d6145da515500382ea2cc6e208a955a2064c81117e6ad6a4348e74668b818" - }, - { - "text": "PA screening requires commonly available and relatively lowcost laboratory tests (aldosterone and renin measurements).", - "tokenCount": 19, - "pageStart": 13, - "pageEnd": 13, - "hash": "ada78c73b8b732da18597d0924023c0562aee758416d2911cfa5b6b07faeb06b" - }, - { - "text": "However, downstream testingsuch as aldosterone suppression tests, adrenal imaging, and adrenal vein sampling (AVS) introduces significant additional costs and is not universally available, particularly in resourcelimited settings.", - "tokenCount": 43, - "pageStart": 13, - "pageEnd": 13, - "hash": "a21f731c5ab54271bb7d4c412a25cfb00f6db409d23a0625556cdf0b706460dd" - }, - { - "text": "While initial screening is affordable at the individual level, implementation of universal screening will increase overall healthcare system costs due to followup testing, specialist referrals, and potential surgical interventions.", - "tokenCount": 34, - "pageStart": 13, - "pageEnd": 13, - "hash": "f078d89fb31f2c9e1c33cbbe216411c0b918043d159c19a5cfdcd57c4db0821b" - }, - { - "text": "Screening for PA in the general hypertensive population has been shown to be costeffective in health economic studies conducted in Japan, Australia, and China.", - "tokenCount": 30, - "pageStart": 13, - "pageEnd": 13, - "hash": "db073d5d061f6877910787f41e7f20039678dcd6de11345f786ca2097b9a878f" - }, - { - "text": "The favorable costeffectiveness is largely driven by the reduction in longterm complications associated with untreated PA.", - "tokenCount": 20, - "pageStart": 13, - "pageEnd": 13, - "hash": "905a7722a2b0f15b489b460fe586c0e0259609f97e284e053e18f6fd90bd48e8" - }, - { - "text": "While upfront screening costs are higher when applied broadly compared to targeted screening of highrisk groups, modeling studies demonstrate that screening remains below commonly accepted willingnesstopay thresholds.", - "tokenCount": 33, - "pageStart": 13, - "pageEnd": 13, - "hash": "9c983a79c0704aee306d1b549d2b3e46d5136c00f3d036e0472c901b1574349a" - }, - { - "text": "In addition to general population studies, costeffectiveness has been demonstrated in specific highrisk groups, such as individuals with resistant hypertension or those with obstructive sleep apnea, where screening prevents cardiovascular complications and reduces longterm healthcare expenditures.", - "tokenCount": 46, - "pageStart": 13, - "pageEnd": 13, - "hash": "8f89731105e13ec6ed686a31278117298712d81bbf059f66f47729ddb6c7f984" - }, - { - "text": "The degree of costeffectiveness, however, varies across healthcare settings.", - "tokenCount": 14, - "pageStart": 13, - "pageEnd": 13, - "hash": "3cc27ed7056f810d75d53f9de1919f8f423e0a627b0401b950f0c8bcbc3329b0" - }, - { - "text": "For the impact of screening on equity, the panel considered that PA is underdiagnosed globally, particularly in underserved populations and minority groups, contributing to health disparities in hypertensionrelated outcomes.", - "tokenCount": 37, - "pageStart": 13, - "pageEnd": 13, - "hash": "ea725e2eed2a0563cb65c9c9cadc822c0e3ec508cfaba472259cb4685c9a538e" - }, - { - "text": "Limited access to screening, confirmatory testing, and specialized careespecially in rural and resourcepoor settingsdelays diagnosis and treatment.", - "tokenCount": 25, - "pageStart": 13, - "pageEnd": 13, - "hash": "45aa07329a0aab31ca197ee203d9a874375309e06d830678b155043ee1fae5d7" - }, - { - "text": "PA screening may reduce disparities by improving detection; however, inequities could be exacerbated if followup services, such as subtype diagnosis and AVS, remain inaccessible to disadvantaged populations.", - "tokenCount": 36, - "pageStart": 13, - "pageEnd": 13, - "hash": "0fcbe6e7cb207ca70a9096d86153ee3fb3879d7e0628651a4e5702a4540fcb5c" - }, - { - "text": "Medications that interfere with PA screening and their effects on aldosterone and renin Effect on renin or aldosterone Medication Lower renin -adrenergic blockers, central acting 2 -agonists (clonidine, -methyldopa), NSAIDs Combined estrogen and progesteronecontaining OCPs and HRT decrease DRC (impact on PRA described below) Raise renin MRAs, diuretics including ENaC inhibitors (amiloride, triamterene), ARBs, ACE inhibitors, SGLT2 inhibitors Combined estrogen and progesteronecontaining OCPs and HRT increase PRA (impact on DRC described above) Drospirenone blocks the MR and thus increases PRA and DRC Lower aldosterone ARBs, ACE inhibitors, -adrenergic blockers, central 2 -agonist (clonidine, -methyldopa) Raise aldosterone Diuretics a , MRAs Combined estrogen and progesteronecontaining OCPs and HRT Drospirenone Abbreviations: ACE, angiotensinconverting enzyme; ARB, angiotensin IIreceptor blocker; CCB, calciumchannel blocker; DRC, direct renin concentration; HRT, hormonereplacement therapy; MRA, mineralocorticoid antagonist; NSAID, nonsteroidal antiinflammatory drug; OCP, oral contraceptive; PRA, plasma renin activity; SGLT2, sodiumglucose cotransporter 2; ENaC, epithelial sodiumchannel.", - "tokenCount": 327, - "pageStart": 13, - "pageEnd": 13, - "hash": "3576358c1a02b0f757aa824e7477aa548afb29dca48e73a7c665b32cbb77fa75" - }, - { - "text": "a By promoting natriuresis, diuretics (including MRAs) may induce a rise in aldosterone secondary to a rise in renin/angiotensin II.", - "tokenCount": 38, - "pageStart": 13, - "pageEnd": 13, - "hash": "345dfa210800347c1da53f1e8a13719ac790024f0fd961cca473f2aa5c9e46fb" - }, - { - "text": "In the case of thiazide or loop diuretics, however, this may be mitigated by the development of hypokalemia (which inhibits aldosterone production).", - "tokenCount": 36, - "pageStart": 13, - "pageEnd": 13, - "hash": "f8d940ac02356f3ac9f441d5f7fb41f643f7ef53bbc183067149fbf017e36f9e" - }, - { - "text": "9 2465 Downloaded from https://academic.", - "tokenCount": 11, - "pageStart": 13, - "pageEnd": 13, - "hash": "f39818c537c8c831455b6a7b1b8d68ebdf3cbc892cab81a5858d31e045cfda17" - }, - { - "text": "panel judged the impact on equity as mixed, taking into account pragmatic treatment pathways provided in Fig.", - "tokenCount": 19, - "pageStart": 14, - "pageEnd": 14, - "hash": "e6bddfbc2ae2f7d1f775b6689a13a5d28a2a7fc37095bc90ee8dc13d199e165e" - }, - { - "text": "2 that permit targeted treatment for PA without extensive testing.", - "tokenCount": 11, - "pageStart": 14, - "pageEnd": 14, - "hash": "f2923b20a1b152c1e14360c05d5db53ce438f1cc7d387142f006635d1fedad46" - }, - { - "text": "The panel judged that acceptability of PA screening will vary among providers.", - "tokenCount": 14, - "pageStart": 14, - "pageEnd": 14, - "hash": "84424f5447a0948270423ed3cbcc7b55eb7a80a35f7871c6716c26709b3f7f79" - }, - { - "text": "Primary care clinicians, in particular, may have lower acceptance due to limited awareness of PA, difficulties interpreting results in patients on interfering medications, and concerns about the complexity and availability of subtype testing.", - "tokenCount": 39, - "pageStart": 14, - "pageEnd": 14, - "hash": "2651be9ba252f2cff73bca0f558f2378c25b2e1d969a31fe50a1814f9ae17695" - }, - { - "text": "Some also view medication washout as burdensome or potentially risky.", - "tokenCount": 13, - "pageStart": 14, - "pageEnd": 14, - "hash": "d3ff7e89a5ceb8039fef021e3cd810a79bdda842a36a9af5752bdc418373f59b" - }, - { - "text": "In contrast, screening is generally wellaccepted by patients, especially at the time of initial hypertension diagnosis.", - "tokenCount": 21, - "pageStart": 14, - "pageEnd": 14, - "hash": "e1ff10f1c10d4d1c7a3d95eca88601249d70f58da98ab82f1ca33f75df23755a" - }, - { - "text": "However, provider hesitancy could limit implementation, particularly in settings with high workloads or limited specialist access.", - "tokenCount": 22, - "pageStart": 14, - "pageEnd": 14, - "hash": "455ce108ff07f7af7d890a81553022caeeffd8dd12c0d9e67554b8819b79bac4" - }, - { - "text": "The panel judged that the feasibility of PA screening will vary by setting and stakeholder perspective.", - "tokenCount": 18, - "pageStart": 14, - "pageEnd": 14, - "hash": "7a881ff7e035827ede707742e51aaab94d87388ac29f7b5569bfd869e58162bb" - }, - { - "text": "While screening relies on simple, widely available biochemical tests and is technically feasible, implementation has remained low.", - "tokenCount": 20, - "pageStart": 14, - "pageEnd": 14, - "hash": "6f4a2ebfb39f274d94bb059eabcca0f3089556a53e9edacfdeb036c08ecb8260" - }, - { - "text": "Description of the most commonly used aldosterone suppression tests Aldosterone suppression test Resource requirements Protocol Metrics Interpretations Comments Oral sodium suppression test Low Individuals are instructed to consume 4-5 g of sodium per day for 3-4 days Collect 24-h urine collection on final day of high sodium intake Measure urinary aldosterone, sodium, creatinine 24-h urine sodium should ideally be > 200 mEq/ 24 hours 24-h urine creatinine is used to assess adequacy of urine collection 24-h urine aldosterone < 10 mcg/nmol/24 hours makes PA unlikely ( 84 ) Oral sodium can be consumed via sodium chloride tablets or sodium rich foods Because hypokalemia may cause falsenegative interpretations, serum potassium should be normalized before the study protocol Interpretation of results is probabilistic and lacks evidence to recommend a precise diagnostic threshold ( 23 ) Protocol can be conducted in the ambulatory setting Captopril challenge test Moderate After sitting for 1 hour, blood is drawn to mark t = 0 Individuals are then given 50 mg of captopril and remain seated for 2 hours following administration Blood should be drawn at t = 2 hours to complete the study Measure plasma aldosterone and renin at t = 0 and t = 2h In the context of a postcaptopril suppressed renin ( < 1.", - "tokenCount": 272, - "pageStart": 14, - "pageEnd": 14, - "hash": "e9ff707dd39c1ae2c1479f3a0ff451a58be13d95cf072fa235615d33bc28699c" - }, - { - "text": "0 ng/mL/h or < 10 mU/L), a 2-h postcaptopril plasma aldosterone level < 277 pmol/L (10 ng/dL) by immunoassay or < 203 pmol/L (7.", - "tokenCount": 54, - "pageStart": 14, - "pageEnd": 14, - "hash": "c95cb87b4db55bf5ae48b57d8055b6055f6b089ffc8878cec338013860166035" - }, - { - "text": "5 ng/dL) by LCMS/MS makes PA unlikely ( 84 ) ( 112 ) Many individuals with hypertension are actively treated with ACE inhibitors or ARBs; plasma aldosterone and renin values measured after taking these routinely prescribed medications may serve as a proxy for the captopril challenge test Interpretation of results should be considered to be probabilistic as the evidence to support a singular diagnostic threshold is not firm ( 26 ) Protocol requires an inperson visit and space and staff to accommodate the procedures Saline suppression test Moderate After sitting for 1 hour, blood should be drawn to mark t = 0 Two liters of normal saline are infused over 4 hours (500 mL/h for 4 hours), while maintaining a seated position, after which blood should be drawn Measure plasma aldosterone and serum potassium at t = 0 and t = 4 hours Plasma aldosterone < 162 pmol/L (5.", - "tokenCount": 183, - "pageStart": 14, - "pageEnd": 14, - "hash": "183dc8ee307e7ec00f92f4b94a39bd91378120c1e81271faae813ebf66b5f77a" - }, - { - "text": "8 ng/dL) via LCMS/MS assay makes PA unlikely Plasma aldosterone < 217 pmol/L (7.", - "tokenCount": 27, - "pageStart": 14, - "pageEnd": 14, - "hash": "88b63d300979fbb0997e06e5677e901690b03d692dca1f89023e8d64bd41f679" - }, - { - "text": "8 ng/dL) via immunoassay assay makes PA unlikely ( 84,100 , 102,113 ) Because hypokalemia may cause falsenegative interpretations, serum potassium should be normalized before the study protocol Interpretation of results should be considered to be probabilistic as the evidence to support a singular diagnostic threshold is not firm ( 25 ) Protocol requires an inperson visit, space and staff to accommodate the procedures, and IV infusion of saline Protocol should not be performed if baseline BP is uncontrolled, or in patients at high risk for pulmonary edema (such as in heart failure or advanced chronic kidney disease) Abbreviations: ACE, angiotensinconverting enzyme; ARB, angiotensin IIreceptor blocker; IV, intravenous.", - "tokenCount": 156, - "pageStart": 14, - "pageEnd": 14, - "hash": "9ba3dd6703e48577c372acb04a2b4743dc53662e8f328842aaf52b914d6dcf87" - }, - { - "text": "2466 The Journal of Clinical Endocrinology & Metabolism , 2025, Vol.", - "tokenCount": 18, - "pageStart": 14, - "pageEnd": 14, - "hash": "0b8d64c2dbaf1d3af38cdbf8c3fb7087780a5b059ea108f8d124b2dbb81c2f93" - }, - { - "text": "likely due more to the complexity of prior diagnostic algorithms than to challenges with performing the tests themselves.", - "tokenCount": 19, - "pageStart": 15, - "pageEnd": 15, - "hash": "b87bf8d1c695c36a83460f914669126dd95050df05a8d02c22a4696237725055" - }, - { - "text": "The current guideline offers suggestions for more pragmatic and feasible approaches to PA testing and treatment ( Figs.", - "tokenCount": 20, - "pageStart": 15, - "pageEnd": 15, - "hash": "cf72210fdb38160178e460b7238432f07fd5000b315f096fd6be46e45d19ceeb" - }, - { - "text": "Justification for the Recommendation The panel suggests PA screening for individuals with hypertension based on the high prevalence of PA, its underdiagnosis, and the potential to reduce cardiovascular morbidity and mortality through targeted treatment.", - "tokenCount": 42, - "pageStart": 15, - "pageEnd": 15, - "hash": "fcd68eded816341476d86eef1138e3c0f7c4101ed0879d2351c423f31452278c" - }, - { - "text": "However, this is a conditional recommendation, reflecting important limitations in the evidence base.", - "tokenCount": 16, - "pageStart": 15, - "pageEnd": 15, - "hash": "8236637115b6da822998c9a4df3a55191dae723b1d7700442fadb6938eb56d59" - }, - { - "text": "The certainty of evidence for both benefits and harms is low, primarily due to reliance on indirect data and observational studies.", - "tokenCount": 23, - "pageStart": 15, - "pageEnd": 15, - "hash": "3b1e44cbe66702abfaf7358f570ed92362f8b56fd2b7cf1b78c52861c1775ee1" - }, - { - "text": "While existing evidence suggests improved BP control and reduced longterm complications with screening, the magnitude of benefit remains uncertain.", - "tokenCount": 22, - "pageStart": 15, - "pageEnd": 15, - "hash": "8c6f105a1763bc86aac221ec1cbb4dfa1577354a26d483dd663816c8ae4427bc" - }, - { - "text": "No direct comparative studies between screening and no screening were identified for critical clinical outcomes.", - "tokenCount": 16, - "pageStart": 15, - "pageEnd": 15, - "hash": "4680c59511f53cd64bab58c7f7cfe03cd7fdeb698697e7fdcaee9494f49a4ad4" - }, - { - "text": "Despite these limitations, the panel judged that the potential benefits of early detection and specific treatment for PA likely outweigh potential harms, including falsepositive results and unnecessary downstream testing.", - "tokenCount": 33, - "pageStart": 15, - "pageEnd": 15, - "hash": "84c22aafb94bc06733b6d87d56ec33ac9e68d41b221235f1075c98163cff8479" - }, - { - "text": "In making this decision, the panel placed high value on offering patients the opportunity for evaluation and identification of an endocrine etiology for hypertensionone that is treated differently from primary hypertension and that offers the possibility of cure in cases of lateralizing PA.", - "tokenCount": 49, - "pageStart": 15, - "pageEnd": 15, - "hash": "20aad5b7934d42c73b77a2b832fcbff62b79ebc2f9584bfaa2ea728627850d86" - }, - { - "text": "The panel also acknowledged feasibility concerns, particularly the burden on healthcare systems and specialist services, especially in primary care and resourcelimited settings.", - "tokenCount": 26, - "pageStart": 15, - "pageEnd": 15, - "hash": "909a8755eed6a274a0447e59f14ac4c3eba61835d3b8083449e618a5809ddf38" - }, - { - "text": "Therefore, the recommendation emphasizes that implementation should be contextsensitive, depending on available resources, local expertise, and healthcare system capacity.", - "tokenCount": 25, - "pageStart": 15, - "pageEnd": 15, - "hash": "5c787f2da1620718e3057d896ee23c21071211bae1acc0cc519450a7690b3250" - }, - { - "text": "It also underscores the need for additional guidance to help clinicians interpret and manage screening results, especially when interfering medications are present.", - "tokenCount": 24, - "pageStart": 15, - "pageEnd": 15, - "hash": "8a53b8c4c4d68d87cab0d4ac58b9d0bee009afc1bc6bbb5676d50b34f7063924" - }, - { - "text": "Ultimately, this conditional recommendation supports screening to improve PA detection and treatment but leaves room for adaptation based on local resources, feasibility, and priorities.", - "tokenCount": 28, - "pageStart": 15, - "pageEnd": 15, - "hash": "89642d81906946a45d6595f5a0e846552745bae8d60ed58c2740adb3ceac2004" - }, - { - "text": "The panel judged that, on balance, the likely benefits outweigh the harms but that the recommendation should be applied flexibly.", - "tokenCount": 24, - "pageStart": 15, - "pageEnd": 15, - "hash": "fa6ce5ecb1afa34422630e2669d8961dc4b04b36e8b228c9f837593cf903a8d6" - }, - { - "text": "Implementation Considerations This is a conditional recommendation, and its implementation will vary depending on contextual factors at both the healthcare system and clinicianpatient levels. Health systemlevel considerations When healthcare systems consider implementing this conditional recommendation, they must weigh several interconnected factors that will shape feasibility, sustainability, and equity.", - "tokenCount": 59, - "pageStart": 15, - "pageEnd": 15, - "hash": "b72dc3cdaf9b3fa03ee4aaf3c7b876af12db3f5a9624920a8e17b6db87f692ef" - }, - { - "text": "Expanded PA screening may improve detection but will also introduce systemlevel demands that vary depending on resources, infrastructure, and workforce capacity.", - "tokenCount": 26, - "pageStart": 15, - "pageEnd": 15, - "hash": "1e73810f84ef24434fc403c538fbcc2b3cdb2bb70ef50bbf68f376d417960cf7" - }, - { - "text": "Availability of laboratories to conduct aldosterone, renin, and potassium testing, as well as capacity for downstream evaluations such as aldosterone suppression testing, adrenal imaging, or AVS, varies widely.", - "tokenCount": 42, - "pageStart": 15, - "pageEnd": 15, - "hash": "bc5ee8452fac7eadadc61763fe4a92f875296b7e0da5fd0fb9c4d76f85701313" - }, - { - "text": "In settings where advanced diagnostics or specialist services are limited, alternative approachessuch as empiric MRA therapy following a positive screening resultmay be appropriate.", - "tokenCount": 32, - "pageStart": 15, - "pageEnd": 15, - "hash": "ade76a92410b6a3c371c05cb764c4b09f5e03dd026b0e17e56eb5acccf76c64a" - }, - { - "text": "Key indices and cutoffs for adrenal vein sampling interpretation AVS index Index formula Cutoff values Diagnostic significance Selectivity index (SI) [cortisol] AV /[cortisol] IVC Unstimulated > 1.", - "tokenCount": 48, - "pageStart": 15, - "pageEnd": 15, - "hash": "dfc62bff56f0a7bdb03cd439b43d4a583693fe54352ccefac2b962406d7fb91b" - }, - { - "text": "4 to 3 Indication of successful AV cannulation Cosyntropinstimulated > 5 Lateralization index (LI) ([aldosterone]/[cortisol]) highAV / ([aldosterone]/[cortisol]) lowAV Unstimulated or cosyntropinstimulated 4 Distinguishes lateralizing from bilateral PA Contralateral suppression index (CSI) ([aldosterone]/[cortisol]) lowAV / ([aldosterone]/[cortisol]) IVC Unstimulated or cosyntropinstimulated < 1 Consistent with suppressed aldosterone production by the contralateral adrenal gland Abbreviations: AV, adrenal vein; highAV, adrenal vein measurement from the dominant adrenal; IVC, inferior vena cava; lowAV, adrenal vein measurement from the nondominant adrenal gland.", - "tokenCount": 181, - "pageStart": 15, - "pageEnd": 15, - "hash": "48aa6d8b570437a3cb3d15d6d7275e01151e5c48d631cfd3a35a6cc8ddfee287" - }, - { - "text": "Comparisons of MRA and ENaC inhibitors a Drug Typical starting dose in PA Possible maximum dose in PA b Usual cost Spironolactone 12.", - "tokenCount": 33, - "pageStart": 15, - "pageEnd": 15, - "hash": "d942469e7733aa6e6ff51f0398b4ff5df409c17780193e2affae29f82da749a4" - }, - { - "text": "5-25 mg/d 200 mg/d $ Eplerenone 25-50 mg twice daily 200 mg twice daily $$-$$$ Finerenone c Unknown; 10-20 mg/d unknown $$$$ Amiloride 5-10 mg/d 40 mg/d $ Triamterene d 50-100 mg/d 300 mg/d $ a Data are very limited, mostly from observational studies using fixed doses in hypertension, uncertain outcomes and titration protocols.", - "tokenCount": 100, - "pageStart": 15, - "pageEnd": 15, - "hash": "d26ff721281cb634838ed3140250d15e992049604b3de00e1b32d7de7517b831" - }, - { - "text": "b Specialist consultation recommended if doses above these ranges appear to be necessary.", - "tokenCount": 14, - "pageStart": 15, - "pageEnd": 15, - "hash": "f18ab8b84b9d7c9812070d50ecba221c544ea04ff812c1eb3c9d0e4f16ffea18" - }, - { - "text": "d Often supplied as combination with hydrochlorothiazide.", - "tokenCount": 12, - "pageStart": 15, - "pageEnd": 15, - "hash": "2ccd5666bba72ac767c79aab1fa51856b4e4bd6e765eadf922032234d162de62" - }, - { - "text": "9 2467 Downloaded from https://academic.", - "tokenCount": 11, - "pageStart": 15, - "pageEnd": 15, - "hash": "fbc940710d9418e6e3d48e843b728ee73687733faa7b9bf2b6b78b3fe9d597a3" - }, - { - "text": "The ability to integrate PA screening into existing hypertension care pathways will depend on clinical workflow structures and systemlevel coordination between primary care and specialty services.", - "tokenCount": 28, - "pageStart": 16, - "pageEnd": 16, - "hash": "64d0b0d89f66f0f93da663fc21202177a785937730f477605bc49fd02861ecac" - }, - { - "text": "This includes managing referrals, followup testing, and treatment decisions following abnormal results.", - "tokenCount": 16, - "pageStart": 16, - "pageEnd": 16, - "hash": "9de0b3e5d0249a83d821ad6271d6939d74e57d13f7b4b1ad18f86284da31929a" - }, - { - "text": "Widespread screening may increase healthcare costs, particularly when considering downstream diagnostics and treatment.", - "tokenCount": 17, - "pageStart": 16, - "pageEnd": 16, - "hash": "6896544adca77c1681f4a722d42d9f376a7e959d854d466813c9d31f47102c4c" - }, - { - "text": "Equity concerns are particularly relevant in rural and underserved regions, where infrastructure may be lacking and specialist access is limited.", - "tokenCount": 24, - "pageStart": 16, - "pageEnd": 16, - "hash": "63ee249179425b0cd7027357478ec199d930b3aa742222c16714946e37580f17" - }, - { - "text": "Mitigating strategies could include developing regional referral hubs, streamlining diagnostic algorithms, or creating contextsensitive care pathways that balance feasibility and effectiveness.", - "tokenCount": 27, - "pageStart": 16, - "pageEnd": 16, - "hash": "606248b24d4553babe519b04d2aa69e1e3fddef0150523ecad6275d0528a4e2c" - }, - { - "text": "Successful implementation requires investment in education for primary care clinicians and other frontline providers on PA screening protocols, including management of interfering medications and appropriate referral thresholds.", - "tokenCount": 30, - "pageStart": 16, - "pageEnd": 16, - "hash": "4b88cc9ceca2399421abd7dd31348f6615c797947e359b3f14928710f24e5b0f" - }, - { - "text": "Clinicianand patientlevel considerations and implementation tools At the clinician and patient level, implementation is shaped by knowledge, attitudes, and available decisionsupport tools.", - "tokenCount": 33, - "pageStart": 16, - "pageEnd": 16, - "hash": "f60d1e9e5c02fe9ab09a89aef3ffeb522c61d60c10151ba71975c911e783eac5" - }, - { - "text": "Clinicians may be hesitant to adopt screening due to limited familiarity with PA, perceived testing complexity, or concerns about managing false positives and interpreting results in patients on interfering therapies.", - "tokenCount": 35, - "pageStart": 16, - "pageEnd": 16, - "hash": "49dc165e591d64dc25ca10455c9c13d057676b577c0cf6c5cdaea3894a49578d" - }, - { - "text": "To address this, the guideline provides practical toolsincluding Figs.", - "tokenCount": 13, - "pageStart": 16, - "pageEnd": 16, - "hash": "7af9fedaae8416704110764262203e5af6727d4a8f3f080045174bd7240c4d7d" - }, - { - "text": "1 and 2 to streamline clinical decision making, guide result interpretation, and clarify pathways for management or referral based on patient characteristics and available resources.", - "tokenCount": 30, - "pageStart": 16, - "pageEnd": 16, - "hash": "0a4f7d9fc5b8fb2df4f27f333fe164fd13512120c1a802a2224ec70178311831" - }, - { - "text": "Additional implementation considerations include: Some panel members consider every hypertensive individual with low renin levels as affected by PA.", - "tokenCount": 24, - "pageStart": 16, - "pageEnd": 16, - "hash": "3a1536c9a017fffc91f30a5a647452b9f931dad83d69aed3448a3de87c3f0baf" - }, - { - "text": "Despite almost all individuals with PA having low renin concentration or activity, a number of individuals with low renin do not have PA (eg, individuals with high salt intake or Liddle syndrome), hence a nonsuppressed aldosterone concentration should be required together with low renin to consider the individuals at risk of PA.", - "tokenCount": 65, - "pageStart": 16, - "pageEnd": 16, - "hash": "39a16ffc223742da7ac09d197ba0aba612c2f72579221eafa9640dd151b8805e" - }, - { - "text": "The recommendation is applicable to individuals older than age 16 years.", - "tokenCount": 12, - "pageStart": 16, - "pageEnd": 16, - "hash": "de20440399b6aeff1776a11a3873c90e46d3da674a478bbf093877849dd4b988" - }, - { - "text": "Pediatric individuals should be considered to have a positive screening test at an ARR cutoff lower than for adults ( 78,79 ).", - "tokenCount": 26, - "pageStart": 16, - "pageEnd": 16, - "hash": "9283944d4c64e5a8ff6e188ea4a7aa1b72d2078a28ca05509ca00aa259d63491" - }, - { - "text": "The interpretation of aldosterone and renin levels and the ARR and subsequent management is also different in pregnant individuals due to pregnancyrelated changes in the renin angiotensin aldosterone system (RAAS) ( 80,81 ).", - "tokenCount": 51, - "pageStart": 16, - "pageEnd": 16, - "hash": "3ce4c43c52aaaca73737d1552e08bc1f85bb83bff64d5b4e8c2ee9e49b008860" - }, - { - "text": "Individuals with concomitant heart failure may have unsuppressed renin levels, and diagnosis requires expert input.", - "tokenCount": 23, - "pageStart": 16, - "pageEnd": 16, - "hash": "6c6ac2ddfddfce2897043030c6f7718a4039e900d52f8b0bee85e8859276b7ea" - }, - { - "text": "Elderly patients with hypertension and patients with concomitant renal failure are more likely to have a low renin and increased ARR.", - "tokenCount": 28, - "pageStart": 16, - "pageEnd": 16, - "hash": "3c11df38ffd3b2ba6c999360e1a7e1f07c11c9fb53c18ac5f7a12fea3f1e2001" - }, - { - "text": "The approach for subsequent investigations or pragmatic therapy with MRA should be weighed in individual evaluation.", - "tokenCount": 18, - "pageStart": 16, - "pageEnd": 16, - "hash": "7b6151e25d419a5be37b72fa1df97c314b0625bda70ee576d66bd1f05d616d29" - }, - { - "text": "Screening tests should be performed by primary care clinicians or by specialists in an outpatient setting.", - "tokenCount": 18, - "pageStart": 16, - "pageEnd": 16, - "hash": "8e948ce2d7411b0d90a98f3710da46ad91525e2f069aab255ff76bed8c41dedb" - }, - { - "text": "Referral to specialized centers should be considered for aldosterone suppression testing, and, if positive, further subtyping to differentiate lateralizing from bilateral forms of PA.", - "tokenCount": 34, - "pageStart": 16, - "pageEnd": 16, - "hash": "b7c3e015d1f848535e224742cd711fc3479c026f5859e1ed549c59450525ca45" - }, - { - "text": "Research Considerations Current gaps in knowledge call for further research in the following areas: Determining the benefit of MRA treatment (vs other nonspecific antihypertensive treatments) in individuals with an increased ARR but a negative aldosterone suppression test Determining the efficacy of nonsteroidal MRAs and aldosterone synthase inhibitors compared with spironolactone in individuals with PA and in those with low renin or an elevated ARR who do not meet the current diagnostic criteria for PA Evaluating the efficacy and cost of novel strategies for screening outside the ARR (eg, steroid profiling, omic signatures, clinical scores, and machinelearning methods ( 82,83 ) Conducting a goldstandard prospective randomized controlled trial (RCT) in which individuals with newly diagnosed PA are randomized to treatment with standard medical therapy vs PAspecific medical therapy in order to assess cardiovascular outcomes (however, for ethical reasons, this study is not likely to be undertaken) Treatment of Primary Aldosteronism: Specific vs Nonspecific Therapies Background Specific therapies directed against aldosterone excess are available: treatment with mineralocorticoid receptor antagonists (MRAs) and, if appropriate, unilateral adrenalectomy ( 84,85 ).", - "tokenCount": 258, - "pageStart": 16, - "pageEnd": 16, - "hash": "28c89b6817dd8e5ec4492034781e37bf02316f5482cf387b4216fc3b2d4b6c30" - }, - { - "text": "If those therapies result in better outcomes than nonspecific antihypertensive therapy, encouraging their implementation among hypertensive individuals with PA is appropriate.", - "tokenCount": 29, - "pageStart": 16, - "pageEnd": 16, - "hash": "6bda021276ee9d91feb8a92575c9b9dedd8f63e1df1779a54ef4f8dfc1f60c3c" - }, - { - "text": "Technical remarks: In individuals with lateralizing PA who are not surgical candidates or do not desire surgery, and in individuals with bilateral PA, medical treatment with MRAs should be considered preferable over nonspecific antihypertensive therapy. In individuals with lateralizing PA who are surgical candidates and desire surgery, unilateral adrenalectomy should be considered preferable over nonspecific antihypertensive therapy.", - "tokenCount": 79, - "pageStart": 16, - "pageEnd": 16, - "hash": "a5f61d8e5134d8d3a69fd6908143e6ca83a3425b3c89efc5783c8a23087e741d" - }, - { - "text": "2468 The Journal of Clinical Endocrinology & Metabolism , 2025, Vol.", - "tokenCount": 18, - "pageStart": 16, - "pageEnd": 16, - "hash": "f248f945f401c9afa9b1c1cc436831af3fe32c91764ae6b508abf441e28c84a2" - }, - { - "text": "Summary of the Evidence The metaanalysis results, a detailed summary of the evidence and Evidence to Decision (EtD) tables can be found online at https:/ /guidelines.", - "tokenCount": 36, - "pageStart": 17, - "pageEnd": 17, - "hash": "760e165624ed21ca1af1d9d48557950cfb8621c1e098df03adc280fdadde3b9d" - }, - { - "text": "org/profile/LGYDlKeCN6A .", - "tokenCount": 13, - "pageStart": 17, - "pageEnd": 17, - "hash": "94fb9fef2a816339ae83a8c9a4ac2794f321891a347300687ef258ac89ce164c" - }, - { - "text": "Benefits and Harms The panel voted for the following patientimportant outcomes for Question 2 decision making: 1) percent of individuals achieving blood pressure (BP) control, 2) number of antihypertensive agents, 3) dosage of antihypertensive agents, 4) systolic BP (SBP) level, 5) major adverse cardiovascular events (MACEs), 6) atrial fibrillation, 7) stroke, 8) ischemic heart disease, 9) heart failure, 10) cardiovascular mortality, 11) allcause mortality, and 12) adverse events.", - "tokenCount": 118, - "pageStart": 17, - "pageEnd": 17, - "hash": "de55f729eccd945eb6d9efcb0274c48c52aa8c158bc2fa01cfe9aeb4a9c99a6d" - }, - { - "text": "Our systematic review yielded only 2 studies, both of which were observational in nature.", - "tokenCount": 16, - "pageStart": 17, - "pageEnd": 17, - "hash": "006f77cb7e767d19013bb7f9756c0e3c292602ec0168a8d0153b668511e23bd3" - }, - { - "text": "One ( 4 ) showed that (a) all individuals who underwent unilateral adrenalectomy displayed complete biochemical resolution of PA at 6-month followup assessment; (b) individuals receiving an MRA showed a reduction of SBP and diastolic BP (DBP) without a significant increase in antihypertensive treatment; (c) individuals with primary hypertension treated with nonspecific antihypertensive agents showed SBP and DBP reductions at 6 months but with increased treatment.", - "tokenCount": 97, - "pageStart": 17, - "pageEnd": 17, - "hash": "db06ad42c99ace3063323385c6323f8f7ed9be6cefb625977b6e0a24c5eb0a45" - }, - { - "text": "Due to the limited availability of studies directly evaluating the comparative effectiveness and potential harms of PAspecific treatment vs nonspecific hypertension management, this recommendation also relies on indirect evidence.", - "tokenCount": 36, - "pageStart": 17, - "pageEnd": 17, - "hash": "677cbdcf62c45edc51a3aa3ed50a0eba53d05fdba60f3719df5fd0a366191896" - }, - { - "text": "This indirect evidence derived from noncomparative observational studies.", - "tokenCount": 12, - "pageStart": 17, - "pageEnd": 17, - "hash": "7eb3bd49a479d11f7e417aad6dd6a4354ed864a05a94f6bd7e7b1954484fe15b" - }, - { - "text": "Individuals with PA who are not receiving PAspecific therapy demonstrate higher rates of cardiovascular, cerebrovascular, and renal complications than do individuals with primary hypertension and an otherwise similar risk profile ( 1,2 ).", - "tokenCount": 44, - "pageStart": 17, - "pageEnd": 17, - "hash": "c7f1bc851e3069ab7039b3239fb53f11c8d41dc5d63a1f90e7bfc0613e02e966" - }, - { - "text": "This excess risk is abrogated, and quality of life (QOL) improved following the institution of PAspecific medical or surgical treatment ( 7,86 ).", - "tokenCount": 34, - "pageStart": 17, - "pageEnd": 17, - "hash": "d52e2f6938a581b31f69f429456781f8d0d02a21deac98f537ba638e786bb57e" - }, - { - "text": "Individuals with PA who undergo surgery demonstrate a lower rate of cardiovascular and cerebrovascular complications than do matched individuals (based on BP and cardiovascular risk profile) with primary hypertension ( 7 ).", - "tokenCount": 38, - "pageStart": 17, - "pageEnd": 17, - "hash": "62a9c5923de81b2efe74965eeace6c0f24c6ca163b83cfdca87ea6b7a064bd77" - }, - { - "text": "Individuals with bilateral PA undergoing sufficient MRA therapy to unsuppress renin, display a similar (rather than higher) risk to matched individuals with primary hypertension, whereas individuals treated with MRA therapy in doses that are insufficient to unsuppress renin still display increased risk ( 7 ).", - "tokenCount": 58, - "pageStart": 17, - "pageEnd": 17, - "hash": "aa8e1d355176641323e066eab0a4076d65cf0e482ef88fd844630d0bfe32e54d" - }, - { - "text": "PAspecific treatment is associated with significant BP reduction ( 7,86 ), which, in turn, is expected to result in a reduced rate of cerebrovascular, cardiovascular, and renal events. Furthermore, individuals with PA display lower rates of adverse events after diagnosis and initiation of PAspecific treatment than before diagnosis when the treatment is with general antihypertensive drugs ( 87,88 ).", - "tokenCount": 81, - "pageStart": 17, - "pageEnd": 17, - "hash": "4ce90ce32f9e6eaaba9f8534c3473768544fbd9e13d6d7816b69dc86564fc1f8" - }, - { - "text": "In summary, this indirect evidence shows that institution of specific treatment (medical or surgical) in individuals with PA results in a significant improvement of hypertension control.", - "tokenCount": 30, - "pageStart": 17, - "pageEnd": 17, - "hash": "97079468f5bc79391956f0a66e0be1a4f3cf0b2f874559c5161585d26512f7f3" - }, - { - "text": "BP normalization occurs in a significant proportion of those who undergo surgery for lateralizing forms of PA ( 89 ).", - "tokenCount": 22, - "pageStart": 17, - "pageEnd": 17, - "hash": "a9c4c2be6a759055467aefe2ad43139fdd3de25e7f1f7f9d031868254f1aa2ae" - }, - { - "text": "Furthermore, therapies (medical or surgical) that directly target the increased aldosterone in PA reduce the excess cardiovascular, cerebrovascular, and renal complications associated with PA.", - "tokenCount": 35, - "pageStart": 17, - "pageEnd": 17, - "hash": "1b9be98197c78428f1145626862c7b5eab41837a51b129d490d1f8ecf92a8b81" - }, - { - "text": "Spironolactone s dosedependent side effects (including gynecomastia, erectile dysfunction, and menstrual irregularities) limit the efficacy and tolerability of this medication in PA.", - "tokenCount": 40, - "pageStart": 17, - "pageEnd": 17, - "hash": "236e29185eeb1c9da7eabdac966f849eae68ba58672a9b708eb040ff56a41f72" - }, - { - "text": "However, newer MRAs, such as eplerenone, have a much lower side effect profile (see Recommendation 9).", - "tokenCount": 26, - "pageStart": 17, - "pageEnd": 17, - "hash": "30157ebe15d8aa67acf5a6ac5a25897420f630d52c15e481dfe90fe28ffdbbce" - }, - { - "text": "Surgical therapy requires skilled surgeons and adequate postsurgical care to minimize surgical complications.", - "tokenCount": 16, - "pageStart": 17, - "pageEnd": 17, - "hash": "8ad4c1c9c9cec7cc27509339fdcdde73099f06fa5e7bc4474e8308881aea14c0" - }, - { - "text": "Evidence to Decision Factors Costs of medical therapy are minor (in the case of spironolactone) to moderate depending on the medication used, whereas costs of surgical therapy vary.", - "tokenCount": 37, - "pageStart": 17, - "pageEnd": 17, - "hash": "79eff8b4c05b44ef5dc15cd10436673b43eda6bcdc768a5701891f156b1632df" - }, - { - "text": "Three health economic studies in Japan, Australia, and China demonstrated costeffectiveness of screening for PA in the general hypertensive population.", - "tokenCount": 26, - "pageStart": 17, - "pageEnd": 17, - "hash": "5b869a63f1a260ce685034b467fab617f498fc2d00cfd42e316ec57c3c7085cd" - }, - { - "text": "Costeffectiveness was mainly due to a decrease in lifelong complications and their associated costs in individuals with PA who received PAspecific therapy compared with those who did not receive therapies targeting PA ( 70-72 ).", - "tokenCount": 42, - "pageStart": 17, - "pageEnd": 17, - "hash": "2b2fa9692a796e4bc0c429934686f961414734c06cf45ba88914eb37c441ef9d" - }, - { - "text": "Surgical therapy requires skilled surgeons and adequate postsurgical care and has economic consequences for individuals.", - "tokenCount": 18, - "pageStart": 17, - "pageEnd": 17, - "hash": "66476ae7d3c0483490304ffefeef56dac0a4d06a9a18a3c4a5250fbf134fee95" - }, - { - "text": "Medical therapy requires individualized titration and surveillance through regular followup visits.", - "tokenCount": 15, - "pageStart": 17, - "pageEnd": 17, - "hash": "da5dcdb2feb3ba3cc1ceb6adab46e709fa4cf67937e6290b2443b03f7dd26ab1" - }, - { - "text": "In areas where these resources are available, the intervention should be feasible.", - "tokenCount": 14, - "pageStart": 17, - "pageEnd": 17, - "hash": "d33d24ba6be417cffba14662f5526a5445b24d9d776130880967c1883425954b" - }, - { - "text": "Specific medical or surgical treatment of PA should be accepted by individuals since it represents targeted therapy, improved hypertension control (and sometimes cure), improved QOL, and a reduction in the complications associated with PA.", - "tokenCount": 40, - "pageStart": 17, - "pageEnd": 17, - "hash": "91ab61d434746c62847b2b895923f97baf321872bcd2b78bfcfbe44c7183d400" - }, - { - "text": "While PAspecific therapy is likely to be acceptable to primary care clinicians, the steps required to identify individuals with PA who are candidates for specific surgical or medical treatment may reduce acceptance (and, hence, uptake) because of: 1.", - "tokenCount": 48, - "pageStart": 17, - "pageEnd": 17, - "hash": "d48369a8d2f244a2ef6d7f88b38d4deb2ea16b5953b1417d9eae11e4b179de95" - }, - { - "text": "lack of knowledge of prevalence and complications of PA; 2.", - "tokenCount": 13, - "pageStart": 17, - "pageEnd": 17, - "hash": "3bef5e227526683f0f450d884730ad3265ef5016d9840d914d1b65fdf96cffac" - }, - { - "text": "lack of familiarity with implementing and interpreting screening tests; 3.", - "tokenCount": 13, - "pageStart": 17, - "pageEnd": 17, - "hash": "e6d1014e16331e4c7ee702a076035de0237403db477115f6d710c9ee71673c87" - }, - { - "text": "lack of familiarity with using MRAs; and 4.", - "tokenCount": 12, - "pageStart": 17, - "pageEnd": 17, - "hash": "280b5f553d6ae43643f632c56ba8584db71c6e5c37149db19b2fbeeba2cc6387" - }, - { - "text": "costly, invasive, and challenging procedures associated with subtype diagnosis (lateralizing vs bilateral adrenal aldosterone production) for individuals contemplating potential unilateral adrenalectomy.", - "tokenCount": 35, - "pageStart": 17, - "pageEnd": 17, - "hash": "c6411910c0a062d4de17166a87b82a86e48f5c4769d5e43efff0f6a37853ec7a" - }, - { - "text": "Finally, the diagnosis of PA and treatment with MRA should be affordable in most clinical settings.", - "tokenCount": 19, - "pageStart": 17, - "pageEnd": 17, - "hash": "28319f335f3c8618798a2cf658e622c65320d2dcc20139f7f12475be343ff17e" - }, - { - "text": "Subtype diagnosis, especially when using adrenal vein sampling (AVS), and access to surgical intervention may be limited in some settings.", - "tokenCount": 27, - "pageStart": 17, - "pageEnd": 17, - "hash": "623c8fe77651b224cec4715aa6f7e194f2f30ef292b6117339aa868abfead5d3" - }, - { - "text": "After years of implementation with high fidelity, equity will probably be increased.", - "tokenCount": 14, - "pageStart": 17, - "pageEnd": 17, - "hash": "20f5b4917829d17d84d8778b4b629dd0d0791b7fb21d96857631d3b10939effa" - }, - { - "text": "Justification for the Recommendation Aldosterone excess has adverse cardiovascular and renal effects that go above and beyond the effects of hypertension, leading to a higher rate of cardiovascular and renal complications in individuals with PA compared with individuals with primary hypertension matched for BP levels.", - "tokenCount": 50, - "pageStart": 17, - "pageEnd": 17, - "hash": "fc7d858323074a080c5d1634c2670136c6b9c5cf5f2519bdfd6a48e0e3445e45" - }, - { - "text": "Unilateral adrenalectomy in individuals with lateralizing forms of PA often leads to cure of hypertension, and surgically treated individuals demonstrate a lower rate of cardioand cerebrovascular complications than do matched (for BP and cardiovascular risk profile) individuals with primary hypertension.", - "tokenCount": 53, - "pageStart": 17, - "pageEnd": 17, - "hash": "1939d4844c7af090ad95ca98dcffee81fb79cf6253d00c0e3a4c141d37a284d1" - }, - { - "text": "Individuals with PA treated with MRAs in sufficient doses to unsuppress renin demonstrate a similar (rather than higher) risk to matched individuals with primary hypertension.", - "tokenCount": 33, - "pageStart": 17, - "pageEnd": 17, - "hash": "1e94f164605ce9499a74a24e78f29d0c5a8a03ee861cc360cfa0e9580973dc08" - }, - { - "text": "While the certainty of evidence is low, indirect data from noncomparative cohorts support the intervention, The Journal of Clinical Endocrinology & Metabolism , 2025, Vol.", - "tokenCount": 36, - "pageStart": 17, - "pageEnd": 17, - "hash": "c30b16cfa1f40e8c66d1de5244ef427730a7c17cadec933c3f88c1f429f0c904" - }, - { - "text": "9 2469 Downloaded from https://academic.", - "tokenCount": 11, - "pageStart": 17, - "pageEnd": 17, - "hash": "92ab18e4ab6678635615c6faa169755df215bf17ce724ddf92dc06d6a0908c52" - }, - { - "text": "as the benefits observed with all therapies for PA are likely to outweigh the associated harms.", - "tokenCount": 17, - "pageStart": 18, - "pageEnd": 18, - "hash": "6c5a4d0d55be9fee532b02e9a5a7e27c72adc0224b4931c16482424373a95124" - }, - { - "text": "The panel also considered the economic implications of PAspecific therapies.", - "tokenCount": 14, - "pageStart": 18, - "pageEnd": 18, - "hash": "acbb674319a040a1c73c130f7ac98455beaf99d89d5621a20252bb4a8897ef0e" - }, - { - "text": "While medical therapy has negligible costs, surgical treatment is associated with higher and variable costs depending on the country and health care system.", - "tokenCount": 25, - "pageStart": 18, - "pageEnd": 18, - "hash": "3c7ee33b341662ed5cd42f09acd41b8fc4e5ceda609a72cb5daf64005e7d8ec3" - }, - { - "text": "Nonetheless, costeffectiveness analyses generally favor PAspecific therapies.", - "tokenCount": 14, - "pageStart": 18, - "pageEnd": 18, - "hash": "5272cda04dd551102b225ef529d01830e58e4aa2ded5818a75054c510330ca18" - }, - { - "text": "The panel concluded that the acceptability and feasibility of implementing these therapies depend on available resources and clinical expertise.", - "tokenCount": 21, - "pageStart": 18, - "pageEnd": 18, - "hash": "e079b24f1291dfd15b2738bc48dfcf79b57f0885227cef8fe27ba58d8e1c80a4" - }, - { - "text": "Given the overall certainty of the evidence regarding benefits and harms and recognizing that the implementation of PAspecific therapies varies by context, the panel issued a conditional recommendation for the use of PAspecific therapies over nonspecific antihypertensive treatments.", - "tokenCount": 51, - "pageStart": 18, - "pageEnd": 18, - "hash": "f4850822fce5b7c3e48a1f4d9fe54256caee69a1ca118735e85ef8c9d9f4fa1e" - }, - { - "text": "This recommendation reflects the balance of evidence, contextual considerations, and resource variability across different settings.", - "tokenCount": 18, - "pageStart": 18, - "pageEnd": 18, - "hash": "b4c60f83d5333e3e455001ea1dfae9e970e1486df28e869053cefb4a3baeb399" - }, - { - "text": "The risk of MRA side effects can be minimized by commencing at low doses (eg, 12.", - "tokenCount": 21, - "pageStart": 18, - "pageEnd": 18, - "hash": "c1d64ec6ccbfd70b20dab76a6267487911b61c3498ff01b2d62975231f7ef507" - }, - { - "text": "5-25 mg of spironolactone daily) and increasing the dose gradually (eg, every 2-3 months or sooner if clinically indicated) as required to control BP (see Question 9.", - "tokenCount": 41, - "pageStart": 18, - "pageEnd": 18, - "hash": "773695b108997a632430007e334a4a11932631496c3118f0176354f9fa9f328f" - }, - { - "text": "Measurement of renin during MRA titration can assist in treatment decision making, but this is less straightforward if the individual is on other medications that affect renin levels (see Question 7).", - "tokenCount": 39, - "pageStart": 18, - "pageEnd": 18, - "hash": "b04b3345045394bb83d47f32a3ea6c2ad73ede5066425a1d83d617bd01308d67" - }, - { - "text": "Research Considerations Current gaps in knowledge call for further research in the following areas: Assessing health equity after implementation of this recommendation Assessing efficacy and safety of newer nonsteroidal MRAs and aldosterone synthase inhibitors in the medical treatment of PA and developing new medications Conducting comparative effectiveness studies to assess PAspecific therapies (both medical and surgical) against nonspecific antihypertensive treatments in diverse clinical contexts and subgroups Studying the barriers to widespread adoption of PAspecific therapies, including clinician knowledge gaps, individual preferences, and logistical challenges associated with identifying lateralizing vs bilateral aldosterone production and treatment access Establishing large, diverse, and prospective cohorts to monitor longterm outcomes of PAspecific therapies, including cardiovascular and renal events, QOL, and costeffectiveness Investigating disparities in access to PAspecific diagnostic and therapeutic interventions, particularly in lowresource settings and regions with limited access to AVS, surgical expertise, and newer medications Screening for Primary Aldosteronism in Individuals With Hypertension Background Screening for primary aldosteronism (PA) allows for early identification and treatment, which can improve patient outcomes (Question 1).", - "tokenCount": 247, - "pageStart": 18, - "pageEnd": 18, - "hash": "9a416e1dfe1bb4d00e1b1ae5538bb9fea7e7496072ac84b9c1a4839643218923" - }, - { - "text": "Several strategies exist for PA screening, with the most used approach being the measurement of aldosterone and renin (concentration or activity) and calculation of the aldosterone to renin ratio (ARR).", - "tokenCount": 43, - "pageStart": 18, - "pageEnd": 18, - "hash": "8817f693fa3578af18ae004d9939346288783b2cca4d7595c6280a19188d215e" - }, - { - "text": "This method may be more sensitive than relying solely on hypokalemia, as hypokalemia is present in only a minority of PA individuals (9%-37%), and many individuals with PA have normal potassium levels ( 90 ).", - "tokenCount": 46, - "pageStart": 18, - "pageEnd": 18, - "hash": "78f635906e9e14fe3a32a7a5ff95cee177e63fb415787a1cda7b2a6cebdc0974" - }, - { - "text": "Aldosterone and renin testing can identify normokalemic individuals with PA, expanding detection to a broader hypertensive population.", - "tokenCount": 26, - "pageStart": 18, - "pageEnd": 18, - "hash": "4451fe2855a9dc06fe9fcab2ea5345ca738b1c2b80794df4bad9edb300ba8eeb" - }, - { - "text": "However, there are practical challenges to using aldosterone and renin for screening.", - "tokenCount": 17, - "pageStart": 18, - "pageEnd": 18, - "hash": "ba0770204a379eb536aefc719b9b910bdc1edfb2647afc00a5769b5f2a4da696" - }, - { - "text": "The accuracy of these measurements can be influenced by medications, dietary sodium, and sampling conditions, which may lead to false positives or negatives.", - "tokenCount": 27, - "pageStart": 18, - "pageEnd": 18, - "hash": "386030021cb373a3692ba1df81b8e9273ba52d6fd6461f3fae02ec5d5a3ceed0" - }, - { - "text": "Additionally, the availability and cost of testing could limit the feasibility of widespread screening.", - "tokenCount": 16, - "pageStart": 18, - "pageEnd": 18, - "hash": "7d37d96323223909698910890aab5977333d82202fcf4593c9581f9a1da97cc9" - }, - { - "text": "In contrast, hypokalemia is simpler to detect, but screening for hypokalemia may miss many cases of PA, especially milder forms of the disease.", - "tokenCount": 34, - "pageStart": 18, - "pageEnd": 18, - "hash": "0ec1b6db2e781cf957a4838e2af39a497efe036bfd4c9a71f6586c97612b9477" - }, - { - "text": "Given these considerations, the guideline evaluates whether measuring aldosterone and renin (including ARR) is a better strategy for screening for PA compared with relying on the detection of hypokalemia alone in individuals with hypertension.", - "tokenCount": 45, - "pageStart": 18, - "pageEnd": 18, - "hash": "94e49669d5e09f166fce82364ed3992834466c39ffaac0ee3c6f90320ada1a73" - }, - { - "text": "Potassium should be measured alongside renin and aldosteronenot for screening itself, but to aid in the accurate interpretation of aldosteroneas a low potassium may lead to a falsely low aldosterone.", - "tokenCount": 43, - "pageStart": 18, - "pageEnd": 18, - "hash": "102aaac5f2af730bdf1023883e02b9b72f427eddc6ab4f5edc21aa70a2dfa6a5" - }, - { - "text": "The Guideline Development Panel (GDP) outlined both minimalwithdrawal and nowithdrawal strategies of interfering medications before screening ( Tables 6 and 7 , Fig.", - "tokenCount": 34, - "pageStart": 18, - "pageEnd": 18, - "hash": "612af0fb0fc8fd9ea44e6d84c1789fc44a58b9dfd35fb086c87537b4de447dc9" - }, - { - "text": "Renin is low/suppressed (hallmark of the diagnosis) and aldosterone is inappropriately high relative to renin: indicative of PA if plasma renin 2470 The Journal of Clinical Endocrinology & Metabolism , 2025, Vol.", - "tokenCount": 51, - "pageStart": 18, - "pageEnd": 18, - "hash": "b84db7fa325aa5ecf628230f47c24d26bbdb95f28161fb1ee65498bcb5a22e00" - }, - { - "text": "activity (PRA) is 1 ng/mL/h or direct renin concentration (DRC) is 8.", - "tokenCount": 26, - "pageStart": 19, - "pageEnd": 19, - "hash": "604e83cb10319dfe92df8185716c2b8882f3779819783ef38f6dd4e1d7a7e1ce" - }, - { - "text": "Elevated aldosterone to renin ratio (ARR): indicative of PA if the aldosterone [ng/dL] to PRA [ng/mL/h] ratio is > 20 or aldosterone [pmol/L] to DRC [mU/L] ratio is > 70 when aldosterone is measured by immunoassay; the ARR indicative of PA is about 25% lower when aldosterone is measured by LCMS/MS) ( Fig.", - "tokenCount": 101, - "pageStart": 19, - "pageEnd": 19, - "hash": "092c02b7b6335292df037ce003def863582ca7a3da42e11fcdec75e27734e94d" - }, - { - "text": "1 and Table 5 show ARR cut points for differing assays and units) The aldosterone, renin, and ARR values above are provided for guidance.", - "tokenCount": 35, - "pageStart": 19, - "pageEnd": 19, - "hash": "c0a44e402483799c257e80320be1c4a3b9f27e11fe03cd98b4a11bf65d71982b" - }, - { - "text": "If the individuals initial screen is negative and factors are present that could have led to a falsenegative result (eg, hypokalemia or medications), the test should be repeated on a different day, preferably after correcting hypokalemia (where present) and withdrawing interfering medications if it is safe and feasible (for 4 weeks for mineralocorticoid receptor antagonists (MRAs), epithelial sodiumchannel [ENaC] inhibitors [eg, amiloride, triamterene], and other diuretics, and 2 weeks for angiotensinconverting enzyme [ACE] inhibitors and angiotensin receptor blockers [ARBs]), which raise renin or lower aldosterone.", - "tokenCount": 144, - "pageStart": 19, - "pageEnd": 19, - "hash": "18de3e0fb0afc7b261d6e13c201dcd663d891d75968f9184179977d178a8c440" - }, - { - "text": "If the individuals initial screen is negative and the pretest probability of PA is moderate to high (eg, hypokalemia and/or resistant hypertension) or renin is suppressed with aldosterone of 5 to 10 ng/dL (138 to 277 pmol/L) by immunoassay, the test should be repeated on a different day.", - "tokenCount": 72, - "pageStart": 19, - "pageEnd": 19, - "hash": "495b85b090f06563206d651a629a0fc9f3cbe85816d347df565a7bfd53a3b9de" - }, - { - "text": "If all initial screening is negative, consider rescreening in the future if a patient develops: Unexplained worsening of hypertension or resistant hypertension New spontaneous or diureticinduced hypokalemia Atrial fibrillation in the absence of structural heart disease or hyperthyroidism Summary of the Evidence The metaanalysis results, a detailed summary of the evidence and Evidence to Decision (EtD) tables can be found online at https:/ /guidelines.", - "tokenCount": 96, - "pageStart": 19, - "pageEnd": 19, - "hash": "271781e4dcc6c8b09e9458950c52086af4e10e4eb37c54043dba76fbf73616ce" - }, - { - "text": "org/profile/qFJ3iuy78Bw .", - "tokenCount": 14, - "pageStart": 19, - "pageEnd": 19, - "hash": "849f095ef0d43bb4099acd63cb72e8a42fef40f4708a4af84a4ff84cccad45f9" - }, - { - "text": "Benefits and Harms The panel voted for the following patientimportant outcomes for Question 3 decision making: 1) accuracy of PA detection, 2) detection of lateralizing PA, and 3) adverse events.", - "tokenCount": 41, - "pageStart": 19, - "pageEnd": 19, - "hash": "00f6b3920dba6723ed2e9d100dae72f11e573eb36f46a8c0bb6fb7fc3d76f38d" - }, - { - "text": "The systematic review found no studies that directly compared detection rates for PA among individuals screened by serum or plasma potassium levels vs those screened by measuring serum/plasma aldosterone and renin.", - "tokenCount": 38, - "pageStart": 19, - "pageEnd": 19, - "hash": "735e65fcc597a9d8a6293c50a8bf6b3bba82066a012322bdb9f7ca30f51ac7f9" - }, - { - "text": "Therefore, we relied on indirect evidence on the frequency and accuracy of PA detection from observational studies among those with hypertension and hypokalemia vs hypertension and normokalemia.", - "tokenCount": 35, - "pageStart": 19, - "pageEnd": 19, - "hash": "40594301b7c8c6084f113508f278631c740dbf52e498a1a40ab0b0ae540534fb" - }, - { - "text": "In a retrospective evaluation of the diagnosis of PA from 5 continents, after the widespread use of the ARR as a screening test in individuals with hypertension, identification of PA increased 5- to 15-fold ( 90 ).", - "tokenCount": 43, - "pageStart": 19, - "pageEnd": 19, - "hash": "060b5ec19935e716167b43eca3546ad3e8be596e48014a2d7b06a044b7c130e4" - }, - { - "text": "Only between 9% and 37% of individuals had hypokalemia.", - "tokenCount": 15, - "pageStart": 19, - "pageEnd": 19, - "hash": "cb6b79c052ad06914b1f9d9491cadbd1388611593905c73a59e5e9a99263d553" - }, - { - "text": "Three other prospective studies totaling 5797 individuals referred to hypertension centers or from primary care settings reported that only 25% to 30% of those with confirmed PA had hypokalemia ( 34,37 , 91 ).", - "tokenCount": 42, - "pageStart": 19, - "pageEnd": 19, - "hash": "4b40288a316fa7a5d0498451ccf42ca3ff4bd69f1420b07702d01c6cbf87c5a5" - }, - { - "text": "The ARR was effective at screening for PA, and most cases were ultimately diagnosed with bilateral PA.", - "tokenCount": 20, - "pageStart": 19, - "pageEnd": 19, - "hash": "8dcce5b9bb24c347e8f51f8fdc713fcb513de6e11475bf3fda1ae545c5fe49c2" - }, - { - "text": "The presence of hypokalemia is associated with more severe forms of PA and is more common in the lateralizing subtype.", - "tokenCount": 26, - "pageStart": 19, - "pageEnd": 19, - "hash": "200c06b3a72f27d0d75754882d0496c2960433bb202d438e8931c72ea09efb66" - }, - { - "text": "Nevertheless, in a study of 95 individuals with lateralizing PA, more than 90% had suppressed renin preoperatively ( 92 ).", - "tokenCount": 27, - "pageStart": 19, - "pageEnd": 19, - "hash": "e40ba890be5b01f2d3ff3fb8b6e35a933913330dc4ce59fc2f61ee41034415be" - }, - { - "text": "In contrast, 62% to 67% had hypokalemia requiring potassium supplementation preoperatively, suggesting that relying on hypokalemia to detect PA would miss a substantial percentage of individuals with surgically curable PA.", - "tokenCount": 45, - "pageStart": 19, - "pageEnd": 19, - "hash": "f1c92555fbf17bde67795686730010e91ffb0ed9b45e2891c2fcf3855034778e" - }, - { - "text": "9 2471 Downloaded from https://academic.", - "tokenCount": 11, - "pageStart": 19, - "pageEnd": 19, - "hash": "1205c960f6ca7505a791f6f93958175bde3481b6ffa071f124b4c572b4d9c68b" - }, - { - "text": "Although the evidence demonstrated that a large proportion of individuals with PA do not have hypokalemia, and thus the ARR would be more sensitive than the presence of hypokalemia, these data were indirect and were mostly derived from selected populations of individuals referred to hypertension centers.", - "tokenCount": 56, - "pageStart": 20, - "pageEnd": 20, - "hash": "bc59ca2ee5c5e70498b0764bd87a1a68bd79038ed5d16748d99e4a3b070263eb" - }, - { - "text": "In addition to increasing case detection, the ability of the ARR to limit false positives and negatives was another important consideration.", - "tokenCount": 24, - "pageStart": 20, - "pageEnd": 20, - "hash": "ebafe63031730a9afa7b957a8716eb667d57ddcf935527fe86a019511408b47d" - }, - { - "text": "The accuracy of detection of PA using ARR has inherent variability as assays, screening conditions, and patient populations are heterogenous, which can affect the screening test s sensitivity and specificity.", - "tokenCount": 38, - "pageStart": 20, - "pageEnd": 20, - "hash": "1fdd6948c1545d34848741dc90903428b6fdf687c7caa291b4eb3512e9c805b1" - }, - { - "text": "A metaanalysis of 9 studies (974 individuals) determined that the sensitivity and specificity of the aldosterone to PRA and aldosterone to DRC ratios were reasonable and improved when interfering medications were withdrawn ( 93 ).", - "tokenCount": 45, - "pageStart": 20, - "pageEnd": 20, - "hash": "bde22e3512b588fb150a8faf4afb4483499fecbaec9db1f66e956de4e146b0cb" - }, - { - "text": "Regarding false negatives, in a study of 216 individuals with PA with at least 2 aldosterone levels drawn (MRAs were withdrawn prior to testing, but other interfering medications permitted), a lower aldosterone concentration cut point of 10 ng/dL was associated with falsenegative rates for PA screening of 14.", - "tokenCount": 62, - "pageStart": 20, - "pageEnd": 20, - "hash": "d286bc2320649cb04902efc3129d3abfe821e00b90a868d493370d95e3eba9cf" - }, - { - "text": "3% for a single aldosterone measurement, and 4. 6% for 2 aldosterone measurements ( 94 ).", - "tokenCount": 24, - "pageStart": 20, - "pageEnd": 20, - "hash": "3e9748de83fc5b4c81dd041baf200fc164d8aaf4199de10bd9a010805d97ca29" - }, - { - "text": "Although one metaanalysis ( 95 ) demonstrated good overall accuracy, significant variability precludes a single standard cutoff for detecting PA, and false negatives may result.", - "tokenCount": 30, - "pageStart": 20, - "pageEnd": 20, - "hash": "45b6a7502f387741e7b06739f4c3ab2c03d31a532fe462cdfbacf83d847b8835" - }, - { - "text": "Evidence to Decision Factors The GDP considered that measuring aldosterone and renin has low cost and resource implications, making this an attractive screening tool in most regions.", - "tokenCount": 33, - "pageStart": 20, - "pageEnd": 20, - "hash": "09cff4ff4c7b39ef7804710e6b75c70207ef7a38762208716eab855dc1839d1c" - }, - { - "text": "Cost studies across multiple countries indicate low cost of the aldosterone, renin, and potassium measurements.", - "tokenCount": 21, - "pageStart": 20, - "pageEnd": 20, - "hash": "cdf6fc7f97fa7f92bce685adeccb33ed252d9fdd61a8b13b0e852694724bc1c8" - }, - { - "text": "Three health economic studies in Japan, Australia, and China demonstrated costeffectiveness of screening for PA in the general hypertensive population, mainly due to reduced costs of lifelong complications related to untreated PA ( 70,71 , 72 ).", - "tokenCount": 45, - "pageStart": 20, - "pageEnd": 20, - "hash": "04842fb8662864bc453164aa0593d133bfa8d1471b485d1653ad601ea1295380" - }, - { - "text": "The GDP expects that measuring aldosterone and renin should not have a significant impact on health equity, with the caveat that current access to PA screening and to specialists in PA to interpret findings for management varies.", - "tokenCount": 42, - "pageStart": 20, - "pageEnd": 20, - "hash": "f23c3f7417e4de2c8eae1c6d3bb932573b4986496cbaf1f372cef60f17e2ff53" - }, - { - "text": "Although not well studied, available evidence suggests that those living in rural areas and far from tertiary care centers are less likely to be screened with aldosterone and renin ( 51,96 ).", - "tokenCount": 39, - "pageStart": 20, - "pageEnd": 20, - "hash": "235300dee521943c35c9a6f2c3bce34566d551d1f362949025520e203cc51664" - }, - { - "text": "With increased clinician and public awareness, testing should increase in these areas.", - "tokenCount": 15, - "pageStart": 20, - "pageEnd": 20, - "hash": "a0b9c6bfaee6a9f5abe1fec5d855be835efc562f1b58658032874d863257fe98" - }, - { - "text": "A significant barrier to screening is the lack of feasibility of aldosterone and renin testing by clinicians.", - "tokenCount": 21, - "pageStart": 20, - "pageEnd": 20, - "hash": "dc27e07a3ddecd5560ebc7b9235df440ddeedadc7e4dafc55088b204d8d175fd" - }, - { - "text": "Complex testing requirements, in particular withdrawal of interfering medications prior to testing and selecting specific subpopulations for screening, underlie some of the poor detection rates ( 97 ).", - "tokenCount": 34, - "pageStart": 20, - "pageEnd": 20, - "hash": "b4af25842d3784cf6d4508a455f794eef94713c29f68c05fdbcc53047c88e691" - }, - { - "text": "Although withdrawing interfering medications is associated with more consistent and increased accuracy of the ARR, several studies indicated that the ARR retained reasonable accuracy with minimal withdrawal or no withdrawal of interfering medications ( 98,99 ).", - "tokenCount": 41, - "pageStart": 20, - "pageEnd": 20, - "hash": "cf5eb9c7dc3b8383de4d99519f57ba875c3f6a5ae2a73d0b56ba052604cdfe16" - }, - { - "text": "The GDP considered that screening for PA in individuals with newly diagnosed hypertension with an estimated prevalence of PA of 2% to 6% prior to medication initiation would be feasible, facilitate widespread screening, and limit false negatives or positives.", - "tokenCount": 44, - "pageStart": 20, - "pageEnd": 20, - "hash": "aa0648d763a36895bf0b854e8a2ed905a1fe6aa6ddb43e62e64e67a9f83bca6f" - }, - { - "text": "1 , and Tables 5 and 6 , the GDP created a pathway for clinicians to test individuals on antihypertensive medications with minimal or no withdrawal of interfering medications.", - "tokenCount": 33, - "pageStart": 20, - "pageEnd": 20, - "hash": "2b1b6104382552766bb279694ef5e36ed4429f15702725549b10ed49f3fe7080" - }, - { - "text": "Justification for the Recommendation Screening with serum/plasma aldosterone and renin was selected over hypokalemia as the global screening tool for detecting PA based on indirect evidence that PA is more common than previously appreciated and that most individuals with PA do not have hypokalemia.", - "tokenCount": 60, - "pageStart": 20, - "pageEnd": 20, - "hash": "e2879cd383675e9d0a4468ac5b51c73ce65c83c017649f027a7a71f83b93df6f" - }, - { - "text": "Limiting screening to individuals with hypokalemia would miss many cases requiring PAspecific therapy, some with potential for cure, and they would remain at increased risk of cardiovascular and renal events.", - "tokenCount": 40, - "pageStart": 20, - "pageEnd": 20, - "hash": "c2732b25992dd30e0090c1bfbe59a1e61ae029e65aca7f9c090258bc177d5217" - }, - { - "text": "However, screening with serum/plasma aldosterone and renin has notable limitations.", - "tokenCount": 18, - "pageStart": 20, - "pageEnd": 20, - "hash": "ce3e6000e6abcb3fb7ce5df14c97ef0f0f882b1e2b82e95c9aa80d9f91ea9898" - }, - { - "text": "The accuracy is variable and depends on assay type; can be influenced by individual sodium intake/volume status, medications ( Tables 6 and 7 ), and other factors; and has inherent intraindividual variability.", - "tokenCount": 41, - "pageStart": 20, - "pageEnd": 20, - "hash": "bc51133d5ac9c98f6949f1cd4c30e6990a593f535a968edc10fcbb3b9c2dfef0" - }, - { - "text": "Despite these limitations, it is a more sensitive screening tool than hypokalemia, has reasonable accuracy overall with or without interfering medications, and is widely available across regions at low cost.", - "tokenCount": 37, - "pageStart": 20, - "pageEnd": 20, - "hash": "f1bcc9e44f6de466d5664e569d5f4242929f05287321142aa24281f7e35a6e43" - }, - { - "text": "Given the poor uptake of screening for PA and missed opportunity to provide targeted treatment for individuals with PA, the GDP developed several implementation strategies to facilitate aldosterone/renin screening in primary care settings.", - "tokenCount": 40, - "pageStart": 20, - "pageEnd": 20, - "hash": "0e2fbfac37ee679fd3d291a70897139bde1eeeae8e63e5b90c4ab3759f2b5fd0" - }, - { - "text": "Screening with aldosterone and renin in individuals with newly diagnosed hypertension prior to medication start is highly feasible with a more straightforward interpretation.", - "tokenCount": 28, - "pageStart": 20, - "pageEnd": 20, - "hash": "8f53c3b1b0ddf4b3026d76de8a6c8a84e4490985a4a566413007aeee2299e6e3" - }, - { - "text": "Withdrawing a minimum set of interfering medications or not withdrawing them are also screening options for individuals on antihypertensive therapy and should improve the practicality of PA screening especially when medication withdrawal is not practical or safe.", - "tokenCount": 44, - "pageStart": 20, - "pageEnd": 20, - "hash": "fc3ce09e93258f3e965b6880dba3dab33fed5a5e24ca0062c4d3e1d908069e17" - }, - { - "text": "Other approaches for screening include only screening renin or measuring 24-hour urinary excretion of aldosterone.", - "tokenCount": 22, - "pageStart": 20, - "pageEnd": 20, - "hash": "a5dfa3325dca0a16d9c8e7ff855cb0e1511adc2229c3c9f0f505ced565a50369" - }, - { - "text": "However, these strategies do not have sufficient evidence or costeffectiveness data to justify their use for widespread screening.", - "tokenCount": 22, - "pageStart": 20, - "pageEnd": 20, - "hash": "ed56e7d1cf61f79c720bb5aecd6cc8261c44a176112bf1f21d39f56f779f775c" - }, - { - "text": "Also, some individuals with low renin do not have PA (ie, those with high sodium diet or Liddle syndrome); thus, to be diagnosed with PA, individuals should have both a suppressed renin and a nonsuppressed aldosterone.", - "tokenCount": 50, - "pageStart": 20, - "pageEnd": 20, - "hash": "550eebabe30e87f7da2b5f44dcd6ea3decf3b3872863b6528f2c45b0e1ba6e5b" - }, - { - "text": "Implementation Considerations Given that case detection is currently so low ( 67 ), and detecting cases of PA would lead to targeted therapy that would improve BP control and cardiovascular morbidity, and cure hypertension in some cases, high priority was given to increasing the sensitivity of case detection while maintaining reasonable specificity.", - "tokenCount": 58, - "pageStart": 20, - "pageEnd": 20, - "hash": "bba2ad379be6f269dab7bf7ef935cff1348717e32a5a6d975950f8077cedc64e" - }, - { - "text": "Research Considerations Current gaps in knowledge call for further research in the following areas: Conducting prospective studies to refine the thresholds for the ARR and absolute aldosterone concentration across diverse patient populations and laboratory assays, particularly those using LCMS/MS for aldosterone measurement 2472 The Journal of Clinical Endocrinology & Metabolism , 2025, Vol.", - "tokenCount": 74, - "pageStart": 20, - "pageEnd": 20, - "hash": "a50f29d22dc0913aed35c0ac143df11b8ae9ff21635cc2f9253b2147e2168af2" - }, - { - "text": "Investigating novel or other methods of screening for PA, including development of new biomarkers (see Question 4) and assessing 24-hour urine aldosterone Investigating the impact of medication withdrawal protocols on falsepositive and falsenegative rates and developing standardized approaches for testing under realworld conditions, such as minimal or no medication withdrawal Role of Aldosterone Suppression Testing Background The recommended approach to diagnosing PA has generally been a twostep process involving an initial screening step (using a plasma/serum aldosterone and renin with calculation of the aldosterone to renin ratio [ARR]) followed by a second confirmatory step to either confirm or exclude the diagnosis (using an aldosterone suppression test). However, the value of the confirmatory aldosterone suppression test remains uncertain because it is still unclear whether performing an aldosterone suppression test significantly improves the detection of PA or reduces falsepositive results following an initial positive screening.", - "tokenCount": 193, - "pageStart": 21, - "pageEnd": 21, - "hash": "c5dad85fac75c21d64040f6032082f3963fa5b8ff8503e1e6afd6f0016f58d0a" - }, - { - "text": "It is also unclear whether this additional step has any direct impact on important clinical outcomes, such as improved BP control or reduced cardiovascular risk, after treatment with either medical or surgical interventions for PA, and prediction of lateralizing PA.", - "tokenCount": 45, - "pageStart": 21, - "pageEnd": 21, - "hash": "4a5f128226ac658dea6926e3903ec76c8e11271579a102a288e11873eb30fc80" - }, - { - "text": "Given these uncertainties, the guideline addresses whether care guided by aldosterone suppression testing should be used in individuals with a positive PA screening result, before initiating further diagnostic steps and/or specific treatment for PA, or if treatment can proceed without confirmatory testing.", - "tokenCount": 51, - "pageStart": 21, - "pageEnd": 21, - "hash": "2fa6549b09a49d77216b1e9aeb5fa86471c0a300e4028816d3915c077cddc357" - }, - { - "text": "Should care guided by aldosterone suppression testing vs no aldosterone suppression testing be used in individuals with a positive primary aldosteronism screen before initiating primary aldosteronismspecific therapy (medical or surgical)? Recommendation 4 In individuals who screen positive for primary aldosteronism (PA), we suggest aldosterone suppression testing in situations when screening results suggest an intermediate probability for lateralizing PA and individualized decision making confirms a desire to pursue eligibility for surgical therapy (2 | OOO). Technical remarks: Situations in which aldosterone suppression testing may be helpful include: In individuals with an intermediate probability of having lateralizing PA who are willing and able to undergo surgical adrenalectomy ( Fig.", - "tokenCount": 148, - "pageStart": 21, - "pageEnd": 21, - "hash": "9c39f406c88bc041ad7de5e0ff1826faf27ba260e3658f4e59109acd413077e7" - }, - { - "text": "2 ): In individuals with resistant hypertension or hypertension with hypokalemia and overt biochemical evidence of reninindependent aldosterone production (direct renin concentration [DRC] < 2 mU/L or plasma renin activity [PRA] < 0.", - "tokenCount": 54, - "pageStart": 21, - "pageEnd": 21, - "hash": "24cc7a15c1d1298b29c8b8c1b356fc1136b9388ca7ab08e26fa6f97683ffed20" - }, - { - "text": "2 ng/mL/h and plasma aldosterone concentration > 20 ng/dL [ > 554 pmol/L] via immunoassay or > 15 ng/dL [ > 416 pmol/L] via liquid chromatographytandem mass spectrometry [LCMS/MS] assay), aldosterone suppression testing is not recommended due to the risk of falsenegative results, which may exceed the risk of falsepositive screening results.", - "tokenCount": 92, - "pageStart": 21, - "pageEnd": 21, - "hash": "a0a09631c9a388cd9f9e45e0a1a4565b4feae66c434f7137201aeac2ce141832" - }, - { - "text": "Individuals unwilling or unable to pursue adrenal venous sampling (AVS) and adrenalectomy can be empirically treated with mineralocorticoid receptor antagonists (MRAs) based on screening results without aldosterone suppression testing.", - "tokenCount": 48, - "pageStart": 21, - "pageEnd": 21, - "hash": "0eb9cb67daadb8eab86b96e652a4431288251b23404b6a1c5ddca6925d822089" - }, - { - "text": "Aldosterone suppression testing can also be avoided if the likelihood of lateralizing PA is so low that pursuing a formal diagnosis of PA is not justifiable (eg, normokalemia + plasma/serum aldosterone < 11 ng/dL [ < 305 pmol/L] [immunoassay] or < 8 ng/dL [ < 222 pmol/L] [LCMS/MS]).", - "tokenCount": 85, - "pageStart": 21, - "pageEnd": 21, - "hash": "c53ba8932fc10a6a677efb0a015a8f9313879d8c715f8de0d40f55a6c3616b6b" - }, - { - "text": "org/profile/DF0l5-vIoxI .", - "tokenCount": 14, - "pageStart": 21, - "pageEnd": 21, - "hash": "572c3435a6d9e468a73409fa9aa7e4f9d9dabfc8bb79fe8ed25ab18a4d64d395" - }, - { - "text": "Benefits and Harms The panel voted for the following patientimportant outcomes for Question 4 decision making: 1) accuracy of PA detection, 2) detection of lateralizing PA, 3) percent of individuals achieving blood pressure (BP) control, 4) number of antihypertensive agents, 5) dosage of antihypertensive agents, 6) systolic BP (SBP) level, and 7) adverse events (eg, for medications, invasive procedures, surgery, aldosterone suppression tests).", - "tokenCount": 102, - "pageStart": 21, - "pageEnd": 21, - "hash": "3f22713dab305cba0763c73b31fffe51990ba1093f88a1186f6c1e4204da854b" - }, - { - "text": "We found no RCTs that addressed this question.", - "tokenCount": 11, - "pageStart": 21, - "pageEnd": 21, - "hash": "f670cd816a6bce409629dca7e8d58a73508243ed83c7da1dc4aa4de9cc0088f9" - }, - { - "text": "Likewise, no prospective and headtohead studies are available evaluating the value of aldosterone suppression testing, in addition to screening results, on treatment outcomes in PA.", - "tokenCount": 33, - "pageStart": 21, - "pageEnd": 21, - "hash": "8590d0bdf3c5e14bb4e55ea7d868e834a98ef59811e819c290fb0f1bdecd8726" - }, - { - "text": "Therefore, the panel s recommendation relied primarily on evidence derived from retrospective observational studies.", - "tokenCount": 17, - "pageStart": 21, - "pageEnd": 21, - "hash": "266916cce2c08ed3107770419d74a93f9fa01057e6297d713b8c5705f2da5b55" - }, - { - "text": "The systematic review found only one study (retrospective observational study) that was included ( 24 ).", - "tokenCount": 20, - "pageStart": 21, - "pageEnd": 21, - "hash": "9cbaccd6f13ac4ed4392aed4b28321840e96f9412fa190caa88b467b5b0439de" - }, - { - "text": "Cornu et al showed that when conducting the saline suppression test (performed in the supine position) in individuals with highprobability features of PA, all of whom underwent AVS, even very low postsaline aldosterone levels ( < 139 pmol/L or 5 ng/dL) could not definitively exclude lateralizing PA ( 24 ). Similarly, another study showed that lateralizing PA could be detected in 15% of individuals with a postsupine saline suppression test aldosterone below 10 ng/dL ( 25 ); in general, the degree of nonsuppressibility in this study correlated with the likelihood of lateralization of The Journal of Clinical Endocrinology & Metabolism , 2025, Vol.", - "tokenCount": 144, - "pageStart": 21, - "pageEnd": 21, - "hash": "2d77b8231f2057c00cbb16683c472b6f8f77f75cd63f8f26f69a846f086f9eb9" - }, - { - "text": "9 2473 Downloaded from https://academic.", - "tokenCount": 11, - "pageStart": 21, - "pageEnd": 21, - "hash": "14f2cbdfc3f3a5449f5299124ded8ac749f20576a1c2c07bd77323c6d1122618" - }, - { - "text": "AVS, thereby providing a desirable prognostic value.", - "tokenCount": 11, - "pageStart": 22, - "pageEnd": 22, - "hash": "4c3c70f8341b63dd6e008b55446cf511525ac82a61374f266331271918e043d0" - }, - { - "text": "However, the choice of protocol and aldosterone assay are factors that can modify the interpretation of the results.", - "tokenCount": 22, - "pageStart": 22, - "pageEnd": 22, - "hash": "6b62ea1da64b4e9892fa53b4dbf9b4b21c84750c9ad31714aea5a236db912713" - }, - { - "text": "For example, the sensitivity of the saline suppression test at predicting the fludrocortisone suppression test has been shown to be superior when conducted in the seated position vs the supine position ( 100 ).", - "tokenCount": 41, - "pageStart": 22, - "pageEnd": 22, - "hash": "26faad11ed7cd4639135ca7eb29ada7262823379d17d8360214eef8d277d488c" - }, - { - "text": "Moreover, the use of modern LCMS/MS aldosterone assays yield lower aldosterone values than traditional immunoassays, thereby warranting a reassessment of aldosterone interpretations for virtually all aldosterone suppression tests ( 101-105 ).", - "tokenCount": 52, - "pageStart": 22, - "pageEnd": 22, - "hash": "fa31116fccc103405cedf768b45b2db17ec94b94228972ff392b00e6d9b3487d" - }, - { - "text": "Two systematic reviews and metaanalyses ( 106,107 ), including 55 and 31 studies respectively, concluded that the accuracy of aldosterone suppression tests in confirming PA was overestimated and that the number of missed cases (falsenegative interpretations) may exceed the number of overdiagnoses (falsepositive interpretations) ( 106 ).", - "tokenCount": 65, - "pageStart": 22, - "pageEnd": 22, - "hash": "3c2e36067e8489a251f94c6ce97e651aa59162e16e059567d6142af7d0a41a48" - }, - { - "text": "These results were attributed to inflation of diagnostic accuracy due to biased selection of individuals with very high probabilities of having PA.", - "tokenCount": 23, - "pageStart": 22, - "pageEnd": 22, - "hash": "ce791a40612bf4101c8af4689d864534547a843ec6c6e2f0e39128cb79855f1d" - }, - { - "text": "One study reported the anecdotal experience of a hypertension referral center abandoning the use of aldosterone suppression tests entirely from the diagnostic cascade for individuals with highprobability features of PA (ie, hypertension with a high ARR or hypertension with hypokalemia) over a period of 6 years (2005-2011) ( 108 ).", - "tokenCount": 66, - "pageStart": 22, - "pageEnd": 22, - "hash": "80d5862a6aa2ed5bcb81243a3886b9e44dc8c9fc71daf1aad3028020fae927e0" - }, - { - "text": "When using just the screening aldosterone and renin values to guide subsequent decisions, the authors estimated that less than 3% of individuals were at risk of a falsepositive diagnostic interpretation.", - "tokenCount": 37, - "pageStart": 22, - "pageEnd": 22, - "hash": "aefa59b3507864706f915ec62e33baeb43dc4d6c1bda706a6007e739bb50c38f" - }, - { - "text": "Falsenegative determinations after an aldosterone suppression test in individuals with highprobability features of PA is considered to be a substantial undesired effect ( 23-26 ).", - "tokenCount": 37, - "pageStart": 22, - "pageEnd": 22, - "hash": "61f2e7bae67c8326eb2982a2c5864f2b24409b35166c352e1538d7690c74c7a8" - }, - { - "text": "If aldosterone suppression testing is used to enhance knowledge of lateralization and AVS use, the risk of undesirable effects is low.", - "tokenCount": 27, - "pageStart": 22, - "pageEnd": 22, - "hash": "5bd4470cfec6686095c86bd16c4b3a6f5eafd7b7293b9b239d90ac7cae35d9f7" - }, - { - "text": "However, a negative aldosterone suppression test does not preclude the option of commencing specific medical therapy for PA, which has shown to be effective in individuals with lowrenin hypertension and reninindependent aldosterone production even when they do not meet the formal diagnostic criteria for PA ( 19-22 ).", - "tokenCount": 61, - "pageStart": 22, - "pageEnd": 22, - "hash": "be964117006b8ee01c5b24d7a97f337c702b5720f07f98a46e75fb0e90aec2d3" - }, - { - "text": "For example, in one study evaluating the captopril challenge test, aldosteronedirected therapy was highly effective at improving biochemical and clinical outcomes even for patients that did not meet the formal diagnostic criteria for PA ( 26 ).", - "tokenCount": 46, - "pageStart": 22, - "pageEnd": 22, - "hash": "67903833714d74ef2aded99465ff6429a4fe5ac9431c2e791c7606fac5672171" - }, - { - "text": "Evidence to Decision Factors An aldosterone suppression test is costeffective in the long term, particularly if it assists in identifying lateralizing forms of PA that might guide curative surgery.", - "tokenCount": 37, - "pageStart": 22, - "pageEnd": 22, - "hash": "06e645657de72b09fa813bd8803c626026b63180417da6c103d49c4af28b951f" - }, - { - "text": "The cost and resources will depend on the test used.", - "tokenCount": 11, - "pageStart": 22, - "pageEnd": 22, - "hash": "b63bbd255ac86fa7a75ce34b3673c386be6c9fc533a7d6870a139f797b2a2ddc" - }, - { - "text": "Although no specific studies address this aspect, aldosterone suppression testing appears acceptable by clinicians with expertise in PA, as well as by patients.", - "tokenCount": 28, - "pageStart": 22, - "pageEnd": 22, - "hash": "9360177b00ca80b8819f7e67c674b9aeb995abcdaf9efa3d9c2f415535d32951" - }, - { - "text": "In a limitedresource setting, conducting aldosterone suppression testing may be less acceptable. Aldosterone suppression testing can be prohibitively costly or resourceintensive in certain places. As a result, many parts of the world favor aldosterone suppression tests that are less expensive and resourceintensive, whereas other resourcerich institutions rely on more laborious and costly aldosterone suppression tests.", - "tokenCount": 77, - "pageStart": 22, - "pageEnd": 22, - "hash": "2a20baa3797ffd2e05ef29ea89c5077f6338cbe54a43322327feea0ecebf1c6e" - }, - { - "text": "This discrepancy further adds to implications for equitable health care delivery.", - "tokenCount": 12, - "pageStart": 22, - "pageEnd": 22, - "hash": "8019630c5ba44fae8dc46531b684379dffe951776ed88dd82234bde2cd81e161" - }, - { - "text": "Justification for the Recommendation At least 10 aldosterone suppression testing protocols have been described and used to confirm or exclude PA, 4 of which are widely recommended by prior major society guidelines ( 84,109-111 ), and each with their own unique thresholds to interpret a confirmation, or exclusion, of a PA diagnosis.", - "tokenCount": 64, - "pageStart": 22, - "pageEnd": 22, - "hash": "c149627bdf8043ddd71d5d08e9c08273336ea73c510541ab944eb484754c7741" - }, - { - "text": "These tests include, but are not limited to, fludrocortisone suppression, oral sodium suppression, supine and seated saline infusion, captopril challenge, losartan, dexamethasonecaptoprilvalsartan, intravenous (IV) furosemide upright, oral furosemide, and posture stimulation tests.", - "tokenCount": 72, - "pageStart": 22, - "pageEnd": 22, - "hash": "5da3fc741a693170715c0d643838b905900af1636ff10d78d26aa06c8bcdebc5" - }, - { - "text": "Given the heterogeneity and lack of standardization across these tests, the ability to provide general recommendations for their implementation and interpretation is limited.", - "tokenCount": 26, - "pageStart": 22, - "pageEnd": 22, - "hash": "4514189f18df95daff2e2bdaec4a845d557d00602c4b432a70379324944fb6d9" - }, - { - "text": "Table 8 describes the 3 most widely used aldosterone suppression tests.", - "tokenCount": 14, - "pageStart": 22, - "pageEnd": 22, - "hash": "8cb3c3f9c0a3405fdfb79d0a82eb9dd6563e797f6f4c53f9e2cf0ce025aa4088" - }, - { - "text": "Aldosterone suppression testing has traditionally been used to confirm or exclude the diagnosis of PA.", - "tokenCount": 18, - "pageStart": 22, - "pageEnd": 22, - "hash": "1c7fb8e05e04e1586663160bdd1a4b2b0919cf24b43ba5b3cf3c1d9e9dc4deb5" - }, - { - "text": "Limitations of using aldosterone suppression testing as a diagnostic metric include that the numerous protocols are not calibrated against one another, and each has diagnostic thresholds that are not validated against a gold standard. The summary of many studies suggests that a single optimal threshold for most aldosterone suppression tests does not exist and that overreliance on these tests may result in erroneous exclusion of PA cases rather than increased accuracy of diagnosis.", - "tokenCount": 83, - "pageStart": 22, - "pageEnd": 22, - "hash": "4d6898898e26adee584fca881636278b1385e1da2bc0f81bd13c379f866c6895" - }, - { - "text": "The balance of evidence ( 106,107 ) suggests that the quality of evidence to support the accuracy of this practice is low, particularly in relation to confidently excluding the diagnosis.", - "tokenCount": 34, - "pageStart": 22, - "pageEnd": 22, - "hash": "0087021784a8727f04e5212921099c55674b700d16ca6428af4436f121d18a41" - }, - { - "text": "However, if testing results that fall below protocol thresholds are interpreted as implying nonlateralizing PA or lowrenin hypertension and prompting initiation of MRA therapy ( 25,26 , 100 ), the use of aldosterone suppression testing could serve as both a diagnostic and therapeutic tool.", - "tokenCount": 56, - "pageStart": 22, - "pageEnd": 22, - "hash": "3afdb3ed9c1c75c5b988eda549022b26f5d803d64f367c1a5bb14cc155f39d3b" - }, - { - "text": "The caveat for this approach is the implicit assumption that a positive PA screen indicates a high pretest probability for PA.", - "tokenCount": 23, - "pageStart": 22, - "pageEnd": 22, - "hash": "6a486f8a0a7eb11d6335624743b301b0807669adb5b011a8dccae3973e2f257f" - }, - { - "text": "Some studies suggest that the results of aldosterone suppression testing predict the general likelihood that an individual may have lateralizing PA (ie, greater inability to suppress aldosterone indicates greater likelihood of lateralizing PA) ( 25,100 ), thus providing clinicians with probabilistic information on when to refer for AVS or when to forego AVS in favor of targeted medical therapy.", - "tokenCount": 76, - "pageStart": 22, - "pageEnd": 22, - "hash": "c97a274102060cb258a95e910ab76908e61feac3ab5e9f7ab6a5c4c0f9fef419" - }, - { - "text": "Caveats to this approach include its lack of quantifiable metrics to guide such interpretations, supporting data are not uniformly available for all suppression tests/protocols, and highquality comparative effectiveness studies to assess whether other biomarkers may have similar predictive power are also lacking.", - "tokenCount": 54, - "pageStart": 22, - "pageEnd": 22, - "hash": "2dd005f575f2444f6cf42f351aa24e5f1c8ea081cf5b8049632e47adbd397f89" - }, - { - "text": "Nevertheless, this approach may help some clinicians streamline referrals for AVS, especially when this resource is not readily available, for those who need it and spare those who do not.", - "tokenCount": 36, - "pageStart": 22, - "pageEnd": 22, - "hash": "7b6b094352af03a303d1131d9fa2f9f6972103ec28477a94a40e494c66ff615f" - }, - { - "text": "Given the low certainty in the tradeoffs between benefits and harms of aldosterone suppression testing, along with considerations regarding the costs, resource requirements, and expertise needed to perform it, as well as its feasibility, acceptability, and equity implications, the panel suggests conducting aldosterone suppression testing in individuals with an intermediate probability for lateralizing PA who desire to pursue eligibility for surgical therapy ( Fig.", - "tokenCount": 79, - "pageStart": 22, - "pageEnd": 22, - "hash": "c0dd4191c2d4a058fe361b1f93aba9b0e00fb38e4fb6ca50010f708654726897" - }, - { - "text": "Aldosterone suppression testing can be performed without stopping or changing antihypertensive medications as long as renin is low; when treatment with MRAs has been initiated and renin is no longer low, it is advised that these medications be stopped, and aldosterone suppression testing be performed only when renin is low again.", - "tokenCount": 66, - "pageStart": 22, - "pageEnd": 22, - "hash": "799444865ae8c554e16ae56ade3b40eb2d73f12b3b5901091bda0d7afc082cc7" - }, - { - "text": "2474 The Journal of Clinical Endocrinology & Metabolism , 2025, Vol.", - "tokenCount": 18, - "pageStart": 22, - "pageEnd": 22, - "hash": "06977aa95e567e92f59884e46a82ef44767f9cabe99193a8e8f23718048934c3" - }, - { - "text": "Comments The use of aldosterone suppression testing in individuals with a positive PA screen may best serve individuals and clinicians by providing them with a probabilistic framework to determine the optimal treatment pathway ( Fig.", - "tokenCount": 40, - "pageStart": 23, - "pageEnd": 23, - "hash": "7d825d2cc4d71c6b5e127877e5a4ed6fc5e22248facc5a7ec9621068ebd5ca70" - }, - { - "text": "The evidence for the outcomes of the percentage of individuals achieving BP control and detection of lateralizing PA following aldosterone suppression testing was very low.", - "tokenCount": 29, - "pageStart": 23, - "pageEnd": 23, - "hash": "1d48cf80e316619a1229d2fca78796118c82bde6c56de5c4f41d7d4a5647a1ae" - }, - { - "text": "However, conducting relatively safe testing to prognosticate the value of undergoing AVS (and determining the next therapeutic steps) would likely be valuable to individuals.", - "tokenCount": 32, - "pageStart": 23, - "pageEnd": 23, - "hash": "50ef76b1aa606927ff3516060df38c92dd203b482bef1ae5ac634399affc7253" - }, - { - "text": "In resourceconstrained settings, aldosterone suppression testing may be difficult to implement, considering the lack of evidence for major outcomes.", - "tokenCount": 27, - "pageStart": 23, - "pageEnd": 23, - "hash": "a0ac8b6848d9889afe1becea27d8e9caee4df45c0dc62b3067e836421d5ddf9c" - }, - { - "text": "Research Considerations Current gaps in knowledge call for further research in the following areas: Prospective, randomized, comparative outcome studies: The lack of a goldstandard diagnostic to define PA is one of the main reasons why aldosterone suppression tests are not uniformly calibrated to one another or validated against a central benchmark.", - "tokenCount": 62, - "pageStart": 23, - "pageEnd": 23, - "hash": "76f738d515ee33a60f6fb0f3dadb5267fb4814517f265b55ace66debc39c3c37" - }, - { - "text": "As a result, most available evidence provides lowquality information to reliably adjudicate whether the use of aldosterone suppression testing is superior to no aldosterone suppression testing.", - "tokenCount": 34, - "pageStart": 23, - "pageEnd": 23, - "hash": "f8a21f9dd3a462715907c4163dbe2d05c2cb43652c7a85b5a8a21d2f404aebf9" - }, - { - "text": "Prospective studies, employing randomization to each approach, and evaluating clinical efficacy outcomes are needed to robustly assess whether the practice of aldosterone suppression testing adds value in selecting the correct individuals for localization procedures and targeted treatment, and improves outcomes.", - "tokenCount": 49, - "pageStart": 23, - "pageEnd": 23, - "hash": "3cd3eb310647208f6f1efd74c98c46ddcf1dd892eb3f60c8ff9d8c6db3c2f80c" - }, - { - "text": "New diagnostic biomarkers: Novel cuttingedge omics technologies together with the application of artificial intelligence (AI) for disease prediction hold potential for the development of more effective biomarkers to diagnose PA.", - "tokenCount": 38, - "pageStart": 23, - "pageEnd": 23, - "hash": "6355115673d01bc82a4457591e5a17ce1f285218e0c87eb515e6487167f4b4e2" - }, - { - "text": "Besides the improved diagnostic performance of plasma or urinary steroid profiling to diagnose PA ( 82,114 ), a recent approach using multiomics data, including plasma miRNAs, plasma catechol Omethylated metabolites, plasma steroids, urinary steroid metabolites, and plasma small metabolites, integrated by machine learning, was able to correctly diagnose PA with high sensitivity and specificity distinguishing them from individuals with primary hypertension or other forms of endocrine hypertension ( 83 ).", - "tokenCount": 87, - "pageStart": 23, - "pageEnd": 23, - "hash": "f7335f2c481d2091cf922044fa2e5b5d77a2f6532d4860158309212d31076555" - }, - { - "text": "This and similar approaches, combining clinical data with biologic profiles, may provide better performances to diagnose PA and potentially lateralizing PA, thereby possibly eliminating the need for aldosterone suppression tests in the future.", - "tokenCount": 41, - "pageStart": 23, - "pageEnd": 23, - "hash": "219830a62e9a791343877ae714e11f0fc1edbe489edf0673f2e7fb1774c0d917" - }, - { - "text": "Medical Therapy vs Surgical Therapy for Individuals With Primary Aldosteronism Background Effective prevention of excess cardiovascular and cerebrovascular risk in individuals with primary aldosteronism (PA) involves targeted therapies for lateralizing and bilateral forms of the disease.", - "tokenCount": 51, - "pageStart": 23, - "pageEnd": 23, - "hash": "709faccc0ea7378bf965421c06c70faeb967c18bfadff386fc0d632ea937c6b2" - }, - { - "text": "For individuals with bilateral disease and those who do not desire or are not a candidate for surgery, lifelong pharmacotherapy with a mineralocorticoid receptor antagonist (MRA) is the standard approach.", - "tokenCount": 40, - "pageStart": 23, - "pageEnd": 23, - "hash": "a5a215182ffedecd559dccce6bac4eec11220b02f3b60adba884112973e9ca87" - }, - { - "text": "In contrast, surgical intervention is typically recommended for individuals with lateralizing PA who wish to pursue this option.", - "tokenCount": 21, - "pageStart": 23, - "pageEnd": 23, - "hash": "b243017c3bc8bc444e8b00986748f1492ee458fa9ca06f6780bf5c0f7fdc0aa3" - }, - { - "text": "However, surgical intervention requires adrenal venous sampling (AVS) to confirm lateralization, a procedure that demands significant expertise and specialized resources, often limited to tertiary care centers.", - "tokenCount": 37, - "pageStart": 23, - "pageEnd": 23, - "hash": "ae604e8b9abdfc55535f2a6b154df5e6a5db481c14ad9b3a0669e57155ec7235" - }, - { - "text": "These challenges highlight the need to balance the benefits and feasibility of medical vs surgical treatments.", - "tokenCount": 17, - "pageStart": 23, - "pageEnd": 23, - "hash": "b12a4bf45f448dd4c6dc0087c51058659c42829f673ef896e08a5778e8842a52" - }, - { - "text": "Considering these factors, the panel formulated this question to determine the best management strategy for individuals with PA.", - "tokenCount": 20, - "pageStart": 23, - "pageEnd": 23, - "hash": "c67c2515a13105d0b51aef35a1765dbd100cbfef96bc53af65cfb386a27194eb" - }, - { - "text": "Should primary aldosteronismspecific medical therapy vs surgical therapy be used in individuals diagnosed with primary aldosteronism?", - "tokenCount": 27, - "pageStart": 23, - "pageEnd": 23, - "hash": "6a930a493eee6f0f2e7d4a6dd35a7139a76d6ed09d2f53ee0dda2173b2962c91" - }, - { - "text": "2 ): Surgical therapy by total unilateral adrenalectomy, usually by the laparoscopic approach, is mainly offered to individuals with lateralizing PA who choose to pursue the surgical option ( Fig.", - "tokenCount": 40, - "pageStart": 23, - "pageEnd": 23, - "hash": "97027a8dce2981a20f679ceda04916744c2b140879b89756776c9b2d75c1d512" - }, - { - "text": "Lifelong medical therapy that includes an MRA is usually offered to individuals with bilateral PA or lateralization status unknown (refer to Question 6 for definition of lateralization) and to those who decline the surgical option or who are not surgical candidates ( Fig.", - "tokenCount": 52, - "pageStart": 23, - "pageEnd": 23, - "hash": "a013041c8ebcd253a312b282d12a044a04bf8044f78830b6ef7586cf295b59df" - }, - { - "text": "Individuals with mild PA typically have bilateral disease and may bypass AVS, proceeding directly to medical management ( Fig.", - "tokenCount": 23, - "pageStart": 23, - "pageEnd": 23, - "hash": "e27fd2ab7ec1d57de58d692de7a6f9d2e8e514a10ff96a04630fe90b9627c754" - }, - { - "text": "org/profile/FT5oNrFmGsY .", - "tokenCount": 14, - "pageStart": 23, - "pageEnd": 23, - "hash": "fdb2ec7a44f7bb909f191ccc9764ce65faf39d84e39994959259e4114e3bc1c7" - }, - { - "text": "Benefits and Harms The panel voted for the following patientimportant outcomes for Question 5 decision making: 1) percent of individuals achieving blood pressure (BP) control, 2) number of antihypertensive agents, 3) dosage of antihypertensive agents, 4) systolic BP (SBP) level, 5) major adverse cardiovascular events (MACEs), 6) atrial fibrillation, 7) stroke, 8) ischemic heart disease, 9) heart failure, 10) cardiovascular mortality, 11) allcause mortality, and 12) adverse events.", - "tokenCount": 118, - "pageStart": 23, - "pageEnd": 23, - "hash": "d90801ddc135ac4a8614c7cb851d070e71bb22b8b577c0ab66d046fd7a7f57b7" - }, - { - "text": "Systematic review metadata ( 53 ) from 4 randomized controlled trials (RCTs) enrolling 669 individuals with PA (mean age 52.", - "tokenCount": 29, - "pageStart": 23, - "pageEnd": 23, - "hash": "5690c7acd0414b351b796bb33cbfa2c5b98dc5aa83692b1dfd39433df378d8c9" - }, - { - "text": "7% females) and from 52 comparative observational studies with 17 893 individuals with PA (mean age 52.", - "tokenCount": 22, - "pageStart": 23, - "pageEnd": 23, - "hash": "02597813d04c147d86d7fbbfd98a3f85849968f9921210b9dd5e1032b5a4e2de" - }, - { - "text": "9% females) were included for evidence synthesis.", - "tokenCount": 10, - "pageStart": 23, - "pageEnd": 23, - "hash": "0a8d6dfe0e34a5610dbcbd20859001f256b3727d32eeb106c4dd0abffc05c3f2" - }, - { - "text": "9 2475 Downloaded from https://academic.", - "tokenCount": 11, - "pageStart": 23, - "pageEnd": 23, - "hash": "841cec025e3c038315be6134c937ea77b6b24db52e1faa4b58bd4e4469046bf8" - }, - { - "text": "No significant differences between medical and surgical management were identified for hypertension remission.", - "tokenCount": 14, - "pageStart": 24, - "pageEnd": 24, - "hash": "217b4956a1d30d6b621c9685eadc3d42c91762ce1410aba327e144d966c3d9c6" - }, - { - "text": "However, a metaanalysis ( 53 ) of 20 observational studies, including 3209 individuals with PA, showed an association of lower longterm efficacy in achieving BP control with PAspecific medical therapy compared with surgical therapy (odds ratio [OR]: 0.", - "tokenCount": 52, - "pageStart": 24, - "pageEnd": 24, - "hash": "77f3ddde2e8208e8673d1ac29be8ec68f345bb82126fb42ee79e92fa8f001394" - }, - { - "text": "Additionally, longterm SBP levels were higher with medical management in an analysis of 42 observational studies ( 53 ) of 10 286 persons with PA mean difference (MD: 4.", - "tokenCount": 35, - "pageStart": 24, - "pageEnd": 24, - "hash": "081bd881bfd2b4444d7aa9eab3ff8e63e31558b26e6cc614a332ff189bba8cbf" - }, - { - "text": "Observational studies also indicate that medical treatment for PA is associated with a higher number of antihypertensive agents (21 studies, 4998 individuals) and higher dosage of antihypertensive agents (8 studies, 1409 individuals) compared with surgical intervention (MD: 1.", - "tokenCount": 57, - "pageStart": 24, - "pageEnd": 24, - "hash": "914f02230a04b24095a0d9d55bf881bab6357e86518a2856452178566922b7d8" - }, - { - "text": "The higher number of antihypertensive agents with medical treatment was supported by a review of clinical trials including 425 persons with PA (MD: 1.", - "tokenCount": 30, - "pageStart": 24, - "pageEnd": 24, - "hash": "02e3f2a43f40bc11a44c4959a9b0ff36213a5c28cf25111cde0c2da00015bcd9" - }, - { - "text": "830) ( 115-117 ), and the higher dosage of antihypertensive agents associated with medical vs surgical management persisted in an analysis based on lateralizing disease only (MD: 1.", - "tokenCount": 38, - "pageStart": 24, - "pageEnd": 24, - "hash": "080a68d0f15fc99671adccbf3f511da85a1cbbc0bfec8a47852cafae2c231059" - }, - { - "text": "The systematic review ( 53 ) assessed the comparative efficacy of medical vs surgical management for cardiovascular risk.", - "tokenCount": 19, - "pageStart": 24, - "pageEnd": 24, - "hash": "dc0269a328447aa9982aa7ada2472dd08c326a89b8542772963dcf7439eeaf2c" - }, - { - "text": "No statistically significant differences were found between the 2 treatment modalities for ischemic heart disease, atrial fibrillation, MACEs, and cardiovascular mortality.", - "tokenCount": 33, - "pageStart": 24, - "pageEnd": 24, - "hash": "b63989c382bb2f90144001d0c435ce4c705e8b04c16eccac63273b33f3a7b68e" - }, - { - "text": "However, compared with surgical therapy, review of observational studies indicated medical management had an increased risk of stroke (OR: 1.", - "tokenCount": 25, - "pageStart": 24, - "pageEnd": 24, - "hash": "9c22368992b6ef9b3bb8b48bca7b9214b07a085504d8b81d67cf5ad9bc90864c" - }, - { - "text": "The increased risk for heart failure and allcause mortality persisted in a review of metadata based on lateralizing PA only (OR: 2.", - "tokenCount": 27, - "pageStart": 24, - "pageEnd": 24, - "hash": "2e32c9a72ed2fd0bd56d98c89243ed6223d1ab7ffb8bf5e0ddcdd54c57a4109f" - }, - { - "text": "One cohort study reported that MRA therapy compared with adrenalectomy had a higher risk of mortality, major cardiac or cardiovascular events, and combined newonset atrial fibrillation with mortality ( 118 ).", - "tokenCount": 41, - "pageStart": 24, - "pageEnd": 24, - "hash": "886fb2f22d1582d57928e7e1135143055f77f940d40dd83c551d5df79568136a" - }, - { - "text": "However, this increased risk might be mitigated with adequate mineralocorticoid receptor blockade based on unsuppressed renin activity ( 9 ).", - "tokenCount": 29, - "pageStart": 24, - "pageEnd": 24, - "hash": "76c9c4b1d68838899859af635430a272ac6ae9a522443f6cf83080bd3ba41d77" - }, - { - "text": "Due to offtarget androgen receptor antagonism and progesterone receptor agonism, spironolactone has dosedependent side effects of gynecomastia and sexual dysfunction in men and menstrual irregularities in women ( 116,119-121 ).", - "tokenCount": 51, - "pageStart": 24, - "pageEnd": 24, - "hash": "edf99a1827b1998a835d5a008b24badf5068713d889fc969a8a198f41bf19203" - }, - { - "text": "The metaanalysis of a systematic review of 2 observational studies estimated significantly higher medicationrelated adverse events with medical therapy compared to surgical therapy (OR: 29.", - "tokenCount": 30, - "pageStart": 24, - "pageEnd": 24, - "hash": "c1ecf81fa825bda5d076cf8c92947570a254d2854e79eda6444c1eed7d542b4c" - }, - { - "text": "Of note, fewer side effects were associated with eplerenone than spironolactone, consistent with eplerenone s greater specificity for the mineralocorticoid receptor ( 122 ). While the antihypertensive efficacy of eplerenone was lower than that of spironolactone, the eplerenone doses studied were about onethird less potent than the spironolactone doses.", - "tokenCount": 87, - "pageStart": 24, - "pageEnd": 24, - "hash": "63c295e6fd08e29e9b64a88507d8669e517247b863018aa2311b6a69c1c1cb32" - }, - { - "text": "Therefore, the panel concluded that the balance of effects favor surgery, depending on lateralization of aldosterone hypersecretion, individual choice, and suitability for surgery.", - "tokenCount": 34, - "pageStart": 24, - "pageEnd": 24, - "hash": "f8239d3a4af2b6be4b4af69bd553f9451efd87a83d1da3e3c57e339e4e833825" - }, - { - "text": "Refer to Question 6 for a definition of lateralization.", - "tokenCount": 11, - "pageStart": 24, - "pageEnd": 24, - "hash": "cab8889eec2411bb4d0fa552bab187b2a75b614b2c4959068b901a9f6bdbed8a" - }, - { - "text": "Evidence to Decision Factors Medical treatment is cheaper and requires fewer resources ( 124 ).", - "tokenCount": 16, - "pageStart": 24, - "pageEnd": 24, - "hash": "ff3882c475f181b1313ebae22a2f6a4d25cdbc5534eca7246cfc1dc2df5df4e9" - }, - { - "text": "However, in an individual with PA and a remaining life expectancy of 25.", - "tokenCount": 15, - "pageStart": 24, - "pageEnd": 24, - "hash": "c85715f755841fcafaedb658c22622ab7703311b6b7c669cb488fea204a09d3f" - }, - { - "text": "4 years or more, surgery was estimated as the least costly strategy in the longterm due to the decreased risk of PAassociated adverse events ( 125 ).", - "tokenCount": 30, - "pageStart": 24, - "pageEnd": 24, - "hash": "246e8be01fffff6a27c606484c7b8d4468297984a35bcb1ef3073b2c947e5509" - }, - { - "text": "MRAs are readily available, including in resourcepoor settings, whereas surgery requires additional resources.", - "tokenCount": 18, - "pageStart": 24, - "pageEnd": 24, - "hash": "69603525b3140a98ae5ca99478213f97ce462e85de6bf29ca2f0eaaa25b02862" - }, - { - "text": "MRA treatment is equitable and independent of socioeconomic status with no significant inequality of outcomes ( 126 ).", - "tokenCount": 19, - "pageStart": 24, - "pageEnd": 24, - "hash": "260b29e364a25f23324fce63df1f2701995aee70b378848d74fefa127e84a1cb" - }, - { - "text": "MRA therapy is often preferred by health care clinicians due to its accessibility and low cost.", - "tokenCount": 18, - "pageStart": 24, - "pageEnd": 24, - "hash": "d209d5ddf9645a9f5822253a108d80281f5f197fd582b558883ad16145ebfe67" - }, - { - "text": "However, individual adherence to spironolactone is lower compared with other antihypertensive medications, possibly related to its antiandrogen and progestogenic side effects.", - "tokenCount": 35, - "pageStart": 24, - "pageEnd": 24, - "hash": "518295c78047975bfe151163aa56d914a3b9c6475b0e2320e1668a90b3e74686" - }, - { - "text": "Adherence may improve with the use of more selective MRAs, such as eplerenone and potentially finerenone ( 127-129 ).", - "tokenCount": 29, - "pageStart": 24, - "pageEnd": 24, - "hash": "99d0a3aedaae91522d4766a243045d3d1d4787fd328b0bd164985fce96c3cf7b" - }, - { - "text": "Adrenalectomy appeals to individuals seeking a definitive cure for hypertension.", - "tokenCount": 14, - "pageStart": 24, - "pageEnd": 24, - "hash": "bf45dce5ca505e92ad2be53915a33a0aa5ebe6c30151063fdeab698406df42a1" - }, - { - "text": "Justification for the Recommendation Based on the systematic review and indirect evidence, the panel provided a recommendation for either medical therapy or surgical intervention for the treatment of PA.", - "tokenCount": 33, - "pageStart": 24, - "pageEnd": 24, - "hash": "382819aaf8c2ba5d9297670256a00a04f0ef251ef81aac113d41b6140cfd5ca1" - }, - { - "text": "This recommendation is based on the observed benefits of surgical treatment, including lower SBP, more effective BP control, reduced risk of stroke, fewer MACEs, lower incidence of heart failure, decreased need for antihypertensive medications, improved quality of life (QOL), and lower allcause mortality.", - "tokenCount": 61, - "pageStart": 24, - "pageEnd": 24, - "hash": "8946384ca8838baff60ec1dc77d0e5d5143fbd22a7ab614e74313367a01973e7" - }, - { - "text": "While medical therapy with MRAs showed less favorable outcomes overall, the excess risk of hard outcomes might be mitigated by monitoring treatment response based on an increase in renin rather than the BP response alone ( 9 ) (refer to Question 7).", - "tokenCount": 49, - "pageStart": 24, - "pageEnd": 24, - "hash": "fa1838f540563eb399105ba718835146e7d5fc80639bbafcb2fb5e79e8a3698d" - }, - { - "text": "However, individuals often favor surgical therapy due to the possibility of avoiding lifelong medical therapy, overall QOL improvements, limited pharmacologic treatment options, and side effects of some MRAs (eg, spironolactone).", - "tokenCount": 44, - "pageStart": 24, - "pageEnd": 24, - "hash": "11149d8716548221bfa55267dd73e08560bfa68a368f6f9886225955dd3d8ed9" - }, - { - "text": "Thus, surgical treatment is generally preferred by individuals with lateralizing PA and may offer superior outcomes, but the choice between surgical and medical management should be based on individual characteristics, preferences, and the specific presentation of the disease.", - "tokenCount": 44, - "pageStart": 24, - "pageEnd": 24, - "hash": "f7c3fb218db881993bb55212d69d8bbb4ba254c53b251af528668a0ffef8a495" - }, - { - "text": "For a definition of lateralization, refer to Question 6.", - "tokenCount": 12, - "pageStart": 24, - "pageEnd": 24, - "hash": "5a7a841ce29b8192458e9ce4dd23eb3f6114e298e45d42357fdb595a94a82d69" - }, - { - "text": "Comments Individuals managed either medically or surgically should be monitored according to clinical and biochemical outcomes and to ensure clinical safety as recommended by international expert consensuses and in Questions 7 and 9 ( 85,86 ).", - "tokenCount": 41, - "pageStart": 24, - "pageEnd": 24, - "hash": "4ae948d04fecc3b7c0cb7bf901309844203a7dff40a5a2cbde0c9d01e5dd19d3" - }, - { - "text": "Postsurgical outcomes partly depend on successful AVS and the availability of skilled adrenal surgeons, which might be limited outside specialized centers.", - "tokenCount": 26, - "pageStart": 24, - "pageEnd": 24, - "hash": "9114c032ec64ad8a18f074e3d6c39bf9a5e93ce6954154fcf15a106f3227777d" - }, - { - "text": "Preoperative morbidity and length of stay are more favorable in highvolume centers ( 130 ).", - "tokenCount": 18, - "pageStart": 24, - "pageEnd": 24, - "hash": "bfd332206e0cb04e928ce8752fa6dd1f16c85804d2e1236f0b904183de6f8d62" - }, - { - "text": "Adrenalectomy is mainly performed by a laparoscopic approach, but open adrenalectomy can be considered under specific conditions (eg, in individuals who have had multiple prior laparotomies).", - "tokenCount": 40, - "pageStart": 24, - "pageEnd": 24, - "hash": "1cbc47aa8d08c6b74d2e5a8a8f02c40b5e89bba270f75f08d2bc169530c5b979" - }, - { - "text": "Individuals with bilateral PA in whom medical therapy is not welltolerated or effective can be considered for unilateral adrenalectomy although evidence regarding clinical effectiveness in those situations is limited ( 131-133 ).", - "tokenCount": 40, - "pageStart": 24, - "pageEnd": 24, - "hash": "cb3e91a716ff6a8ff8af78230e7908ccc344bad3832c74ebe4237a4acd1dd90b" - }, - { - "text": "2476 The Journal of Clinical Endocrinology & Metabolism , 2025, Vol.", - "tokenCount": 18, - "pageStart": 24, - "pageEnd": 24, - "hash": "a8414fd839943534069c828cb1e0088cae0509ed016771aa38de473b7078056a" - }, - { - "text": "Research Considerations Further research is necessary to investigate the protective effects of aldosterone synthase inhibitor therapy as well as other strategies like adrenal ablation and tailored approaches for milder forms of PA.", - "tokenCount": 41, - "pageStart": 25, - "pageEnd": 25, - "hash": "94a43f4ed7829ad5ed8ae597967984d097ae73285c841c9ef1409d2df6d190f6" - }, - { - "text": "Role of Adrenal Venous Sampling and Computed Tomography Scanning in Determining Lateralization of Primary Aldosteronism Background Crosssectional imaging (eg, computed tomography [CT] or magnetic resonance imaging [MRI]) has limitations in the evaluation of individuals with primary aldosteronism (PA) because it cannot determine the functional activity of adrenal glands.", - "tokenCount": 77, - "pageStart": 25, - "pageEnd": 25, - "hash": "3295c4b024fd0468758467ce1e86fcb2ce4ec46c9e14314d3e410b7dd90cf813" - }, - { - "text": "This can result in misclassification as lateralizing or bilateral PA, especially in those with bilateral adrenal hyperplasia or nonfunctional adrenal nodules.", - "tokenCount": 32, - "pageStart": 25, - "pageEnd": 25, - "hash": "27cc0396a39635bab1b6f7e81b350d7e27291a450fedfbab99bf985d495f2a3b" - }, - { - "text": "While adrenal venous sampling (AVS) can improve diagnostic accuracy and guide treatment decisions, its limited availability raises the question of whether its use significantly improves outcomes compared with CT scanning alone.", - "tokenCount": 38, - "pageStart": 25, - "pageEnd": 25, - "hash": "b97b3823e74763e0adb3751422a4a14d2a85c14d3dab44f49c0d150afe2f70d3" - }, - { - "text": "This guideline question addresses whether care guided by adrenal lateralization using both CT scanning and AVS should be preferred over CT scanning alone for directing the treatment approach in individuals with PA.", - "tokenCount": 36, - "pageStart": 25, - "pageEnd": 25, - "hash": "baf394475ff57323bc8953e1e9de684bf5e917f29c50497c38ecb95969691a0c" - }, - { - "text": "Should care guided by adrenal lateralization with computed tomography scanning and adrenal venous sampling vs computed tomography scanning alone be used for deciding treatment approach in individuals with primary aldosteronism? Recommendation 6 In individuals with primary aldosteronism (PA) considering surgery, we suggest adrenal lateralization with computed tomography (CT) scanning and adrenal venous sampling (AVS) prior to deciding the treatment approach (medical or surgical) (2 | OO). Technical remarks Individuals with PA who desire and are candidates for adrenalectomy should undergo AVS in order to reliably differentiate lateralizing from bilateral forms.", - "tokenCount": 131, - "pageStart": 25, - "pageEnd": 25, - "hash": "196b4f857b3f6bbbe9557b42fb1ddec076fc8054ab6904ec1fec952395408b50" - }, - { - "text": "A potential exception is when the diagnosis of unilateral aldosteroneproducing adenoma (APA) is so likely that AVS could be considered unnecessary (eg, individual age < 35 years with marked PA with hypokalemia and > 1.", - "tokenCount": 50, - "pageStart": 25, - "pageEnd": 25, - "hash": "8c362f358bf3ced54ae991c361461aa57a448fce975d102c21a7a999a980a3a3" - }, - { - "text": "org/profile/FL6i3ZvDYXg .", - "tokenCount": 15, - "pageStart": 25, - "pageEnd": 25, - "hash": "9dd02d6b95be561ee1d4556b3a933fee3d3502d95989d3df6c301880f1298b01" - }, - { - "text": "Benefits and Harms The panel voted for the following patientimportant outcomes for Question 6 decision making: 1) detection of lateralizing PA, 2) biochemical cure rate postadrenalectomy, 3) percent of individuals achieving blood pressure (BP) control, 4) number of antihypertensive agents, 5) dosage of antihypertensive agents, 6) systolic BP (SBP) level, and 7) adverse events.", - "tokenCount": 90, - "pageStart": 25, - "pageEnd": 25, - "hash": "d20c1b1bef96634c457b119bc831a0184552898f36a7da2e1fc8e043da93227a" - }, - { - "text": "A systematic review of 38 studies including 950 individuals reported that when AVS was used as the criterion standard test for the diagnosis of lateralizing PA, CT/MRI misdiagnosed the cause of PA in 37.", - "tokenCount": 42, - "pageStart": 25, - "pageEnd": 25, - "hash": "ccf1a82c8024a6861c42af521ef327ef0a1b92476f866bbce93b2b5d591eb112" - }, - { - "text": "Several retrospective studies reported lowlevel concordance between CT scanning alone and CT scanning plus AVS ( 89,135 , 136 ).", - "tokenCount": 26, - "pageStart": 25, - "pageEnd": 25, - "hash": "4f94353eaba7258a99ab96ae5cacd707f1bf5cac7266df4f1528e8c401f9a35d" - }, - { - "text": "In individuals who were biochemically cured after surgery with AVSbased management, CT/MRI alone correctly detected lateralizing PA in 58.", - "tokenCount": 28, - "pageStart": 25, - "pageEnd": 25, - "hash": "9535a47abb2ce3a6f810090b3bec77bb94cb6cd88374bb8cb0582f71a1595f65" - }, - { - "text": "6% ( 135 ) and 64% of cases ( 89 ).", - "tokenCount": 13, - "pageStart": 25, - "pageEnd": 25, - "hash": "4d287c2e346d43392a10ebce5f9c5b4665ee63d8884ce8996e02b1dd928f4a9c" - }, - { - "text": "These studies highlight the limitations of adrenal CT in the diagnosis of unilateral aldosteroneproducing adenomas (APAs). Small unilateral APAs may not be visible on CT, leading to misinterpretation as normal adrenal glands.", - "tokenCount": 46, - "pageStart": 25, - "pageEnd": 25, - "hash": "c1cf5a371a16ab96f6ae6aa5b1de99551a5f8b60bb414e1900ea4722fa6cb567" - }, - { - "text": "Conversely, apparent microadenomas on CT might actually be areas of hyperplasia, making unilateral adrenalectomy inappropriate.", - "tokenCount": 25, - "pageStart": 25, - "pageEnd": 25, - "hash": "e03c01fe1f2824e1b92d9a77aff9c5d9d0800f0b78e89ce6c7cfa1144089ff02" - }, - { - "text": "Furthermore, nonfunctioning unilateral adrenal macroadenomas, which are common in individuals older than age 35 years, cannot be distinguished from APAs on CT.", - "tokenCount": 33, - "pageStart": 25, - "pageEnd": 25, - "hash": "904250974c083865edfe80cfa61ca8c2277cccf35ddbe747f9223332662cbcd7" - }, - { - "text": "Therefore, to address the performance of adrenal lateralization with CT scanning plus AVS vs CT scanning alone for the management of PA, the systematic review ( 53 ) identified one randomized controlled trial (RCT) ( 117 ) enrolling 200 individuals with PA (mean age 53.", - "tokenCount": 56, - "pageStart": 25, - "pageEnd": 25, - "hash": "677e1dfa44ccbd41ec114e4baf538f94d945941e702e45e9f318d99c94e181c0" - }, - { - "text": "7% female) and 29 comparative observational studies with 8375 participants (mean age 50.", - "tokenCount": 18, - "pageStart": 25, - "pageEnd": 25, - "hash": "aca885ec1c40c856c57e9259ab9190dba13d437c6fee0ccb775dbcbf1f677234" - }, - { - "text": "Data from the RCT alone did not show differences in intensity of antihypertensive medications, BP control, or biochemical remission after 1-year of followup.", - "tokenCount": 33, - "pageStart": 25, - "pageEnd": 25, - "hash": "f40f1be3d8983a1d708a190dfd5206bcfe0ea5d04d109306c38aa9b79365d5b2" - }, - { - "text": "Metaanalysis of 4 observational studies including 1070 individuals with PA indicated that compared with AVSbased management, CT scanning alone may be associated with lower postoperative biochemical cure (odds ratio [OR]: 0.", - "tokenCount": 41, - "pageStart": 25, - "pageEnd": 25, - "hash": "3675738a40215ad9a73526b30931ba9bdff454b90620a73ee37eeac2e644488b" - }, - { - "text": "Otherwise, comparable outcomes were observed between AVSand CTbased management approaches for the detection of lateralizing PA, achieving BP control, number or dosage of antihypertensive medications, and SBP levels.", - "tokenCount": 40, - "pageStart": 25, - "pageEnd": 25, - "hash": "ccb67a571469fd988f8252be23447a6bfd8756ec3492e4b8753a7ca221385dd2" - }, - { - "text": "Additionally, an observational, retrospective, multicenter study reported an overall adrenal vein rupture during 0.", - "tokenCount": 20, - "pageStart": 25, - "pageEnd": 25, - "hash": "88c46d4598044fa7d3dbd8bdbf6f55d37d144989da0824831c0cdc8809f79aeb" - }, - { - "text": "61% of AVS procedures, with an inverse correlation between rupture incidence and the radiologist s experience in performing AVS studies ( 140 ).", - "tokenCount": 29, - "pageStart": 25, - "pageEnd": 25, - "hash": "d575a1b7a3e6ad46150edd6a6232798949b342f008853d33c1229348084ca5d4" - }, - { - "text": "Evidence to Decision Factors Resource requirements for AVS include training and time of expert interventional radiologists, accurate laboratory measurements, and interpretation of AVS results ( 141 ).", - "tokenCount": 34, - "pageStart": 25, - "pageEnd": 25, - "hash": "e4ec661e02dad3337e143340b8ee6feba74a10556538a699e2757694f6f1728c" - }, - { - "text": "One RCT reported increased average health care costs for individuals undergoing AVS ( 117 ), but decisiontree modeling and incremental costeffectiveness ratios (ICERs) based on qualityadjusted life years (QALYs) report that AVSbased care is more costeffective ( 124,142 ).", - "tokenCount": 59, - "pageStart": 25, - "pageEnd": 25, - "hash": "d73cfabaa53ed53f915d088f9b506fe16bb06963c81402da47aa7d9cc767a871" - }, - { - "text": "AVS has low feasibility to implement due to the requirement for a highly trained interventional radiologist and other additional resources and is probably less acceptable The Journal of Clinical Endocrinology & Metabolism , 2025, Vol.", - "tokenCount": 44, - "pageStart": 25, - "pageEnd": 25, - "hash": "0a6ed59438ffcf04ad2a0f8402c8063480514aa8f56691cdb3e8c5c6fb824cce" - }, - { - "text": "9 2477 Downloaded from https://academic.", - "tokenCount": 11, - "pageStart": 25, - "pageEnd": 25, - "hash": "5650bd278fd8d6cc37b55bd242f94f8a5f026763cf0c573ad6e3226420a16365" - }, - { - "text": "to care clinicians who do not have local or regional access to a center that performs AVS with a high bilateral adrenal vein cannulation success rate.", - "tokenCount": 30, - "pageStart": 26, - "pageEnd": 26, - "hash": "bdda9e68728d81a95009ece1c7b8ec98736b979dea9b3e99b6d9e30f02dba7b2" - }, - { - "text": "AVS might be unacceptable to some individuals unwilling to undergo an invasive procedure but should be acceptable to individuals who want to achieve hypertension cure and avoid both noncurative surgery based on CT findings alone and lifetime pharmacotherapy.", - "tokenCount": 43, - "pageStart": 26, - "pageEnd": 26, - "hash": "927173b81fa2ab708e19568eec9efdb0664eaefb04c033d34267ad6fc1288c1d" - }, - { - "text": "AVS has higher costs relative to CTguided care, is not widely available in most countries, and is offered only in highly specialized centers and not at all in resourcepoor countries.", - "tokenCount": 36, - "pageStart": 26, - "pageEnd": 26, - "hash": "c207a12e27ccfe83751bf660da9202955f1137954731b57f2795b967bdee63aa" - }, - { - "text": "Although AVS is more accurate than crosssectional imaging, it is substantially more costly and difficult to implement.", - "tokenCount": 21, - "pageStart": 26, - "pageEnd": 26, - "hash": "017ec0947fe9e2dde366375c6176bd32476bbda764893daf0b907616c5f2c17b" - }, - { - "text": "Individuals with PA prioritize the accurate detection of surgically treatable forms; therefore, AVS is acceptable and desired by those who favor a cure of PA over lifelong mineralocorticoid receptor antagonist (MRA) therapy.", - "tokenCount": 46, - "pageStart": 26, - "pageEnd": 26, - "hash": "801eec05d5cfdb4ec940a015f3486fe758ac21a75b29a0887a829d83ea479c32" - }, - { - "text": "Justification for the Recommendation The panel recommended that for individuals diagnosed with PA who are candidates for surgical intervention, the treatment approach should be guided by adrenal lateralization using both CT scanning and AVS.", - "tokenCount": 41, - "pageStart": 26, - "pageEnd": 26, - "hash": "a161125e82420ef75be14e5f498d61f13d5754a0d55fc8caa41f48b3946614d1" - }, - { - "text": "This recommendation is based primarily on indirect evidence, and partially supported by direct evidence, highlighting the low detection rate of lateralizing PA with CT scanning alone compared with combined CT scanning and AVS.", - "tokenCount": 38, - "pageStart": 26, - "pageEnd": 26, - "hash": "f745897315187a544c1dc5c7703c4dbf889d3fb8b16fccce40f45080312caf6c" - }, - { - "text": "Also considered was the value that clinicians place on the accuracy of aldosterone lateralization because it leads to successful surgical outcomes in those individuals who want to pursue a surgical cure.", - "tokenCount": 35, - "pageStart": 26, - "pageEnd": 26, - "hash": "02cd97da71fe6295880e0fc0e934bba49af1d1716ab86e60f08a100c07fe7fd6" - }, - { - "text": "CT (or MRI) cannot assess the functional activity of adrenal glands and may misclassify individuals, particularly those with bilateral adrenal hyperplasia or nonfunctional adrenal nodules.", - "tokenCount": 38, - "pageStart": 26, - "pageEnd": 26, - "hash": "ddaf44f11e6496cf995f725eca299227a5c44692f1493bf272f9d88744543490" - }, - { - "text": "Thus, in individuals who are surgical candidates, an additional localization step is needed, and the most accurate currently available option is AVS.", - "tokenCount": 27, - "pageStart": 26, - "pageEnd": 26, - "hash": "e695f351b821961739c4e13c4d7d9ef9d5fe12a517da41a8872110cf54b5b06a" - }, - { - "text": "Although a prospective randomized trial reported no apparent outcome differences between CTbased and cosyntropinstimulated AVSbased management ( 117 ), several caveats need to be considered.", - "tokenCount": 34, - "pageStart": 26, - "pageEnd": 26, - "hash": "8399a01158d64fc6b057a95164d9c16bdaeee929c0b8ffd5f60ff986bf8ba74d" - }, - { - "text": "For example, medication and BP outcome data at 1 year after intervention were pooled from the surgical and medically managed individuals in each arm of the study, which failed to recognize that MRA treatment is a surgical equivalent.", - "tokenCount": 43, - "pageStart": 26, - "pageEnd": 26, - "hash": "55bed0094f90cc01bf28c85389cbf603936512a64817df77af14d1e78174e0cf" - }, - { - "text": "The study was not powered to detect outcome differences in those individuals treated only with surgery based on CT vs AVS.", - "tokenCount": 23, - "pageStart": 26, - "pageEnd": 26, - "hash": "0eceb656b6e707addef67daf7e7efcab7ee65e1bfb6089d0d18a597475eba706" - }, - { - "text": "Additional issues with this study included the selection bias toward more florid forms of PA, which limited its generalizability, and a suboptimal selectivity index cutoff for AVS ( > 3:1 with a cosyntropin infusionstimulated protocol) that may have led to surgical management in individuals with bilateral adrenal disease in the AVSbased care cohort.", - "tokenCount": 75, - "pageStart": 26, - "pageEnd": 26, - "hash": "83b6177d4dfbe4bbe1ae0ce8098f2fa3603369741bd51448fe3c1e55e2dfe502" - }, - { - "text": "In addition, 5 of the 92 individuals in the CTbased management group had apparent unilateral adrenal disease on CT scan but were not managed surgically.", - "tokenCount": 30, - "pageStart": 26, - "pageEnd": 26, - "hash": "e4b1a3831aae85b6305791755329b6a58123b79ccd25b9ad986790b5e82a84d5" - }, - { - "text": "Implementation Strategies AVS success rates depend on the experience of the operators and thus performance in centers with high expertise is recommended ( 143 ).", - "tokenCount": 27, - "pageStart": 26, - "pageEnd": 26, - "hash": "6ce422297c01315fdabfb2a66b90cf52e6e7bdf92bfbe782f4a89023b388c44f" - }, - { - "text": "Most centers use radiographic contrast administration during AVS to help localize the adrenal veins.", - "tokenCount": 19, - "pageStart": 26, - "pageEnd": 26, - "hash": "a902fd734c5654ecf485f62a45f171eea8d9eb6d627ab443f414ad901e122c6b" - }, - { - "text": "Contrast administration carries a risk of a contrast allergy reaction, as does contrastenhanced adrenal CT.", - "tokenCount": 21, - "pageStart": 26, - "pageEnd": 26, - "hash": "ca59a7ff61fefedc6908f14600435497f39dd28b1a01f7960598543027165548" - }, - { - "text": "A contrast allergy may necessitate the use of cosyntropin for AVS for those individuals treated with exogenous corticosteroids for contrastassociated allergic reaction prevention ( 144 ).", - "tokenCount": 36, - "pageStart": 26, - "pageEnd": 26, - "hash": "4defec7758bbc744eee427a182a653e7b9e14016bd9f72a18877c4170c514304" - }, - { - "text": "Three protocols have been used successfully for AVS: 1.", - "tokenCount": 12, - "pageStart": 26, - "pageEnd": 26, - "hash": "1268891ea1055b1395804a2e75986b095e1aad4b7a3a7bed98f010da32b6b05c" - }, - { - "text": "Unstimulated sequential or simultaneous bilateral AVS; 2. Unstimulated sequential or simultaneous bilateral AVS followed by bolus cosyntropinstimulated sequential or simultaneous bilateral AVS; and 3. Continuous cosyntropin infusion with sequential bilateral AVS.", - "tokenCount": 53, - "pageStart": 26, - "pageEnd": 26, - "hash": "5aff9bb53e5f7288f2a1fd09bded72938710700b4eff9aae2bd8b7b2ff7022ff" - }, - { - "text": "Simultaneous bilateral AVS is difficult to perform and is not used at most centers ( 145,146 ).", - "tokenCount": 22, - "pageStart": 26, - "pageEnd": 26, - "hash": "fdd85bd546e57501fa3604fc9680e51f0cfd1cc878aa6e9fa99a8d4d304cc8ba" - }, - { - "text": "Many groups advocate the use of continuous cosyntropin infusion during AVS to minimize stressinduced fluctuations in aldosterone secretion during nonsimultaneous (sequential) AVS, maximize the gradient in cortisol from adrenal vein to inferior vena cava and thus confirm successful sampling of the adrenal vein, and maximize the secretion of aldosterone from an APA and thus avoid the risk of sampling during a relatively quiescent phase of aldosterone secretion ( 85,147-149 ).", - "tokenCount": 101, - "pageStart": 26, - "pageEnd": 26, - "hash": "97527d93409055e6a868e6ba43b3c3881854e86c42f246500b10b0d297d00a6e" - }, - { - "text": "However, there is a lack of consensus on the use of cosyntropin stimulation to assess for lateralization ( 150 ).", - "tokenCount": 25, - "pageStart": 26, - "pageEnd": 26, - "hash": "24b9620ecdcef25904ec3b5a4814aa32933d3fd26a846833cdc63b377ffcdf7f" - }, - { - "text": "Aldosterone and cortisol concentrations are measured in the blood from all 3 sites (right and left adrenal veins and inferior vena cava [IVC]).", - "tokenCount": 32, - "pageStart": 26, - "pageEnd": 26, - "hash": "11e172927f79615d4afdc8c527c7002e72645541ba9dbff9b828bf2bfad7df63" - }, - { - "text": "The IVC sample may be obtained from veins that are even more peripheral (eg, external iliac vein) ( 141 ).", - "tokenCount": 26, - "pageStart": 26, - "pageEnd": 26, - "hash": "22bca51f17d9e8a2b475042ca1f03be8fd117a133ccb55b5e9ce4bde30638319" - }, - { - "text": "All of the blood samples should be assayed at 1:1,1:10, and 1:50 dilutions; absolute values and accurate laboratory assays for cortisol and aldosterone are essential for successful interpretation of the AVS data.", - "tokenCount": 49, - "pageStart": 26, - "pageEnd": 26, - "hash": "69477c76167ef7fde81bceb7bfea7041a2d4d411dfe1bfc3db2635125275ab88" - }, - { - "text": "The interpretation of AVS results relies on several key indices and their corresponding cutoff values, which help determine the success of the sampling procedure and the lateralization of aldosterone excess ( Table 9 ).", - "tokenCount": 39, - "pageStart": 26, - "pageEnd": 26, - "hash": "cb5225e780277ccb092603769314d8284f4da2ff2f12dd166711604beaef75d1" - }, - { - "text": "The cortisol concentrations from the adrenal veins and IVC are used to confirm successful cannulation of both adrenal veins. With cosyntropin protocols, an adrenal vein to IVC cortisol ratio (referred to as the selectivity index ) of more than 5:1 is required to be confident that the adrenal veins were successfully catheterized ( 141 ).", - "tokenCount": 74, - "pageStart": 26, - "pageEnd": 26, - "hash": "a69a66dc0f7eb3a0b49b7641ce83b67cf5077d52d2d35a22705dbc18e41b6d6e" - }, - { - "text": "When cosyntropin is not used, a selectivity index of more than 1.", - "tokenCount": 18, - "pageStart": 26, - "pageEnd": 26, - "hash": "9aec6cc23f8d3a95ede383f509cd0973e0ad177e7bbaadbe85d2563922f35648" - }, - { - "text": "0 is a threshold that has been used to verify successful catheterization ( 150-152 ).", - "tokenCount": 19, - "pageStart": 26, - "pageEnd": 26, - "hash": "c597b972cc4aa77336d5749841a0a2ba2532246bb1eaf2c54e7bd28c0e0299e0" - }, - { - "text": "Use of intraprocedural cortisol measurement has been shown to improve bilateral adrenal vein catheterization success rates ( 153 ).", - "tokenCount": 25, - "pageStart": 26, - "pageEnd": 26, - "hash": "2d5ae070cec4eeb3368a1e869e8c92519a61661a378e6e991fde04889f8650bd" - }, - { - "text": "Dividing the right and left adrenal vein aldosterone concentrations by their respective cortisol concentrations corrects for dilutional effects of the inferior phrenic vein flowing into the left adrenal vein and, if suboptimally sampled, of IVC flow into the right adrenal vein catheter.", - "tokenCount": 61, - "pageStart": 26, - "pageEnd": 26, - "hash": "e6d00f0469ca2fea15ebc9c7ad4a76a6ab4f1077ecb81f6b3647b6f2b0e658fb" - }, - { - "text": "These are termed cortisolcorrected aldosterone ratios .", - "tokenCount": 11, - "pageStart": 26, - "pageEnd": 26, - "hash": "6e06cace1263b53935981126a33ede27f16166381422846312eaa80b48951f3a" - }, - { - "text": "With unstimulated or continuous cosyntropin administration, clinicians use a cutoff of the cortisolcorrected aldosterone ratio from highside to lowside of more than 4:1 (referred to as the lateralization index ) to indicate lateralizing aldosterone excess ( 85 ); a lateralization index less than 3:1 suggests bilateral aldosterone hypersecretion.", - "tokenCount": 76, - "pageStart": 26, - "pageEnd": 26, - "hash": "50212102378baef5793b5daa5cf5bb527fe07b4ede5d6757d940f4c987b4ab64" - }, - { - "text": "Individuals with a lateralization index between 3:1 and 4:1 may have either lateralizing or bilateral disease, and the AVS results must be cautiously interpreted in conjunction with the clinical setting, CT scan, and the contralateral suppression of aldosterone secretion.", - "tokenCount": 55, - "pageStart": 26, - "pageEnd": 26, - "hash": "237ff9e3d1d66ea58de947ea7ec50824ca1b4ec3c2a4156cbfe839865bdf592c" - }, - { - "text": "2478 The Journal of Clinical Endocrinology & Metabolism , 2025, Vol.", - "tokenCount": 18, - "pageStart": 26, - "pageEnd": 26, - "hash": "989c564c117942f5dd1f14a8381fffe3e0327a7e56adf5c9473af390c4a656b6" - }, - { - "text": "Although the use of cosyntropin clearly improves the selectivity index, there is debate on its impact on accurate lateralization.", - "tokenCount": 26, - "pageStart": 27, - "pageEnd": 27, - "hash": "5c2d571dbf381e42534108f39d0981086a0d3ad19ffd5c57fe7a5ac38188d1ef" - }, - { - "text": "In a retrospective cohort study of 340 patients with primary aldosteronism, bilateral simultaneous AVS was performed before and after the administration of cosyntropin ( 154 ).", - "tokenCount": 35, - "pageStart": 27, - "pageEnd": 27, - "hash": "7614d71f96f6af5efb548841bb9339a76273d6fda715e8c691e1c2a0bea35f6f" - }, - { - "text": "Using a lateralization index of > 4:1, there was a 19% discordance rate between preand postcosyntropin data sets.", - "tokenCount": 30, - "pageStart": 27, - "pageEnd": 27, - "hash": "98ec6e3e450d6db0f6d81960b8e2c0d4948490223e51989d7e9cdc4bda1eabc9" - }, - { - "text": "More than half (64%) of the discordance was due to apparent lateralizing adrenal disease prior to cosyntropin administration that was reinterpreted as bilateral disease after cosyntropin ( 154 ).", - "tokenCount": 42, - "pageStart": 27, - "pageEnd": 27, - "hash": "5ae5ae515f97d38234f59544a705f0477c729755de682552d03240dad274f8f6" - }, - { - "text": "In the same publication, the authors reported that 10 of 11 similar studies that they reviewed demonstrated either no change or a decrease in lateralization rates following cosyntropin stimulation.", - "tokenCount": 35, - "pageStart": 27, - "pageEnd": 27, - "hash": "637e51f2baa5f56106bf8a9c3a3ae82ed5891db5f42e538f4336b3fc010d57cb" - }, - { - "text": "Most studies have found no difference in postadrenalectomy outcomes with or without cosyntropinstimulated AVS ( 151,154 , 155 ) while others found that the postcosyntropin lateralization index correlated better with positive postoperative clinical outcomes than the unstimulated lateralization index ( 156 ).", - "tokenCount": 63, - "pageStart": 27, - "pageEnd": 27, - "hash": "8d9a10c9e9ca4981d51247dfb70a29fd8efe474c52d6ce7fbae546cf0c38629f" - }, - { - "text": "Finally, in most individuals with lateralizing disease, with cosyntropinstimulated AVS, the aldosterone to cortisol ratio from the nondominant adrenal vein is lower than the aldosterone to cortisol ratio in the IVC, termed the contralateral suppression index ( 157 ). When AVS is performed without cosyntropin stimulation, and the aldosterone concentration from the nondominant adrenal is divided by the IVC aldosterone concentration, a cutoff of < 2.", - "tokenCount": 102, - "pageStart": 27, - "pageEnd": 27, - "hash": "c0e68519cb8dcbfb0e8d405768e1193a895ba2775f29e16278923ff32f449eb1" - }, - { - "text": "15 correlates with postoperative clinical outcomes ( 158 ).", - "tokenCount": 10, - "pageStart": 27, - "pageEnd": 27, - "hash": "b73c1d3aa374e2b95e0e520a478091889b6d8304dbfcbf47b8a2ab116e45fbf8" - }, - { - "text": "Use of the contralateral suppression index remains controversial and more work is required to validate this and other indices of lateralization.", - "tokenCount": 25, - "pageStart": 27, - "pageEnd": 27, - "hash": "20f7f26592e91fbde6bfc8ba0b69248700db7c40286119638ce21d8d545ee04c" - }, - { - "text": "Comments For accurate interpretation of AVS, it is important that serum potassium concentration is normal and renin is suppressed.", - "tokenCount": 23, - "pageStart": 27, - "pageEnd": 27, - "hash": "a11d1c75fef1d94b7ae321f2f7a713bf63385db0896fbc97211bac55bfe064c4" - }, - { - "text": "It is also important that blood pressure is well controlled, and this may necessitate the use of antihypertensive agents.", - "tokenCount": 25, - "pageStart": 27, - "pageEnd": 27, - "hash": "cbbdd5873177ca07ebb6aa1dcc0f59921c4627b646ad4d18859cdbdcca69ac54" - }, - { - "text": "Antihypertensive agents (eg, diuretics, angiotensinconverting enzyme [ACE] inhibitors, angiotensin receptor blockers [ARBs], or MRAs) do not interfere with AVS as long as renin is low ( 159,160 ).", - "tokenCount": 57, - "pageStart": 27, - "pageEnd": 27, - "hash": "7a08fc782273245a24b8f1a76a50547c2dddcc8f9c93cea01f0ede70262258a3" - }, - { - "text": "If renin is not suppressed, changes in the antihypertensive program should be considered before AVS.", - "tokenCount": 22, - "pageStart": 27, - "pageEnd": 27, - "hash": "c5ece540eb05f6cc2dcd741470dbca3b99f6497eff85e19d89452492fdb92657" - }, - { - "text": "Drugs that have minimal effect on renin may include selective 1 -receptor antagonists (eg, doxazosin, terazosin, prazosin) and longacting dihydropyridine (eg, amlodipine, felodipine) or nondihydropyridine calciumchannel blockers (eg, verapamil, diltiazem).", - "tokenCount": 82, - "pageStart": 27, - "pageEnd": 27, - "hash": "5cdcf900df7335dfd718662dc507e4c907cf2b91bfc9865be412300b578268a5" - }, - { - "text": "There are 4 exceptions to the suggested requirement for AVS prior to surgery: Most young individuals (eg, age < 35 years) who have marked PA (eg, spontaneous hypokalemia, plasma aldosterone concentration > 30 ng/dL [ > 832 pmol/L] by immunoassay or > 22.", - "tokenCount": 68, - "pageStart": 27, - "pageEnd": 27, - "hash": "5064c2653e556d449b7913dde879f31758b4cc6c00ee999c5ea09de045866315" - }, - { - "text": "5 ng/dL [ > 624 pmol/L] by liquid chromatography tandem mass spectrometry [LCMS/MS], and suppressed renin), and a unilateral adrenal mass with radiologic features consistent with a cortical adenoma on adrenal CT scan.", - "tokenCount": 57, - "pageStart": 27, - "pageEnd": 27, - "hash": "1085edf7a8c66a5c08ca595de97d345dbeaaf5e407ee0e0a4d16106b22c9cb16" - }, - { - "text": "Adrenal incidentalomas are very uncommon in individuals aged < 35 years (0.", - "tokenCount": 17, - "pageStart": 27, - "pageEnd": 27, - "hash": "39555260eb14aca92c4361c0279cb6c6b2ba9f643b5dae77f085d3cb52a6e4ae" - }, - { - "text": "28%) ( 161 ), and marked PA is usually associated with a CTdetectable adrenal nodule ( 162-164 ).", - "tokenCount": 26, - "pageStart": 27, - "pageEnd": 27, - "hash": "76f57af41c299eb82bea4839b56a04ce243960f523f5aa05ee034b5163821107" - }, - { - "text": "Thus, in young individuals (eg, age < 35 years) with marked PA and a > 1.", - "tokenCount": 21, - "pageStart": 27, - "pageEnd": 27, - "hash": "0cf4600ce65c458359edae23b091fef091a5b1c3e09aeaefac52817469b0b769" - }, - { - "text": "0-cm unilateral adrenal nodule on CT, unilateral adrenalectomy without prior AVS can be considered.", - "tokenCount": 23, - "pageStart": 27, - "pageEnd": 27, - "hash": "50185f274658866f2c48a07b2364e5720224663f220852c56ae480a16a6c3645" - }, - { - "text": "Individuals with a unilateral adrenal macroadenoma ( > 1 cm) who have both PA and clinically important cortisol secretory autonomy. The source of clinically important cortisol secretory autonomy is the unilateral adrenal macroadenoma, and a localization study (eg, AVS) is not needed.", - "tokenCount": 61, - "pageStart": 27, - "pageEnd": 27, - "hash": "13d2436b51a2d3a72e1927b9af2af28f11650ddaa797ddd720eb83c8d5b09bd9" - }, - { - "text": "Individuals with familial hyperaldosteronism (types IIV).", - "tokenCount": 14, - "pageStart": 27, - "pageEnd": 27, - "hash": "97ea5bc4c99a8d46c0f14e2467585bea477473179854fbc3125a5c17e6934231" - }, - { - "text": "These autosomaldominant disorders are each linked to specific germline pathogenic variants ( 165,166 ).", - "tokenCount": 22, - "pageStart": 27, - "pageEnd": 27, - "hash": "a16a01e2df513ed06960175e0a1280ff8c039d02454674dd7bf9196ca26172b7" - }, - { - "text": "These individuals have bilateral adrenal disease, and AVS is not required (Question 4.", - "tokenCount": 18, - "pageStart": 27, - "pageEnd": 27, - "hash": "172d4915b9173fc0ed0cad9a55253e6661dc4a0f1cec27f4132e7326931e4526" - }, - { - "text": ") Adrenalectomy is usually not indicated in individuals with familial PA.", - "tokenCount": 14, - "pageStart": 27, - "pageEnd": 27, - "hash": "458085fc4ca6672f6c7a9a91a67850a1247128093794ee72b227978a52929865" - }, - { - "text": "Individuals with primary bilateral macronodular adrenal hyperplasia (PBMAH) who have excessive production of both cortisol and aldosterone ( 167 ).", - "tokenCount": 33, - "pageStart": 27, - "pageEnd": 27, - "hash": "1aab363e19ea3a6d6ec2f414b1e5c545f7e9bf6ba52f846d41616756e856a8b2" - }, - { - "text": "These individuals have bilateral adrenal disease, and AVS is not required.", - "tokenCount": 15, - "pageStart": 27, - "pageEnd": 27, - "hash": "e54ac888abcf6b938fcb68c7f656f6f78bd88b35f00f2b6ec42cfcd58ea98dba" - }, - { - "text": "Research Considerations One of the longterm goals for subtype evaluation is to decrease the reliance on specialized interventional radiologists for AVS.", - "tokenCount": 28, - "pageStart": 27, - "pageEnd": 27, - "hash": "7c43b4fd23b7ec20d38fb6690271edb575850cd7025d959d7d2b068fb4cc0b30" - }, - { - "text": "Positron emission tomography (PET)-based imaging with aldosterone synthase specific molecules is under investigation as a method to identify whether excess adrenal aldosterone production is lateralizing or bilateral ( 168-170 ).", - "tokenCount": 46, - "pageStart": 27, - "pageEnd": 27, - "hash": "5d49f1a45aae02d5cba1e14d714866413b589c10d7a26a56d504aa9cbe6ac1e3" - }, - { - "text": "A recent study showed that pretreatment with dexamethasone converts 11 Cmetomidate from a nonselective ligand for CYP11B1 and CYP11B2 into an in vivo selective CYP11B2 ligand ( 171 ).", - "tokenCount": 53, - "pageStart": 27, - "pageEnd": 27, - "hash": "2017bdb9bef4d518c9e037ee60bece00c2284be4c2b3b85879263b5d706cb49e" - }, - { - "text": "In 93 patients with PA and CTdetected adrenal nodules who were treated surgically, dexamethasonesuppressed 11 Cmetomidate PETCT was noninferior to AVS in diagnosing lateralizing PA ( 171 ).", - "tokenCount": 50, - "pageStart": 27, - "pageEnd": 27, - "hash": "5d08afc865b9c426177c089d20ca3acc426b11ebf823ba6633835766a8a333ce" - }, - { - "text": "In addition, the CX-C chemokine receptor 4 (CXCR4) is a G proteincoupled transmembrane receptor overexpressed in APAs and exhibits low to undetectable expression levels in normal adrenal tissues and nonfunctional adenomas ( 172 ).", - "tokenCount": 60, - "pageStart": 27, - "pageEnd": 27, - "hash": "39e7c3e5ad6462f64df4050d389de0d65f9d5f9eeebdb0f8c93764e5fa7508b1" - }, - { - "text": "68 Gapentixafor is a radionuclide imaging ligand specifically targeting CXCR4 ( 173 ).", - "tokenCount": 24, - "pageStart": 27, - "pageEnd": 27, - "hash": "1170a71d6108b7dd20f60a8320e8d6eeb5be8ee61a19e2a8d8cd3f831da0ed24" - }, - { - "text": "In 63 patients with PA who were treated surgically, 68 Gapentixafor PETCT was noninferior to AVS in diagnosing lateralizing PA ( 174 ).", - "tokenCount": 36, - "pageStart": 27, - "pageEnd": 27, - "hash": "fd7d94e3cefbc7789a30c90be61beccf7789956459fd242fcb58d8b087ebcc98" - }, - { - "text": "Suppressed vs Unsuppressed Renin in Individuals With Primary Aldosteronism Receiving Primary AldosteronismSpecific Medical Therapy Background Although aldosteronedirected medical therapy has been shown to be beneficial in primary aldosteronism (PA), the optimal approach to dosing and surveillance is uncertain.", - "tokenCount": 63, - "pageStart": 27, - "pageEnd": 27, - "hash": "ff674f547882800c0775fdff39e0c90e07cd626f4dd4c495fb6d56b5dbbbef4c" - }, - { - "text": "Whether renin should be used to guide treatment has been considered in prior studies and by consensus groups.", - "tokenCount": 20, - "pageStart": 27, - "pageEnd": 27, - "hash": "54112557409f79c0ee218e264865d77044fffb4cec3312f531241fe043b29c40" - }, - { - "text": "The premise of using renin as a biomarker of PAspecific medical therapy stems from the general knowledge of the physiology of endocrine hormone excess (ie, decline in hormone excess or activity is reflected in a rise of the proximal regulatory hormone).", - "tokenCount": 51, - "pageStart": 27, - "pageEnd": 27, - "hash": "7ffd2c4181fee0462cf42bba2e58c0010829048a79a1299d0422bc55da518f2a" - }, - { - "text": "Since PA is characterized and diagnosed by aldosterone production despite suppression of renin and angiotensin II, a rise in renin induced by aldosteronedirected medical therapy should reflect the reversal of PA pathophysiology that may portend improved clinical outcomes ( 175 ).", - "tokenCount": 57, - "pageStart": 27, - "pageEnd": 27, - "hash": "622485c3860a1333a04739bd6f5129e676f1b81f01d67f639a2ac691f8d985bd" - }, - { - "text": "9 2479 Downloaded from https://academic.", - "tokenCount": 11, - "pageStart": 27, - "pageEnd": 27, - "hash": "6ee2957f47bccda6be2f35a91e447872011ac4c2d27ea17eed75ae55ab922a6e" - }, - { - "text": "org/profile/EHqkK_8QHm8 .", - "tokenCount": 15, - "pageStart": 28, - "pageEnd": 28, - "hash": "dd66940d9e1e4eff3207bc5dd3eee7b835c2bd21c10e77d9d7b6fbfec3f89584" - }, - { - "text": "Benefits and Harms The panel voted for the following patientimportant outcomes for Question 7 decision making: 1) percent of individuals achieving BP control, 2) number of antihypertensive agents, 3) dosage of antihypertensive agents, 4) systolic BP (SBP) level, 5) major adverse cardiovascular events (MACEs), 6) atrial fibrillation, 7) stroke, 8) ischemic heart disease, 9) heart failure, 10) cardiovascular mortality, 11) allcause mortality, and 12) adverse events.", - "tokenCount": 114, - "pageStart": 28, - "pageEnd": 28, - "hash": "51760c97602e0c7335d3631675ef46bd9dbf8e15a531a0a6986d6b581335d086" - }, - { - "text": "Our systematic review ( 53 ) identified 11 studies that evaluated the impact of increasing renin with aldosteronedirected medical therapy when compared with persistently suppressed renin. When compared with unsuppressed renin, suppressed renin during aldosteronedirected medical therapy was associated with increases in mortality; risk for stroke, atrial fibrillation, and hypokalemia; and number of antihypertensive medications.", - "tokenCount": 88, - "pageStart": 28, - "pageEnd": 28, - "hash": "108b55441c67b4d74dae5ee63afe82ab61a6e3d4eda8d517f9e8a594eae991c9" - }, - { - "text": "There were no statistically significant differences in MACEs (eg, ischemic heart disease, heart failure) in the metaanalysis.", - "tokenCount": 27, - "pageStart": 28, - "pageEnd": 28, - "hash": "706b5fc4856ffff7368df66594e1a36b59ed2a4d79d73d1925e91650c41d66a5" - }, - { - "text": "In individual retrospective cohort studies, a rise in renin to a level higher than 1.", - "tokenCount": 18, - "pageStart": 28, - "pageEnd": 28, - "hash": "1244a8a2f1559f8e0dce7a9abed573de961983c98c9db2b30e74d61991c6039e" - }, - { - "text": "0 ng/mL/h was associated with lower risk for MACEs when compared with persistently suppressed renin ( 7,69 ).", - "tokenCount": 28, - "pageStart": 28, - "pageEnd": 28, - "hash": "b27e875bd1536bc15b2e0dde43fe689e6dd9877bb171b3055c7177d699a7e4d1" - }, - { - "text": "In this regard, the addition of renin measurements does not pose a substantial increase in resource utilization.", - "tokenCount": 20, - "pageStart": 28, - "pageEnd": 28, - "hash": "ce90e32f82f9e036f0793ce6fcd13f7d7d52274cbc3015173da916e7e8dd74e0" - }, - { - "text": "However, the additional costs of measuring renin may be a limiting factor or prohibitive to some clinicians and increase health disparities.", - "tokenCount": 25, - "pageStart": 28, - "pageEnd": 28, - "hash": "c3a3af651635411204d59df88b9270352823da7bc4f7bf3819bddbc4d04e17bc" - }, - { - "text": "In balance, targeting a rise in renin may be associated with a lower risk of death, stroke, and atrial fibrillation, but the pooled analysis did not demonstrate statistically significant reduction in the risk for MACEs.", - "tokenCount": 46, - "pageStart": 28, - "pageEnd": 28, - "hash": "353c9773e6bad42df54d37eeef808b9eb16d64999290d123ef62b53753008ec0" - }, - { - "text": "Evidence to Decision Factors No studies were found that assessed the costeffectiveness of targeting renin in PAdirected medical therapy.", - "tokenCount": 27, - "pageStart": 28, - "pageEnd": 28, - "hash": "e4d91821f54503dd193874183a9c107a3c46d1b3e860a4c9e53a21ef90094413" - }, - { - "text": "There is an obligate cost associated with measuring renin and measuring it frequently during longitudinal care.", - "tokenCount": 19, - "pageStart": 28, - "pageEnd": 28, - "hash": "94e1c533b19b99d59caabf01b94886636ec9ed4769007e2a1bc67d7cc1d7bc72" - }, - { - "text": "If the studies suggesting that increasing renin with mineralocorticoid receptor antagonist (MRA) therapy can mitigate some of the risk for incident cardiovascular and kidney disease are confirmed or validated, the additional cost of measuring renin is likely to be costeffective.", - "tokenCount": 52, - "pageStart": 28, - "pageEnd": 28, - "hash": "8143eb1d4d8fea4d5ef6ee17cf9ec3e84bae865bf364a5359836c61c2396d0b4" - }, - { - "text": "No studies were found that assess the impact of targeting renin in PAdirected therapy on health equity.", - "tokenCount": 22, - "pageStart": 28, - "pageEnd": 28, - "hash": "ffb9a0dc5ccb1b82077bf5ceadbf8a1cdee781737b5c03b65a495f44a39532f8" - }, - { - "text": "As stated, the costs of measuring renin, in addition to the standard longitudinal followup and monitoring for medical therapy for PA, may be a limiting factor for some clinicians (specifically in areas where this test is not readily available).", - "tokenCount": 47, - "pageStart": 28, - "pageEnd": 28, - "hash": "01fa4354abe22e246db2e0d88884f1e23b6381c7ec3e2e95d66eea796900f628" - }, - { - "text": "No research evidence was identified for acceptability by the health care workers or feasibility.", - "tokenCount": 16, - "pageStart": 28, - "pageEnd": 28, - "hash": "111ab567bf19167e9609048e83a011cce12556d36aa7edeb3e267bbbf14f47d0" - }, - { - "text": "Measurement of renin to guide medical therapy is likely feasible at most centers that routinely treat individuals with PA.", - "tokenCount": 22, - "pageStart": 28, - "pageEnd": 28, - "hash": "c6aa4bde391adc261a3b555e317a59d746c98b92d600639c58cadcc9ee890e4c" - }, - { - "text": "Justification for the Recommendation Because the pathophysiology of PA in most individuals manifests with suppressed renin, a rise in renin with MRA therapy serves as a biomarker indicating a restoration of physiology (ie, sufficient mineralocorticoid receptor [MR] blockade and reduction in extracellular volume) ( 175 ).", - "tokenCount": 66, - "pageStart": 28, - "pageEnd": 28, - "hash": "1ef4c82d71a3992102daada6398bdb5f6f4818381eeb8349826d3f8cc1b18ebf" - }, - { - "text": "The summary of several observational studies suggests that this practice is associated with statistically lower risks of death and atrial fibrillation as well as a lower number of antihypertensive medications and risk for hypokalemia.", - "tokenCount": 44, - "pageStart": 28, - "pageEnd": 28, - "hash": "20b75eda64391fae7cc09876a7aeef26173b159508565a15215a08664253056b" - }, - { - "text": "Importantly, the primary clinical objective of MRA therapy remains normalizing BP with the fewest number of medications (and normalizing potassium, when applicable); however, achieving a rise in renin is suggested as an additional objective that reflects a better prognosis ( 175 ).", - "tokenCount": 54, - "pageStart": 28, - "pageEnd": 28, - "hash": "30f6cbf4936653443262f3783537721171da1ca14f1abfbfefbc12b0097d1a3a" - }, - { - "text": "Caveats to this approach include that this evidence stems from observational studies susceptible to bias and residual confounding, that there is no direct evidence to dictate what renin threshold to target as optimal, that this approach may not be possible or feasible or necessary in all individuals, that there are different methods to measure renin (activity and concentration) and no consensus on which one is more accurate, and that intensification of MRA therapy to achieve this objective may induce more adverse effects.", - "tokenCount": 95, - "pageStart": 28, - "pageEnd": 28, - "hash": "350f1cb4f6c6f1dc070bb406cade2b2ad4fc7cbe0c55c6ee10b654328fbd0f79" - }, - { - "text": "For these reasons, we suggest focusing on dose intensification of MRA therapy to raise renin, particularly in individuals whose BP is not controlled.", - "tokenCount": 29, - "pageStart": 28, - "pageEnd": 28, - "hash": "4bffaeae04e77c56f98046de3c2053f268c3291e6956629659275e22a8bc2e9f" - }, - { - "text": "Once BP is controlled, nonMRA medications can be lowered or removed, when possible, thus allowing further increases of MRA dosing and attempts to raise renin ( Fig.", - "tokenCount": 36, - "pageStart": 28, - "pageEnd": 28, - "hash": "cccd9ea4341c9e3e5e393eb20e80899ed1d0207c2b90cc6eb86510e34ab36a47" - }, - { - "text": "Furthermore, interpretation of renin levels may be hampered in individuals concomitantly receiving other medications that affect renin levels (eg, -adrenergic blockers that lower renin or renin angiotensin aldosterone system [RAAS] inhibitors that may raise renin in synergy with MRAs).", - "tokenCount": 66, - "pageStart": 28, - "pageEnd": 28, - "hash": "97f79bb3ea8920abdfbb72f0f58d401e79d33335dad4b2463f614a0f62bd5b8c" - }, - { - "text": "Rather than targeting a specific renin threshold, we suggest that the observation that renin has increased from its pretreatment baseline should provide some reassurance of treatment efficacy.", - "tokenCount": 33, - "pageStart": 28, - "pageEnd": 28, - "hash": "a9b1fd78f3ce947906b5b4d4983089d8ad26b926d95f50b772d5a88215222374" - }, - { - "text": "Consistent with this recommendation, a recent large international consensus group endorsed targeting a rise in renin when implementing aldosteronedirected medical therapy to a level higher than 1.", - "tokenCount": 36, - "pageStart": 28, - "pageEnd": 28, - "hash": "414bd431ce04d7b42e0cd4f62c385bc4abe2b1ce73144cf2db7a5316e019ace7" - }, - { - "text": "0 ng/mL/h (plasma renin activity [PRA]) or 10 mU/L (direct renin concentration [DRC]) ( 85 ).", - "tokenCount": 34, - "pageStart": 28, - "pageEnd": 28, - "hash": "96fb5ada05858db1e141687bf4d2dfd593884e8e6e1cb8cbab368b5a635e53e7" - }, - { - "text": "2480 The Journal of Clinical Endocrinology & Metabolism , 2025, Vol.", - "tokenCount": 18, - "pageStart": 28, - "pageEnd": 28, - "hash": "04e496e3a6ae934ee83e2c4d8701788bfca1ca372a122b42c846bcedfb3d3932" - }, - { - "text": "Comments Special populations: Individuals with hyperkalemia/chronic kidney disease (CKD) stage 3 and above: Achieving an increase in renin with MRA therapy is challenging in individuals with CKD. The ability to produce and secrete renin may be impaired with advanced CKD and higher MRA doses, which may increase the risk for hyperkalemia.", - "tokenCount": 79, - "pageStart": 29, - "pageEnd": 29, - "hash": "c69b95349b5da3f7114a2e925e6b1c79735361ed69164e6c876a2e0d666578a2" - }, - { - "text": "As such, targeting an increase in renin in CKD may not always be a feasible or practical clinical objective.", - "tokenCount": 23, - "pageStart": 29, - "pageEnd": 29, - "hash": "2fe4f1efeab471616d61978c8c74752a4514c5cf0360b67d2a32cc4cce258191" - }, - { - "text": "However, since the nonsteroidal MRA finerenone has been shown to reduce adverse cardiovascular and kidney outcomes in 3 large randomized controlled trials (RCTs) of individuals with diabetes and CKD or heart failure ( 176-178 ), it is reasonable to treat individuals with PA and CKD with MRAs as long as serum potassium is monitored.", - "tokenCount": 70, - "pageStart": 29, - "pageEnd": 29, - "hash": "7f33074c390b848c4d1b84b127844a5ebc5096abeb8a0c10180343caf29ce3ac" - }, - { - "text": "When encountering hyperkalemia in CKD, the use of concurrent diuretics, sodiumglucose cotransporter (SGLT2) inhibitors, and patiromer/novel potassium binders have all been shown to mitigate the risk of MRAinduced hyperkalemia in RCTs ( 179,180 ).", - "tokenCount": 69, - "pageStart": 29, - "pageEnd": 29, - "hash": "5da5e4e6ce0fc25e70c41e1bbd3bd4729567fec74c6bdc90ae7cb7b082d78b6a" - }, - { - "text": "Individuals taking medications that influence renin: The use of some concurrent medications may confound the interpretation of renin.", - "tokenCount": 24, - "pageStart": 29, - "pageEnd": 29, - "hash": "2cdc6a6e3df194524ec04ca91736cdffcf87a13060c10ab93b98f7cb6829a566" - }, - { - "text": "-Adrenergic blockers can lower renin secretion; therefore, individuals on high doses may not manifest an increase in renin with MRAs.", - "tokenCount": 29, - "pageStart": 29, - "pageEnd": 29, - "hash": "1c5bac7eb83cbe909f9bf4e3d267de91562a1de2005b3b971a90a8d69bfe457e" - }, - { - "text": "High dietary sodium intake can lower renin, whereas a sodiumrestricted diet can increase renin ( 181 ); however, most of the global population consumes a relatively high dietary sodium content known to expand intravascular volume and put downward pressure on renin.", - "tokenCount": 50, - "pageStart": 29, - "pageEnd": 29, - "hash": "510bf00a77e9a33bcfa462241dd8818ae456ef9572714e652e6d1e33b770fbcc" - }, - { - "text": "The use of angiotensinconverting enzyme [ACE] inhibitors/angiotensin receptor blockers [ARBs] and diuretics can raise renin and thereby potentially confound the isolated effect attributable to MRA therapy.", - "tokenCount": 47, - "pageStart": 29, - "pageEnd": 29, - "hash": "7259207ac7a665e4b74b1d6a3a08ad85f85ee6b344f3815217229372ca242d79" - }, - { - "text": "Research Considerations Current gaps in knowledge call for further research in the following area: Conducting prospective, randomized, controlled studies with surrogate outcomes (eg, cardiac imaging, vascular dynamics) and hard outcomes to robustly assess the efficacy of targeting a rise in renin with aldosteronedirected medical therapy Dexamethasone Suppression Testing in Individuals With Primary Aldosteronism and an Adrenal Adenoma Background Assessing cortisol production is considered routine practice in individuals with an adrenal adenoma due to the increased cardiometabolic risks of excess cortisol exposure.", - "tokenCount": 116, - "pageStart": 29, - "pageEnd": 29, - "hash": "aa1ab21a3fc95f546f0ef63f343c70e0827ab42cb213e64836cd0e323f1bcd5d" - }, - { - "text": "In individuals with primary aldosteronism (PA), 24-hour urine steroid metabolome studies and dexamethasone suppression tests indicate that autonomous cortisol secretion (ACS) is not uncommon.", - "tokenCount": 41, - "pageStart": 29, - "pageEnd": 29, - "hash": "c978f69e7238acc3fc78852f0f926f7b0918d907278ba2b7982c4dab73fd337c" - }, - { - "text": "Furthermore, excess cortisol production in individuals with PA may affect interpretation of AVS results and/or lead to postoperative glucocorticoid deficiency in those with adenomas cosecreting aldosterone and cortisol.", - "tokenCount": 45, - "pageStart": 29, - "pageEnd": 29, - "hash": "7230168e72188801e286637885ecb8e578516981ed844dcb9137257807d60f37" - }, - { - "text": "Technical remarks A dexamethasone suppression test should be performed, and a positive test should prompt further evaluation for Cushing syndrome as detailed in the Endocrine Society Clinical Practice Guidelines.", - "tokenCount": 38, - "pageStart": 29, - "pageEnd": 29, - "hash": "e139d3f7fb6cbb55987433d18c26048a9e1eb7617ac47cdab0f4c8cec5b5c76b" - }, - { - "text": "For individuals with mild ACS, measuring plasma metanephrine during adrenal venous sampling (AVS) may help lateralize both aldosterone and cortisol secretion although further research is needed.", - "tokenCount": 39, - "pageStart": 29, - "pageEnd": 29, - "hash": "6fe7b5e072a0209a33c9b98d1371b799e1d3d9767f77ef2e23c1823d944c08e0" - }, - { - "text": "org/profile/vRFNnZpoKZY .", - "tokenCount": 14, - "pageStart": 29, - "pageEnd": 29, - "hash": "644418ab34c758d6737bd89b68f00f96324f5451380da61525d2ea6e974e0353" - }, - { - "text": "Benefits and Harms The panel voted for the following patientimportant outcomes for Question 8 decision making: 1) postoperative adrenal insufficiency, 2) ACS detection, 3) false lateralization, 4) AVS accuracy and 5) adverse events.", - "tokenCount": 52, - "pageStart": 29, - "pageEnd": 29, - "hash": "6ea36c218f69639511c639fb36c1e3270883a6dc043155a08ef82ee8ddde171e" - }, - { - "text": "As the systematic review did not identify any studies that directly address this question, additional relevant studies were evaluated.", - "tokenCount": 21, - "pageStart": 29, - "pageEnd": 29, - "hash": "a1c1dfe0e2f9304cb5d50e3428d854f2a530d9e0e8de714150ae06b534702e62" - }, - { - "text": "A number of retrospective cohort studies reported that approximately 5% to 15% of individuals with PA have ACS as defined by a positive 1-mg dexamethasone suppression test with a cortisol concentration more than 1.", - "tokenCount": 43, - "pageStart": 29, - "pageEnd": 29, - "hash": "ca656a7a88f379ce1ba4a90ad0e0edee586a88070e09ed2ce62efa70d1dc61ad" - }, - { - "text": "8 g/dL (50 nmol/ L) ( 182-186 ).", - "tokenCount": 17, - "pageStart": 29, - "pageEnd": 29, - "hash": "1b0fd775efedd270acd23594c02267a68f9735550a57898721d1e9b2e7b2ada6" - }, - { - "text": "A more recent systematic review of 16 studies published between 2000 and 2020, with data from 2862 individuals with PA, reported a prevalence of 5% to 27% ( 187 ).", - "tokenCount": 35, - "pageStart": 29, - "pageEnd": 29, - "hash": "efe3b8d5f45aadac9f4847a1731e9ecfa003de709050af22f68db476253bd2a8" - }, - { - "text": "Studies have also reported increased cardiometabolicrenal complications in individuals with PA and concurrent cortisol excess.", - "tokenCount": 21, - "pageStart": 29, - "pageEnd": 29, - "hash": "b7dbde274bdf958855b6111326e6061d929c6e15ea3c45e0959ff3e4aae40cf8" - }, - { - "text": "The adverse consequences include worse glucose tolerance and diabetes ( 188-191 ), higher left ventricular mass index ( 192 ), more cardiovascular events ( 189,193 ), osteopenia/osteoporosis ( 189,194 ), and renal dysfunction ( 195 ).", - "tokenCount": 51, - "pageStart": 29, - "pageEnd": 29, - "hash": "f9c6ad344c36819eb413329aa9bfed14970d53b76538882e919b2ecd506a03e5" - }, - { - "text": "In individuals with PA who undergo AVS, studies indicate that ACS may complicate the interpretation of adrenal vein selectivity and lateralization of aldosterone production.", - "tokenCount": 32, - "pageStart": 29, - "pageEnd": 29, - "hash": "db6dbadc43eff5149c1c3042fd10016ee2b7a4b7b5302a2b5a277a5042af8760" - }, - { - "text": "Excess cortisol secretion may lead to lateralization of cortisol to The Journal of Clinical Endocrinology & Metabolism , 2025, Vol.", - "tokenCount": 28, - "pageStart": 29, - "pageEnd": 29, - "hash": "399919b3f270dd35ab39ec8d8468ef4731a56ae668e6bfd64fb5c25398bf0c78" - }, - { - "text": "9 2481 Downloaded from https://academic.", - "tokenCount": 11, - "pageStart": 29, - "pageEnd": 29, - "hash": "284743531a45778458a30bef1a43fe1517f199f27f01ea3656a029ea692e0c2a" - }, - { - "text": "one side with underestimation of aldosterone production, as reflected by the aldosterone to cortisol ratio, on the same side ( 182,196 , 197 ).", - "tokenCount": 33, - "pageStart": 30, - "pageEnd": 30, - "hash": "e1dd0526bd7ef35e8025c378704843d33506bbc9c59ba259ae7df3df95fe5122" - }, - { - "text": "Cortisol production on the contralateral side may be suppressed and lead to the false assessment of inadequate adrenal vein cannulation ( 196 ).", - "tokenCount": 29, - "pageStart": 30, - "pageEnd": 30, - "hash": "242bf4f41066562fa60cd049592d73d2e495a254d15bd2d31b41b24248d6520a" - }, - { - "text": "Current evidence suggests that measurement of plasma metanephrine, which displays minimum fluctuation during stress and a higher adrenal to peripheral gradient compared to cortisol ( 198,199 ), is useful in these cases to assess selectivity and lateralization.", - "tokenCount": 48, - "pageStart": 30, - "pageEnd": 30, - "hash": "a447201b13d49abdb387caff2cc5d252676a1a0bebcd51e2769afef9a665d1a8" - }, - { - "text": "Suggested thresholds include selectivity index > 12 and lateralization index > 4 where metanephrine replaced cortisol in the assessment of selectivity and lateralization ( 197,199-203 ).", - "tokenCount": 38, - "pageStart": 30, - "pageEnd": 30, - "hash": "59434dabf57abbe3df97e74d1c8440898ac1a76ef69eaebc712221cb0f3cc889" - }, - { - "text": "However, issues with selectivity of adrenal vein catheterization and lateralization of aldosterone production have not been reported in all studies ( 183 ), possibly because AVS interpretation was mainly affected in individuals with postdexamethasone cortisol more than 5 ug/dL (138 nmol/L) ( 204 ).", - "tokenCount": 67, - "pageStart": 30, - "pageEnd": 30, - "hash": "78f7e897cb5ec7f8270a8f06c42fcda4d1af6f5944a5b76ce1ae3f03cd818767" - }, - { - "text": "One study suggested that AVS performance under cosyntropin stimulation, instead of during unstimulated conditions, may overcome the need to measure metanephrines for the assessment of selectivity and lateralization ( 197 ).", - "tokenCount": 45, - "pageStart": 30, - "pageEnd": 30, - "hash": "f5e2468c06d392778a7be1e477dfac1ee1ad55caf4b736b7850a98d6e668f102" - }, - { - "text": "For those with concurrent PA and ACS, surgical resection of the adrenal adenoma may lead to postoperative glucocorticoid insufficiency. A study of 108 individuals who underwent unilateral adrenalectomy for a range of reasons reported that 50% of those with concurrent PA and hypercortisolism (n = 12) developed adrenal insufficiency requiring glucocorticoid replacement for a median period of 0.", - "tokenCount": 88, - "pageStart": 30, - "pageEnd": 30, - "hash": "114d2fda7175594df7bb5a0520ea2518bc8e816ec7b4c80a00fb9e8d7354c636" - }, - { - "text": "The potential undesirable effect of performing a 1-mg dexamethasone suppression test may be related to falsepositive or falsenegative results.", - "tokenCount": 29, - "pageStart": 30, - "pageEnd": 30, - "hash": "6ecea18680a08a087df7ce3d19ae85498c6ae58b5c1862b881af2a665af298e0" - }, - { - "text": "Falsepositive results may lead to unnecessary further investigations, although 24-hour urinary free cortisol and midnight salivary cortisol are noninvasive and relatively accessible tests.", - "tokenCount": 32, - "pageStart": 30, - "pageEnd": 30, - "hash": "9fb95c7d44ccf4906a15dd1c976d6f96dc40929894d379fa43a364f29445e587" - }, - { - "text": "More invasive testing would only be conducted if multiple screening tests are positive.", - "tokenCount": 14, - "pageStart": 30, - "pageEnd": 30, - "hash": "11c3f45269b7f52c914f0fdc65bd54d2ebf2e79bd663432e67e2fd95fbd6a0e5" - }, - { - "text": "The dexamethasone suppression test is considered the most sensitive screening test, and false negatives are uncommon.", - "tokenCount": 22, - "pageStart": 30, - "pageEnd": 30, - "hash": "3bf62c47f0ab20c93105e5f53663711b7e1e5f44d39a420c0e37b9a97253d546" - }, - { - "text": "Falsepositive results can occur due to failure to correctly take dexamethasone, interfering medications such as anticonvulsants and other CYP3A4 inducers that increase dexamethasone degradation, and malabsorption of dexamethasone ( 207 ).", - "tokenCount": 57, - "pageStart": 30, - "pageEnd": 30, - "hash": "fce0d7c3de0846c5499b19f693407bb0797a163a38941b2d654b33b9f92fb9a6" - }, - { - "text": "This issue can be resolved with serum dexamethasone measurement.", - "tokenCount": 14, - "pageStart": 30, - "pageEnd": 30, - "hash": "5ebf1b48f932e2469a4e1de8e241765a18b9742bfe2b4b247843960986d7010e" - }, - { - "text": "A range of other conditions may cause falsepositive results, including oral estrogen use, obesity, major depression, alcohol use disorder, and acute illnesses.", - "tokenCount": 29, - "pageStart": 30, - "pageEnd": 30, - "hash": "e0e65749643dd60b819fb3d864d9921cc420f2943146db8aeba4d1c58dbd4d12" - }, - { - "text": "These are covered by guidelines for Cushing syndrome ( 208 ).", - "tokenCount": 12, - "pageStart": 30, - "pageEnd": 30, - "hash": "d1094c00ce3cc4fed853aea8f8ab89ade22c1e1cb1503b950d08f3bfa04c998e" - }, - { - "text": "Evidence to Decision Factors The potential benefits obtained from doing a 1-mg dexamethasone suppression test outweigh the potential harms, as outlined.", - "tokenCount": 30, - "pageStart": 30, - "pageEnd": 30, - "hash": "5a75cfbd0a7e1a0b458c743d70f13f43d4a76596146363d375eb471186c0069e" - }, - { - "text": "The dexamethasone suppression test requires minimal resources, which include dexamethasone tablets and a blood test for plasma cortisol concentration, and it is widely available worldwide.", - "tokenCount": 36, - "pageStart": 30, - "pageEnd": 30, - "hash": "ea1c3c8abe71a073ae8009ae9131865ee0445a2085d6d949333b9dfaab947b85" - }, - { - "text": "We did not find any published studies on the costeffectiveness of conducting a 1-mg dexamethasone suppression test.", - "tokenCount": 26, - "pageStart": 30, - "pageEnd": 30, - "hash": "92f2e98eed50f7fb3a6675e5a49202603ceadd2fc74cbb546e479b5be950e176" - }, - { - "text": "However, it is known to be a relatively cheap and commonly ordered test in endocrinology.", - "tokenCount": 19, - "pageStart": 30, - "pageEnd": 30, - "hash": "b869fe43a7f2b43c4dc80ca3b38999c5ebd6583c2aa71896afc8a58b1e11b41f" - }, - { - "text": "If the result is abnormal, 2 followup tests (24-hour urinary free cortisol and midnight salivary cortisol) are also accessible and inexpensive.", - "tokenCount": 30, - "pageStart": 30, - "pageEnd": 30, - "hash": "e6b84a63f82dea5a3ff038f6bc8406ffaccd41e30ae6bc60b6b6905a8a3a4cce" - }, - { - "text": "Furthermore, an understanding of normal adrenal cortisol secretion will reduce confounding in the interpretation of AVS results.", - "tokenCount": 21, - "pageStart": 30, - "pageEnd": 30, - "hash": "e19a7ec98a43ee609102c90a2b2ccc3b742adc4dadd3c7ed8a04682b345f4ef0" - }, - { - "text": "Repeating AVS due to uninterpretable results is much more expensive ( $2000-3000 USD) than doing a 1-mg dexamethasone suppression test ( $20) and planning AVS accordingly.", - "tokenCount": 46, - "pageStart": 30, - "pageEnd": 30, - "hash": "b591d5edb1b92e1affead12efc7b7509e926130bfd66f5cda57631528dbc407b" - }, - { - "text": "Individuals rarely decline the dexamethasone suppression test in clinical practice.", - "tokenCount": 16, - "pageStart": 30, - "pageEnd": 30, - "hash": "4290e942bd592615764e419730fce080c3f8be58e3926a8ae2ee347c2fe0e129" - }, - { - "text": "They may occasionally experience adverse effects from the dexamethasone, but these effects are transient, as the dose of dexamethasone is low and the medication is given only once.", - "tokenCount": 39, - "pageStart": 30, - "pageEnd": 30, - "hash": "98c160825699a2ef9754f424fa854a7e4c8f8d0cdfc528edb09aa810a535a406" - }, - { - "text": "Justification for the Recommendation The panel based its recommendation on evidence demonstrating that ACS is not uncommon in individuals with PA and can be detected by dexamethasone suppression testing.", - "tokenCount": 36, - "pageStart": 30, - "pageEnd": 30, - "hash": "f73e000e6df0c1e77e3eb6e281ae97c8b36eddf298a82e7f9541ebe866bbe65d" - }, - { - "text": "Having ACS may lead to adverse cardiometabolic consequences, complicate the interpretation of AVS results, and predispose the individual to postoperative adrenal insufficiency following unilateral adrenalectomy.", - "tokenCount": 39, - "pageStart": 30, - "pageEnd": 30, - "hash": "1e3779d24c6b64d8685305eea64ab7fabc36f0c8d5fe740649ca34e58185a16f" - }, - { - "text": "The potential for harm from doing the dexamethasone suppression test is low and relates mainly to unnecessary investigations for Cushing syndrome.", - "tokenCount": 27, - "pageStart": 30, - "pageEnd": 30, - "hash": "359b6ad2b88583cbbd7dbe5ca9c24384e5d3d7a6f57063739963a67da4870c22" - }, - { - "text": "Therefore, the panel concluded that the balance of effects probably favors the intervention and that the test is feasible, accessible, and costeffective.", - "tokenCount": 27, - "pageStart": 30, - "pageEnd": 30, - "hash": "14bb4f785b797da0fa137b1286fb4648f22b837b8642e89d81d7423c561ae7d0" - }, - { - "text": "Comments Individuals with adrenally mediated, overt Cushing syndrome and unilateral adrenal adenoma may proceed to surgery, without AVS, to remove the source of excess cortisol.", - "tokenCount": 35, - "pageStart": 30, - "pageEnd": 30, - "hash": "e6ecdead10efc74d84c0896944b67db92d3543def3f6468ada706154e628c168" - }, - { - "text": "Research Considerations Current gaps in knowledge call for further research in the following areas: Determining the prevalence of mild autonomous cortisol excess, as indicated by an abnormal 1-mg dexamethasone suppression test, in individuals with PA who do not have an adrenal adenoma Evaluating the role of adrenal and peripheral vein metanephrine for assessing selectivity and lateralization with the goal of improving guidelines on AVS interpretation in individuals with ACS Prospectively evaluating dexamethasone suppression test results and their correlation with AVS and surgical outcomes to establish cortisol cutoffs that guide the need for specific care during AVS (eg, measurement of adrenal vein metanephrine) and the need for perioperative glucocorticoid administration Medical Treatment for Individuals With Primary Aldosteronism: Spironolactone vs Other Mineralocorticoid Receptor Antagonists Medical therapy for primary aldosteronism (PA) will likely become the central issue in PA care over the next decade as PA becomes more widely recognized ( 209 ).", - "tokenCount": 217, - "pageStart": 30, - "pageEnd": 30, - "hash": "5d32e6a36635c581618acdf6120a8b28d6c890e979b748a6e0aca9d566e22ec5" - }, - { - "text": "Modern PA series already show that, with expanded PA screening, an increasing majority of PA cases are nonsurgical, bilateral adrenal 2482 The Journal of Clinical Endocrinology & Metabolism , 2025, Vol.", - "tokenCount": 43, - "pageStart": 30, - "pageEnd": 30, - "hash": "6714b007755e2c41df2ace3c8e5fe17a99b46a9b038235cd06ff48e4377a0d65" - }, - { - "text": "Further, lack of access to AVS necessitates guidance on specific MRA selection.", - "tokenCount": 17, - "pageStart": 31, - "pageEnd": 31, - "hash": "7237f80f795ada3878b19006521900ab8ca114af2423967495b5d78c18eec04e" - }, - { - "text": "Should spironolactone vs other mineralocorticoid receptor antagonists be used for primary aldosteronismspecific medical therapy?", - "tokenCount": 29, - "pageStart": 31, - "pageEnd": 31, - "hash": "7e6b8177a48ac3744f73f2e84ffe69cc21fc3799ebea4b04a4bc62ffbadc4462" - }, - { - "text": "MRAs with greater mineralocorticoid receptor (MR) specificity and fewer androgen/ progesterone receptormediated side effects may be preferred.", - "tokenCount": 32, - "pageStart": 31, - "pageEnd": 31, - "hash": "81e5ab49c7a4c3dec80dea49de9ad469a078d562418605c2c9acc64f1e523800" - }, - { - "text": "When initiating MRAs, consider hypertension severity for dosing and potential discontinuation of other antihypertensive medications ( Fig.", - "tokenCount": 25, - "pageStart": 31, - "pageEnd": 31, - "hash": "1b9088d1704b39b159423e1c2304deb249539710ca179bea4aaea8338014dbf7" - }, - { - "text": "Monitor potassium, renal function, renin (concentration or activity), and blood pressure (BP) response during followup to guide MRA dose titration.", - "tokenCount": 33, - "pageStart": 31, - "pageEnd": 31, - "hash": "0424aa7c23015abe60aff8ab80c72c98bed4f6e4c838602c1811a48fc938b0af" - }, - { - "text": "org/profile/FUa-5ocTKo4 .", - "tokenCount": 13, - "pageStart": 31, - "pageEnd": 31, - "hash": "dba8cf03066e268fcd0ca2022f7388e2f6bc821dd2794c49e701a3a9ddef502b" - }, - { - "text": "Benefits and Harms The panel voted for the following patientimportant outcomes for Question 9 decision making: 1) percent of individuals achieving BP control, 2) number of antihypertensive agents, 3) dosage of antihypertensive agents, 4) systolic BP (SBP) level, 5) control of hypokalemia, 6) quality of life (QOL), and 7) adverse events.", - "tokenCount": 85, - "pageStart": 31, - "pageEnd": 31, - "hash": "0f64b10d1b39f98c62c73995412659df02a37396645985450e8d9b0b01f4ec46" - }, - { - "text": "The systematic review ( 53 ) identified 3 relevant randomized controlled trials (RCTs) ( 122,211 , 212 ), (n = 229) and 1 comparative observational study (n = 188) with an equal distribution of women and men ( 29 ).", - "tokenCount": 50, - "pageStart": 31, - "pageEnd": 31, - "hash": "2dae6ffc693310ac70fca69b81030418f055489895fac97e59f3ecf83cd337cb" - }, - { - "text": "The metaanalysis concluded that eplerenone, compared with spironolactone, was associated with a higher number of antihypertensive agents and dosage of antihypertensive agents.", - "tokenCount": 39, - "pageStart": 31, - "pageEnd": 31, - "hash": "256fa7848c3fb244bd9136b454e58b4a2964d15b3728193e9ec049212e3aed76" - }, - { - "text": "However, the doses of the medications were not reninguided to ensure doseequivalent MR blockade.", - "tokenCount": 22, - "pageStart": 31, - "pageEnd": 31, - "hash": "e611e886dac6c6ca2bad2fbe2d952b08b75f4ceeca900edf74b9d22c4c6f5844" - }, - { - "text": "There were no statistically significant differences in achieving BP control, control of hypokalemia, and SBP level.", - "tokenCount": 23, - "pageStart": 31, - "pageEnd": 31, - "hash": "f778b51cbd7929a9cbd345412d5367c07ff6e6dd2dd2e0ba80d6dadd3a69f00b" - }, - { - "text": "Data from the direct evidence were insufficient to inform on broad issues of adverse events or QOL, although increased female breast pain and male gynecomastia were reported with spironolactone use.", - "tokenCount": 41, - "pageStart": 31, - "pageEnd": 31, - "hash": "1ce82f6d724392a07495dedefb51c9afdbc16a3b2bc14cb76e1b4d9744fed1db" - }, - { - "text": "After completion of the systematic review, but prior to publication of these guidelines, a new study comparing shortterm finerenone and lowdose spironolactone in PA was published demonstrating comparable blood pressure lowering efficacy and effects upon serum potassium and renin concentration ( 213 ).", - "tokenCount": 55, - "pageStart": 31, - "pageEnd": 31, - "hash": "502fd566ed7d7543de1a4252a47a3f1e49f21f2bf0dd6f88e75505caf3d36a7e" - }, - { - "text": "Spironolactone has far greater ability to block androgen action and affect progesterone action than does eplerenone.", - "tokenCount": 27, - "pageStart": 31, - "pageEnd": 31, - "hash": "6f4b8257441d77cef8b6cdc1886ccc6cc5db14a0891b8d5a4df33a26f0956120" - }, - { - "text": "As this may be relevant to the issue of individual tolerability, the Guideline Development Panel (GDP) considered indirect evidence in the form of studies reporting use other than for a PA indication.", - "tokenCount": 39, - "pageStart": 31, - "pageEnd": 31, - "hash": "f19816492cb3f1d107c06741cd724f03d83447d41c9ee285f1e838b24a9b96e9" - }, - { - "text": "Two systematic reviews/metaanalyses were found that compared spironolactone with eplerenone or canrenone ( 214,215 ).", - "tokenCount": 30, - "pageStart": 31, - "pageEnd": 31, - "hash": "068a00b454ce9cb40fe6614e56bb0cb01bb3602a42ebe6349bb7053de28b79c4" - }, - { - "text": "One metaanalysis of 14 studies and including 3745 individuals using spironolactone for nonPA indications showed a male gynecomastia incidence rate of 7.", - "tokenCount": 34, - "pageStart": 31, - "pageEnd": 31, - "hash": "acd22bbb2802ebb7bbf88a9e2ec3ea287fac20a7b481acae67d7cc5b384bc23d" - }, - { - "text": "6% among placebo users (OR: 8.", - "tokenCount": 10, - "pageStart": 31, - "pageEnd": 31, - "hash": "b495f6be21039a51d7faa3eb54bf81522b6863d09879b44a844dae60232dec6e" - }, - { - "text": "99]), although this was still less than that observed in users of antiandrogens or risperidone ( 214 ).", - "tokenCount": 24, - "pageStart": 31, - "pageEnd": 31, - "hash": "f20076a8fbb7c75969406e6c85755acc934a75af858dbc1f05bcaff17a4dd783" - }, - { - "text": "Among users of MRAs or placebo for heart failure, spironolactone had a relative odds of 8.", - "tokenCount": 23, - "pageStart": 31, - "pageEnd": 31, - "hash": "af59df39cad93c8d27a463344e6616fc8c34bc1eb0e9c168e4354c910cdd7e34" - }, - { - "text": "88) for male gynecomastia ( 215 ).", - "tokenCount": 12, - "pageStart": 31, - "pageEnd": 31, - "hash": "599f5859a62d96a263d9b37c57f9db800f2588a2a1d072665f90b4d30c22f113" - }, - { - "text": "Evidence to Decision Factors Studies specifically comparing spironolactone vs other MRAs in medical PA treatment were few in number, small in size, and judged to be low quality.", - "tokenCount": 37, - "pageStart": 31, - "pageEnd": 31, - "hash": "c5452fde7aaec87b3485db22d6c2adab82001dc71db0cf180b8cba43eb345511" - }, - { - "text": "All used surrogate outcomes (eg, BP changes or serum potassium levels), typically ascertained after short treatment intervals.", - "tokenCount": 22, - "pageStart": 31, - "pageEnd": 31, - "hash": "57d8f8846b59234cbc04f2064d4ea067deb5c9ded7450e2b38300a03eba51d7f" - }, - { - "text": "Heterogeneity and unbalanced baseline characteristics in study PA individuals (severe vs mild or mixed PA, lateralizing vs bilateral PA, hypoor eukalemia) limited the interpretability of metaanalysis.", - "tokenCount": 41, - "pageStart": 31, - "pageEnd": 31, - "hash": "97a999fb18fbebeab9f58ec375876d613a3ceaeafd2ba2728ca742fce03c1ea7" - }, - { - "text": "MRblocking potencies of various MRA agents were not routinely built into treatment protocols, and nonequivalent drug doses were sometimes compared.", - "tokenCount": 27, - "pageStart": 31, - "pageEnd": 31, - "hash": "ca5e4fa47fff3347c28fead5305127b100b77a994c2244a693e32b165f276d3e" - }, - { - "text": "Dose titration was not uniformly part of the study designs, and, even if so, titration schemes generally did not reflect modern (ie, reninguided) titration paradigms or BP targets.", - "tokenCount": 44, - "pageStart": 31, - "pageEnd": 31, - "hash": "1ca83daf370ed9738b28955060ed01c79780656c45a03980244451eaa4209187" - }, - { - "text": "In order to proceed despite the evidence gaps, the GDP agreed to make the following 5 assumptions as part of the EtD process: Each MRA, titrated appropriately, by blocking the MR, likely has an equal chance of eventually achieving the same degree of BP and potassium control in individuals with PA.", - "tokenCount": 61, - "pageStart": 31, - "pageEnd": 31, - "hash": "0d97d5f384760f4ddfca9e332c6f3d5a77cccdbce2004f7b33e7c4856d7de342" - }, - { - "text": "Each MRA, once titrated to equivalent MR blockade, likely has an equal chance of permitting discontinuation of other antihypertensives.", - "tokenCount": 29, - "pageStart": 31, - "pageEnd": 31, - "hash": "fd994662649a5b52778e369a8bf1d0e8cbf0cdb1c27c6fb17100bcb23e7c1a08" - }, - { - "text": "Rates of adverse events may differ between the MRAs.", - "tokenCount": 12, - "pageStart": 31, - "pageEnd": 31, - "hash": "c103a34cff2be81cc01c80bae8b3375546b5bddc02329fca4bd17110fd03f082" - }, - { - "text": "QOL differences may be explained by adverse event rates. QOL differences may exist outside of adverse event occurrences but would need appropriately designed headtohead comparisons of sufficient duration to detect.", - "tokenCount": 36, - "pageStart": 31, - "pageEnd": 31, - "hash": "bdc50c54114a17fed37ba9dc1b4901dd7b463628a56def235b06e3d5005851f7" - }, - { - "text": "Expected costs of medical therapy were considered in detail by the GDP, although highquality costeffectiveness modeling data in PA specifically is scarce ( Table 10 ).", - "tokenCount": 31, - "pageStart": 31, - "pageEnd": 31, - "hash": "7b5d0875272c697d5387014d1682cdbe00c22f4c5068926e3cf136d4bc269d5c" - }, - { - "text": "It was acknowledged that available studies focused on expected costs would not necessarily translate to all individuals and countries, even among highresource health systems.", - "tokenCount": 27, - "pageStart": 31, - "pageEnd": 31, - "hash": "5ba0993aa54945270fe92159e8fb91c4fba56ca03f24be5b49abdff85e71dec6" - }, - { - "text": "It was also noted that modeling costeffectiveness in a PA setting would be highly complex and difficult to perform without highquality, doseequivalent MRA comparison studies to rely on.", - "tokenCount": 37, - "pageStart": 31, - "pageEnd": 31, - "hash": "d78cc4243bb0f245856ce9b9c0157a9bed298aad39bf71e59869d95041a8dc52" - }, - { - "text": "9 2483 Downloaded from https://academic.", - "tokenCount": 11, - "pageStart": 31, - "pageEnd": 31, - "hash": "768cfd96c9a70edf03841d30996797f37fa4bc584a634efbca9b8d0a4334e69e" - }, - { - "text": "Additionally, with PA diagnosed at young or middle ages, a lifetime model must include very longterm costs of therapy balanced against the longterm cost trajectory of reduced disease burden.", - "tokenCount": 34, - "pageStart": 32, - "pageEnd": 32, - "hash": "461571c65d41e264983e46295e0a01a8bee8594854084c070018ece30e5e7f17" - }, - { - "text": "Nonetheless, attempts at cost estimates in other cardiovascular conditions ( 216-218 ) consistently demonstrate markedly lower costs for spironolactone vs eplerenone; newer MRA drugs will likely have the highest costs.", - "tokenCount": 43, - "pageStart": 32, - "pageEnd": 32, - "hash": "b21a3e38fdefeb889586b83a307acd6f9aaa034d3f46761938c2bb1250adf9a1" - }, - { - "text": "In costmodeling studies of PA diagnosis and therapy, given the lifelong requirement for MRA treatment in those who do not receive surgery, the cost of medication is expected to rapidly dominate the cost inputs for all but the oldest individuals.", - "tokenCount": 46, - "pageStart": 32, - "pageEnd": 32, - "hash": "d13db19fc6767ca8f1d8e389c3dc6eba4d9b067f0d03b5bc87dd6905072da634" - }, - { - "text": "The GDP made specific note of the individual concerns about tolerability and side effect risk, recognizing the important role of individual preference in choice of MRA, beyond cost considerations alone.", - "tokenCount": 35, - "pageStart": 32, - "pageEnd": 32, - "hash": "111cf10b47a2f08010d5470da839bbc65d475b7af7bd4e3ec01669a5aae23d90" - }, - { - "text": "Justification for the Recommendation Although legitimate individual concerns about tolerability of spironolactone exist, there is no scientific basis in studies of medical efficacy to recommend an alternative MRA as firstline therapy to replace spironolactone.", - "tokenCount": 49, - "pageStart": 32, - "pageEnd": 32, - "hash": "efe014817b5d1c89518c722bbeabd8c79679ef58c6b199881bd4cc9ea268dc0e" - }, - { - "text": "Cost considerations or risk of unwanted antiandrogen effects may be secondary concerns and are likely highly significant when comparing spironolactone vs other MRAs.", - "tokenCount": 31, - "pageStart": 32, - "pageEnd": 32, - "hash": "371a870402013ad6808b4771bb85c94b0e3295d31dae9f0fe1a7f364189676f9" - }, - { - "text": "Shared decision making with individual patients allows for use of a nonspironolactone MRA in PA treatment where desired.", - "tokenCount": 26, - "pageStart": 32, - "pageEnd": 32, - "hash": "b8eceabd3bf4663fe26854d5b772bf65eaa6df6be199e3dba65c3e85e10d19be" - }, - { - "text": "Comments A recent international consensus document regarding the specific targets and means of implementing optimized MRA therapy has been published ( 85 ).", - "tokenCount": 24, - "pageStart": 32, - "pageEnd": 32, - "hash": "e1e9f06c39b016d7936c71f8199ec2108be128acd1b5e475963c35077d5d5606" - }, - { - "text": "As new evidence for new MRAs in PA emerges, recommendations may require updating, although major differential cost considerations may continue to dominate for many years.", - "tokenCount": 29, - "pageStart": 32, - "pageEnd": 32, - "hash": "a703741bd65d19f21ac36fe3c14f9d7493f9314c76d0c6503f39808719c4954f" - }, - { - "text": "Research Considerations Current gaps in knowledge call for further research in the following areas: Evaluating aldosterone synthase inhibitors with appropriately designed PAspecific research studies to determine their optimal position within a PA treatment framework; ongoing trials of MRA drugs such as esaxerenone and aldosterone synthase inhibitors such as dexfadrostat should help clarify relative efficacies in PA therapies both as monotherapy and in combination Specifically studying PA with individualrelevant hard clinical endpoints Designing and studying more complex treatment paradigms including surgical or proceduralbased debulking strategies with and without adjuvant medical therapy Implementation Considerations Expanded PA screening in hypertensive individuals is expected to increase diagnosis rates, requiring greater access to additional tests such as adrenal computed tomography (CT) scans and adrenal venous sampling (AVS).", - "tokenCount": 171, - "pageStart": 32, - "pageEnd": 32, - "hash": "e3570ef814e29a7739df1dd8b34e128fc92138a8b32d1921eb9c92374d4f4dc6" - }, - { - "text": "These demands may challenge health care systems with limited resources, where access to specialized equipment, expertise, and followup care could be uneven.", - "tokenCount": 27, - "pageStart": 32, - "pageEnd": 32, - "hash": "02ce407b3e2d18e24c0b057b9eb6c6c49f87d3d3c561be108388dea450fdaa8f" - }, - { - "text": "In such settings, pathways involving direct medical treatment, such as initiating MRAs based on screening results alone, may be considered when further testing is not feasible.", - "tokenCount": 31, - "pageStart": 32, - "pageEnd": 32, - "hash": "c98c9a7bef82e224a4e7984b92843b12f4fc8f8c4717b3de52fd2b152de8b4d3" - }, - { - "text": "Variability in resources across settings highlights potential inequities, with rural and lowresource areas facing the greatest barriers.", - "tokenCount": 22, - "pageStart": 32, - "pageEnd": 32, - "hash": "1fabbd53066ada6e59378482cc3ae2943a1f972b24f6c7b0171268cc71f56059" - }, - { - "text": "Practical adaptations, such as simplified diagnostic algorithms or regional hubs for specialized care, could mitigate these challenges.", - "tokenCount": 21, - "pageStart": 32, - "pageEnd": 32, - "hash": "edf3f7d254cc4d64d215499beca063a196293fffc6b2dc8b1b545e16d35b15c9" - }, - { - "text": "Broader implementation will depend on embedding PA screening within existing hypertension management frameworks, supported by education for clinicians and individuals, and ongoing monitoring to ensure benefits reach all populations equitably.", - "tokenCount": 36, - "pageStart": 32, - "pageEnd": 32, - "hash": "03b3cca283d4a2ff240b4c0146701699d5b9f98763f845a2c4fa03505e72e5d3" - }, - { - "text": "To support the adoption of this recommendation and address challenges in implementation, the guideline offers PA screening and management algorithms as practical tools ( Figs.", - "tokenCount": 28, - "pageStart": 32, - "pageEnd": 32, - "hash": "2e7b3205c79ed8a2f69eab66e73cb405b20bdab145fe5ff220e474f8468e9c71" - }, - { - "text": "Medical Therapy With Epithelial SodiumChannel Inhibitors vs Mineralocorticoid Receptor Antagonists (Steroidal and Nonsteroidal) for Individuals With Primary Aldosteronism Background With increased screening and diagnosis of primary aldosteronism (PA), the need for medical treatment will continue to grow ( 209 ).", - "tokenCount": 66, - "pageStart": 32, - "pageEnd": 32, - "hash": "9b7071fc9b1c06d8422c1a44a128e563194900b6bc5ae59de9f53dc9584d02a8" - }, - { - "text": "The most commonly used and targeted medical treatments are mineralocorticoid receptor antagonists (MRAs), which are generally widely available and inexpensive.", - "tokenCount": 28, - "pageStart": 32, - "pageEnd": 32, - "hash": "0c6c71043f389d317f39063457ab702c0622b98e653280b5750b0dbb8b6b6d3e" - }, - { - "text": "For individuals who cannot tolerate MRAs (eg, due to effects on androgen or progesterone receptors), a lowercost, secondline option such as epithelial sodiumchannel (ENaC) inhibitors may be a consideration.", - "tokenCount": 46, - "pageStart": 32, - "pageEnd": 32, - "hash": "02fa11d02c20d90a74d4ebea79c10d89a252fa0cbb1d79587537af9a30d5e9f6" - }, - { - "text": "PA is often associated with resistant or refractory hypertension ( 219 ).", - "tokenCount": 14, - "pageStart": 32, - "pageEnd": 32, - "hash": "e164fa73284076e9752ae73e14ed50dcb7247f93cf00e1f4bc64c6bea2d7877b" - }, - { - "text": "The significance of aldosterone in resistant hypertension is supported by studies demonstrating that aldosterone synthase inhibitors reduce blood pressure (BP) in treatmentresistant hypertension ( 220 ).", - "tokenCount": 34, - "pageStart": 32, - "pageEnd": 32, - "hash": "cc60137365da1191a8ab38eb027d022bc0cfeffb931318f001b28d1c01dd3d27" - }, - { - "text": "In PA, renal sodium reabsorption is increased, leading to volume expansion and higher BP.", - "tokenCount": 19, - "pageStart": 32, - "pageEnd": 32, - "hash": "b0f356d03be5f266d113df1d4e212a618417276bce13dfb36342f0ce7cca2af2" - }, - { - "text": "The increased sodium reabsorption is due to aldosteronemediated activation of renal mineralocorticoid receptors (MRs) and consequent increased expression and activation of the renal ENaCs ( 221 ).", - "tokenCount": 44, - "pageStart": 32, - "pageEnd": 32, - "hash": "7ca5aa3adb48a8872b67f82e599f611fd39a8dfc307b2d3bf0fae2ee25539f41" - }, - { - "text": "Increased ENaC activity leads to increased sodium reabsorption and potassium excretion in the distal convoluted nephron.", - "tokenCount": 25, - "pageStart": 32, - "pageEnd": 32, - "hash": "33af1162089c3a5f56fbf34861135ff6d6636e9492266f8f9e82995c9b6e9d72" - }, - { - "text": "ENaC is a major regulator of sodium excretion during feedback regulation of BP by the renin angiotensin aldosterone system (RAAS) ( 221,222 ).", - "tokenCount": 39, - "pageStart": 32, - "pageEnd": 32, - "hash": "b315a9bde79f4b77446bc21c45645c9e74aaca128767fda9559cb4ee0ab9e7a9" - }, - { - "text": "Endorgan damage in individuals with PA is more severe than in individuals with primary hypertension, and includes left ventricular hypertrophy, cardiac fibrosis, arterial stiffness, tubulointerstitial fibrosis, microalbuminuria, and microvascular damage ( 2,223 , 224 ).", - "tokenCount": 57, - "pageStart": 32, - "pageEnd": 32, - "hash": "4a6b60736b948f6750723ef989af9691dce9f3273f2a1da6b0064890f62c992b" - }, - { - "text": "ENaCs are also expressed in the cardiovascular system, and their activation promotes cardiovascular fibrosis, vascular dysfunction, and arterial stiffening ( 222,225 ).", - "tokenCount": 32, - "pageStart": 32, - "pageEnd": 32, - "hash": "e2120e94e4208219141b335a954a8d7e85907135d9e3f8baa31fe90d5bd9d821" - }, - { - "text": "Reducing effects of excess aldosterone by blocking MRs or inhibiting ENaC activation could attenuate PAinduced hypertension, sodium reabsorption, and cardiovascular damage.", - "tokenCount": 35, - "pageStart": 32, - "pageEnd": 32, - "hash": "e458a1a63712296c09887825f7a9c5311951ffcd66e51c1082ef3d3ba896f94d" - }, - { - "text": "This suggests the potential utility of ENaC inhibitors like amiloride and triamterene in the treatment of individuals with PA.", - "tokenCount": 29, - "pageStart": 32, - "pageEnd": 32, - "hash": "1358d4df1c515c0f6580ffa3d018452b5066c964bd1384788fa2522f3ddb9aef" - }, - { - "text": "2484 The Journal of Clinical Endocrinology & Metabolism , 2025, Vol.", - "tokenCount": 18, - "pageStart": 32, - "pageEnd": 32, - "hash": "224379d1ed0bd3656ceb14ff77d6a89a26e6d3b29ca67b5bfe3ae4a643a0168b" - }, - { - "text": "org/profile/CssZc_4Ppmg .", - "tokenCount": 14, - "pageStart": 33, - "pageEnd": 33, - "hash": "59196623c6afb05f026df4acd2cb2f7a8a9704b04554cc2addfd411b811f1a16" - }, - { - "text": "Benefits and Harms The panel voted for the following patientimportant outcomes for Question 10 decision making: 1) percent of individuals achieving BP control, 2) number of antihypertensive agents, 3) dosage of antihypertensive agents, 4) systolic BP (SBP) level, 5) adverse cardiovascular events (MACEs), 6) atrial fibrillation, 7) stroke, 8) ischemic heart disease, 9) heart failure, 10) cardiovascular mortality, 11) allcause mortality, and 12) adverse events.", - "tokenCount": 113, - "pageStart": 33, - "pageEnd": 33, - "hash": "2e94a9ec66850d07359a625589dcc2ed308047f226c686be5bd26847381c0296" - }, - { - "text": "The systematic review did not find any studies directly comparing ENaC inhibitors vs MRAs in the medical treatment of PA, although a few studies compared ENaC inhibitors and spironolactone (but not eplerenone) in resistant hypertension.", - "tokenCount": 51, - "pageStart": 33, - "pageEnd": 33, - "hash": "e2fe5a62d2e4517275f9f947d36cef3cdb92221777e500977c538693642eedb2" - }, - { - "text": "Because most individuals with resistant hypertension have PA, we used these studies as indirect evidence of hyperaldosteronism ( 40,164 ).", - "tokenCount": 27, - "pageStart": 33, - "pageEnd": 33, - "hash": "b68fb216be149e843be284b20bd1ea81edd2633cbf1ba3ebfdda8dcc2cca075f" - }, - { - "text": "The largest study was a substudy of the PATHWAY-2 study, which was a randomized, doubleblind crossover trial in individuals with resistant hypertension ( 19 ).", - "tokenCount": 33, - "pageStart": 33, - "pageEnd": 33, - "hash": "f80e591a05791420a988f5accb9e9f29667ac73c8b4bb0fa2e48ad256d72b5f8" - }, - { - "text": "Results showed similar BPlowering effects of spironolactone and amiloride.", - "tokenCount": 20, - "pageStart": 33, - "pageEnd": 33, - "hash": "b81a7b3c2fd734bc06602e65cb86a2bd3dbb63fec8654aaece8f36cc9161822d" - }, - { - "text": "In the spironolactone, amiloride, losartan, and thiazide (SALT) doubleblind crossover trial in individuals with lowrenin hypertension and elevated aldosterone to renin ratio (ARR), spironolactone and highdose amiloride had similar antihypertensive effects ( 226 ).", - "tokenCount": 70, - "pageStart": 33, - "pageEnd": 33, - "hash": "b45bfb5c2f3e4385c37b4591425045d1e2bc63842413ceb93df1dfb2bd568b7d" - }, - { - "text": "Several smaller studies also demonstrated that amiloride and spironolactone were similarly effective at lowering BP in individuals with resistant hypertension ( 227-229 ).", - "tokenCount": 32, - "pageStart": 33, - "pageEnd": 33, - "hash": "86c4246962c1c8b3112d576efb2fdc327b941f7304e68ea2c2f7b73a4ec41a52" - }, - { - "text": "In individuals with hypertension and supranormal aldosterone secretion, effects of spironolactone were better than those of amiloride ( 230 ).", - "tokenCount": 33, - "pageStart": 33, - "pageEnd": 33, - "hash": "211932dceab3feab26d6b943c56d301d8ed820795b7943789b5e5b586572dc44" - }, - { - "text": "In lowrenin hypertension, BPlowering effects of spironolactone and a hydrochlorothiazide/triamterene combination were similar ( 231 ). In volumedependent hypertension, spironolactone and triamterene reduced BP, with spironolactone having greater effects ( 232 ).", - "tokenCount": 68, - "pageStart": 33, - "pageEnd": 33, - "hash": "96858431eae5a0f8ae177250e00182b599d9eb9a56c427d4947a29056a37c3ac" - }, - { - "text": "Together, these studies in resistant hypertension suggest ENaC inhibitors as a viable substitute for spironolactone when spironolactone is not tolerated ( 233,234 ).", - "tokenCount": 36, - "pageStart": 33, - "pageEnd": 33, - "hash": "3a32ba232f603dd2dd62404908f5a6d7a24e3caa6453a4b38829717f4ca7005a" - }, - { - "text": "Beyond similar antihypertensive effects, both amiloride and spironolactone equally improved quality of life (QOL) in individuals with PA ( 234,5 ).", - "tokenCount": 37, - "pageStart": 33, - "pageEnd": 33, - "hash": "a155281f164c1560e7b095a9b617978830310037c8ec3f6af82ecc037dc91a28" - }, - { - "text": "Amiloride may be an effective antihypertensive drug in individuals with PA.", - "tokenCount": 18, - "pageStart": 33, - "pageEnd": 33, - "hash": "28678e998ec92028b5094138bdd962e628bd9de8118bf2ebddb261bd7319bd16" - }, - { - "text": "However, whether the effects are superior or not to MRAs is unknown because headtohead trials comparing them in PA are lacking.", - "tokenCount": 26, - "pageStart": 33, - "pageEnd": 33, - "hash": "0dbe8b209e97a8c94e275f653e27e80b05810b830a2e5d3c49d0244b7fc2b37c" - }, - { - "text": "In a small clinical study in individuals with PA, lowdose amiloride controlled BP within 1 to 4 weeks of initiation, with effects sustained for up to 20 years ( 227 ).", - "tokenCount": 37, - "pageStart": 33, - "pageEnd": 33, - "hash": "aa11c8e9366ceed4ab606e6ce10751d36a8ac992678f25b221ca178475372a59" - }, - { - "text": "This was associated with improved vascular function (pulsewave velocityindicating cardiac output, vascular resistance, and arterial stiffness) and no cardiovascular events.", - "tokenCount": 30, - "pageStart": 33, - "pageEnd": 33, - "hash": "e86025ff8fff694b3b3b4c9f4854eba25fe1ff62412b629f5ba82fd93cfd5702" - }, - { - "text": "Amiloride at higher doses corrected hypokalemia and normalized BP in individuals with PA ( 228 ).", - "tokenCount": 22, - "pageStart": 33, - "pageEnd": 33, - "hash": "605f22307f74e8b7c51686265234a4ffcda447376ffbec7b99f8f60a6b0850b8" - }, - { - "text": "A major assumption (as required with reliance on indirect evidence) is that both ENaC inhibitors and MRAs would likely yield equivalent clinical outcomes based on observations that they probably yield similar BP reductions in a PA population.", - "tokenCount": 43, - "pageStart": 33, - "pageEnd": 33, - "hash": "61df5bb29ffbac52df6cca0adecd5aa1fe334a9f35a9dd618855e5ad5e5a1ce5" - }, - { - "text": "However, ENaC inhibitors do not block aldosterone directly; therefore, the impact of ENaC inhibitors and MRAs on aldosteronespecific endorgan injury may differ.", - "tokenCount": 39, - "pageStart": 33, - "pageEnd": 33, - "hash": "0184452273c76781c234096772ff000c42ad774a310e20f2df1c85c51364b7cb" - }, - { - "text": "Evidence to Decision Factors Costeffectiveness data do not exist for ENaC inhibitors in medical PA treatment.", - "tokenCount": 22, - "pageStart": 33, - "pageEnd": 33, - "hash": "b2d5b1a0a4cc33aba5c56baf22b2d3907f34e3c44d54415fd1e46249d4fcadfe" - }, - { - "text": "However, cost estimates in the United States demonstrated equally low prices for equipotent amiloride and spironolactone.", - "tokenCount": 26, - "pageStart": 33, - "pageEnd": 33, - "hash": "c99328b733fbd25ea18af3070e35d7d918ef1ffc0373269a00cc5198137452ab" - }, - { - "text": "Accordingly, amiloride as an alternative to spironolactone may be costneutral.", - "tokenCount": 21, - "pageStart": 33, - "pageEnd": 33, - "hash": "f621cfed3109208fbedb473e5b2d78c778ec21fcaddc1a544881878f25268b31" - }, - { - "text": "(See Question 9 for discussion of costeffectiveness of spironolactone.", - "tokenCount": 17, - "pageStart": 33, - "pageEnd": 33, - "hash": "67e28599a90d0aeceec8743d6896130c5a9226ebdb8e31472e53f1fd73b23efe" - }, - { - "text": ") Since the clinical impact (BPlowering) of ENaC inhibitors is the same as spironolactone and given their similar low costs, similar costeffectiveness is expected from any future model using ENaC inhibition.", - "tokenCount": 49, - "pageStart": 33, - "pageEnd": 33, - "hash": "43f172428acce066f0348703f8d945a250da2672e9c026df2e1dfc9b88b6acbf" - }, - { - "text": "Cost neutrality may be especially relevant in Black individuals who are more likely to have lowrenin hypertension ( 231 ).", - "tokenCount": 22, - "pageStart": 33, - "pageEnd": 33, - "hash": "18a2df22ad6296715b82e00c76ec02a097e49999ce981c732e2a30e7933690ca" - }, - { - "text": "Some evidence exists that a significant proportion of these individuals may also have a Liddlesyndrometype biochemical phenotype, which is strongly responsive to ENaC inhibitors ( 235 ).", - "tokenCount": 36, - "pageStart": 33, - "pageEnd": 33, - "hash": "5eca31fb64d6fcb4f1086d053f9883658d7e3eb2bad73be88fee2cd05b29026a" - }, - { - "text": "Accordingly, inclusion of ENaC inhibitors as an option for lowrenin/PA hypertension could increase health equity.", - "tokenCount": 24, - "pageStart": 33, - "pageEnd": 33, - "hash": "397d956e8dbd5859674c2648d57e873402981fbc92eed35cf0a7810195fdea04" - }, - { - "text": "Justification for the Recommendation Although the evidence is limited and indirect, amiloride seems to be as effective as spironolactone in reducing BP in individuals with resistant hypertension, which the Guideline Development Panel (GDP) used as a surrogate of PA.", - "tokenCount": 55, - "pageStart": 33, - "pageEnd": 33, - "hash": "dcb0ea63c1c944d98bf533247a86936d7b5815b58ef656fe870153545ad9628a" - }, - { - "text": "Both drugs are low cost and both improve QOL.", - "tokenCount": 11, - "pageStart": 33, - "pageEnd": 33, - "hash": "84fc40c11163146f74ed176dd850fdb397b11048e57b1fd8f4a6956a47d09fb9" - }, - { - "text": "In addition to a lack of direct clinical evidence to recommend the ENaC amiloride over the MRA spironolactone as firstline therapy, questions remain as to whether amiloride would offer all the same benefits as an MRA.", - "tokenCount": 53, - "pageStart": 33, - "pageEnd": 33, - "hash": "292c95e2536d35dc4b991c5312e4f3a4483d631904fdc27dcec3bd3b2cb253f2" - }, - { - "text": "There is some justification that MRA should be the preferred treatment in PA based on a small study of 10 individuals with hypertension and supranormal aldosterone secretion in which spironolactone (400 mg/day) had greater BPlowering effects than did amiloride (40 mg/day) as well as on the clear evidence that MRAs are effective in PA (see Question 9). When spironolactone is not tolerated and other MRAs are not available, amiloride may be an alternative therapy in the management of PA.", - "tokenCount": 116, - "pageStart": 33, - "pageEnd": 33, - "hash": "8ba74cc22d3833175d70562b05cd4214da702e41f27b5fc89bc156b503cc9540" - }, - { - "text": "9 2485 Downloaded from https://academic.", - "tokenCount": 11, - "pageStart": 33, - "pageEnd": 33, - "hash": "b69182adab17a6ae93f4cda3bbad08f385b672954ea59405dcbc76426620dd98" - }, - { - "text": "Comments and Future Research Considerations Many gaps in knowledge need to be addressed through robust clinical studies before ENaC inhibitors could be considered a replacement, or addon therapy, to MRAs, including: Comparing ENaC inhibitors vs MRAs in PA Studying the potential longterm effects of ENaC inhibitors on endorgan damage in PA, including cardiac, vascular, and renal fibrosis Considering diverse populations of PA, including those who are saltsensitive Acknowledgments The Endocrine Society and the Guideline Development Panel thank Marie McDonnell, MD, and Roma Gianchandani, MD, who served as Clinical Guidelines Committee chairs during the development of this clinical practice guideline.", - "tokenCount": 137, - "pageStart": 34, - "pageEnd": 34, - "hash": "783314c4294073873f5f8066d35d8c114b23030162546a9f91aa277203b5c9cc" - }, - { - "text": "The panel thanks Endocrine Society staff including Maureen Corrigan, MA, Elizabeth York, MPH, Laura Mitchell, MA, and Emma Goldberg, PhD, for their expert guidance and assistance with all aspects of guideline development.", - "tokenCount": 44, - "pageStart": 34, - "pageEnd": 34, - "hash": "167cdbe9a811cd8d1f4d6ad996ad7232f8c840e480f4a93f835a564dc56f6a2d" - }, - { - "text": "We also thank the numerous contributors from the Mayo EvidenceBased Practice Center, especially Magdoleen Farah, MBBS, for their contribution in conducting the evidence reviews for the guideline.", - "tokenCount": 37, - "pageStart": 34, - "pageEnd": 34, - "hash": "f6d36f3266f57d18f732dc2f3ea2d25ecde34a157a3c31e5e317cba279638bbc" - }, - { - "text": "We are grateful to Robert Carey, MD, for his contributions to this guideline and to the field.", - "tokenCount": 20, - "pageStart": 34, - "pageEnd": 34, - "hash": "c3ebe70df23f201cb4394caf1ef6bdaabcf86c4c48bc7fbff96197b658c96987" - }, - { - "text": "Funding Funding for the development of this guideline was provided by The Endocrine Society.", - "tokenCount": 17, - "pageStart": 34, - "pageEnd": 34, - "hash": "429a51d41a8c6af4a72221ae666503205c521bb90ee9a07ffbfbc4aa9f2dcb67" - }, - { - "text": "Disclaimer The Endocrine Society s clinical practice guidelines are developed to be of assistance to endocrinologists by providing guidance and recommendations for particular areas of practice.", - "tokenCount": 31, - "pageStart": 34, - "pageEnd": 34, - "hash": "39b964c24e877747eaa611e4bb373ffe9c61f62a146fd298caf559eeca95f9c0" - }, - { - "text": "The guidelines should not be considered as an allencompassing approach to individual care and not inclusive of all proper approaches or methods, or exclusive of others.", - "tokenCount": 31, - "pageStart": 34, - "pageEnd": 34, - "hash": "df591830e8c58c0182bb034d817b9588f682804400172839ead2db9e94e395d2" - }, - { - "text": "The guidelines cannot guarantee any specific outcome or successful treatment, nor do they establish a standard of care.", - "tokenCount": 20, - "pageStart": 34, - "pageEnd": 34, - "hash": "76eed29d675b7161ca0bd503bf6bf7fce3e2441ab271c562804c3c047f499c4e" - }, - { - "text": "The guidelines are educational tools, not medical advice, and are not intended to dictate the treatment of a particular individual.", - "tokenCount": 23, - "pageStart": 34, - "pageEnd": 34, - "hash": "7ec3772e649895a06c7399c1d07a6573c1e40d7bbf90b24914db59f1e7c1b834" - }, - { - "text": "Treatment decisions must be made based on the independent judgment of health care clinicians and each person s individual circumstances.", - "tokenCount": 23, - "pageStart": 34, - "pageEnd": 34, - "hash": "31cb660a9dec576376d8cbd6fada4db113cd3c10a00bee04f59a83deebc712f3" - }, - { - "text": "The Endocrine Society makes every effort to present accurate and reliable information, and this guideline reflects the best available data and understanding of the science of medicine at the time the guideline was prepared.", - "tokenCount": 37, - "pageStart": 34, - "pageEnd": 34, - "hash": "af742f9f8b7f49af2011d1f57d0ab07ad0b987420383774dadd5cbf043c61d3c" - }, - { - "text": "The results of future studies may require revisions to the recommendations in this guideline to reflect new data.", - "tokenCount": 19, - "pageStart": 34, - "pageEnd": 34, - "hash": "399e9a007617b9fc6d0adf1704de0fd9e811ee6fc9f4588345c91152e5a13abc" - }, - { - "text": "This publication is provided as is and the Society makes no warranty, express or implied, regarding the accuracy and reliability of these guidelines and specifically excludes any warranties of merchantability and fitness for a particular use or purpose, title, or noninfringement of thirdparty rights.", - "tokenCount": 56, - "pageStart": 34, - "pageEnd": 34, - "hash": "6287116bff18dc3f9c0624342cc129fb5212a8ef9088a66757c324a6b9f88155" - }, - { - "text": "The Society, its officers, directors, members, employees, and agents (including the members of the Guideline Development Panel) shall not be liable for direct, indirect, special, incidental, or consequential damages, including the interruption of business, loss of profits, or other monetary damages, regardless of whether such damages could have been foreseen or prevented, related to this publication or the use of, inability to use, results of use of, or reliance on the information contained herein, based on any legal theory whatsoever and whether or not there was advice on the possibility of such damages.", - 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"pageStart": 34, - "pageEnd": 34, - "hash": "66709665f4ab9dc2691a993b8ca82f598ae56ee97241ee886e4590f5adde3445" - }, - { - "text": "Representative Chair Gail Adler No CoChair Michael Stowasser No Members Ricardo Correa Yes AACE Nadia Khan No ISH Gregory Kline No Michael McGowan No PAF Paolo Mulatero Yes ESH Rhian Touyz No AHA Anand Vaidya Yes Tracy Williams No ESE Jun Yang No William Young Yes Maria Christina Zennaro No Methodologists M.", - "tokenCount": 80, - "pageStart": 34, - "pageEnd": 34, - "hash": "810a9d2b9bd43d2c0342a8171d4264f16198833cc9fd0618abbb870e8ca319b8" - }, - { - "text": "Brito No Abbreviations: AACE, American Association of Clinical Endocrinology; AHA, American Heart Association; COI, conflict of interest; ESE, European Society of Endocrinology; ESH, European Society of Hypertension; ISH, International Society of Hypertension; PAF, Primary Aldosteronism Foundation.", - "tokenCount": 73, - "pageStart": 34, - "pageEnd": 34, - "hash": "c4f32d139907239779fc514f4d986b57ea6af283d8f413f4979b804dce76c532" - }, - { - "text": "2486 The Journal of Clinical Endocrinology & Metabolism , 2025, Vol.", - "tokenCount": 18, - "pageStart": 34, - "pageEnd": 34, - "hash": "d3e73d57ee78093315637d366eedf2c3472ef71839a27b86afa2c6f3832742c2" - }, - { - "text": "ParisCardiovascular Research Center (PARCC) INSERM U970, France, Member of Scientific Advisory Board 2012-2022 Open Payments Database: https:/ /openpaymentsdata.", - "tokenCount": 38, - "pageStart": 35, - "pageEnd": 35, - "hash": "b4060b674e037e0a0bb14b592b69f8592b18b214a484699a4ed3a158e45088cd" - }, - { - "text": "gov/physician/1040596 Assessment and Management: No COI relevant to this CPG.", - "tokenCount": 22, - "pageStart": 35, - "pageEnd": 35, - "hash": "067c90dfb0c6ae27037bfce635cbc0d91012e03021bd7cbe0705b159703d8497" - }, - { - "text": "CoChair: Michael Stowasser, MBBS, FRACP, PhD University of Queensland Expertise: Adult endocrinology Disclosures (2021-2025): Springer, EditorinChief for Journal of Human Hypertension Open Payments Database: n/a Assessment and Management: No COI relevant to this CPG.", - "tokenCount": 69, - "pageStart": 35, - "pageEnd": 35, - "hash": "3db18c92f8596d33881553a72e5f46165ebce5e5fb7eb709b237df07ecc8da8a" - }, - { - "text": "Ricardo Correa, MD Cleveland Clinic Expertise: Adult endocrinology Disclosures (2022-2025): Dynamed American Medical Association IMG section American Federation of Medical Research Association of Program Director of Endocrinology Maricopa Medical Association ModernaTX, Consulting Ascendis Pharma, Speaker Neurocrine Biosciences, Consulting NovoNordisk, Consulting Boehringer Ingelheim (Boehringer Ingelheim manufactures and markets Micardis (telmisartan), Micardis HCT (telmisartan and hydrochlorothiazide), and Twynsta (telmisartan and amlodipine) and is developing vicadrostat, an aldosterone synthetase inhibitor.", - "tokenCount": 169, - "pageStart": 35, - "pageEnd": 35, - "hash": "7edb3b66d9164ec3502091b11de413b0c5f4f8d6a212a8061601d6b42f87234a" - }, - { - "text": "), Consulting Pfizer (Pfizer manufactures and markets aldosterone antagonist and Aldactone (spironolactone) and the antihypertensive agents Accupril (quinapril HCl), Accuretic (quinapril HCl/ hydrochlorothiazide), Norvasc (amlodipine) and Minipress (prazosin hydrochloride).", - 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"tokenCount": 59, - "pageStart": 35, - "pageEnd": 35, - "hash": "771c554c70c95eb43a7f2a744b471c02939423ff1a04c7f982a554faf08bb4e6" - }, - { - "text": "Michael McGowan Primary Aldosteronism Foundation Expertise: Patient representative Disclosures (2023-2025): Cemosoft, consultant Brainiest AI Technology, VP and Architect Primary Aldosteronism Foundation, various leadership roles Open Payments Database: n/a Assessment and Management: No COI relevant to this CPG.", - "tokenCount": 72, - "pageStart": 35, - "pageEnd": 35, - "hash": "20ead0b08ad2b9dc533b853dd785fb9ad97d4df6e6879de68f69fff2673c06c8" - }, - { - "text": "Paolo Mulatero, MD University of Torino Expertise: Adult hypertension Disclosures (2022-2025): Diasorin (Diasorin manufactures and markets Liaison Hypertension Diagnostic Solution, which includes aldosterone and renin assays.", - "tokenCount": 60, - "pageStart": 35, - "pageEnd": 35, - "hash": "06e3fa8d32f9ef49f1073a47db2362e8d9da8700180167a45b14a935bfa05d7b" - }, - { - "text": "), speaker Open Payments Database: n/a Assessment and Management: Dr.", - 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}, - { - "text": "Rhian Touyz, MBBCh, MSc, PhD McGill University Expertise: Adult hypertension Disclosures (2022-2025): American Heart Association, EditorinChief Hypertension journal, Council on Hypertension European Society of Cardiology, Cochair, 2024 ESC guidelines on elevated blood pressure and hypertension Open Payments Database: n/a Assessment and Management: No COI relevant to this CPG.", - "tokenCount": 88, - "pageStart": 36, - "pageEnd": 36, - "hash": "509e41b32d262ce42ce815ff529084f59b1b75d278e9d253a1d1f5cd67e91ec6" - }, - { - "text": "Anand Vaidya, MD Brigham and Women s Hospital Expertise: Adult endocrinology Disclosures (2021-2025): Mineralys Therapeutics (Mineralys Therapeutics is developing lorundrostat, an aldosterone synthase inhibitor.", - "tokenCount": 59, - "pageStart": 36, - "pageEnd": 36, - "hash": "2b8b5b2e41a899872bfc9d7d3a37fdfc6052137543a383ebdd8ba8b3a75c6032" - }, - { - "text": "), Advisory Board HRA Pharma, Advisory Board Corcept, Advisory Board, Consulting Open Payments Database: n/a Assessment and Management: Dr.", - 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"tokenCount": 30, - "pageStart": 36, - "pageEnd": 36, - "hash": "fb3c22b6ff20dc77031613299dc051fc93cd4d5acfc0dfa377b3b494086e094d" - }, - { - "text": "Vaidya was not involved in systematic reviews for PICO questions directly related to the above considerations.", - "tokenCount": 20, - "pageStart": 36, - "pageEnd": 36, - "hash": "6725b19c6300825333b4b38554f495310092f2fc13499703d2eb7b7a05be00f8" - }, - { - "text": "Vaidya did not vote on matters directly related to the above considerations.", - "tokenCount": 15, - "pageStart": 36, - "pageEnd": 36, - "hash": "339f4e6fe61246c275fdb3579ad1b8aac9c25d7d3a9d4b61804ef8f0b7d7485d" - }, - { - "text": "Vaidya did not draft guideline sections directly related to the above considerations.", - "tokenCount": 15, - "pageStart": 36, - "pageEnd": 36, - "hash": "9e01953288106b8b37fe5d7078a3b8941bdfde7acc92dd0afa8fdc6bcc8fedbe" - }, - { - "text": "Vaidya s potentially relevant industry relationship.", - "tokenCount": 10, - "pageStart": 36, - "pageEnd": 36, - "hash": "ac3cdcc5e876c6d1294a201459331902fbe5ae65bd3e68b7ba601ebaefb9d230" - }, - { - "text": "Tracy Williams, PhD Ludwig Maximilian University, Munich Expertise: Adult endocrinology Disclosures (2022-2025): None Open Payments Database: n/a Assessment and Management: No COI relevant to this CPG.", - "tokenCount": 52, - "pageStart": 36, - "pageEnd": 36, - "hash": "3a03ba19358d83ea8bb5b69d587b7990b173e459c4aa451089f74055afe12d00" - }, - { - "text": "Jun Yang, MBBS, FRAC, PhD Hudson Institute of Medical Research Expertise: Adult endocrinology Disclosures (2023-2025): Primary Aldosteronism Foundation, Patient Engagement Officer New Zealand Health and Disability Commission, Expert Endocrine Society, Annual Meeting Steering Committee Member National Hypertension Taskforce, Member Open Payments Database: n/a Assessment and Management: No COI relevant to this CPG.", - "tokenCount": 94, - "pageStart": 36, - "pageEnd": 36, - "hash": "ee3b6d6b109d24a664935d99ee5fda6b314efd4af99fd77e0b79feac26b45ff9" - }, - { - "text": "William Young, MD Mayo Clinic Expertise: Adult endocrinology Disclosures (2021-2025): Bayer AG (Bayer manufactures and markets the antihypertensive agents Pritor (telmisartan), Adalt LA (nifedipine), Baycaron (mefruside), and Adempas (riociguat), and the mineralocorticoid receptor antagonist Kerendia (finerenone).", - "tokenCount": 100, - "pageStart": 36, - "pageEnd": 36, - "hash": "21275127607c2c7f8d8232082d88aa5c3861de8edd7e181781b709d4bc492f1e" - }, - { - "text": "), Consulting, Data Safety Monitoring Board AstraZeneca (AstraZeneca manufactures and markets the antihypertensive agents Atacand (candesartan cilexetil), Plendil (felodipine), and Zestril (lisinopril) and is developing Baxdrostat, an aldosterone synthetase inhibitor.", - "tokenCount": 80, - "pageStart": 36, - "pageEnd": 36, - "hash": "9f2f84f6b2e7e4929ed9f841cd66e077a6bd5084a086bdabef2666e419ea8606" - }, - { - "text": "), Consulting Merck Sharp & Dohme (Merck Sharp & Dohme, manufactures and markets the antihypertensive Inspra (eplerenone).", - 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"pageStart": 36, - "pageEnd": 36, - "hash": "c40236d48370de1ac4361d163f1bff10a36bf780c6a1554ab419f06ea573d3c7" - }, - { - "text": "Young was not involved in systematic reviews for PICO questions directly related to the above considerations.", - "tokenCount": 18, - "pageStart": 36, - "pageEnd": 36, - "hash": "c51f41a4da8b6a31fa67758072a5e8ccbfb6642b52ae708777983ed9930983cc" - }, - { - "text": "Young did not vote on matters directly related to the above considerations.", - "tokenCount": 13, - "pageStart": 36, - "pageEnd": 36, - "hash": "c0ccc690b5b9f23f8e56174b26ae34ebd20a9514a16415b26807310a666766bd" - }, - { - "text": "Young did not draft guideline sections directly related to the above considerations.", - "tokenCount": 13, - "pageStart": 36, - "pageEnd": 36, - "hash": "99d926ee7daf3ca3f21d0e1ad3eb23ee91e9df9c24c7edf5fdc18c6a97cdda66" - }, - { - "text": "2488 The Journal of Clinical Endocrinology & Metabolism , 2025, Vol.", - "tokenCount": 18, - "pageStart": 36, - "pageEnd": 36, - "hash": "d52752ee73c5ea5d63f895b54f856a9b5f6078b6abbf2b957213bb263567dacb" - }, - { - "text": "Maria Christina Zennaro, MD, PhD Universit Paris Cit, Inserm, PARCC Assistance PubliqueHpitaux de Paris, Hpital Europen Georges Pompidou, Service de Gntique Expertise: Adult endocrinology Disclosures (2022-2025): Springer Nature, Associate Editorial Board, 2022 French Society of Endocrinology, Leadership European Society of Endocrinology, Leadership (completed 2024) Endocrine Society, Annual Meeting Steering Committee Member (completed 2022) Open Payments Database: n/a Assessment and Management: No COI relevant to this CPG.", - "tokenCount": 132, - "pageStart": 37, - "pageEnd": 37, - "hash": "fcea198e5f0dc32cd087debe54bb33048134a979d9ac1e84dace3e1165554446" - }, - { - "text": "Hassan Murad, MD, MPH Mayo Clinic Expertise: Epidemiology, guideline methodology Disclosures (2021-2025): Society for Vascular Surgery, methodologist American Society of Hematology, methodologist CHEST, methodologist World Health Organization, methodologist Evidence Foundation, methodologist Open Payments Database: No entries.", - "tokenCount": 74, - "pageStart": 37, - "pageEnd": 37, - "hash": "6731ee73b5fee6888d1cdced7bdc58c9e84e6a86f02fb788005a1e5451d51861" - }, - { - "text": "Assessment and Management: No COI relevant to this CPG.", - "tokenCount": 15, - "pageStart": 37, - "pageEnd": 37, - "hash": "5296d32ac19ed4f0c2706b7e06736098d5db5f4a8c1bb5c570773bc32378f620" - }, - { - "text": "Brito, MBBS Mayo Clinic Expertise: Adult endocrinology, guideline methodology Disclosures (2021-2025): Gordon and Betty Moore Foundation National Heart, Lung, and Blood Institute Open Payments Database: No entries.", - "tokenCount": 49, - "pageStart": 37, - "pageEnd": 37, - "hash": "48a55c63df66678fc6dafd3cf5770130d0a81a657ce7f856447680a6187f6988" - }, - { - "text": "NOTES ON PRIOR PANEL MEMBERS: 1.", - "tokenCount": 13, - "pageStart": 37, - "pageEnd": 37, - "hash": "0b8262b549bef12c01c2f2c7e864f49ab8c7a0df3c44185e3b7a4be22e5eb2d1" - }, - { - "text": "An individual with no relevant conflicts of interest was appointed as cochair at the outset of guideline development but stepped down from the panel in July 2023.", - "tokenCount": 30, - "pageStart": 37, - "pageEnd": 37, - "hash": "cf57b616f564cedea211b0da7908d5cf42e8901641338503d9f3adef74433f97" - }, - { - "text": "This occurred after the development of the PICO questions and prioritization of outcomes, but before the Evidence to Decision process and development of recommendations.", - "tokenCount": 28, - "pageStart": 37, - "pageEnd": 37, - "hash": "72344c2cc48d3945b304071fc887133bad570a836618796c1447df3d3fdc5315" - }, - { - "text": "An individual with the following relevant relationships was appointed to the panel: (a) Daiichi Sankyo (Daiichi Sankyo manufactures and markets the antihypertensive agents Olmetec / Rezaltas /Sevikar (Olmesartan medoxomil), Nilemdo (bempedoic acid) and Nustendi (bempedoic acid and ezetimibe), and is developing mineralocorticoid receptor inhibitor esaxerenone.", - "tokenCount": 108, - "pageStart": 37, - "pageEnd": 37, - "hash": "161a3747d92fee4b12118878f6dd9156f60f57f50504dbb56f11b487706008fc" - }, - { - "text": "): Speaker (b) Pfizer manufactures and markets aldosterone antagonist and Aldactone (spironolactone) and the antihypertensive agents Accupril (quinapril HCl), Accuretic (quinapril HCl/hydrochlorothiazide), Norvasc (amlodipine) and Minipress (prazosin hydrochloride).", - "tokenCount": 86, - "pageStart": 37, - "pageEnd": 37, - "hash": "e8c9c0baeef7613f11981eab1eb0be7b5eb39c2f8877095c82904613a1e56bba" - }, - { - "text": "Speaker This individual s participation on the panel ended in July 2023, after the development of the PICO questions and prioritization of outcomes, but before the Evidence to Decision process and development of recommendations.", - "tokenCount": 42, - "pageStart": 37, - "pageEnd": 37, - "hash": "e6559c7a86acb85a70eb95c4311800c47d092d260a8e322ef1dd037f4a58ea72" - }, - { - "text": "An individual with the following relevant relationships was appointed to the panel: (a) Mineralys Therapeutics (4Mineralys Therapeutics is developing lorundrostat, an aldosterone synthase inhibitor.", - "tokenCount": 45, - "pageStart": 37, - "pageEnd": 37, - "hash": "9bab539b71b02e67fcc55a4967afb82686a6537e7a128705c40f3ec78370770e" - }, - { - "text": "): Site Primary Investigator (b) Astra Zeneca (AstraZeneca manufactures and markets the antihypertensive agents Atacand (candesartan cilexetil), Plendil (felodipine), and Zestril (lisinopril) and is developing Baxdrostat, an aldosterone synthetase inhibitor.", - 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"tokenCount": 10, - "pageStart": 37, - "pageEnd": 37, - "hash": "e53d1d5d41a68e2051ef45a1d37513c5b7b4114ab23fa3ccdf285fe49dc31da3" - }, - { - "text": "Monticone S, D Ascenzo F, Moretti C, et al.", - "tokenCount": 18, - "pageStart": 37, - "pageEnd": 37, - "hash": "4c6dcc36e505d351aab43c16327059e7519f69ba1f6c0ce1acae30b1cd70b44a" - }, - { - "text": "Cardiovascular events and target organ damage in primary aldosteronism compared with essential hypertension: a systematic review and metaanalysis.", - "tokenCount": 26, - "pageStart": 37, - "pageEnd": 37, - "hash": "6317ce0a1c256588835e181be933da9048c8e27c9f57f27db4a46aba9f728e70" - }, - { - "text": "2018;6(1):41-50.", - "tokenCount": 10, - "pageStart": 37, - "pageEnd": 37, - "hash": "ee0188042e41ae4bb81af590bbc276879252261feb1b69026032f519a59c58bd" - }, - { - "text": "Tan YK, Kwan YH, Teo DCL, et al.", - "tokenCount": 17, - "pageStart": 37, - "pageEnd": 37, - "hash": "e49878460fcdbbcab9f8b82dd18e5446d4e878369ea513dbdbf39670989e4de8" - }, - { - "text": "Improvement in quality of life and psychological symptoms after treatment for primary aldosteronism: Asian cohort study.", - "tokenCount": 23, - "pageStart": 37, - "pageEnd": 37, - "hash": "ffab31e7948129ac0a2c331f737711196d20ad020012c834416f83993c468ccf" - }, - { - "text": "2021;10(8): 834-844.", - "tokenCount": 13, - "pageStart": 37, - "pageEnd": 37, - "hash": "2c240c7686b5d28a864c1490719c7675ff9e1aa76cd750799ea295ab2f3697ea" - }, - { - "text": "Buffolo F, Cavagli G, Burrello J, et al.", - "tokenCount": 17, - "pageStart": 37, - "pageEnd": 37, - "hash": "6c632ba6c91953982773e5deb3d376436c15a54544171a2f2a98920a8d2bce20" - }, - { - "text": "Quality of life in primary aldosteronism: a prospective observational study.", - "tokenCount": 16, - "pageStart": 37, - "pageEnd": 37, - "hash": "de560c590543d5e65f88a83ab9475b390f655e4f34ca223e7f1b3e34abef838f" - }, - { - "text": "2021;51(3):e13419.", - "tokenCount": 11, - "pageStart": 37, - "pageEnd": 37, - "hash": "c072645e627bcaaeb3985dc7539e93c1291997d7c8a4aaddca2931860498ba09" - 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}, - { - "text": "OConnor, BS, a , * Alekya Poloju, MD, b Samantha K.", - "tokenCount": 21, - "pageStart": 1, - "pageEnd": 1, - "hash": "a9591869e5873355c693c6b6210c2d3256635004878fa2b8df35de555c118c63" - }, - { - "text": "Pabich, MD, b Betty Allen, MD, c Rebecca Sippel, MD, c Amy Kind, MD, PhD, d , e and Alexander Chiu, MD, MPH c a University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin b Division of Endocrinology, Diabetes, and Metabolism, University of Wisconsin, Madison, Wisconsin c Section of Endocrine Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin d Center for Health Disparities Research, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin e Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin article info Article history: Received 3 January 2025 Received in revised form 31 March 2025 Accepted 19 April 2025 Available online 26 May 2025 Keywords: Adrenal incidentaloma Adrenal nodule Endocrine surgery Health disparities Health equity Incidental adrenal mass Population health abstract Introduction: Adrenal incidentalomas are increasingly detected, yet infrequently evaluated for hormonal excess.", - "tokenCount": 209, - "pageStart": 1, - "pageEnd": 1, - "hash": "b49660c09bed71b2cf75f8628827f0cde1a9276c67c4eba9acc389a15e21ec07" - }, - { - "text": "We investigated if patient neighborhood disadvantage is associated with the rate of workup of adrenal nodules.", - "tokenCount": 20, - "pageStart": 1, - "pageEnd": 1, - "hash": "03b3f318107c57968e582ae269669d30f3718b5fd836046c0d97878aa627b9b5" - }, - { - "text": "Methods: We performed a retrospective analysis of chest and abdomen CT scans between January 1,2021, and January 6,2022, at a single tertiary care center in adults with an incidentally found adrenal mass.", - "tokenCount": 44, - "pageStart": 1, - "pageEnd": 1, - "hash": "8c565db44e3e32bd1df4448640108b8dc0db131cefcdfb1ea6c67429d3d0405b" - }, - { - "text": "Chart review was conducted to categorize patients neighborhood disadvantage utilizing the Area Deprivation Index and evaluate for biochemical workup.", - "tokenCount": 24, - "pageStart": 1, - "pageEnd": 1, - "hash": "bbc3df15c1aa14e3788c1f778cd4366e2a8c9358fb475299a67d74f66b4625cb" - }, - { - "text": "Multivariate logistic regression was performed to determine factors associated with adrenal mass evaluation.", - "tokenCount": 17, - "pageStart": 1, - "pageEnd": 1, - "hash": "0fce76c942438b9c80a66017a35cde8899813aaa0f286cfdf30b3f7b82e21e52" - }, - { - "text": "A secondary chart review was conducted to ascertain reasons for incomplete adrenal nodule workup among disadvantaged patients.", - "tokenCount": 21, - "pageStart": 1, - "pageEnd": 1, - "hash": "70551cce437791468239e3c9d56efcefa6179a605ee3e02c41f9af948e8eb3f5" - }, - { - "text": "Results: Among 245 included patients, most (71%) had no biochemical workup and only 11% received a guidelineconcordant full evaluation.", - "tokenCount": 30, - "pageStart": 1, - "pageEnd": 1, - "hash": "568e7d6ea797c9ee28d0ed99f46c16cc0f188d1468457a6a6511c19d794d04bb" - }, - { - "text": "Patients living in disadvantaged neighborhoods were less likely to receive biochemical workup compared to patients in advantaged neighborhoods (odds ratio 0.", - "tokenCount": 27, - "pageStart": 1, - "pageEnd": 1, - "hash": "86d7dbaad55360c886895293330547b2a63ecc237b67b0692666dbfc25a44aad" - }, - { - "text": "Additionally, scans ordered by primary care providers were associated with greater evaluation rates compared to emergency medicine providers (odds ratio 4.", - "tokenCount": 25, - "pageStart": 1, - "pageEnd": 1, - "hash": "c17eac74840fad04d1b796f7000f605a2c5e8c89cc647315e7519052f3ae3b92" - }, - { - "text": "We identified three issues potentially contributing to low workup rates: radiologists recommended no further workup, primary care providers did not order additional tests, and patients were lost to followup.", - "tokenCount": 37, - "pageStart": 1, - "pageEnd": 1, - "hash": "35a0fb9d3abf08507430a8d5f2a1ee5bc25724533053f89b4f8a1274f0850e9e" - }, - { - "text": "Conclusions: The rate of guidelinebased biochemical workup of adrenal incidentalomas was low at 11%, and over 70% had no evaluation at all.", - "tokenCount": 31, - "pageStart": 1, - "pageEnd": 1, - "hash": "6020a62cd0a46c653e16243fc07a17494e4ddbb0cb625c23c0a94b03979b3231" - }, - { - "text": "Patients from disadvantaged neighborhoods were significantly less likely to receive workup, as were patients seen through the emergency department.", - "tokenCount": 23, - "pageStart": 1, - "pageEnd": 1, - "hash": "74b28220a53d457228f36ccbd51dab3a03378e3c194285dedacef54767699ea4" - }, - { - "text": "All rights are reserved, including those for text and data mining, AI training, and similar technologies.", - "tokenCount": 20, - "pageStart": 1, - "pageEnd": 1, - "hash": "389e86dfc71f736cd364f6043977a5f3fb3f4702656c3f78553bbcce65014cb9" - }, - { - "text": "University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue H4/724, Madison, WI 53792.", - "tokenCount": 26, - "pageStart": 1, - "pageEnd": 1, - "hash": "549bb3eaad634def353ce7a65c05bf7e7e9461798638f539bff9679eb585c5bf" - }, - { - "text": "Email address: jpoconnor4@wisc.", - "tokenCount": 12, - "pageStart": 1, - "pageEnd": 1, - "hash": "3465246eacfcec826e6add7e2faae0ac3871d061ff6f21bc4ad29da436fa4525" - }, - { - "text": "com journalofsurgicalresearch july 2025 (311) 143 e 150 0022-4804/$ e see front matter 2025 Elsevier Inc.", - "tokenCount": 32, - "pageStart": 1, - "pageEnd": 1, - "hash": "cb1688bdd604c08968ffbf830376b09c3594ec9daf990e64345ab13053ac424c" - }, - { - "text": "Introduction The prevalence of adrenal tumors has increased over the last several decades, largely due to advancements in imaging techniques.", - "tokenCount": 23, - "pageStart": 2, - "pageEnd": 2, - "hash": "9cb641042a19a42f719cd92b99622f04011f800fc065f8b99f6272974a4f99fc" - }, - { - "text": "1,2 As a result, the term adrenal incidentaloma was created to describe the abnormal unexpected finding.", - "tokenCount": 22, - "pageStart": 2, - "pageEnd": 2, - "hash": "ab23428ba0cbe510536177f44200f50bb5506f46c8049a029938e127f9c228e7" - }, - { - "text": "3 Currently, an incidental adrenal mass (IAM) is defined as a tumor > 1 cm first discovered when investigating a problem unrelated to the adrenal glands.", - "tokenCount": 33, - "pageStart": 2, - "pageEnd": 2, - "hash": "789fec963fa73bca012accc7e7c7855326d638902b4e24fb2b92109daaa5fcc0" - }, - { - "text": "4 Approximately 2%-8% of relevant imaging scans identify an IAM.", - "tokenCount": 15, - "pageStart": 2, - "pageEnd": 2, - "hash": "64840d364426e0a58e6c00939967ae8b21589f59a8bd7e4e3cb8ed15e3e68041" - }, - { - "text": "1,5 Although the majority of adrenal incidentalomas are benign and nonfunctional, an estimated 20%-30% of IAMs are functional and require further treatment.", - "tokenCount": 34, - "pageStart": 2, - "pageEnd": 2, - "hash": "4ed41230773a77d4572c14351b942f5cb0964cd53e7ae2c72a2ba64ed6c2e140" - }, - { - "text": "6-8 All major endocrine, urologic, and radiologic societies recommend additional studies to determine neoplastic potential of IAMs.", - "tokenCount": 30, - "pageStart": 2, - "pageEnd": 2, - "hash": "0fd384f6fc30d22e9328b68d1faad79b2abd22f09415fb73fc1b61fdf40e03b9" - }, - { - "text": "4,6 , 9 Precontrast and postcontrast crosssectional imaging is imperative to accurately determine lesion size, enhancement, and likelihood of malignancy.", - "tokenCount": 33, - "pageStart": 2, - "pageEnd": 2, - "hash": "0cc8c8d24e27900faa2495e8edd52f58a3cebe8ae14b4e3e477663c50fdd2fe9" - }, - { - "text": "Beyond determining malignant potential, IAMs should also be evaluated for hormonal excess using biochemical testing to rule out a functional tumor (i.", - "tokenCount": 28, - "pageStart": 2, - "pageEnd": 2, - "hash": "5372475b470515cc9a8cd8dcccd8f65f91b9bfe054595193266aee65467a104a" - }, - { - "text": ", cortisolsecreting adenomas, pheochromocytomas, and aldosteronomas) d which, if left untreated, can lead to significant morbidity and downstream health consequences.", - "tokenCount": 42, - "pageStart": 2, - "pageEnd": 2, - "hash": "b1e4bfa7f2ea0c4df668f1eae5b14c3ef1de8ad689edb79ebc88899a442fe952" - }, - { - "text": "10,11 Despite consensus guidelines from worldwide societies, rates of IAM workup remain low.", - "tokenCount": 19, - "pageStart": 2, - "pageEnd": 2, - "hash": "5f355df12f48504f0b8b8f05b2dcec7c8f514ff8ee45ea0a4b67de87d5ba47de" - }, - { - "text": "4,6 , 9 A 2021 systematic review determined less than onethird of patients undergo necessary followup imaging and roughly onefifth of patients receive recommended biochemical testing.", - "tokenCount": 33, - "pageStart": 2, - "pageEnd": 2, - "hash": "c100c8b6564ca6e32138c94e03cf432eb4641f1b125e02d0aaec9e9de1c42586" - }, - { - "text": "12 While compliance with IAM evaluation is low for all patients, some populations may be more affected than others.", - "tokenCount": 22, - "pageStart": 2, - "pageEnd": 2, - "hash": "377aed63424d0b6a8a57d8c149e72cd23e560753de9e3be6f742b1b22e3728cf" - }, - { - "text": "Previous studies have demonstrated social determinants such as race, socioeconomic status, and insurance coverage can influence rates of followup imaging after other incidental radiologic findings, including in the liver and pancreas.", - "tokenCount": 40, - "pageStart": 2, - "pageEnd": 2, - "hash": "fbdb22fcd3cc6713cb8c1661979d1b4610f65247f19c37c657e5fd71f281542e" - }, - { - "text": "13,14 In this paper, we assess the rates of IAMs in a tertiary care setting and social factors associated with appropriate workup compliance.", - "tokenCount": 31, - "pageStart": 2, - "pageEnd": 2, - "hash": "d532cde9c90ca6bd2780293da18e1c2c02758c19bb0ba2d27dc5b9590d9853ed" - }, - { - "text": "We hypothesize socioeconomic disadvantage at the neighborhood level, as measured by the Area Deprivation Index (ADI), will be associated with lower rates of followup and IAM evaluation.", - "tokenCount": 37, - "pageStart": 2, - "pageEnd": 2, - "hash": "abf75f11dc3b10d13eabdee94b1f2c86ecdb0ab9a0e2d0ccc8b94f473e701f04" - }, - { - "text": "Methods We performed a retrospective analysis of all chest and abdominal CT scans between January 1,2021, and June 1,2022, in adults 18 y at a single tertiary care center.", - "tokenCount": 40, - "pageStart": 2, - "pageEnd": 2, - "hash": "befaf45d72acc266472225f2baed609dfe74baf99906106a07804523993e5762" - }, - { - "text": "Radiology reports were screened for the key phrases Adrenal Nodule, Adrenal Mass, or Adrenal Incidentaloma to obtain scans with IAMs.", - "tokenCount": 34, - "pageStart": 2, - "pageEnd": 2, - "hash": "d29a8fc9351fc155e6265af17dc052f13ed82f116d99b7e644b2c805d5631bd7" - }, - { - "text": "Chart reviews were conducted to confirm the reported nodule and evaluate for followup imaging and biochemical evaluation.", - "tokenCount": 20, - "pageStart": 2, - "pageEnd": 2, - "hash": "59c44b18c52e9a5e2ad21caf741bf2ed0c67fd496a0d3be506cdd92f538db9de" - }, - { - "text": "Tumor size and density on noncontrast study was abstracted when available, as well as the specialty of the ordering provider, categorized as primary care provider (PCP), emergency medicine (EM) provider, or subspecialists (i.", - "tokenCount": 50, - "pageStart": 2, - "pageEnd": 2, - "hash": "525f2cc6e378313cfdef688302433fcb3f2b33639b5a99b1429b8fcfb921196a" - }, - { - "text": ", medical subspecialist, general surgery, and surgical subspecialty).", - "tokenCount": 15, - "pageStart": 2, - "pageEnd": 2, - "hash": "b6f171efcbae14c0105b7e00509eb39d534b084fe0d9c023b11f398ef5497878" - }, - { - "text": "Additionally, patient demographic data were abstracted, including patient age, sex, race, insurance status, and comorbidity via calculation of the Charlson Comorbidity Index (CCI), a 10-y survival predictor based on the presence of common diseases.", - "tokenCount": 54, - "pageStart": 2, - "pageEnd": 2, - "hash": "ffd6c38aa56550544500dc8ec1f8950832e6e508afc95c8a1258bf57c8563595" - }, - { - "text": "15 Charts abstractions were performed by two investigators (A.", - "tokenCount": 13, - "pageStart": 2, - "pageEnd": 2, - "hash": "255f5d003d2a4a6b80e53c7dcf3a95d3901689c798d41169dbd6b09b97f33b71" - }, - { - "text": "), with validity and reliability confirmed after 20 doubly abstracted charts.", - "tokenCount": 14, - "pageStart": 2, - "pageEnd": 2, - "hash": "5584a5c08bfc1c4608e2858a579fb57c8376bd26292a90e27e7387ce4a7b6586" - }, - { - "text": "Patients, who on review were seen to have their adrenal nodule previously identified, had a nodule measuring < 1cm, or who were deceased within 2 y of CT scan (shortening their time frame for potential workup), were excluded from analysis.", - "tokenCount": 53, - "pageStart": 2, - "pageEnd": 2, - "hash": "b2240890b2abd22afa14673f199807a5cb096baf14995fbfa8f71d61e75587fc" - }, - { - "text": "The Internal Review Board of the University of Wisconsin e Madison reviewed this study and deemed it exempt from full review.", - "tokenCount": 22, - "pageStart": 2, - "pageEnd": 2, - "hash": "1a68ec5ac976998de39d6228ab6fe0ac3e9cd8d8d8fab294fb8fb59b111dd00b" - }, - { - "text": "For each patient, we also determined their statebased ADI ranking from the ninedigit zip code of their primary address in the electronic health record at the time of the CT scan.", - "tokenCount": 38, - "pageStart": 2, - "pageEnd": 2, - "hash": "3b4527150d696bfa93bd30a4657e7e3759d19f95ec16cc84d500f60b2dc978d2" - }, - { - "text": "ADI is calculated using a methodology including 17 factors such as income, education, employment, and housing quality.", - "tokenCount": 22, - "pageStart": 2, - "pageEnd": 2, - "hash": "1f10e27ed67ed046db35a8188f2eed4a81c14842e71cc1ca6f174b0c50df18a4" - }, - { - "text": "16,17 ADI creates a composite index to measure socioeconomic disadvantage within geographic areas, highlighting how communitylevel variables influence health outcomes.", - "tokenCount": 26, - "pageStart": 2, - "pageEnd": 2, - "hash": "ffa8c649a544866a6749bf5eec1ecf213ab7e14613789fe6cf2f209845b797e8" - }, - { - "text": "The tool was validated using US census block data to rank neighborhood socioeconomic disadvantage.", - "tokenCount": 15, - "pageStart": 2, - "pageEnd": 2, - "hash": "13c7f5987051299db84a905ca1a819bda282b5d0a1b69af85cff885a517b5039" - }, - { - "text": "16 Based on recent studies, patients were categorized as being from disadvantaged (upper 50th percentile) or advantaged (lower 50th percentile) neighborhoods according to their ADI score.", - "tokenCount": 36, - "pageStart": 2, - "pageEnd": 2, - "hash": "2cadf880ad61bd83a913015c2b1939b5a83efb12d197a0647eaf8ffee4ecd5bf" - }, - { - "text": "18,19 Primary analysis examined rates at which patients received subsequent biochemical and radiologic evaluations within 2 y of their index scan.", - "tokenCount": 25, - "pageStart": 2, - "pageEnd": 2, - "hash": "44625d81c029493ae739f3c17e57285fcd23f1bd0ea6bacd59d25d54b82a05ef" - }, - { - "text": "If the nodule was identified on a noncontrast CT, patients were considered to have a full workup if they had a proper biochemical evaluation based on imaging and clinical characteristics.", - "tokenCount": 36, - "pageStart": 2, - "pageEnd": 2, - "hash": "519dab1c4b16ba6a5a0c69778cdf7e22efb0a7ad387855be4266ecdcbfff9573" - }, - { - "text": "For lowdensity lesions ( < 10HU), complete workup was considered cortisol evaluation (24-h urine cortisol, multiple midnight salivary cortisol levels, or lowdose dexamethasone suppression test) and an aldosterone/renin ratio if the patient had a history of hypertension or hypokalemia. For lesions > 10HU, complete biochemical workup included cortisol evaluation, metanephrine evaluation (24 h urine or plasma), and plasma aldosterone:renin ratio if the patient had a history of hypertension or hypokalemia.", - "tokenCount": 116, - "pageStart": 2, - "pageEnd": 2, - "hash": "c6640e8d2f313a8fe647d07c3ccf175711205a2075acee26a6edbfe81a0725dc" - }, - { - "text": "If patients had a nodule identified on a contrast CT, proper evaluation included repeat adrenal protocol CT (pre-, early-, and latecontrast phases) or noncontrast CT, as well as the corresponding biochemical workup described above.", - "tokenCount": 48, - "pageStart": 2, - "pageEnd": 2, - "hash": "8e9f9a4010efa3d04d5a6b32d183cf008303c506946bdebd56880d874a995063" - }, - { - "text": "We considered partial workup as the completion of any, but not all, of these recommended tests.", - "tokenCount": 20, - "pageStart": 2, - "pageEnd": 2, - "hash": "21ab730831b165e455482edefb74f394626a904e37a54ef9dfcd37d6d850ec19" - }, - { - "text": "For certain analyses, partial and full workup were combined as any workup due to low numbers of partial and full workups.", - "tokenCount": 26, - "pageStart": 2, - "pageEnd": 2, - "hash": "f999157270169591224a84a76130e7305991dcd05704ad94cf794be5048287d2" - }, - { - "text": "To better understand the reasons for low workup, we performed an additional secondary chart review of 30 patients from disadvantaged neighborhoods who received no workup.", - "tokenCount": 29, - "pageStart": 2, - "pageEnd": 2, - "hash": "4e719209ba5f4b1dc01578ad7a6f5ae394f9ef551b856374e776920eba2deed8" - }, - { - "text": "Clinical notes from the time of imaging and followup PCP notes were evaluated to better understand if any workup was recommended and why it was not completed.", - "tokenCount": 32, - "pageStart": 2, - "pageEnd": 2, - "hash": "80c28a6c187a6bae66600b2e4bf398b61c777b560c404d50f08f173e72d8b5f8" - }, - { - "text": "To analyze clinical notes, two authors (J.", - "tokenCount": 10, - "pageStart": 2, - "pageEnd": 2, - "hash": "8a6d154ff4db0e663da8633a34f92c9fa841c193b931103edc0e0629c4d419ca" - }, - { - "text": "Using a deductive thematic approach, noncompliance themes were identified and categorized.", - "tokenCount": 16, - "pageStart": 2, - "pageEnd": 2, - "hash": "8d6e6d5f33b5c532a72d184f821b3ad1ca8d8eedb84ebffa186f1a3451adab17" - }, - { - "text": "Upon completion, themes were compared and differences were resolved by A.", - "tokenCount": 13, - "pageStart": 2, - "pageEnd": 2, - "hash": "2b390973b043c94ccaef1dd5953d10cadaf3b7acebcdfe32a296e945e5e03cf9" - }, - { - "text": "categorizing clinical notes using our established themes with the ability to create new classifications if necessary.", - "tokenCount": 20, - "pageStart": 3, - "pageEnd": 3, - "hash": "ab9dcd524e98295168b85bbfe34c99963ae949aead4a4bc52af3541b1ea7b4e1" - }, - { - "text": "Following completion, we again reviewed our results as a team to finalize our results.", - "tokenCount": 17, - "pageStart": 3, - "pageEnd": 3, - "hash": "432adbb1d25d847982fbd777197c2275f246b84c012ed26a231582c479a2d69e" - }, - { - "text": "A bivariate analysis was performed using chisquared and Students ttest analysis.", - "tokenCount": 17, - "pageStart": 3, - "pageEnd": 3, - "hash": "1ca13e270d4b37694483cc94fcec126eb9537ad57391521e79ed1b8af42bcaee" - }, - { - "text": "Multivariate logistic regression was performed to evaluate factors associated with biochemical workup.", - "tokenCount": 16, - "pageStart": 3, - "pageEnd": 3, - "hash": "4991061698652378f5319b6c3133a9973863003635faa29c39eb3ae078beeb60" - }, - { - "text": "Results Study cohort During the study period, 9022 patients had a qualifying CT scan performed and 533 (5.", - "tokenCount": 23, - "pageStart": 3, - "pageEnd": 3, - "hash": "df518aefebb5c12c328b288c0a84804b1aa292f43f04368b23e7c6b32e811e9f" - }, - { - "text": "9%) individuals with IAMs were identified.", - "tokenCount": 10, - "pageStart": 3, - "pageEnd": 3, - "hash": "256a0f12ae5c5c6c3c4754af220b5fcb9f752122ebd72c79ff97c71ab372f647" - }, - { - "text": "0%) of 533 patients were included in our final analysis ( Fig.", - "tokenCount": 15, - "pageStart": 3, - "pageEnd": 3, - "hash": "ed19d71adbe764ffdbb0755cee51e25060dd41c12221208d66ca6e4264ebe6ff" - }, - { - "text": "Demographics Overall, the final patient cohort was 58.", - "tokenCount": 11, - "pageStart": 3, - "pageEnd": 3, - "hash": "a63941d675aa900ffd0e5faf59dfe5f6e8e2126c012e5c76a35a29b982116c5c" - }, - { - "text": "0% over 65 y of age, and 86.", - "tokenCount": 11, - "pageStart": 3, - "pageEnd": 3, - "hash": "6e1bd559365123a932ea1d924590fc7e8e19f05151afd6693d4faf065ce13b32" - }, - { - "text": "6% reporting a CCI of 0 or 1.", - "tokenCount": 11, - "pageStart": 3, - "pageEnd": 3, - "hash": "43814a9ca3f37bba5160750af84d0576ef8977fe2ed42bd2a962593edb3bd265" - }, - { - "text": "The most common ADI deciles were 4 or 5, making up 17.", - "tokenCount": 16, - "pageStart": 3, - "pageEnd": 3, - "hash": "6f66fad6b6854f0c26e43a699a0c8fd6791059c6a4a743d272be462fab767089" - }, - { - "text": "0%) were from advantaged neighborhoods (lower 50th percentile ADI).", - "tokenCount": 15, - "pageStart": 3, - "pageEnd": 3, - "hash": "05e36ac9ad81283d7d8bc61caa3337fffa6d870ac567215d0919c8547f0fb662" - }, - { - "text": "Imaging and ordering provider characteristics The majority of the imaging which discovered the IAM was ordered by EM providers (50.", - "tokenCount": 24, - "pageStart": 3, - "pageEnd": 3, - "hash": "954611b750e3d4ef3f4be30904fa01173f74cf390a731697d0eced4680b898e6" - }, - { - "text": "6%), followed by subspecialists (36.", - "tokenCount": 10, - "pageStart": 3, - "pageEnd": 3, - "hash": "7a0a06739299a034aedfdb385dcdcbe7ef28676b10e82e61671a0f5fa5e277c5" - }, - { - "text": "1% of ordering providers were physicians, while the remainder were physician assistants or nurse practitioners.", - "tokenCount": 18, - "pageStart": 3, - "pageEnd": 3, - "hash": "19d0d016a9441614720ce9bcc47a623a8f55de405a018ba864fd37d0c92ca01a" - }, - { - "text": "The vast majority of the CTs ordered were with contrast (93.", - "tokenCount": 14, - "pageStart": 3, - "pageEnd": 3, - "hash": "71e781fd0539abbd79618c202e1e6f79b76e9139ae77c0db032abe20541bb2e7" - }, - { - "text": "Rate of IAM workup Most (71%) IAM patients received no further workup, 18% had partialevaluation,and11%hadfullassessment( Fig.", - "tokenCount": 36, - "pageStart": 3, - "pageEnd": 3, - "hash": "0582203935db25c3eb8ca6dd3d340f0aa7bf8a1c263e4426501517e13c901afa" - }, - { - "text": "A chisquare test revealed statistically significant associations between sex, neighborhood disadvantage, and ordering provider with IAM workup.", - "tokenCount": 25, - "pageStart": 3, - "pageEnd": 3, - "hash": "c41b164363b02f4778a53c5641309082c68da7cbf78a1cbb9b1411cede3ffdd5" - }, - { - "text": "03) patients had a significantly higher rate of workup, while patients with imaging ordered by EM providers had a significantly lower rate of workup compared to those ordered by primary care (54.", - "tokenCount": 38, - "pageStart": 3, - "pageEnd": 3, - "hash": "8b985bed16a843239813d95a1e6f7de65545d1031f2e180ba73e47ba0fd343bd" - }, - { - "text": "5% from PCPs, P < 0.", - "tokenCount": 10, - "pageStart": 3, - "pageEnd": 3, - "hash": "5259926197b18652554f0836f01f0553c138920e2b6cd4ed65eff90afc019f0f" - }, - { - "text": "8% had scans ordered by EM providers and 17. 8% had scans ordered by PCPs ( Table 2 ).", - "tokenCount": 23, - "pageStart": 3, - "pageEnd": 3, - "hash": "b446adad7c41046e905ec792aa48fd218c569dfcec3adcbcf532e650666b3da2" - }, - { - "text": "Of the disadvantaged patients, scans ordered by EM providers and PCPs were 45.", - "tokenCount": 16, - "pageStart": 3, - "pageEnd": 3, - "hash": "bc9a038a3fe92b5002cf78de3376bbd34fc790d989849344c69c56e0524ea12d" - }, - { - "text": "Comparison of patients who hadapartialorfullworkupispresentedin Supplementary Table 1 .", - "tokenCount": 20, - "pageStart": 3, - "pageEnd": 3, - "hash": "eb2c5deca1390e080a82a6b9880e90d75f216c1f58b8134f26b4a86446395daa" - }, - { - "text": "Factors associated with biochemical evaluation Logistic regression demonstrated disadvantaged patients were less likely to undergo any workup compared to advantaged patients (odds ratio [OR] 0.", - "tokenCount": 34, - "pageStart": 3, - "pageEnd": 3, - "hash": "02526a4422eccf1efaeca862e824eeaf5c048a334fa333998166b13886509a11" - }, - { - "text": "Other factors significantly associated with receiving any workup included female sex (OR 2.", - "tokenCount": 16, - "pageStart": 3, - "pageEnd": 3, - "hash": "7c74ab440cdfe26a9af66f05ce02d6da3f278f2533f49ac4cc2ad2b98557f2f6" - }, - { - "text": "31) and scans ordered by PCPs (OR 4.", - "tokenCount": 12, - "pageStart": 3, - "pageEnd": 3, - "hash": "4c9737010234f21b6c5ebc9baf515f76d48f6e55577af7dc4fbbb53705b5d074" - }, - { - "text": "There was no statistically significant difference in workup based on age, race, ethnicity, insurance status, or CCI.", - "tokenCount": 24, - "pageStart": 3, - "pageEnd": 3, - "hash": "887fad859fc7bda19043bf6d0d91fa79c4f27571bf4a1f5db5343059ed1d626b" - }, - { - "text": "Secondary chart review Examination of physician notes and radiology reports from 30 disadvantaged patients without IAM workup revealed three main themes which may have contributed to the lack of evaluation ( Table 4 ).", - "tokenCount": 38, - "pageStart": 3, - "pageEnd": 3, - "hash": "fca74128cc4db9d1d46eee113fb19b46972dc165a2d5cd943dc935c85be7b375" - }, - { - "text": "The most common theme of missed evaluation related to radiology reports recommending no further workup.", - "tokenCount": 18, - "pageStart": 3, - "pageEnd": 3, - "hash": "6454ee7945cbfdd8341f4df656be95f7285ab19d341c40b367af7adb10e0dad9" - }, - { - "text": "While this was likely meant to signal that the lesion needed no further radiographic workup to evaluate for malignant potential, this was often interpreted as no further workup was needed at all, including biochemical workup.", - "tokenCount": 44, - "pageStart": 3, - "pageEnd": 3, - "hash": "b0c3ea8ed850b6c400bf55b0f193bb930aefb7d95c484e84bdaed1691c4b1bb7" - }, - { - "text": "For instance, a communication from one PCP to a patient with an adrenal nodule noted that the scan demonstrated an adrenal lesion that was benign, and echoed the report that no further evaluation was needed, even though a functional workup was never performed.", - "tokenCount": 53, - "pageStart": 3, - "pageEnd": 3, - "hash": "2e6dff2a9f7ed88d2878e2091861cba2a99366234648324405f259cbea1973b0" - }, - { - "text": "Second most common was PCPs not acknowledging the nodule nor ordering additional tests, suggesting these incidental findings were missed.", - "tokenCount": 23, - "pageStart": 3, - "pageEnd": 3, - "hash": "1c739631aa23da965b19735fdd23bfe172ad1a32f9c53010b4dbf023aa355df9" - }, - { - "text": "patients were frequently lost to followup after imaging and never completed biochemical testing when recommended.", - "tokenCount": 18, - "pageStart": 4, - "pageEnd": 4, - "hash": "2365a039aa0b07fcf0ede9e4ca4a4f66b296bad0c17ff9d0cb26184ae01091b9" - }, - { - "text": "Discussion In our study, the rates of complete guidelineconcordant biochemical workup or partial evaluations of adrenal incidentalomas were 11% and 18%, respectively.", - "tokenCount": 33, - "pageStart": 4, - "pageEnd": 4, - "hash": "2a65e42beaf429fd51c68699c024442d3d31eaa613ff343be5572ce381206050" - }, - { - "text": "These alarmingly low rates align with other publications, confirming absent or incomplete IAM evaluations are commonplace.", - "tokenCount": 20, - "pageStart": 4, - "pageEnd": 4, - "hash": "f9e75031b7a6989bf8ae30e841a4858ede6f0a92df21685a88ef8351cf2f4cb7" - }, - { - "text": "2,12 , 20 For instance, Ebbehoj et al .", - "tokenCount": 15, - "pageStart": 4, - "pageEnd": 4, - "hash": "b969f17959cafbc08cf63b0a58617d2c85a33cd247b560a4e29f8c14a4424282" - }, - { - "text": "(2020) reported appropriate workup of IAMs was completed in only 15.", - "tokenCount": 17, - "pageStart": 4, - "pageEnd": 4, - "hash": "46942053f5d28300e711896d010ba5404f4d9b05f5b1c838c2c4386120c9a3e4" - }, - { - "text": "2 These low rates of workup undoubtedly lead to poor patient outcomes, as untreated hormonally active adrenal incidentalomas have been tied to higher rates of cardiovascular events and even mortality.", - "tokenCount": 37, - "pageStart": 4, - "pageEnd": 4, - "hash": "c65d2d40db910bfb09b570ead5f37704a497841e815c6323f76fc3457fd507b3" - }, - { - "text": "10,11 , 21 Workup rates were particularly low for patients living in disadvantaged neighborhoods.", - "tokenCount": 18, - "pageStart": 4, - "pageEnd": 4, - "hash": "1d4fd18c85cf085e4b83de8fa675f1bd47265c74bff1b29d3e2167faf5151289" - }, - { - "text": "We found patients from these neighborhoods had roughly half the odds of obtaining any IAM workup compared to those from advantaged neighborhoods.", - "tokenCount": 26, - "pageStart": 4, - "pageEnd": 4, - "hash": "2b70c6b2ab41bc39264ac0d476465fd0338bddcbfd610454631d04c64ca949b1" - }, - { - "text": "Our findings are consistent with literature linking neighborhoodlevel disadvantage with poorer health outcomes and disease management.", - "tokenCount": 18, - "pageStart": 4, - "pageEnd": 4, - "hash": "aea72adba63fa384c9ba769918ba9b4b48a1ec2d4bf8877bb9df1b926304f682" - }, - { - "text": "22,23 Similarly, Schut and Mortani Barbosa (2020) reported racial/ethnic disparities in incidental pulmonary nodule management.", - "tokenCount": 27, - "pageStart": 4, - "pageEnd": 4, - "hash": "e74b5c023eef9fc85da4c4c4b49e0136de55fc6ac2f445a595f13a7c80fa33ce" - }, - { - "text": "24 Differences in care of IAMs may have downstream effects, potentially exacerbating preexistent disparities in comorbidities such as diabetes and hypertension.", - "tokenCount": 31, - "pageStart": 4, - "pageEnd": 4, - "hash": "c3746907a3f444f85b44efe1386ebce518ee087e8d5274c5966615d838db7058" - }, - { - "text": "25,26 The relationship is likely multifactorial and involves patient access to PCPs, reliance on safety net programs or emergency departments (EDs), and more fragmented care.", - "tokenCount": 35, - "pageStart": 4, - "pageEnd": 4, - "hash": "5d7f920163226c00d65aa31f979d3286404a4b9109aee5f18bb3d9e642e8c730" - }, - { - "text": "23,27 Furthermore, our secondary chart analysis revealed lack of followup as a common theme among patients in disadvantaged neighborhoods, reinforcing that many of the issues revolve around the ability to access Table 1 e Demographics.", - "tokenCount": 43, - "pageStart": 4, - "pageEnd": 4, - "hash": "af04aec920841684a8259bc59221e778edab71e5db23762e3673cbebcb3ab816" - }, - { - "text": "No workup (n 174) % Any workup (n 71) % Total cohort (n 245) % P value Sex < 0.", - "tokenCount": 32, - "pageStart": 4, - "pageEnd": 4, - "hash": "a225ba89652354225bf2435338c956b5f8b8fa065a9bd9ad7cf8def811bbe32c" - }, - { - "text": "03 Advantaged ( < 50 percentile) 51.", - "tokenCount": 11, - "pageStart": 4, - "pageEnd": 4, - "hash": "d5d7f80f6ceac4347c666601be6d54ecb4969e9ce64e7c2b836a17f24ac25f62" - }, - { - "text": "0 Disadvantaged ( > 50 percentile) 48.", - "tokenCount": 11, - "pageStart": 4, - "pageEnd": 4, - "hash": "a9a37d281ff7b68089e18eb614561ec89f1a9b50392164223b6c3b7164d08107" - }, - { - "text": "Additionally, clinics serving disadvantaged patients typically have limited resources, and as a result, prioritization of other urgent health matters may supersede evaluation of incidentalomas.", - "tokenCount": 31, - "pageStart": 5, - "pageEnd": 5, - "hash": "47e1cf17b99e997585432ebce7be489291d5a96e10687cc700fae5126c6a1174" - }, - { - "text": "28 While our study demonstrated poor IAM workup compliance across all medical/surgical fields, investigations were significantly lower when diagnoses were established during ED visits.", - "tokenCount": 31, - "pageStart": 5, - "pageEnd": 5, - "hash": "f16b64df717dbf176a6f55c276e4fe4e652f7cf29048bf79b52e5e9260905d9e" - }, - { - "text": "(2020) reported a threefold lower rate of followup imaging if the index study was performed while the individual was an inpatient or in the ED compared to outpatient.", - "tokenCount": 34, - "pageStart": 5, - "pageEnd": 5, - "hash": "6ea8e7a5bade0d8c041b7a636fbf3b6e2883c8a368e52f254104a94705cc0879" - }, - { - "text": "29 Interestingly, several previous publications focused on poor IAM workup compliance in primary care outpatient settings.", - "tokenCount": 20, - "pageStart": 5, - "pageEnd": 5, - "hash": "e24bf745604564cd8c173a6bb3060c7d5ad2527fc0040ca659ffe50116d1608f" - }, - { - "text": "30,31 The authors suggested PCPs may lack time and/or knowledge of appropriate biochemical evaluations to adequately address IAMs.", - "tokenCount": 26, - "pageStart": 5, - "pageEnd": 5, - "hash": "3d0634c5ede1f7b1f9a2c83b9ec6db8b37a2b3148db91c3e348218181243c70d" - }, - { - "text": "However, our study suggests the emergency room as a potentially larger source of missed IAM management.", - "tokenCount": 19, - "pageStart": 5, - "pageEnd": 5, - "hash": "6c046ff5828c92e806bdfae83790a2ed263a9a54670a1f921d8d9319bc7489fa" - }, - { - "text": "Although disadvantaged patients had higher rates of detection by EM providers, ordering provider remained a significant factor even when controlling for socioeconomic deprivation.", - "tokenCount": 25, - "pageStart": 5, - "pageEnd": 5, - "hash": "d93ab61a5a27ee0d09d737d7303f29d6787db5cc1530221172ef639f89a8ae94" - }, - { - "text": "Our chart review noted PCPs failing to acknowledge the nodule as a major reason for missed workup, and suggests that communication between EM and PCPs remains a challenge to properly addressing IAMs.", - "tokenCount": 40, - "pageStart": 5, - "pageEnd": 5, - "hash": "d283c238fe9cab18933c35a97cd1ca95aeb52347059aab9fa8c787835e1c1645" - }, - { - "text": "One strategy to improve coordination of care is the development of an adrenal nodule identification system which uses artificial intelligence natural language processing to create automated messages for PCPs regarding the nodule and guidelines for next steps.", - "tokenCount": 42, - "pageStart": 5, - "pageEnd": 5, - "hash": "2e5e82bdb84a4021428cb978f26660e47c3482754060c64c95014f07b6ec9260" - }, - { - "text": "A recent study utilized artificial intelligence technology to flag patient electronic health records with adrenal nodules 32 and pairing similar technology with notifications to PCPs can be an effective way to reduce the amount of IAMs lost during the transition of care.", - "tokenCount": 48, - "pageStart": 5, - "pageEnd": 5, - "hash": "b4aa1499bf364d934e7d3dc7e964dec8968aa0ca6897aaf26ce8c747330c0508" - }, - { - "text": "Another problem contributing to incomplete IAM evaluation is radiologists recommending no further workup.", - "tokenCount": 17, - "pageStart": 5, - "pageEnd": 5, - "hash": "535e4a58d06bac955f7096d65dc83c4ea43ac4bee9bbce0c7b079c981b495fb8" - }, - { - "text": "Although radiologists rule out malignant potential and label the nodule as benign, biochemical workup is required to understand the functional potential.", - "tokenCount": 27, - "pageStart": 5, - "pageEnd": 5, - "hash": "2f1453dcbc48c5d5192cc919b4735acf9f5c5478ac163719dc509a3936ce73f2" - }, - { - "text": "To combat the issue, the use of radiology reporting templates which encourage additional testing and provide specific followup recommendations have led to increased rates of followup imaging and biochemical testing.", - "tokenCount": 35, - "pageStart": 5, - "pageEnd": 5, - "hash": "a5316c7ad59eb3dcbfa10b731160671c1fef262fd8330cab432da25de5fff2fa" - }, - { - "text": "33-35 While modifications to radiology reporting language (e.", - "tokenCount": 13, - "pageStart": 5, - "pageEnd": 5, - "hash": "c40503c7e08986888e63cc5ad5b37d0bc4284654e687148f9307982b75f16a63" - }, - { - "text": ", low concern for malignancy, could consider a functional workup) are a step in the right direction, additional protocols and interdisciplinary teams are necessary to ensure even more patients are adequately evaluated.", - "tokenCount": 40, - "pageStart": 5, - "pageEnd": 5, - "hash": "0d794fdb106b185853b9788314df2c8d0857048f1323cd9897191acb048ff761" - }, - { - "text": "Recently, a program combining standardized radiologic reporting, chartbased messages to PCPs, and easier referrals to a multispecialty adrenal clinic resulted in an approximate 4x increase in the number of biochemical testing orders placed by PCPs.", - "tokenCount": 49, - "pageStart": 5, - "pageEnd": 5, - "hash": "0e0c293aa01d5860b08972acf972110528af10b53dd92c3200af5adb03ff84cb" - }, - { - "text": "36 Similarly, interdisciplinary collaboration between radiologists, EM physicians, nurse case managers, and PCPs resulted in 95% of ED patients with incidental radiology findings having followup plans for evaluation after discharge.", - "tokenCount": 41, - "pageStart": 5, - "pageEnd": 5, - "hash": "e566176ef79efff7847706705523b836b3585a79ec6c6d4081bce94788e6063e" - }, - { - "text": "37 While these interventions highlight the promising outcomes for incidentaloma management using providers from multiple areas of health care, no studies to date have examined if these interventions have reduced disparities in Fig.", - "tokenCount": 36, - "pageStart": 5, - "pageEnd": 5, - "hash": "7e7ac7fec65082b0b85f4f3f8d70c9cd04d82b9c33088c38ffc75f8f83a8790f" - }, - { - "text": "DST [ dexamethasone suppression test; HTN [ hypertension.", - "tokenCount": 16, - "pageStart": 5, - "pageEnd": 5, - "hash": "62055d8ad3aac997b28fbfd1f2493b55939a5e4025e16c52ea3da8dbca6361a4" - }, - { - "text": "Ordering provider ADI Advantaged ( < 50 percentile) Disadvantaged ( > 50 percentile) N% n % EM 74 54.", - "tokenCount": 29, - "pageStart": 5, - "pageEnd": 5, - "hash": "d4bce6fba25299343e5726b2661168153ec8b7ead42b9db3901b3bb966891781" - }, - { - "text": "It is not hard to imagine positive resources directed to identify IAM patients may be unequally distributed and benefit wellresourced clinics.", - "tokenCount": 26, - "pageStart": 6, - "pageEnd": 6, - "hash": "6417d285a6e174daaa8f314924dc903901135b0bc63d012e8aa94ff4b1c66945" - }, - { - "text": "Thus, to further improve health outcomes and equity, interventions must consider the patient population and setting.", - "tokenCount": 19, - "pageStart": 6, - "pageEnd": 6, - "hash": "ae4372db834f0626ff16707ac64d598ba9c63bae4b5be6bdc57032180b4150fb" - }, - { - "text": "One relevant model to help achieve these goals is the Health Disparities Framework, developed by the National Institute on Minority Health and Health Disparities.", - "tokenCount": 30, - "pageStart": 6, - "pageEnd": 6, - "hash": "101d4014dd5214de576935c5ac277890a899ea788a897e1c9eed98151baaea2a" - }, - { - "text": "38 The adaptation of the socioecological model evaluates five domains (biological, behavioral, physical/built environment, sociocultural environment, and healthcare system) and drives research and interventions toward solutions which address the fundamental causes of disparities.", - "tokenCount": 48, - "pageStart": 6, - "pageEnd": 6, - "hash": "62373bad51f2ae5eda97cd814c0068a4b3f87a32535b6034e6ecce91c6a6591c" - }, - { - "text": "Building upon this and the findings of our study, we encourage researchers and doctors to consider patient and neighborhoodlevel disparities when implementing subsequent interventions.", - "tokenCount": 27, - "pageStart": 6, - "pageEnd": 6, - "hash": "45d9622cb961af9a6d99298331bd5d0dbc703c5780a63d69dce27b1269d49b64" - }, - { - "text": "We found a major obstacle for patients in disadvantaged communities is following up with PCPs after the identification of an IAM.", - "tokenCount": 24, - "pageStart": 6, - "pageEnd": 6, - "hash": "3ab8b9b29bebbb3ac1865d2f33d59bb844871290403945ca8a82a0ba97e1107b" - }, - { - "text": "Although we cannot determine the exact reason for each patient, one proposal could be the use of patient navigators who can help overcome environmental and neighborhood factors such as transportation, costs, and insurance coverage.", - "tokenCount": 39, - "pageStart": 6, - "pageEnd": 6, - "hash": "76141c0abbc78ec07bffce9c06a47455c0e11e0518b1003bac56f4e541535f73" - }, - { - "text": "This strategy has demonstrated success in improving cancer management and treatment.", - "tokenCount": 12, - "pageStart": 6, - "pageEnd": 6, - "hash": "41cd72910a52d6fc865230f8a83d4cd4aeadf58fc1086ec92f21d6d387814e8b" - }, - { - "text": "39,40 For instance, one randomized control trial found patient navigation led to significantly greater compliance with followup among minority women with abnormal mammograms.", - "tokenCount": 29, - "pageStart": 6, - "pageEnd": 6, - "hash": "5ae1c9a95df8a04618b0e69895ae6384f1ae80897ae8b64db5b8f203f41e6c75" - }, - { - "text": "41 As a result, navigators remain a promising method through which to eliminate disparities in care for IAMs, although obvious barriers such as costs and workflow burden require more indepth investigation.", - "tokenCount": 39, - "pageStart": 6, - "pageEnd": 6, - "hash": "65cf0d099edec5cdb1be229c018683f4302ef6115f45c14b10b5892d554635ef" - }, - { - "text": "Overall, the low rates of IAM followup, particularly among patients from disadvantaged neighborhoods, suggest the need for new protocols considering health disparities to ensure more patients are adequately evaluated.", - "tokenCount": 35, - "pageStart": 6, - "pageEnd": 6, - "hash": "e17bb58f0ae949b381465ac593642c43a7dd076dba9be303c257c2e179704f12" - }, - { - "text": "For one, retrospective data and inherent inaccuracies in the electronic medical record may skew results.", - "tokenCount": 18, - "pageStart": 6, - "pageEnd": 6, - "hash": "b4d17b95df08e91edbbbc2f98c3045904be0027b80ad381d218ebd586664fdf8" - }, - { - "text": "The data were only from a single institution and the population skewed more toward White and insured, making the results less generalizable.", - "tokenCount": 25, - "pageStart": 6, - "pageEnd": 6, - "hash": "fb4acc152d6e7ef58b9ae0a6a96ce06b87660c4bdaad1eab9efc2bd2f88e8f17" - }, - { - "text": "Including a greater percentage of nonWhite or Medicaid patients could allow for further elucidation of barriers to workup which specifically constrain these populations.", - "tokenCount": 29, - "pageStart": 6, - "pageEnd": 6, - "hash": "701b17f48720354cde4c1fc21cb755af5914820b763d7db079edee67c1d4248f" - }, - { - "text": "In addition, due to the retrospective nature, we cannot determine the direction of the relationship between neighborhood disadvantage and lower rates of biochemical workup.", - "tokenCount": 28, - "pageStart": 6, - "pageEnd": 6, - "hash": "a553f8fd0620304e77d7b4bb2ad155eb7288652ea583cd4f75ae28ec66c57625" - }, - { - "text": "We are also unable to determine any verbal or other communication provided to the patient regarding their identified nodule.", - "tokenCount": 21, - "pageStart": 6, - "pageEnd": 6, - "hash": "288dedef3306b1b7d24248fc4bffa6141d08c267de0c2f337a49750449bed105" - }, - { - "text": "Variable OR (95% CI) Sex Male ref Female 2.", - "tokenCount": 13, - "pageStart": 6, - "pageEnd": 6, - "hash": "b5d6afdbd5fcf678bb680d4a1e03f256f003bbf04df341cb025cc68a862b5f6a" - }, - { - "text": "31) Age > 65 ref < 65 1.", - "tokenCount": 10, - "pageStart": 6, - "pageEnd": 6, - "hash": "a4a756c8e386b0c5150d0b286bc4114534c59860f71dd1e3b80988631ee8ed13" - }, - { - "text": "73) Race/Ethnicity White ref Black 1.", - "tokenCount": 12, - "pageStart": 6, - "pageEnd": 6, - "hash": "64100175afe7d9a0abc1c56ad17cc6cc33e17f02dfe53b3ce49654200a8433d0" - }, - { - "text": "88) Other * Ordering provider ED ref PCP 4.", - "tokenCount": 13, - "pageStart": 6, - "pageEnd": 6, - "hash": "f7efaf96b575f66ad766d238e8d1e9119bd7a73da50f5a49ec207eb5daba9f27" - }, - { - "text": "01) ADI < 50 ref > 50 0.", - "tokenCount": 11, - "pageStart": 6, - "pageEnd": 6, - "hash": "ecf3f50168a81aa53fe392b51c69a4b480f01e1b957659b8674c406db613cd81" - }, - { - "text": "48) Tricare * * Not enough patients for analysis.", - "tokenCount": 13, - "pageStart": 6, - "pageEnd": 6, - "hash": "5e12ce95ae834c8d671a63be3cae2ab51de8a8eb2ca75555995a5b5b0cefa759" - }, - { - "text": "Table 4 e Common themes for lack of workup among disadvantaged patients Radiologist recommended no workup PCP did not acknowledge nodule Patient lost to followup Number of patients 11 13 6 Selected quote from Electronic Health Record Benign 1.", - "tokenCount": 47, - "pageStart": 6, - "pageEnd": 6, - "hash": "c60bed8f5104a0f35e975c5c09988f9a194ba43bcbbfbfb243e2f68b7affeb9a" - }, - { - "text": "No followup imaging is necessary Partially imaged, indeterminant 4.", - "tokenCount": 16, - "pageStart": 6, - "pageEnd": 6, - "hash": "c90cbdf023d4820faddbfa6a75b8dbf44bf5203e489372e0dc832473bd40bd54" - }, - { - "text": "6 cm right adrenal mass, likely adenoma or adrenal myelolipoma, both benign.", - "tokenCount": 23, - "pageStart": 6, - "pageEnd": 6, - "hash": "3d9baf574ecc9efcbcaec9c2aba8951c9def0223a4e60103ed1f7db1177890b1" - }, - { - "text": "Consider nonurgent adrenal protocol CT or MR for further characterization.", - "tokenCount": 14, - "pageStart": 6, - "pageEnd": 6, - "hash": "084a6dc474c12da4d27436366881c609cb13a311a084353beb95de230186b87a" - }, - { - "text": "Consider followup in 12 mo if no history of malignancy versus nonurgent evaluation with adrenal protocol CT or MRI.", - "tokenCount": 26, - "pageStart": 6, - "pageEnd": 6, - "hash": "0c965f3f6891445cde4396c0cec1b7070290b5481adeb3fb9dfbf6add35c4dd2" - }, - { - "text": "Discussed the need to complete testing for evidence of hypercortisolism or pheochromocytoma.", - "tokenCount": 24, - "pageStart": 6, - "pageEnd": 6, - "hash": "2d631ae163737044fc47ac2130736998000d6b4ee026b032cfadc52b1f9d9dbf" - }, - { - "text": "MR magnetic resonance; MRI magnetic resonance imaging.", - "tokenCount": 11, - "pageStart": 6, - "pageEnd": 6, - "hash": "7811b3d2bd18aca0fc3709090f32512c8c6ee4642c3343e8c4647e99cae9cc24" - }, - { - "text": "Conclusions Overall, the rates of complete or partial guidelinebased biochemical workup of adrenal incidentalomas in our study population were low at 11% and 18%, respectively.", - "tokenCount": 34, - "pageStart": 7, - "pageEnd": 7, - "hash": "ab29dfc491d0f875957e405a4d868a4615d1423b8840fd27ae1158d8ce3c9755" - }, - { - "text": "Patient neighborhood disadvantage and studies ordered by EM providers were associated with lower rates of biochemical workup.", - "tokenCount": 20, - "pageStart": 7, - "pageEnd": 7, - "hash": "3f02e39818ae2e75d049bcb3f2653dee5081fac9912c1e19ceb761af3fd5258b" - }, - { - "text": "Further investigation into barriers to IAM workup and focused interventions to improve the rate of IAM workup for patients in disadvantaged settings are needed.", - "tokenCount": 29, - "pageStart": 7, - "pageEnd": 7, - "hash": "6f7f027357380f514a13f3469b3062a84395c2f77b32b7bf4888dc332b112775" - }, - { - "text": "Supplementary Materials Supplementary data related to this article can be found at https://doi.", - "tokenCount": 17, - "pageStart": 7, - "pageEnd": 7, - "hash": "4162caf3be37d9c7e0740995ed2c0d87f86c09c17ec11a8bf79ae4e65ca27299" - }, - { - "text": "OConnor reports that financial support was provided by Herman and Gwendolyn Shapiro Foundation.", - "tokenCount": 17, - "pageStart": 7, - "pageEnd": 7, - "hash": "45d1652351fa4976f32e7075d70bd1f879daf13fc091f2a0fc9719a5d52e0fd8" - }, - { - "text": "Amy Kind reports financial support was provided by National Institute on Aging.", - 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}, - { - "text": "Catching those who fall through the cracks: integrating a followup process for emergency department patients with incidental radiologic findings.", - "tokenCount": 24, - "pageStart": 8, - "pageEnd": 8, - "hash": "b4aacde5d17aa8de8e73dbcb0e0d768d8eb9429addf4bcb9d561e68ed9c40a8b" - }, - { - "text": "Alvidrez J, Castille D, LaudeSharp M, Rosario A, Tabor D.", - "tokenCount": 22, - "pageStart": 8, - "pageEnd": 8, - "hash": "c6387dbbcfb526fe21ffce5095de7ccf9c1e855eb64910b285649d030a9fd6ef" - }, - { - "text": "The national Institute on minority health and health disparities research Framework.", - "tokenCount": 12, - "pageStart": 8, - "pageEnd": 8, - "hash": "2fa126cf046149d6551b20eb1663885247154b4e532c246ea4228abc7cfc35a5" - }, - { - "text": "2019;109:S16 e S20 .", - "tokenCount": 10, - "pageStart": 8, - "pageEnd": 8, - "hash": "f55ca7c29304bb66fb6170134aa1da02bc66906cd2bc7f3bd25d4683cb59c424" - }, - { - "text": "Freund KM, Battaglia TA, Calhoun E, et al.", - "tokenCount": 16, - "pageStart": 8, - "pageEnd": 8, - "hash": "83a291b01e91c3655f6698d1a47cbacd321a0039452fbdf570d75e80820386d8" - }, - { - "text": "Impact of patient navigation on timely cancer care: the patient navigation research program.", - "tokenCount": 16, - "pageStart": 8, - "pageEnd": 8, - "hash": "91cfa318c664c00ef66d7ba86908704dbbf3a8959040183894991156c736070d" - }, - { - "text": "Shusted CS, Barta JA, Lake M, et al.", - "tokenCount": 14, - "pageStart": 8, - "pageEnd": 8, - "hash": "f82ab4b0e90f6374c920a3d4afdc8471a2b9936b96810689585af3f907e3fa20" - }, - { - "text": "The case for patient navigation in lung cancer screening in vulnerable populations: asystematicreview.", - "tokenCount": 18, - "pageStart": 8, - "pageEnd": 8, - "hash": "461797f356519199b18311c64a2cd53a8d76a4f09c3ef5563745d88b7f8d28e4" - }, - { - "text": "Ell K, Vourlekis B, Lee PJ, Xie B.", - "tokenCount": 16, - "pageStart": 8, - "pageEnd": 8, - "hash": "570fb11d6264b933d4392769a06da726ac436403e2d0951bc88d0f25e8d78508" - }, - { - "text": "Patient navigation and case management following an abnormal mammogram: a randomized clinical trial.", - "tokenCount": 17, - "pageStart": 8, - "pageEnd": 8, - "hash": "6f13097334c21aa54b8436b069b0260a568a70c78347c52e8fdf0751ad45ba0d" - } -] \ No newline at end of file diff --git a/Capstone Course Adrenal Nodule information/primary-aldosteronism Family Medicine Clinical Guidelines.pdf_semantic.json b/Capstone Course Adrenal Nodule information/primary-aldosteronism Family Medicine Clinical Guidelines.pdf_semantic.json deleted file mode 100644 index 7d82e8228b7d6b499e29d8de32e92994ddc54cf3..0000000000000000000000000000000000000000 --- a/Capstone Course Adrenal Nodule information/primary-aldosteronism Family Medicine Clinical Guidelines.pdf_semantic.json +++ /dev/null @@ -1,1570 +0,0 @@ -[ - { - "text": "September 2023 Volume 108, Number 3 www.", - "tokenCount": 11, - "pageStart": 1, - "pageEnd": 1, - "hash": "78098a0123730b42a8d892eb16ac45e756f45f80d58654ef4bd8d317bed179b5" - }, - { - "text": "org/afp American Family Physician 273 Primary aldosteronism, first described by Dr.", - "tokenCount": 21, - "pageStart": 1, - "pageEnd": 1, - "hash": "e25f5cefbc49bafa6b65a3329f2b064f142706d6fe0413fb9290156e4d359a8a" - }, - { - "text": "Jerome Conn in 1955, has long been considered a rare secondary cause of hypertension.", - "tokenCount": 17, - "pageStart": 1, - "pageEnd": 1, - "hash": "f595030d615b1c10b8f3fd4a0c45b53823bdf0358c6c9967a7ec83e69aee7c44" - }, - { - "text": "1 Newer evidence, however, suggests that primary aldosteronism is common and largely underrecognized.", - "tokenCount": 23, - "pageStart": 1, - "pageEnd": 1, - "hash": "9fca5f0a0bd4cb019f3d4330fee4aee5bf6315614bbbd1d33f92974eed0c74c7" - }, - { - "text": "It has been shown to be the underlying cause of hypertension in about 6% of patients in primary care settings 2 and in more than 20% of patients with stage 2 hypertension.", - "tokenCount": 35, - "pageStart": 1, - "pageEnd": 1, - "hash": "43130cc18e496545e5565e7425e57e76cb58dd265b228257657cc85a8ec3862f" - }, - { - "text": "3 Even for patients with an indication for case detection, appropriate testing is performed in only 1.", - "tokenCount": 19, - "pageStart": 1, - "pageEnd": 1, - "hash": "f4b09898a0d05ae03b77d89e0619904a35c2d416f4259f8900103ad149b1d732" - }, - { - "text": "4,5 This underrecognition of primary aldosteronism can lead to delayed diagnosis and treatment, which can cause irreversible endorgan damage.", - "tokenCount": 30, - "pageStart": 1, - "pageEnd": 1, - "hash": "741a04400aa35c9a7e4c939d9ec800d688ba6d00de977d5f88ab90b85c8e3a79" - }, - { - "text": "6 Background Primary aldosteronism is the overproduction and oversecretion of aldosterone, occurring independently of the reninangiotensinaldosterone system (RAAS).", - "tokenCount": 38, - "pageStart": 1, - "pageEnd": 1, - "hash": "fd7d669074c609d725fd7fc963f4250f460b946c59249be740abec438f3c6538" - }, - { - "text": "Aldosterone can cause sodium retention and potassium excretion in the renal tubules.", - "tokenCount": 17, - "pageStart": 1, - "pageEnd": 1, - "hash": "2e22069c977a4587fdab4c98dce8bb0f3dda84ef2076d7ecccc6ac98eee7add3" - }, - { - "text": "Aldosterone (mineralocorticoid) receptors are also present in vascular endothelial smooth muscle cells and the myocardium.", - "tokenCount": 28, - "pageStart": 1, - "pageEnd": 1, - "hash": "3b8fe2ab6b4ca045e44d0058002783c8d23e39b0d2ea8018706368dc0a262a37" - }, - { - "text": "Chronic activation of these receptors is associated with proinflammatory and profibrotic effects, 7 likely explaining the increased risk of cerebrovascular, cardiovascular, and renal disease in primary aldosteronism compared with essential hypertension 8-12 (Table 1 10 -12 ) .", - "tokenCount": 57, - "pageStart": 1, - "pageEnd": 1, - "hash": "a6ddb2592e62e4e54f8291736d1c96a08853d1c62837b1c82bb38e15f65d73a9" - }, - { - "text": "(Bruin) Rugge, MD; and Olga Senashova, MD Oregon Health & Science University, Portland, Oregon CME This clinical content conforms to AAFP criteria for CME.", - "tokenCount": 42, - "pageStart": 1, - "pageEnd": 1, - "hash": "db844d9d063cdfe02f592677024772eefb4d60a153f2d764c8ae4bb11163df17" - }, - { - "text": "Primary aldosteronism is the underlying cause of hypertension in primary care settings in approximately 6% of cases, and it is even more common in patients with resistant hypertension.", - "tokenCount": 35, - "pageStart": 1, - "pageEnd": 1, - "hash": "65cbb24a4c77dfd6559f05c48eae44168af0d32453899df09f9387b43e0d5dd4" - }, - { - "text": "However, it is estimated that only about 2% of patients who have risk factors for primary aldosteronism have been formally tested or diagnosed.", - "tokenCount": 30, - "pageStart": 1, - "pageEnd": 1, - "hash": "6aba630216ecefe5ab4c43cb91c3facb5bb7b980a312eecb323adda4e44d486c" - }, - { - "text": "The first step in the diagnosis of primary aldosteronism is case detection and involves testing patients who are at risk, including individuals with resistant hypertension, as well as those with wellcontrolled hypertension and a firstdegree relative with primary aldosteronism, hypokalemia, an adrenal nodule, atrial fibrillation, obstructive sleep apnea, or a family history of an early stroke (i.", - "tokenCount": 86, - "pageStart": 1, - "pageEnd": 1, - "hash": "04cc64a93df034cacd7c44b00ed8e12c83e7f07cec11509ee71258fdf81a0d7d" - }, - { - "text": "Initial case detection is performed by simultaneously measuring plasma aldosterone concentration and plasma renin activity; an elevated aldosteronerenin ratio (greater than 30) indicates independent aldosterone secretion (i.", - "tokenCount": 42, - "pageStart": 1, - "pageEnd": 1, - "hash": "210a6d263130092cfda7a07822cf92474cd80d360fc55603c71d479bc06c01ed" - }, - { - "text": "After a positive case detection, confirmatory testing should be performed.", - "tokenCount": 13, - "pageStart": 1, - "pageEnd": 1, - "hash": "3777be425e9360f55dac7901165aae652afc8e5b664ca3d061322727e60a1acc" - }, - { - "text": "Confirmatory tests include the captopril challenge, oral or intravenous salt loading, or fludrocortisone suppression.", - "tokenCount": 27, - "pageStart": 1, - "pageEnd": 1, - "hash": "232a9c88d2992fafd0330d324d9743eccdde212141b194dc9074f0b3ce5bb8ce" - }, - { - "text": "Results are positive if aldosterone levels remain high after interventions that suppress or interrupt physiologic production of aldosterone.", - "tokenCount": 24, - "pageStart": 1, - "pageEnd": 1, - "hash": "26d86eed294d92db44c19b5a06d15f5e3d0e5baeba07c8e842f3cc0490e900e0" - }, - { - "text": "If the confirmatory test is positive, adrenal computed tomography and adrenal vein sampling should be performed to differentiate unilateral from bilateral adrenal production of aldosterone.", - "tokenCount": 34, - "pageStart": 1, - "pageEnd": 1, - "hash": "574c7ab276853fbebe1d758af6f42f20f5fdfd6842a93e7a2919dd546935dda7" - }, - { - "text": "Patients with unilateral primary aldosteronism should undergo adrenalectomy, whereas those with bilateral production should be treated with mineralocorticoid receptor antagonists, such as spironolactone or eplerenone.", - "tokenCount": 46, - "pageStart": 1, - "pageEnd": 1, - "hash": "3e80b46c37dd0439fbdde0ebf6fb1724f4999b88ea4adb0304f915a16bff1366" - }, - { - "text": "2023; 108(3):273-277.", - "tokenCount": 11, - "pageStart": 1, - "pageEnd": 1, - "hash": "7734fbb05ad1a2f88faa9385f0aa7e0003b2ef0f64521846ddbf26aa02a67133" - }, - { - "text": "Copyright 2023 American Academy of Family Physicians.", - "tokenCount": 10, - "pageStart": 1, - "pageEnd": 1, - "hash": "74198e7cc33b1d67c407b461ce4f22253b51010de199a4f4a969b0cc067c2365" - }, - { - "text": ") TABLE 1 Adverse Effects of Primary Aldosteronism Compared With Essential Hypertension Risk Odds ratio (95% CI) Atrial fibrillation 3.", - "tokenCount": 34, - "pageStart": 1, - "pageEnd": 1, - "hash": "9819cff9e87f6bbf0d775fcac0b2cc9509f3a857810de1394f1424cb8cc23b7b" - }, - { - "text": "45) Left ventricular hypertrophy 2.", - "tokenCount": 10, - "pageStart": 1, - "pageEnd": 1, - "hash": "925e04a7899418b9b99bf5c4bc5f271a23d3f36aaf98187ef61566270906f658" - }, - { - "text": "Downloaded from the American Family Physician website at www.", - "tokenCount": 12, - "pageStart": 1, - "pageEnd": 1, - "hash": "fa4f80ff9dcfaa4a7c148facd542059d6e8c9328675b16422b4a28ffc15cba30" - }, - { - "text": "For the private, noncommercial use of one individual user of the website.", - "tokenCount": 15, - "pageStart": 1, - "pageEnd": 1, - "hash": "14e67a948643ee4635781c166e20e7a147f0278be7b44ef2a9c359d42098d8c7" - }, - { - "text": "org for copyright questions and/or permission requests.", - "tokenCount": 10, - "pageStart": 1, - "pageEnd": 1, - "hash": "ca8bf4b330cd6e3d1751b8fc42790f445843bb887abeece320fe347960a22e5e" - }, - { - "text": "org/afp Volume 108, Number 3 September 2023 PRIMARY ALDOSTERONISM Case Detection The first step in diagnosing primary aldosteronism is case detection.", - "tokenCount": 40, - "pageStart": 2, - "pageEnd": 2, - "hash": "91b9f53e41bd978daf3d2ccd9489ae6a5b3970f5015520388b8db9c61449f727" - }, - { - "text": "Current guidelines recommend performing case detection in patients with resistant hypertension, as well as those who have wellcontrolled hypertension with certain clinical characteristics (Table 2) .", - "tokenCount": 30, - "pageStart": 2, - "pageEnd": 2, - "hash": "e0b8bb6f20e228226003ed3654a4a3a6978975752f3061cfdc2e60d2e66d296f" - }, - { - "text": "13 Normokalemia should not dissuade clinicians from considering the diagnosis of primary aldosteronism.", - "tokenCount": 22, - "pageStart": 2, - "pageEnd": 2, - "hash": "557d075ec71c7d36dfd8092685d12c995550a1814bb9ab6ef2fffbd8035b5a7b" - }, - { - "text": "Hypokalemia is the exception, not the rule, and is seen in only about 30% of patients with primary aldosteronism.", - "tokenCount": 30, - "pageStart": 2, - "pageEnd": 2, - "hash": "7ea001ab40a655b194c6a65a867d30ae2387af43f07518b28ebe9af58b98d1af" - }, - { - "text": "14 Initial case detection for primary aldosteronism is performed by simultaneously measuring plasma aldosterone concentration and plasma renin activity.", - "tokenCount": 27, - "pageStart": 2, - "pageEnd": 2, - "hash": "a9a7bd8c3fc993b8256248f2aef01824aac09c323e4e636b5444618e77916777" - }, - { - "text": "10 Aldosterone elevation with suppressed plasma renin activity identifies patients with potential primary aldosteronism 10,13 (Figure 1 10,13,15 ) .", - "tokenCount": 33, - "pageStart": 2, - "pageEnd": 2, - "hash": "5f6b08d5fdfa25202b8a3f42759dcbaf557736f8beaf9feaf5dde7d7e8ed3c60" - }, - { - "text": "An aldosteronerenin ratio of greater than 30 is considered positive.", - "tokenCount": 15, - "pageStart": 2, - "pageEnd": 2, - "hash": "bf1d3f22d4dfab82cb06d1eec29cc09e28571fe4554adcf682374b5d15c285a0" - }, - { - "text": "Medications that significantly alter the RAAS, such as spironolactone, eplerenone, and amiloride, are ideally held before testing and, if needed, other antihypertensives should be substituted (Table 3) .", - "tokenCount": 52, - "pageStart": 2, - "pageEnd": 2, - "hash": "a49d3b59238e8c0a3ba505d0473ac199018a25f3b562d30ff63eec0aa8144fd2" - }, - { - "text": "13 Confirmatory Testing Confirmatory testing is often needed to make a formal diagnosis of primary aldosteronism.", - "tokenCount": 25, - "pageStart": 2, - "pageEnd": 2, - "hash": "3bc7939e2438232b303f72070525dade9bd4e0cf905cd8a291084fce377a4933" - }, - { - "text": "However, in some patients with a high probability of primary aldosteronism based on clinical presentation and initial biochemical screening (e.", - "tokenCount": 27, - "pageStart": 2, - "pageEnd": 2, - "hash": "b75b86f251c9c85e91ad8ae43de7d5098619fd13d77b18134a64944431140c51" - }, - { - "text": ", spontaneous hypokalemia [potassium level of less than 3.", - "tokenCount": 15, - "pageStart": 2, - "pageEnd": 2, - "hash": "3d56b2ee805c91b25eae0f0d66974da77eabd26ad9918f961652c3813e29725a" - }, - { - "text": "5 mEq per L] with suppressed plasma renin activity and elevated plasma aldosterone concentration), confirmatory testing can be omitted.", - "tokenCount": 28, - "pageStart": 2, - "pageEnd": 2, - "hash": "742daaafe8cc426e55161f7ddbb3f5690fd807ade3a7c0133430c2d3272b420e" - }, - { - "text": "16 Confirmatory testing had a near 100% specificity for a final diagnosis of primary aldosteronism in cases where plasma aldosterone concentration was greater than 30 ng per dL and plasma renin activity was less than 0.", - "tokenCount": 48, - "pageStart": 2, - "pageEnd": 2, - "hash": "d60c0d50e7db4a60b323216446428982b1443f25b9905ff2c21e3208fe1cdb0b" - }, - { - "text": "15 For patients who require confirmatory testing, several tests are available, but there is no consensus on which one is preferred.", - "tokenCount": 25, - "pageStart": 2, - "pageEnd": 2, - "hash": "c739c7aad798696bee66ea620059e72ac5816157452dcb900de923e5eb848b9d" - }, - { - "text": "17 Test results are considered positive when aldosterone levels remain elevated despite an intervention that would suppress physiologic aldosterone production.", - "tokenCount": 26, - "pageStart": 2, - "pageEnd": 2, - "hash": "f301f3ad53fb3affbf799b061619489b7452372f63452fc6b0d3ca32f95d9ecf" - }, - { - "text": "Salt loading and synthetic mineralocorticoid administration can worsen hypertension and hypokalemia; therefore, monitoring of blood pressure and serum potassium levels is recommended.", - "tokenCount": 32, - "pageStart": 2, - "pageEnd": 2, - "hash": "8d1b5ab382f9c3346318a5a99219daffa82f4f060f3d0423396309465157406b" - }, - { - "text": "These tests are timeconsuming and require meticulous attention to detail; therefore, physicians may consider referral to an endocrinologist for confirmatory testing.", - "tokenCount": 28, - "pageStart": 2, - "pageEnd": 2, - "hash": "0cca28baa218e28143ccdc48dd219f18afa0c9f66b4f95b6634f3ccd3c53b3fe" - }, - { - "text": "CAPTOPRIL CHALLENGE TEST In the captopril challenge test, aldosterone levels are measured at baseline and then two hours after oral administration of 25 to 50 mg of the angiotensinconverting enzyme inhibitor captopril.", - "tokenCount": 51, - "pageStart": 2, - "pageEnd": 2, - "hash": "f114e8658f42e7a67f1956535fc671bedc0ea0fcc575ebeb13e085ce6aa045bd" - }, - { - "text": "In patients without primary aldosteronism, interruption of the RAAS by an angiotensinconverting enzyme inhibitor will cause a significant decrease in plasma aldosterone levels.", - "tokenCount": 37, - "pageStart": 2, - "pageEnd": 2, - "hash": "278283ff31b6902074dcee35e0170b7e53e81218763edc8b6b4b7869b66937f6" - }, - { - "text": "A decrease of less than 30% is consistent with autonomous aldosterone secretion (i.", - "tokenCount": 18, - "pageStart": 2, - "pageEnd": 2, - "hash": "a818d78008e45b913752c299c06ade47220795572d8b8a3104a03f92dfc69255" - }, - { - "text": "SORT: KEY RECOMMENDATIONS FOR PRACTICE Clinical recommendation Evidence rating Comments Case detection for primary aldosteronism should be done in patients with resistant hypertension and in patients who have wellcontrolled hypertension with hypokalemia, atrial fibrillation, obstructive sleep apnea, adrenal incidentaloma, a firstdegree relative with primary aldosteronism, or a family history of early stroke (i.", - "tokenCount": 88, - "pageStart": 2, - "pageEnd": 2, - "hash": "92473683a489423115487bc864acd7b285a6fbbd5ad95ae81e30bedf0a26d599" - }, - { - "text": "11,13 C Expert opinion and limitedquality diseaseoriented evidence Initial case detection for primary aldosteronism is performed by simultaneously measuring plasma aldosterone concentration and plasma renin levels.", - "tokenCount": 38, - "pageStart": 2, - "pageEnd": 2, - "hash": "afa667127742069592baf7bfa50bbd79a63f2f2921909e04e7a1ed514b646289" - }, - { - "text": "Aldosterone elevation with suppressed renin levels identifies patients with potential primary aldosteronism.", - "tokenCount": 20, - "pageStart": 2, - "pageEnd": 2, - "hash": "46035f0d9452c7fe006f3e890ea3ceca45547b607d34dd57013d170cd284af0f" - }, - { - "text": "10,13 C Expert opinion and diseaseoriented evidence Patients with a high probability of primary aldosteronism based on clinical presentation and initial biochemical screening (e.", - "tokenCount": 33, - "pageStart": 2, - "pageEnd": 2, - "hash": "5b1b9c46c96b4e515c0cb217e5e5696ebe4b819371316f8019f267ed9fd648fe" - }, - { - "text": ", spontaneous hypokalemia with suppressed plasma renin activity and elevated plasma aldosterone concentration) may not require confirmatory testing.", - "tokenCount": 27, - "pageStart": 2, - "pageEnd": 2, - "hash": "5202941640706c2e737dadb084bde00dc81115df2e7e29681960c7410dbc478f" - }, - { - "text": "16 C Diseaseoriented case series Once primary aldosteronism has been diagnosed, the next step is to determine if aldosterone production is unilateral or bilateral.", - "tokenCount": 33, - "pageStart": 2, - "pageEnd": 2, - "hash": "224a09b9f1e059a5c9cb57f7a0f3ad39d9f18f6a6dfc4e72a9896b81151f98e8" - }, - { - "text": "This subtyping is accomplished with adrenal computed tomography and adrenal vein sampling.", - "tokenCount": 18, - "pageStart": 2, - "pageEnd": 2, - "hash": "642dceab3331d04b8f054dc42a99e0fcd2b4e15b6c3cfed22e34179ea80e30a6" - }, - { - "text": "13,18,19 C Expert opinion and diseaseoriented studies Adrenalectomy is recommended in cases of unilateral aldosterone production and is superior to medical treatment.", - "tokenCount": 32, - "pageStart": 2, - "pageEnd": 2, - "hash": "cc89dc66bffc7942a8f8783219d6d08b2848525c1fa7b4686ddfd1fc5e0530b2" - }, - { - "text": "Patients treated with adrenalectomy have reduced adverse cardiovascular outcomes and superior qualityoflife measures compared with patients who are managed medically.", - "tokenCount": 26, - "pageStart": 2, - "pageEnd": 2, - "hash": "5c67f5997e77e0e148c4aa6150253fbe85d08e3d5c24a766690502a8425a0f94" - }, - { - "text": "31,32 B Patientoriented outcomes A = consistent, goodquality patientoriented evidence; B = inconsistent or limitedquality patientoriented evidence; C = consensus, diseaseoriented evidence, usual practice, expert opinion, or case series.", - "tokenCount": 45, - "pageStart": 2, - "pageEnd": 2, - "hash": "422d52ac3e71e896dd8125b4554d90934009fc536f6380e8da2dcf88706cc803" - }, - { - "text": "For information about the SORT evidence rating system, go to https:// www.", - "tokenCount": 16, - "pageStart": 2, - "pageEnd": 2, - "hash": "08d0c78d7ffd5e1cdc93a70e0603ec5fbd85cd5e9c378b034c5d1460792db51b" - }, - { - "text": "org/afp American Family Physician 275 ORAL SALT LOADING TEST For the oral salt loading test, a highsalt diet supplemented with sodium chloride tablets is consumed for three days with a goal sodium intake of 6 g per day.", - "tokenCount": 49, - "pageStart": 3, - "pageEnd": 3, - "hash": "6c9dfae1e8edd2d1ac42bee3572bf8ab0b657bb345910fae3496a5f0bf4103d7" - }, - { - "text": "High salt intake should cause physiologic suppression of the RAAS and a marked decrease in aldosterone levels.", - "tokenCount": 22, - "pageStart": 3, - "pageEnd": 3, - "hash": "373065b6ad924b9becf8adb2c67be8cf5d21d1a993f376f2930f9ea2e1f6309a" - }, - { - "text": "A 24-hour urine collection is performed on the third day.", - "tokenCount": 13, - "pageStart": 3, - "pageEnd": 3, - "hash": "820fdb89618dcd3b06d9a7a4d7f331349138a2e6edaa05f602d6fb7e596097fe" - }, - { - "text": "Persistently elevated 24-hour urine aldosterone levels (more than 12 mcg in 24 hours) are consistent with nonphysiologic production of aldosterone and confirm the diagnosis of primary aldosteronism.", - "tokenCount": 46, - "pageStart": 3, - "pageEnd": 3, - "hash": "09d48cfc05f39e92e2d17208d063efc727b57176c54761c5a3ba2cc57873f912" - }, - { - "text": "The saline infusion test can also confirm pathologic aldosterone production if plasma aldosterone concentration is greater than 10 ng per dL after an infusion of 2 L of normal saline.", - "tokenCount": 37, - "pageStart": 3, - "pageEnd": 3, - "hash": "03ad7b2f180f38e47a6083169c0771ecc25775e005ec77b43b964f4b8370bf1a" - }, - { - "text": "FLUDROCORTISONE TEST The fludrocortisone test involves administration of the synthetic mineralocorticoid fludrocortisone at a dosage of 0.", - "tokenCount": 38, - "pageStart": 3, - "pageEnd": 3, - "hash": "2f6f24c8cb8ca7ab518295d9b5b9fc76414ea34af5503c9e43461484b489af67" - }, - { - "text": "Exogenous mineralocorticoid administration should suppress serum aldosterone levels.", - "tokenCount": 16, - "pageStart": 3, - "pageEnd": 3, - "hash": "c4e1562c8227ee3fe4625b4d3a6211c94706e11942d5a36094635b8f5dfd1310" - }, - { - "text": "A plasma aldosterone concentration of greater than 6 ng per dL on day 4 confirms the diagnosis of primary aldosteronism.", - "tokenCount": 28, - "pageStart": 3, - "pageEnd": 3, - "hash": "3ea23fb8d5420eb3f539c7260ddc3fb47fb8c81169b08e46a21dac8678441893" - }, - { - "text": "Subtyping Once primary aldosteronism has been diagnosed, the next step is to determine if aldosterone production is unilateral or bilateral.", - "tokenCount": 30, - "pageStart": 3, - "pageEnd": 3, - "hash": "6977147639e9be07f19cc67b5f3d5f979ad359a548954d78e684bb9e927c2798" - }, - { - "text": "13,18,19 Unilateral production is typically caused by an aldosteroneproducing adenoma and should be treated surgically, whereas bilateral production is typically from idiopathic hyperplasia and is treated medically.", - "tokenCount": 45, - "pageStart": 3, - "pageEnd": 3, - "hash": "a61af531513c237f70dbba3f960c929b6ee3f7e95f96cbac9eac56d85bdfb3ce" - }, - { - "text": "This differentiation, termed subtyping, is accomplished with adrenal computed tomography (CT) and adrenal vein sampling.", - "tokenCount": 25, - "pageStart": 3, - "pageEnd": 3, - "hash": "9c0dec54fea971e78cceeb27fdf08ee1fbc44ff0c2045e31f7a4692d37ed81dc" - }, - { - "text": "13,18,19 Adrenal CT has three phases: an initial scan without contrast media, a scan at 60 to 75 seconds after contrast media administration, and again at 15 minutes.", - "tokenCount": 37, - "pageStart": 3, - "pageEnd": 3, - "hash": "4af1a599205937f027144ebf8830aef36a2eecb4e07cd19985f617b5093d9228" - }, - { - "text": "By assessing baseline nodule density, as well as contrast media uptake and subsequent washout, benign adenomas can be reliably distinguished from malignant masses.", - "tokenCount": 31, - "pageStart": 3, - "pageEnd": 3, - "hash": "0a8b9d68670544448903ec372490580dcfabdbfaac39cabec6b5c812f234f74e" - }, - { - "text": "20 CT has limited sensitivity for the detection of subcentimeter nodules.", - "tokenCount": 15, - "pageStart": 3, - "pageEnd": 3, - "hash": "f64595d928da5ede9828c528a48aefff364e4f883d25e84374d3b7540ebd3582" - }, - { - "text": "Additionally, CT is unable to distinguish nonfunctioning adenomas from functioning adenomas.", - "tokenCount": 19, - "pageStart": 3, - "pageEnd": 3, - "hash": "37e451b2c349f6a40434b0d1f88d9346550d5bec23d172bc6ab6500ef10b8046" - }, - { - "text": "A systematic review showed an almost 40% rate of discordance between CT and adrenal vein sampling in subtyping patients with primary aldosteronism.", - "tokenCount": 32, - "pageStart": 3, - "pageEnd": 3, - "hash": "eb1a1cf26d0712887235abaa36db44c02312eb593c6b8e8b7ffc90f16b6f5cbf" - }, - { - "text": "21 Therefore, adrenal vein sampling is considered the preferred method of subtyping.", - "tokenCount": 17, - "pageStart": 3, - "pageEnd": 3, - "hash": "d56dab812efbfae62d0f3d32ae6cadcc256b4ceaed90f8267df78be5015b0520" - }, - { - "text": "A systematic review and metaanalysis performed in 2022 found a statistically FIGURE 1 Suggested interpretation of initial case detection testing for primary aldosteronism.", - "tokenCount": 31, - "pageStart": 3, - "pageEnd": 3, - "hash": "3030c5be6106af7520fae4a44274e3d3c6b0d1db3e7d7cfaf0006aa7217608ea" - }, - { - "text": "Note: An aldosteronerenin ratio > 30 is the most common cutoff during initial case detection when plasma aldosterone concentration and plasma renin activity are in conventional units (ng per dL and ng per mL per hour, respectively).", - "tokenCount": 49, - "pageStart": 3, - "pageEnd": 3, - "hash": "a92820769b162fbb54c503d7026e61ef62b418f92c0ad20558d632a495ccfb6b" - }, - { - "text": "Values above the threshold should not be viewed in isolation because the aldosteronerenin ratio may be exaggerated in cases of very low renin levels without significant elevation of aldosterone.", - "tokenCount": 37, - "pageStart": 3, - "pageEnd": 3, - "hash": "1fe4db42398fe125824d8abd9e3bd387acf8dd93068d18a4898026ba99142fcb" - }, - { - "text": "Information from references 10,13, and 15.", - "tokenCount": 10, - "pageStart": 3, - "pageEnd": 3, - "hash": "66f0a597ca60581de3efc109e5777ad39955dff8ff5027cdb816dd3bd172962b" - }, - { - "text": "Aldosteronerenin ratio Plasma renin activity > 1 ng per mL per hour Diagnosis unlikely Plasma renin activity 0.", - "tokenCount": 26, - "pageStart": 3, - "pageEnd": 3, - "hash": "629ca7383e5d889f1a7727e8f0f8a83d258676c89b39e40ed37b2506e3ba0d59" - }, - { - "text": "6 to 1 ng per mL per hour Perform confirmatory testing Plasma renin activity < 0.", - "tokenCount": 19, - "pageStart": 3, - "pageEnd": 3, - "hash": "009d3aa358afd55306c862b9aadc800ea5e331d6a164b9b9d77118c37e1ffb86" - }, - { - "text": "6 ng per mL per hour Plasma aldosterone concentration 20 to 29 ng per dL Plasma aldosterone concentration 30 ng per dL Diagnosis confirmed Plasma aldosterone concentration 11 to 19 ng per dL Perform confirmatory testing Plasma aldosterone concentration 10 ng per dL Diagnosis unlikely Potassium < 3.", - "tokenCount": 67, - "pageStart": 3, - "pageEnd": 3, - "hash": "22914b194ba3cf3ac8faec4e13039db6dc2d627d37b5d595d6aced632162f0e4" - }, - { - "text": "5 mEq per L Diagnosis confirmed Potassium 3.", - "tokenCount": 14, - "pageStart": 3, - "pageEnd": 3, - "hash": "2e4028e18e4ef69b8089b58c8184b14e72ce23ff3fbaf8d2e9c2d4b8c14e9806" - }, - { - "text": "org/afp Volume 108, Number 3 September 2023 significant higher rate of complete biochemical success when adrenalectomy was guided by adrenal vein sampling compared with adrenalectomy guided by CT alone (odds ratio = 2.", - "tokenCount": 47, - "pageStart": 4, - "pageEnd": 4, - "hash": "fca2b119fdf73eb84435acf92eb4de0c0d430e6aa81db8a52c7220430700d4bf" - }, - { - "text": "18 Adrenal vein sampling is a nuanced procedure.", - "tokenCount": 10, - "pageStart": 4, - "pageEnd": 4, - "hash": "b04bf0054426f25d7895c798af3cd8aaab1a14c59331fb0a5b29cfaa8d7aefe5" - }, - { - "text": "Blood samples are taken from a peripheral vein and the right and left adrenal veins and tested for aldosterone and cortisol levels.", - "tokenCount": 26, - "pageStart": 4, - "pageEnd": 4, - "hash": "d49b61dfd741038cd3c9b83ce66d3438bab5a415f947e6fb3f19257ae6542961" - }, - { - "text": "22 Success rates for adequate sampling range from 30.", - "tokenCount": 10, - "pageStart": 4, - "pageEnd": 4, - "hash": "4a3aab5d8d707a53a04c7ab797a1e76048e20e4cdf1dc756a19232f80461a086" - }, - { - "text": "24 Operator experience at a center that performs at least 12 procedures per year has been shown to be associated with higher sampling adequacy.", - "tokenCount": 26, - "pageStart": 4, - "pageEnd": 4, - "hash": "2c39df52fb14356958860877ba96dde0c3834a13c41ca571952525971ed1b578" - }, - { - "text": "25,26 An experienced and dedicated laboratory is necessary for a successful adrenal vein sampling program, 27 and the results should be interpreted based on expert consensus guidelines.", - "tokenCount": 32, - "pageStart": 4, - "pageEnd": 4, - "hash": "2e6eb349bd22745e39dee68fa0e3f9a80d554fdce0de11f8c5b84f167a4ce11c" - }, - { - "text": "28,29 Treatment UNILATERAL ALDOSTERONE PRODUCTION Adrenalectomy is recommended in cases of unilateral aldosterone production.", - "tokenCount": 29, - "pageStart": 4, - "pageEnd": 4, - "hash": "76e4a045703a771381071bd1789adc72c5dbfd7c5f4928ed24855179342d33f5" - }, - { - "text": "Although hypertension is cured in only approximately onethird of cases, biochemical cure is achieved in 94% of cases.", - "tokenCount": 23, - "pageStart": 4, - "pageEnd": 4, - "hash": "179d524318b7eb98daf3e4908ff40bdaf86ad1b1357c471ffc16be88340c05c8" - }, - { - "text": "30 Compared with medical management, adrenalectomy reduces the rate of composite adverse cardiovascular outcomes by onehalf 31 and is associated with superior quality of life.", - "tokenCount": 30, - "pageStart": 4, - "pageEnd": 4, - "hash": "f7d2f1f01d63271052396524adb4e1309141755df7dd81651da69dec03e44531" - }, - { - "text": "32 BILATERAL ALDOSTERONE PRODUCTION When aldosterone production is bilateral, medical therapy is necessary.", - "tokenCount": 25, - "pageStart": 4, - "pageEnd": 4, - "hash": "3a2e240b89e7650791f9a2e242f06665b241031045a00261e29ae9743e90a2b0" - }, - { - "text": "Mineralocorticoid receptor antagonists are the cornerstone of therapy for patients with primary aldosteronism.", - "tokenCount": 23, - "pageStart": 4, - "pageEnd": 4, - "hash": "429263048ab6314ad169a3989b7717fc3354153c6c11775c64b155d324f33e37" - }, - { - "text": "They are often used concurrently with other antihypertensives.", - "tokenCount": 13, - "pageStart": 4, - "pageEnd": 4, - "hash": "ebfad5431f0da5e4e35e15905c8cc93a11ab77734125cf950e0b03e9ba51585c" - }, - { - "text": "Dietary sodium restriction of less than 1,500 mg per day is recommended.", - "tokenCount": 17, - "pageStart": 4, - "pageEnd": 4, - "hash": "012e02cf37416c113eec7370539953f07740b72fda6a947e4e7de1039aed5fa5" - }, - { - "text": "33 Spironolactone is a nonselective mineralocorticoid receptor antagonist and is the initial medication of choice.", - "tokenCount": 26, - "pageStart": 4, - "pageEnd": 4, - "hash": "8305a433bba991b133cd411f3f0f0445dd833bdae05baf04b7621146863ee121" - }, - { - "text": "5 to 25 mg per day and are increased, as needed, to a maximum dosage of 400 mg per day.", - "tokenCount": 23, - "pageStart": 4, - "pageEnd": 4, - "hash": "a2ec289d7c3b0de2fba75da9af4345cf55a53a38c5370db5cc4e3584f132dc00" - }, - { - "text": "10 Its dosedependent antiandrogenic properties can lead to adverse effects, such as gynecomastia (more than 10%), erectile dysfunction, decreased libido, and irregular menses (1% to 10%).", - "tokenCount": 46, - "pageStart": 4, - "pageEnd": 4, - "hash": "532ecf3e35491cb5ef80d45749014358cea062fabb3b530861d7ff22788bfa1c" - }, - { - "text": "34 If these adverse effects occur, eplerenone, a more selective but less potent and more expensive mineralocorticoid receptor blocker, may be used.", - "tokenCount": 33, - "pageStart": 4, - "pageEnd": 4, - "hash": "106d1e213070d43afc4cccab9edeefe50481dcd67ba66e53b5de9cf526c0f44c" - }, - { - "text": "13,34 Recent observational studies have shown that titrating mineralocorticoid receptor antagonists based on plasma renin concentrations may lead to better outcomes.", - "tokenCount": 30, - "pageStart": 4, - "pageEnd": 4, - "hash": "f84d7e21d1e6370e812416400ef37b648f004c4b2c07acceb2a89cf69ba6b7bc" - }, - { - "text": "35,36 Therefore, future guidelines may include interval measurements of renin as part of the mineralocorticoid receptor antagonist dosing strategy.", - "tokenCount": 29, - "pageStart": 4, - "pageEnd": 4, - "hash": "b1ea5e184c59bd802efc366ce1b22bcb7bd09834bca654a8404858255ce02dff" - }, - { - "text": "36 Data Sources: A PubMed search of clinical trials, metaanalyses, randomized controlled trials, and systematic reviews from 2000 to 2022 was completed using the key terms primary hyperaldosteronism, primary aldosteronism, and hyperaldosteronism.", - "tokenCount": 53, - "pageStart": 4, - "pageEnd": 4, - "hash": "3e36284d6271aa1298155cc27018d1cc2f2e098b48e91be4abb594191c701cce" - }, - { - "text": "We also searched the Cochrane database, Agency for Healthcare Research and Quality (AHRQ), and Essential Evidence Plus using the same terms, but with limited results.", - "tokenCount": 33, - "pageStart": 4, - "pageEnd": 4, - "hash": "3342a3383ba3939e7a265f4687a4912eb7d872bafe5c819cdc9c0ed9f8bd6fa4" - }, - { - "text": "If studies used race and/ or gender as a patient category but did not define how these TABLE 3 Medications to Hold Before Primary Aldosteronism Te s t in g* Medications Hold priority Duration of hold (weeks) Mineralocorticoid receptor antagonists Mandatory 4 Angiotensinconverting enzyme inhibitors, angiotensin receptor blockers, beta blockers, diuretics, dihydropyridine calcium channel blockers Optional 2 to 4 Alpha blockers, nondihydropyridine calcium channel blockers, vasodilators ContinueNote: Because of interference with the reninangiotensinaldosterone system, certain antihypertensive medications may alter renin and angiotensin levels.", - "tokenCount": 144, - "pageStart": 4, - "pageEnd": 4, - "hash": "071877e0f8f7ca9da472b30bca3f14419bd0f79f78ee07aa6168d1654bf0f6ad" - }, - { - "text": "*Based on the 2016 Endocrine Society Guidelines.", - "tokenCount": 10, - "pageStart": 4, - "pageEnd": 4, - "hash": "08a1287ca0801627d18dab05653252342c150b66d5f3c1419a637f769ed27c55" - }, - { - "text": "Lowdose mineralocorticoid receptor antagonists may not need to be held before aldosteronerenin ratio testing, especially if renin levels are not suppressed.", - "tokenCount": 33, - "pageStart": 4, - "pageEnd": 4, - "hash": "2139642ddd4ed70ff887ca999826f0e1b778d14eebe63885394ba04da10ec235" - }, - { - "text": "TABLE 2 Clinical Criteria for Patients Who Require Case Detection Testing for Primary Aldosteronism Controlled hypertension (any one of the following) Adrenal nodule Atrial fibrillation* Family history of early stroke (i.", - "tokenCount": 46, - "pageStart": 4, - "pageEnd": 4, - "hash": "0d87121869b6f981ad249d036b8f9d53560fd14863494cc1e5ecef3bb2ffcdc3" - }, - { - "text": ", younger than 40 years) Firstdegree relative with primary aldosteronism Hypokalemia Obstructive sleep apnea Resistant hypertension All patients Note: Criteria are based on the 2016 Endocrine Society Guidelines.", - "tokenCount": 46, - "pageStart": 4, - "pageEnd": 4, - "hash": "b0be98147cd1d210605d22930366e1fbab4f6ece0c881bf5d65d83c0b499b3f6" - }, - { - "text": "*The Endocrine Society does not distinctly list atrial fibrillation as criteria, but it acknowledges that some centers recommend testing given its association with primary aldosteronism.", - "tokenCount": 36, - "pageStart": 4, - "pageEnd": 4, - "hash": "9f558d9d11230dab2efdcaa3471d1d108c4621152a0ce90fa2d417872f35835d" - }, - { - "text": "Resistant hypertension is hypertension that persists despite the concurrent use of three different classes of antihypertensive medications or the use of four antihypertensive medications to achieve adequate blood pressure control.", - "tokenCount": 38, - "pageStart": 4, - "pageEnd": 4, - "hash": "bb8b9340ef91229089746fd693f64ac819f663e72bf35aae57500d8fb3d06685" - }, - { - "text": "org/afp American Family Physician 277 PRIMARY ALDOSTERONISM categories were assigned, they were excluded.", - "tokenCount": 26, - "pageStart": 5, - "pageEnd": 5, - "hash": "cbd34e63cc74146f6576859238254334ba24e274780d56b34254b28713f0392f" - }, - { - "text": "Physicians may need to exercise caution in applying such guidelines to populations not included (e.", - "tokenCount": 18, - "pageStart": 5, - "pageEnd": 5, - "hash": "1541bd03e01051e4b445a59aeccd5dc21d9c1d21b9182a41b5c88ad9c6b9c7ee" - }, - { - "text": "Search dates: October 2,2022, and May 19,2023.", - "tokenCount": 16, - "pageStart": 5, - "pageEnd": 5, - "hash": "8eb38ecd3b8c9e3b9cf581ca90ac2a482363d32a55fe81f2e8bc194b83ec4f5b" - }, - { - "text": "QUENCER, MD, is an associate professor in the Department of Interventional Radiology at Oregon Health & Science University, Portland.", - "tokenCount": 27, - "pageStart": 5, - "pageEnd": 5, - "hash": "96abbbe21318abb1dacf05afd8a450d434f23b7d270d4e2a6c23cec8a3410be5" - }, - { - "text": "(BRUIN) RUGGE, MD, is an associate professor in the Department of Family Medicine at Oregon Health & Science University.", - "tokenCount": 28, - 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{ - "text": "Primary aldosteronism, a new clinical entity.", - "tokenCount": 12, - "pageStart": 5, - "pageEnd": 5, - "hash": "da51b7c4a49bbb4da9c3e9fa02b0b694a24a2f632858c82cbb6c49812682afb8" - }, - { - "text": "1956; 44(1): 1-15.", - "tokenCount": 11, - "pageStart": 5, - "pageEnd": 5, - "hash": "2c887311bb905ebd6514f344671e32cf0ecd51fd5b1fdd272b9b3f74cf582fa8" - }, - { - "text": "Monticone S, Burrello J, et al.", - "tokenCount": 12, - "pageStart": 5, - "pageEnd": 5, - "hash": "a8e0ee952ac4177c952f3b5b23662258a397b36992957bbeb1676243167bd0aa" - }, - { - "text": "Prevalence and clinical manifestations of primary aldosteronism encountered in primary care practice.", - "tokenCount": 19, - "pageStart": 5, - "pageEnd": 5, - "hash": "5c23cbeed39a1bde071b9b856d5011d0f6b32d29c1db00509f8148e0c9b08cd3" - }, - { - "text": "2017; 69(14): 1811-1820.", - "tokenCount": 12, - "pageStart": 5, - "pageEnd": 5, - "hash": "21eb7ca6dc0220e8e60904ea84a78a7c39ff70068ef400e5952b431f950608dd" - }, - { - "text": "Brown JM, Siddiqui M, et al.", - 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