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n engl j med 384;16 nejm.org April 22, 2021 1544 The new england journal of medicine vertebral fractures, and death were higher among patients with mild autonomous cortisol excess than among those with nonfunctioning adrenal incidentaloma at baseline. These conditions were more likely to develop in patients with nonfun... | 449 | 3 | 3 | 4bc52e34d3b7b4b63c2e1d0a94f9e42e319c204eb148fcbadc5e591378bad55c |
n engl j med 384;16 nejm.org April 22, 2021 1545 Clinical Pr actice Table 1. | 26 | 4 | 4 | e0a54156a00f8f6ced3250e5a2989174fdfa05913c6a310f65d5ee7dbcbc9e1e |
Biochemical Evaluation in Patients with Adrenal Incidentaloma.* 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 ser... | 450 | 4 | 4 | 695844a227b97bd5743d9471b21f7ca5f85f883a0187e9bfc754f1670e286721 |
receiving high-sodium diet, aldoste- rone suppression test, and testing with saline infusion while patient is sitting False positives can be caused by beta-blockers, methyldopa, clonidine, nonsteroidal anti- inflammatory drugs, and oral contraceptives and estrogen; false negatives can be caused by angiotensin-convertin... | 238 | 4 | 4 | 170cbbc07147200d7b8876fbad1f3e25701ac98d101b2b821c3a2a313056dc47 |
DHEAS denotes dehydroepiandrosterone sulfate. † Additional laboratory tests may include measurement of plasma chromogranin A levels, 24-hour urinary 3-methoxytyramine levels, or both, especially when a malignant pheochromocy- toma is suspected because of the presence of potential metastatic disease sites or local invas... | 77 | 4 | 4 | daaebef6824f2af92b9b4dc50f4f86031770c183ebd7dce1f034a12bcf39e551 |
The New England Journal of Medicine is produced by NEJM Group, a division of the Massachusetts Medical Society. Downloaded from nejm.org at Indiana University School of Medicine on December 29, 2025. | 41 | 4 | 4 | f15a1aef005e974d3558003352ac030bed9f5778b5d4fd31cdf2ac83c7a3fbc7 |
n engl j med 384;16 nejm.org April 22, 2021 1546 The new england journal of medicine among those with mild autonomous cortisol ex- cess (defined as a morning cortisol level >1.8 μg per deciliter after a 1-mg dexamethasone sup- pression test) than among those with nonfunc- tioning tumors, and the risks were greater with... | 100 | 5 | 5 | 10593d68918751966ad1ae980d304481606499ac524b88856a5cb98cfcb8973f |
>1.8 to 5.0 μg per deciliter). 16-20 The care of patients with mild autonomous cortisol excess may involve active surveillance or adrenalectomy. Data comparing outcomes with the use of these strategies are limited. | 47 | 5 | 5 | 2151d0660144a3a7e3059c89973732e5eb3878bfc2ec475e43cf0b248fcfcc2d |
One small randomized, controlled trial comparing adrenal- ectomy (in 23 patients) with surveillance (in 22 patients) for mild autonomous cortisol excess showed that after surgery, there was normaliza- tion or improvement in the condition of patients with type 2 diabetes mellitus (in 5 of 8 patients [62%]), hypertension... | 113 | 5 | 5 | 4ec75f86fd2fe08e5e7e1196f36474d167177ab22df5b768b7f737325aea6ca9 |
21 Three of 6 patients in the surgi- cal group were reported to have postoperative decreases in obesity, whereas no changes in bone measures were seen in 5 patients who had osteoporosis; comparative data were lacking for the control group. | 49 | 5 | 5 | 0ca1ff93de57f8a2a0a10a91964090b878ecc9c23c587dad94236eb2ad7e6656 |
In retrospective cohort stud- ies, patients who underwent adrenalectomy had lower glucose levels and less hypertension and dyslipidemia than those who were cared for with surveillance. 22,23 Pheochromocytoma Although pheochromocytoma may manifest as an adrenal incidentaloma, on careful history and physical examination,... | 100 | 5 | 5 | 3dd199779b0eca78c2a9926d3b3adceec4832e5b0f575a17e1776c31dfe2aac1 |
A total of 1.5 to 14.0% of adrenal inciden- talomas are found to be pheochromocytomas. 9 Imaging features on CT may be helpful in sug- gesting pheochromocytoma (Fig. | 55 | 5 | 5 | 3dcedd8d4d05dad6dd6e9505e1cef2fbb3a06c8f24a7ceba88787e047161dc0c |
These fea- tures include an attenuation of more than 10 Hounsfield units on unenhanced CT, the pres- ence of areas of increased vascularity and necro- sis on enhanced CT, and delayed washout of contrast medium. | 54 | 5 | 5 | d15c4c50903e3c6b8f06b5277aef17c89fa68eb54043d62779536855728ff80b |
On magnetic resonance imag- ing (MRI), pheochromocytoma may have high T2-weighted intensity (Fig. Guidelines recommend that all patients with adrenal incidentaloma undergo biochemical screening for pheochromocytoma because these tumors may be clinically silent. | 57 | 5 | 5 | 66d020afab60cd0bfdedc42ef1c1afd9e09d2753dd08b4ba4bccffedd84b8370 |
9,24-27 However, some investigators have suggested that biochem- ical screening for pheochromocytoma is not necessary in a patient who has a lipid-rich tumor with a CT attenuation of 10 Hounsfield units or less, because these tumors are rarely pheochro- mocytomas (<0.5% of cases). | 76 | 5 | 5 | 8a1221d48efd03a765a010e0ef4b8d25232f6bb484664cbd78200583a8759287 |
28,29 The most accu- rate screening tests to detect pheochromocytoma are measurement of the levels of plasma-free metanephrines (sensitivity, 89 to 100%, and specificity, 79 to 98%) or 24-hour urinary frac- tionated metanephrine level (sensitivity, 86 to 97%, and specificity, 69 to 95%). | 79 | 5 | 5 | 06cb98d013dd3fb616ea465b918c0004a4688eb74677fbd804371dcb6b37b373 |
30 To minimize the risk of perioperative illness and death, pa- tients with a diagnosis of pheochromocytoma should undergo adrenalectomy only after suffi- cient alpha-blockade followed by beta-blockade, if necessary, is achieved (Fig. | 59 | 5 | 5 | b620f36f736f09c6432d0696a128310eabf3799ed18d27e47284474ff0f4ddeb |
Figure 2. Imaging Features of Adrenal Masses. Panel A (left image) shows an unenhanced CT scan that reveals a left adrenal mass (arrow) with high attenuation (>10 Hounsfield units). Panel A (right image) shows a left adrenal mass, presumed to be an adenoma (arrow), with low attenuation (≤10 Hounsfield units). Panel B s... | 110 | 5 | 5 | 4c70e0576cb11120d14fd766e681efbc580ccd52f53e4d9c096e77d880f86f67 |
The pathological find- ings were consistent with adrenocortical carcinoma. Panel C (left image) shows MRI of a right pheochromocytoma (arrow) that was hyper- intense on a T2-weighted image. | 51 | 5 | 5 | 2a825fc0c8f85a219651043a31c0e4f7e2323a14984d2120ec3c5e284b9520b7 |
Panel C (right image) shows a right adrenocortical carcinoma (arrows) with local invasion. A B C The New England Journal of Medicine is produced by NEJM Group, a division of the Massachusetts Medical Society. | 47 | 5 | 5 | bb553d95281ecc4ebb628893c781e19cb00e8635c0c9fd48fd9ff1f4aa0994c7 |
Downloaded from nejm.org at Indiana University School of Medicine on December 29, 2025. n engl j med 384;16 nejm.org April 22, 2021 1547 Clinical Pr actice Primary Hyperaldosteronism Among patients with adrenal incidentaloma, pri - mary hyperaldosteronism is less common than mild autonomous cortisol excess and pheochro... | 105 | 5 | 6 | 93658006689c0fb958ee933a2a223299a268ab0b1fe9cd749c34861258fa315d |
9 However, any patient with adrenal incidentaloma and hyper - tension or hypokalemia should be screened for primary hyperaldosteronism with measurement of the mid-morning plasma aldosterone concen - tration and plasma renin activity; patients should not be taking medications that could cause false positive or false neg... | 70 | 6 | 6 | c894fda58ef7739e51f9ceec808adc5905b95c11acbefd998f1a02c826a00396 |
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 consid - ered to be a reliable indicator of the diagnosis; if the ratio is high but below this level, confir - matory testing is recommen... | 71 | 6 | 6 | 1287b6c8d35024972f20eb64ad0d218621d8d3b000ec5800315cd71fd5f4c7ff |
31,32 Once the diagnosis is established, patient-specific factors guide decisions regarding medical versus surgical therapy (Fig. Additional Hormonal Secretion It is extremely rare for patients with adrenal in - cidentaloma to have sex hormone (estrogen or testosterone)–secreting tumors without appre - ciable clinical ... | 65 | 6 | 6 | b0e85e4b5d03fd16b97e573dce522a455802f87a0f9dd841c8a09262e62f8ae3 |
In women, excess testosterone is associated with features of viril - ization such as facial hair growth, acne, and deepening of the voice, and excess estrogen is associated with irregular uterine bleeding and breast tenderness. | 44 | 6 | 6 | bfd6691a81fd23781186d286dcd9e9f9a02b4fc5b9e464d41f355a50ee6040db |
In men, estrogen-secreting tu - mors can cause gynecomastia, testicular atrophy, and decreased libido. 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 tu - mor. | 84 | 6 | 6 | c3fad7b2a4c214f41df20e38b8dfb25d6c99c1b983c52ef94f4aeb602b903534 |
Adrenocortical carcinoma, which accounts for 1.2 to 11.0% of adrenal incidentalomas, 9 de - pending on the study population, may secrete excess hormones or be nonfunctioning. | 45 | 6 | 6 | eb733ba9549703ac66d277b6342170a6c5e243fe2b2dd0693271a5469b0b75da |
Up to 21% of adrenal incidentalomas in patients with a history of or known current primary cancer indicate adrenal metastasis. 9,33 Cancers that are most likely to spread to the adrenal glands are lung cancer, gastrointestinal cancer, melanoma, and renal-cell carcinoma. | 59 | 6 | 6 | 574c5d5103adb9024b10137bfa577063351a47237145e606d6bc0b8ed5aab455 |
33 Tumor size and imag - ing features are key to determining the likeli - hood of cancer and guiding treatment (Table 2 and Figs. 1 and 2). 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... | 99 | 6 | 6 | a0a4199fc0ff68f46246a5036e9876e8509683ec059799f3b3f86a6b9759a7d0 |
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. | 61 | 6 | 6 | 2f0f89aaef0e9118976d43bac2754fbf9fe22815e4aeee772eddd628857e3e3e |
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 tu - mors (<4 cm in diameter) in this age group. | 51 | 6 | 6 | 8064946d916d6cd8ad57396a2f7cfc184972f4d07951ae65822d8f186fb4dd09 |
It is important to measure the adrenal tumor in three dimensions (the greatest length, width, and height) because two-dimensional (cross-sectional) measurements often underestimate size. Imaging Features Suggestive of Cancer On CT imaging, features other than tumor size can help to differentiate benign from malignant a... | 80 | 6 | 6 | dfaa29bf8be4f24e4805511b3a70b6610a5177aa1cf7fa7fd6e3fad5cd85bf94 |
34,37 Irregular tumor margins, heterogeneity, necrosis, vascularity, and calcifi - cation are features that arouse suspicion for can - cer (Table 2). 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... | 93 | 6 | 6 | a2c7565696855c0e6a75c9ffd29ff47a4ef540fbd5856e1ab8aec40b82c227d9 |
38 In patients who have incidentalomas with an attenuation of more than 10 Hounsfield units, follow-up imaging may include contrast-enhanced CT (to measure the percentage of washout of contrast medium at various times), MRI with chemical-shift analysis, or positron-emission to - mography (PET)–CT with 18 F-f luorodeoxy... | 89 | 6 | 6 | 841460cb7d751f8b9883bcaafccbf7759c0074bf071848426f26aa74c6512c06 |
On contrast-enhanced CT, adenomas commonly enhance more rapidly and have faster washout of intravenous contrast medium when The New England Journal of Medicine is produced by NEJM Group, a division of the Massachusetts Medical Society. | 46 | 6 | 6 | 46fa02665045d8f5c1b6e485b9b92cc13c58ba67a5436579ad47d81dec1d3f57 |
Downloaded from nejm.org at Indiana University School of Medicine on December 29, 2025. n engl j med 384;16 nejm.org April 22, 2021 1548 The new england journal of medicine Table 2. | 49 | 6 | 7 | b2d873e3e21a4a07c67dd39a48c018aa5f220e2e8c7b98cb2bd97bf57d94ecad |
Imaging Features of Adrenal Incidentaloma.* Feature Adrenocortical Adenoma Pheochromocytoma† Adrenocortical Carcinoma Metastasis Size Usually small, <4 cm in diameter Variable, frequently large Large, usually >6 cm in diameter Variable Margins and shape Smooth margins, round or oval Smooth margins, round or oval Irregu... | 450 | 7 | 7 | d08013600eb44d8f0d5531bc656ba101ee47eb45395308d407d5600ea2776f19 |
and or magnetic resonance imaging (MRI). 18 F-FDG PET-CT denotes positron-emission tomography (PET)–CT with 18 F-fluorodeoxyglucose, and SUV max maximum standardized uptake value. | 49 | 7 | 7 | 071a7dd21c722e41ce715cf187c342b7b7b2e5aa9619078179cefc3049162b16 |
† The presence of metastasis is the only way to determine whether a pheochromocytoma is malignant. Metastatic pheochromocytoma is associated with larger tumors (>6 cm in diam- eter) and irregular margins. | 53 | 7 | 7 | 5e823889e2a518501aa5f4795c66b3bd2d3013072eba78f8135b25d45c50f7dd |
‡ Washout of contrast medium has been measured at various times (60 to 90 seconds [early] and 10 to 15 minutes [late]) with both relative and absolute values. 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 o... | 134 | 7 | 7 | c7b18e8c7ee7fed4b7f78984df5025417cdda8f2284f4110638902d2b9af76de |
Absolute washout values greater than 60% and relative washout values greater than 40% suggest an adenoma. 34 § Some studies have used an SUV max cutoff value that is less than 5. | 41 | 7 | 7 | 45428c84257261807537488e7e66c1692f02eb2b2b29b65085c26787e161c1d0 |
¶ The adrenal-to-spleen signal-intensity ratio (i.e., the signal intensity of the adrenal mass divided by the signal intensity of the spleen) and the adrenal-to-liver signal-intensity ratio (i.e., the signal intensity of the adrenal mass divided by the signal intensity of the liver) are based on meta-analyses and prosp... | 83 | 7 | 7 | 446c99746ee617af247ff8afd38348a0b9f5c0f07d65756e91524e1c4ef72d65 |
34 Some studies have used adrenal-to-spleen or adrenal-to-liver SUV max ratios. The New England Journal of Medicine is produced by NEJM Group, a division of the Massachusetts Medical Society. | 46 | 7 | 7 | 7eba9ad32eeabc25b27bb7ad0743166ebfda0742deab32afad5fdc6a2817d9cc |
Downloaded from nejm.org at Indiana University School of Medicine on December 29, 2025. n engl j med 384;16 nejm.org April 22, 2021 1549 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 carci... | 78 | 7 | 8 | 6987de848ab3fc09a989a215a5dd0b9eca022a4c9822b0192bf6d4afa7af3699 |
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... | 99 | 8 | 8 | 03c5be6a10e42081da35f455a424460e3f695a62593bb17a8e6fd452a7013cc7 |
Absolute washout of more than 60% of the contrast medium and relative washout of more than 40% of the contrast medi- um are suggestive of an adenoma, but the sensi - tivities and specificities of these cutoff values vary across studies owing to variations in tech - nique and timing of measurement of washout. | 69 | 8 | 8 | 5a329987fbf943b84a53d0d03c1d3dfab64253fe75099ab4ba33c2f73e52366d |
34 MRI with chemical-shift analysis, which as - sesses qualitative loss of signal intensity, quan - titative loss of signal intensity, or both between in-phase and out-of-phase imaging, is especially useful to avoid radiation exposure in pregnant women and children and in patients who are allergic to iodinated contrast... | 67 | 8 | 8 | fe839870abaeb5a6540a9e939b3d91d5b01ca005ce5e616908b8e73b155ccc74 |
In a sys - tematic review, qualitative (visual) analysis of the adrenal signal-intensity index and quantitative assessment of the adrenal-to-spleen ratio (i.e., the signal intensity of the adrenal mass divided by the signal intensity of the spleen) both had high accuracy (pooled sensitivities and specifici - ties, 94% ... | 86 | 8 | 8 | f207c3a3ae249d5c649f40e388a75628cf26f2f0ab5d0047350ed20d493723d0 |
37 In a meta-analysis of 29 studies, findings on 18 F-FDG PET-CT adrenal imaging that determined the maximum standardized uptake value and the ratio of the maximum standard - ized uptake value in the adrenal tumor as com - pared with the spleen or liver effectively distin - guished benign from malignant tumors (pooled ... | 88 | 8 | 8 | 124f2bbdef45b66d407ff40be9ec78c25d98412acae6038b8f5d8b2b36b121ab |
39 Adrenal Biopsy Biopsy of an adrenal incidentaloma is rarely indi - cated, 33 since it has low accuracy for distinguish - ing benign from malignant adrenal tumors and may lead to tumor seeding if the mass is an adrenocortical carcinoma. | 57 | 8 | 8 | eee2dee6f5bf0d77b55d16cda3514d442a5001aa21f4e11479080b0cc4f9951d |
An exception is the rare case in which adrenal metastasis is strongly sus - pected 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. | 62 | 8 | 8 | 7b05f159258faaec96ef27eae9ce6633fc92ed82b4a0082b4c96ee19933ffdfd |
Assessment of Bilateral Adrenal Masses Approximately 15% of patients with adrenal in - cidentaloma have bilateral adrenal masses. 40 The differential diagnosis of bilateral adrenal masses includes primary bilateral macronodular adrenal hyperplasia and adenomas, bilateral pheochromo - cytomas, congenital adrenal hyperpl... | 126 | 8 | 8 | ee7fdaa4d39e4066ac704d3dcb2a56624fab157773b8b1935a2b3b7a3a21bede |
In addition to the hormonal assessments described for a solitary adrenal incidentaloma, measure - ment of the serum 17-hydroxyprogesterone level is indicated to rule out congenital adrenal hyper - plasia. | 44 | 8 | 8 | 6989e78bf7f0d7ad538cc5b4c90e8f5b56ed84699efc64f2824455b870dbc8ea |
41 In addition, if bilateral adrenal masses appear on imaging to be hemorrhagic or infil - trative, the patient should undergo testing for adrenal insufficiency. In patients with bilateral adrenal masses, the imaging characteristics of each adrenal lesion should be evaluated indepen - dently in determining appropriate ... | 66 | 8 | 8 | 37c3c7f6983097cdc6805148ce697dc6128090cccfebb8e2bae874e49a5d4d53 |
Follow-up in Patients with Nonfunctioning Lesions Nonfunctioning adrenal incidentalomas with fea - tures 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 addi - tional follow-up imaging. | 73 | 8 | 8 | d41a0383cc0516ba6ee0dcf8730e9baee5005bc66ff62ad1640ca15ec96e2262 |
In a meta-analysis in - volving 4121 patients with nonfunctioning adre - nal lesions, the mean tumor growth was 2 mm over a median of 52.8 months of follow-up; only 2.5% of the patients had tumor enlargement of 1 cm or more, and adrenocortical carcinoma did not develop in any of the patients. | 77 | 8 | 8 | 6970ab82d71bd88f33951f27079845c1282c6f1c69b09ec3f381463cab1bb32c |
15 Follow-up with imaging and biochemical tests is recommended for patients with nonfunction - ing tumors with indeterminate features on im - aging. However, the most appropriate time inter - vals for reassessment are unclear, and they vary among different guidelines. | 52 | 8 | 8 | 3b8153916f99ba007e5a25f9d9572637255ec5572e2ab6034bdbd7adfc9e42fe |
Areas of Uncertainty The diagnostic criteria for and management of mild autonomous cortisol excess are uncertain. The New England Journal of Medicine is produced by NEJM Group, a division of the Massachusetts Medical Society. | 41 | 8 | 8 | 506b53be40f2e862ee1bd2f7b5ed41f45c1775ec703ca0c2835299d72175dc72 |
Downloaded from nejm.org at Indiana University School of Medicine on December 29, 2025. | 20 | 8 | 8 | 7321be191f7e6e133b8b7f7c68e9f9fd53a70dc83d0b3321f84576ba73d747e0 |
n engl j med 384;16 nejm.org April 22, 2021 1550 The new england journal of medicine More data are needed to better identify patients with metabolic abnormalities that are most likely to be related to the adrenal lesion and to reverse the metabolic abnormalities with surgery. Stud - ies are lacking to compare outcomes ... | 450 | 9 | 9 | d3287a1137ada9bf4024f76a50043d2870b9890ba583e475645bebc1dc0387be |
has pheochromocytoma, she should undergo a unilateral minimally invasive adrenalectomy (open if imaging features arouse suspicion for cancer) after pretreatment. If bio - chemical testing shows mild autonomous corti - sol excess or primary hyperaldosteronism, im - aging features arouse suspicion for cancer, or both, in... | 450 | 9 | 9 | 659a4bb47fe19441108fb2e48c2c319509c95938a2bb9b4f8711c18aa9ebfecb |
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executive summary of recom - mendations. Endocr Pract 2009; 15: 450-3. Tabarin A, Bardet S, Bertherat J, et al. Exploration and management of adrenal incidentalomas. Ann Endocrinol (Paris) 2008; 69: 487-500. Terzolo M, Stigliano A, Chiodini I, et al. AME position statement on adrenal inci - dentaloma. Eur J Endocrinol ... | 203 | 10 | 10 | a2e619e007157462053d27c5211c73d61b7e6cd58f3e304e180cac94027a5c4b |
Buitenwerf E, Korteweg T, Visser A, et al. Unenhanced CT imaging is highly sensitive to exclude pheochromocytoma: a multicenter study. Eur J Endocrinol 2018; 178: 431-7. Lenders JWM, Duh Q-Y, Eisenhofer G, et al. Pheochromocytoma and paragangli - oma: an Endocrine Society clinical practice guideline. J Clin Endocrinol ... | 192 | 10 | 10 | 2328197fc6f55e1b750452eeaf28fcc42bba74796c4b41a48a2e320aa74f9058 |
SFE/ SFHTA/AFCE consensus on primary aldo - steronism. Confirmatory testing. Ann Endocrinol (Paris) 2016; 77: 202-7. Bancos I, Tamhane S, Shah M, et al. Diagnosis of endocrine disease: the diag - nostic performance of adrenal biopsy: a systematic review and meta-analysis. Eur J Endocrinol 2016; 175: R65-R80. | 100 | 10 | 10 | 8026281c1aacc95d114af7388a6e3a2066cc07b5765b264424b6a2ff6e369280 |
Dinnes J, Bancos I, Ferrante di Ruffano L, et al. Management of endocrine disease: imaging for the diagnosis of malignancy in incidentally discovered adrenal masses: a systematic review and meta-analysis. Eur J Endocrinol 2016; 175: R51-R64. | 65 | 10 | 10 | 56564ff4fdec888f4a07386247264f3d8e7b2864f2c6db43d2e7cd57bdbc2783 |
NIH state-of-the-science statement on management of the clinically inapparent adrenal mass (“incidentaloma”). NIH Con - sens State Sci Statements 2002; 19(2): 1-25. | 47 | 10 | 10 | 4f444d35ef377e1532b197e04ed1009b9483848e730858eed903accfdc360a01 |
Sturgeon C, Shen WT, Clark OH, Duh Q-Y, Kebebew E. Risk assessment in 457 adrenal cortical carcinomas: how much does tumor size predict the likelihood of malignancy? J Am Coll Surg 2006; 202: 423-30. | 59 | 10 | 10 | 216595523a21bedb5fed808c13415953bcfcdcd34fe3a65d1f6d814bd10b4062 |
Platzek I, Sieron D, Plodeck V, Borkowetz A, Laniado M, Hoffmann RT. Chemical shift imaging for evaluation of adrenal masses: a systematic review and meta-analysis. Eur Radiol 2019; 29: 806-17. | 60 | 10 | 10 | 43e7fb53d92846db1c36632163126c1b3589bfa17e19c0faa5dc51419399f7d0 |
Buitenwerf E, Berends AMA, van Asselt ADI, et al. Diagnostic accuracy of com - puted tomography to exclude pheochromo - cytoma: | 43 | 10 | 10 | 518d25c5688b474ddd180e396b889ef06b7c7b3ef4300a6ec23e8e5375aa1567 |
a systematic review, meta-analy - sis, and cost analysis. Mayo Clin Proc 2019; 94: 2040-52. Kim S-J, Lee S-W, Pak K, Kim I-J, Kim K. | 48 | 10 | 10 | a92824fcd2fa1c58202cd4c999d3281058345c02fbebd65bdc411ac92d1abe30 |
Diagnostic accuracy of 18 F-FDG PET or PET/CT for the characterization of ad - renal masses: a systematic review and meta-analysis. Br J Radiol 2018; 91(1086): 20170520. | 47 | 10 | 10 | d2bd445f11d54d5173b2123ca008be75e2910aea4a515002160f1d1298d8c71a |
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Eur J Endocrinol 2018; 179: R57-R67. Falhammar H, Torpy DJ. Congenital adrenal hyperplasia due to 21-hydroxylase deficiency presenting as adrenal inciden - taloma: | 52 | 10 | 10 | e8b8ec760dbff17d8183aed77aba4b2efdd4731a99130b884ea56d963558f9a9 |
a systematic review and meta- analysis. Endocr Pract 2016; 22: 736-52. The New England Journal of Medicine is produced by NEJM Group, a division of the Massachusetts Medical Society. | 41 | 10 | 10 | 14e174c9fda4110f88441821be9a55c78c2d562f06912a8479a4250fd6048688 |
Downloaded from nejm.org at Indiana University School of Medicine on December 29, 2025. | 20 | 10 | 10 | 7321be191f7e6e133b8b7f7c68e9f9fd53a70dc83d0b3321f84576ba73d747e0 |
about the balance between risks and benefits; strong recommen- dations based on low-quality evidence usually indicate the pan- el’s strong preference against the alternative course of action but are subject to change with new research. Given a weak recom- mendation, careful consideration of the patient’s circumstances,... | 298 | 3 | 3 | c63b75de1b3e8a6fdbdcd080759dbf866fa5600f48a611f82d04f3058b8f3ee3 |
Excess cor- tisol production, the biochemical hallmark of endogenous Cush- ing’s syndrome, may be caused by either excess ACTH secretion (from a pituitary or other ectopic tumor) or independent adrenal overproduction of cortisol. Although Cushing’s syndrome is clinically unmistakable when full blown, the spectrum of cl... | 214 | 3 | 3 | 8c4074fc293d42357ddef46ed3915f272540088e3387ff7a4f231696becfe622 |
We en- courage caregivers to consider Cushing’s syndrome as a second- ary cause of these conditions, particularly if additional features of the disorder are present. (see Who should be tested below.) If Cushing’s syndrome is not considered, the diagnosis is all too often delayed. In addition, overactivity of the hypoth... | 200 | 3 | 3 | db697c176d1cfeee1f0cb36c33f620ab11b9507de4cbfa8c04a2402f54b96a08 |
Circulating cortisol concentrations are usually normal (or slightly reduced) in obesity, but severe obesity can raise UFC. It is thought that higher brain centers stimulate CRH release in these conditions, with subsequent activation of the entireHPAaxis(10).Thenegativefeedbackinhibitionofcortisol on CRH and pituitary A... | 433 | 3 | 3 | f70a1ed0a1dee46477ac2c4a0dc975f7a585e8b947c79693ff07afa68fb6574a |
sulting hypercortisolemia. As a result, the overlap in UFC ex- cretion is limited to values up to about 4-fold normal. 2.0 Morbidity and mortality of Cushing’s syndrome: | 50 | 4 | 4 | 5a31899330222051d02d15cd19815d507298a1868d2aa533cb461b6db9624f5a |
rationale for diagnosis and treatment The earliest reports of mortality in Cushing’s syndrome likely described individuals with severe hypercortisolism, representing one end of the clinical spectrum. These reports documented a mediansurvivalof4.6yr,andin1952a5-yrsurvivalofjust50%, with most deaths caused by vascular (m... | 95 | 4 | 4 | 5f358a8ab3d6501224e9285790e4e5f1f0006dd69aa84e889529adcae1aec406 |
However, with modern-day treatments the standard mortality ratio (SMR) after successful normalization of cortisol was sim- ilar to that of an age-matched population during 1–20 yr of follow-up evaluation in one study (13). | 50 | 4 | 4 | ca3b8fd40e532a3e9553f6c325970fbbac8027e3a20f0aff415890c321de8f1a |
Because markers of car- diovascular risk remain abnormal for up to 5 yr after surgery, further studies are needed to assess long-term SMR (14). In pa- tients who have persistent moderate hypercortisolism despite treatment, SMR is increased 3.8- to 5.0-fold, compared with the general population (4, 5). | 75 | 4 | 4 | dfaa357ee4f449b37e8c2920d9aac975417db86ed60e53927e0a4c5db640bb39 |
These data are consistent with the increased cardiovascular mortality and morbidity reported in patients with iatrogenic Cushing’s syndrome secondary to the chronic use of synthetic corticosteroids (15). | 40 | 4 | 4 | cb481f2466da0b3820cdce92d725c18bd4fd9b7c6075df2ee79200436404f92f |
Successful treatment of hypercortisolism reverses, but may not normalize, features of Cushing’s syndrome. Bone mineral density and cognitive dysfunction improve after successful sur- gical treatment of Cushing’s syndrome but do not normalize in all patients (16, 17). | 61 | 4 | 4 | 80a09b0e2b626b91e85624f1803520dac1ea776378b180c75e3fa0bde203bfff |
Additionally, quality of life improves after surgical treatment but remains below that of age- and gender- matched subjects for up to 15 yr (18). Indirect evidence support- ing the need for intervention includes the finding that the risk of infection is lower in patients with mild to moderate, compared with severe, hyp... | 68 | 4 | 4 | 51b20e4af68e098c89fe147b26f54742c895b93e9d78e42d6609515b368ca89a |
There are limited and conflicting data regarding whether sur- gical treatment of patients with mild hypercortisolism in the set- tingofanadrenalincidentalomaissuperiortomedicaltreatment of comorbidities alone (20–23). | 53 | 4 | 4 | dc25a2da0ac4e1e930b14b71ec527bed06beaf53d2a4749bd287952f6d6b89aa |
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