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endocrine.org/clinical-practice-guidelines/methodology ( 10 ). 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 recommenda - tions ( 14 | 56 | 3 | 3 | 304bbcc9aab59bb1868f6c6c4142f27380c3e386a497c49f51e09d1c2934a0d6 |
The process was facilitated by the GRADEpro Guideline Development Tool (GRADEpro GDT) ( 15 ). The GDP consisted of content experts representing the following clin - ical specialties: endocrinology, general internal medicine, genet - ics, hypertension specialists, epidemiology, and a patient representative. Members were... | 296 | 3 | 3 | b76f730a1689a1b2d6c4b6f5909414b68aa523a43e9c5aa29eebc6e166945edb |
The systematic searches for evidence were conducted in February 2022 and updated in October 2024. In parallel with the development of the evidence summaries, the GDP members searched and summarized research evi - dence related to each question (generally observational stud - ies) and to other EtD criteria, such as indi... | 170 | 3 | 3 | 998c5218b463bbc4bad8888ace1745819b03833151eba4b78cd67f791aacfdfb |
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 co- sponsoring organizations, a representative of the Society ’ s Board of Direct... | 287 | 3 | 3 | 343b1a580e3348d35c186273941b362e81403a34d4411904b131cd421e4aee04 |
Very Low ⊕ OOO There is very-low confidence that the true value of the estimate of interest is on one side of a threshold of interest or within a certain range. The true value of the estimate may deviate significantly from target of the certainty rating (i.e. probably fall in a different range). Reprinted with permissi... | 137 | 3 | 3 | a45868581c24be6c0d489bf9eda007de39b222d91cc0f524ad9824d821cecec8 |
The GRADE Book version 1.0 (updated September 2024). The GRADE Working Group ( 12 Table 2. 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 recommendati... | 190 | 3 | 3 | c29b91a36ee95385fcfa1780f9adeb2d2bfb3953e7ce077ef8138378bb9e4e4b |
The majority of individuals in this situation would want the suggested course of action, but many would not. Decision aids may be useful in helping individuals make decisions consistent with their individual risks, values, and preferences. Clinicians should recognize that different choices will be appropriate for each ... | 205 | 3 | 3 | 436aa7ec9f0e9ce3d09b13066dc3e325506c1db805a5c99de20f029725b7f6aa |
manuscript was reviewed before publication by the Journal of Clinical Endocrinology and Metabolism’s publisher ’ s reviewers. This guideline will be reviewed annually to assess the state of the evidence and determine if any developments warrant an update to the guideline. | 52 | 4 | 4 | 4b129bfdb894d3f07e0ffcc4477b6ea29fbeb77f6d71e1584d3dbdf59656d14b |
List of Recommendations Question 1. Should care that includes primary aldosteron - ism screening be applied to all individuals with hypertension, compared with care without screening? Recommendation 1 In all individuals with hypertension, we suggest screening for primary aldosteronism (PA) (2 | ⊕⊕ OO). | 68 | 4 | 4 | 08f6ce1f9a65b03cf39d75df2ac1addb6423e3842c47a711b7b0f156659e6879 |
Technical remarks: • This is a conditional recommendation, with imple - mentation depending on contextual factors such as available resources, local expertise, and health - care system capacity, which may affect feasibility and prioritization. | 43 | 4 | 4 | 353246c15cf33061fe098c1830a11dfc8f3b7aeb1575a9c46e59b8df2359d2eb |
• This recommendation emphasizes care that is in - formed and guided by screening, with a positive screening result serving as the critical first step in the care process for individuals with PA. • PA screening includes measurement of serum/plas - ma aldosterone concentration and plasma renin (concentration or activity... | 76 | 4 | 4 | d58bbec72c3ec9dfd4fd5b8355515d9a3d85a89306789c4be373961a31ed828f |
Potassium is also assessed—not for screening itself—but to aid in the accurate interpretation of aldosterone (refer to Question 3). Question 2. Should primary aldosteronism–specific therapy (medical or surgical) vs nonspecific antihypertensive ther - apy be used in individuals with primary aldosteronism? | 71 | 4 | 4 | 5fdba542b5dd2eafcf78991475580bbcd182739b03c76bd7bf5b0dd27458accb |
Recommendation 2 In individuals with hypertension and primary aldos - teronism (PA), we suggest PA-specific therapy (med - ical or surgical) (2 | ⊕⊕ OO). | 45 | 4 | 4 | 7fbce537e46bf0449a07a26e1e5561553e69bcdba32ec2d93d5e7f153f22e06c |
Technical remarks: • In individuals with lateralizing PA who are not sur - gical candidates or do not desire surgery and in in - dividuals with bilateral PA, medical treatment with mineralocorticoid receptor antagonists (MRAs) should be considered preferable over nonspecific antihypertensive therapy. | 62 | 4 | 4 | f70a8d934ef752d31abd52859a0ff493037ce03b1257b0f7467212fc1ddec323 |
• In individuals with lateralizing PA who are surgical candidates and desire surgery, unilateral adrenalec - tomy should be considered preferable over non - specific antihypertensive therapy. Question 3. Should aldosterone (serum/plasma, or urine), re - nin (concentration or activity), and the aldosterone to renin rati... | 104 | 4 | 4 | 55b43102085e958a2b363a65c4b4e16a6f312cba456d0bd7f37ff746226871c4 |
Recommendation 3 In individuals with hypertension, we suggest primary aldosteronism (PA) screening with serum/plasma al - dosterone concentration and plasma renin (concen - tration or activity) (2 | ⊕⊕ OO). | 56 | 4 | 4 | 747ed5a7342e9190001ffe151c3c42f7dcc3a1a7543d24f3db58cef249a88344 |
Technical remarks: • Screen for PA by measuring serum/plasma aldos - terone and plasma renin (concentration or activity) in the morning with individuals seated and avoid - ing dietary sodium restriction during the few days prior to screening. | 51 | 4 | 4 | a74466a92f9ab277e68b50c1e20855c949f8a13ce84fb63e2afc245e8a1a1898 |
Potassium should be measured alongside renin and aldosterone—not for screen - ing itself but to aid in the accurate interpretation of aldosterone—as low potassium may lead to a falsely low aldosterone. | 44 | 4 | 4 | fc149b8a03a1215dbca1de2fbfd1212298ecc62fa385053a24af85b78138b536 |
• If screening results are negative and the patient has hypokalemia, potassium should be corrected to within the laboratory reference range and screen - ing should be repeated. • Manage interfering medications depending on individual safety and feasibility. | 45 | 4 | 4 | 1a74118704473e3faaff8fe5d3299644a97f0e385d0af583ddfeb84a31a128c0 |
The Guideline Development Panel outlined both minimal- withdrawal and no-withdrawal strategies of inter - fering medications before screening ( Tables 6 and 7 , Fig. • A positive screen meets both of the following con - ditions in most circumstances: | 50 | 4 | 4 | efab828b487c5f8a7eece3cbf88846e740f254dfa9e0e24ebcb25adcd5befdb2 |
Renin is low/suppressed (hallmark of diagno - sis) and aldosterone is inappropriately high relative to renin: indicative of PA if plasma renin activity (PRA) is ≤ 1 ng/mL/h or direct renin con - centration (DRC) is ≤ 8.2 mU/L AND serum/plas - ma aldosterone concentration is ≥ 10 ng/dL ( ≥ 277 pmol/L) when measured by i... | 144 | 4 | 4 | 78d78a03bdf2c7af68c06130d5e6d68dc259fdd0b9169481f7c423e71c7a8d36 |
Elevated aldosterone to renin ratio (ARR): indica - tive 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 LC-MS/MS). | 103 | 4 | 4 | 2f7eb8a29a1cb9ea31037ffdadf9a7e750fbfafd6fb7fdc49064ffcb2b7cdb19 |
( Fig. 1 and Table 5 for ARR cut points for differing assays and units). • The aldosterone, renin, and ARR values above are provided for guidance. However, as with many diagnostic tests based on continuous variables, the sensitivity and specificity depend on the se - lected threshold. | 63 | 4 | 4 | 8e281b9a56735923e5dc1d3fdccf391571219581151bc53890eea281ab2a9ac8 |
Aldosterone and renin levels are further influenced by individual variability, local 2456 The Journal of Clinical Endocrinology & Metabolism , 2025, Vol. 110, No. 9 Downloaded from https://academic.oup.com/jcem/article/110/9/2453/8196671 by University of Wisconsin System user on 20 February 2026 | 77 | 4 | 4 | 424ac00a7f7f5d66deaa998e6c3ccb4869434ffc20a5d424c2bf1798973937a7 |
laboratory assays, and other factors. Where possible, clinicians should rely on local laboratory cut points, as assays may vary. No cut point is perfect—each carries a trade-off between false positives and false negatives. | 47 | 5 | 5 | 4b629d75ea6ade5f102eec9c58ed4b172b739e9551f059c64ab0eccabc341f7a |
Therefore, results should be interpreted within the context of the patient’s pretest probabil - ity for PA, along with potential interfering medica - tions and conditions. • If the individual’s initial screen is negative and fac - tors are present that could have led to a false- negative result (eg, hypokalemia or medi... | 130 | 5 | 5 | f1206744bc535219450cf4334319aeea000e6b13e0edc6ca6e93fdfb0cd8e6a8 |
How to screen for PA in individuals with hypertension. This figure diagrams the process of screening for PA in individuals with hypertension. For individuals whose screening indicates likely PA, the next steps are diagrammed in Fig. | 41 | 5 | 5 | 1b333a2528d51a20c0d45c88b6af896d7323a97157d63f1e39a92115d444486e |
2 , Algorithm for the Management of Adults with Hypertension in Whom PA is Likely Based on Aldosterone, Renin, and ARR. *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 ris... | 76 | 5 | 5 | b001fd0260842343ac64c5f4ced40da52b7ceb5cac1e885d9d4bdb67991f2794 |
**The aldosterone, renin, and ARR values provided in this figure and in greater detail in Table 5 are for guidance. However, as with many diagnostic tests based on continuous variables, the sensitivity and specificity depend on the selected threshold. | 50 | 5 | 5 | fe228b2a7e98690afcf5508053d64489509d0101071af8cc872e7e6a9de69907 |
Aldosterone and renin levels are further influenced by individual variability, local laboratory assays, and other factors. Where possible, clinicians should rely on local laboratory cut points, as assays may vary. No cut point is perfect—each carries a trade-off between false positives and false negatives. | 60 | 5 | 5 | 80de2c357e7e808e1efd5a69532ed8c05c2f3503b460e3fa609e1477f626593c |
Therefore, results should be interpreted within the context of the patient’s pretest probability for PA, along with potential interfering medications and conditions. ***Consider potential false positive induced by β -adrenergic blockers when aldosterone < 15 ng/dL ( < 415 pmol/L) by immunoassay, < 10 ng/dL ( < 277 pmol... | 85 | 5 | 5 | ad5e9d892023607f4f814a38eef0ea494948df1495e5ca962cd90f9a3608d903 |
# Drospirenone in OCPs is an MRA. ## Amiloride and triamterene are ENaC inhibitors. Abbreviations: ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin II – receptor blocker; CCB, calcium-channel blocker; DRC, direct renin concentration; ENaC, epithe - lial sodium-channel; HRT, hormone-replacement therapy; L... | 105 | 5 | 5 | 8895046e76e9196cf2b4e2af396fe99199d1bbccdb1444f69bcdf13339a463a7 |
liquid chromatography – tandem mass spectrometry; MRA, mineralocorticoid antagonist; OCP, oral contracep - tive; PRA, plasma renin activity; SGLT2, sodium-glucose cotransporter 2. | 55 | 5 | 5 | 0edcd2bb79f79148eb82fc426529caf7a592d3dc0b656b87214d67287dc3259e |
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sodium-channel [ENaC] inhibitors [eg, amiloride, triamterene], and other diuretics; and 2 weeks for angiotensin-converting enzyme [ACE] inhibitors and angiotensin receptor blockers [ARBs]), which raise renin or lower aldosterone. | 67 | 6 | 6 | 1ca5394d0b3d4000653225759253a59ed3d5f2c5b2de1bc7dbd0efd46467b1f3 |
For the most ac - curate determination of potassium, measure plas - ma potassium in blood collected slowly with a syringe and needle (preferably not using a vacuum-sealed blood collection tube to minimize the risk of spuriously raising potassium). | 51 | 6 | 6 | ccb330deddfa1246fab2137c9d87ecef50173c8b0754f964e4402dff21e566c0 |
During collection, avoid fist clenching, wait at least 5 sec - onds after tourniquet release (if used) to achieve in - sertion of needle, and ensure separation of plasma from cells within 30 minutes of collection. | 49 | 6 | 6 | 13f5c3185477b8c11b3738dea6a3c52a0c5a86575479447b894c9055594e4b7a |
• If the individual’s initial screen is negative and the pretest probability of PA is moderate to high (eg, hypokalemia and/or resistant hypertension) or re - nin 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. | 78 | 6 | 6 | baeb230258c5553c998d723a16339f4b9ca067ac97b5713aca88218335dae181 |
• If the individual’s initial screen is positive, but they are receiving medications (eg, β -adrenergic blockers and centrally acting α 2 -agonists [eg, clonidine, α -methyldopa]) that can lower renin and thereby cause false-positive results, the test should be repeated after withdrawing those medications for 2 weeks i... | 79 | 6 | 6 | 2fb1504fa50c312c394509a806869f223e979c188297bd4b07ffeff147664f4b |
Consider po - tential false positives induced by β -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 LC-MS/MS; if aldos - terone is above these concentrations, PA is likely despite being on β -adrenergic blockers. | 90 | 6 | 6 | 2fb9d3c0d8a315dc7b85c7077618fd0c5e230e02be24d04ea67111338d7f16fc |
• If screening hypertensive patients with chronic kidney disease, renin decreases proportionately to nephron loss, except in cases where there is re - nal ischemia from renal artery stenosis where re - nin will be elevated. | 48 | 6 | 6 | 2a3f336d029d7c76cd1f07cd94f04fd6f02522c5fb133d7945bbbf85a35bc509 |
Aldosterone can also be elevated in chronic kidney disease, leading to overall increases in false-positive testing. • If all initial screening is negative, consider re- screening in the future if a patient develops: | 42 | 6 | 6 | 71548dd2375ddcfebcf4ceca61f8fd5ecb31e1242d1111839701973b7103f96d |
⚬ Unexplained worsening of hypertension or re - sistant hypertension ⚬ New spontaneous or diuretic-induced hypokalemia ⚬ Atrial fibrillation in the absence of structural heart disease or hyperthyroidism Question 4. | 54 | 6 | 6 | e2f743a646d07aa07ff03f1ed41da224ab78e1c27f90431d92a9d04bf83fc651 |
Should care guided by aldosterone suppression testing vs no aldosterone suppression testing be used in individuals with positive primary aldosteronism screen before initiating primary aldosteronism–specific therapy (medical or surgical)? | 45 | 6 | 6 | a6c9344d348ac6fa64019c55b4f86dd7041d49998dd0c21336ffc5c43b4fd2b3 |
Recommendation 4 In individuals who screen positive for primary aldos - teronism (PA), we suggest aldosterone suppression testing in situations when screening results suggest an intermediate probability for lateralizing PA and in - dividualized decision making confirms a desire to pur - sue eligibility for surgical the... | 68 | 6 | 6 | dd549ff965030dfa20f96fffb6f6c6a3c0eecfd5f700172a567335095f80f8c9 |
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. Situations in which aldosterone suppression testing is not required prior to initia... | 69 | 6 | 6 | de9829a4ad6a085d90822e60fe0f800684974340206cd675475a12893ee24e6a |
• In individuals with resistant hypertension or hyper - tension with hypokalemia and overt biochemical evidence of renin-independent aldosterone produc - tion (plasma renin activity [PRA] < 0.2 ng/mL/h or dir - ect renin concentration [DRC] < 2 mU/L and plasma aldosterone concentration > 15 ng/dL [ > 416 pmol/L] via li... | 158 | 6 | 6 | aec71a25f40bbc7261eab770e8b75263734dd09ff1b4d3cde83d2c4a23aa9dde |
• Individuals unwilling or unable to pursue adrenal ven - ous sampling and adrenalectomy can be empirically treated with mineralocorticoid receptor antagonists (MRAs) based on screening results, without aldoster - one suppression testing. | 49 | 6 | 6 | de4b5e299bce143190e713d296f873eeed80014af1ae05b321b8d063d358b262 |
Aldosterone suppression testing may still provide value in some cases for fur - ther documenting the diagnosis. • Aldosterone suppression testing is unnecessary in individuals from families with germline mutations associated with familial hyperaldosteronism. | 44 | 6 | 6 | 93ad14d42f63377f722617129390c548875fda5d3f7c264bcb2df6d127e6e26e |
Genetic screening is recommended for all first- degree relatives of individuals with familial hyper - aldosteronism and for individuals with young- onset PA ( < 20 years) to enable early diagnosis and treatment. | 42 | 6 | 6 | d5c3ccd3693074907227df980d24122a284bb82b1805b1b35eeccb5fa787d919 |
• 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 al - dosterone <∼ 11ng/dL [ <∼ 305 pmol/L] [immuno - assay] or <∼ 8 ng/dL [ <∼ 222 pmol/L] [LC-MS/MS]). | 95 | 6 | 6 | 7b8e102b8b19be22be5027afa3635f8af545bd03ed3490ab8ce7e193c4b1d93d |
Question 5. Should primary aldosteronism–specific medical therapy vs surgical therapy be used in individuals with di - agnosed primary aldosteronism? Recommendation 5 In individuals with primary aldosteronism (PA), we suggest medical therapy or surgical therapy with the choice of therapy based on lateralization of aldo... | 87 | 6 | 6 | 19539fcae65641c9fedd7163821dd6f3a7aff5ac6d02647e86070731a110602e |
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Technical remarks: • Surgical therapy by total unilateral adrenalectomy, usually by the laparoscopic approach, is mainly of - fered to individuals with lateralizing PA who choose to pursue the surgical option ( Fig. | 44 | 7 | 7 | 93b88fe52a4baccb3fd1dd316500d8081f0234a993b866e700153d0b932f6392 |
• Lifelong medical therapy that includes a min - eralocorticoid receptor antagonist (MRA) is usu - ally 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. | 67 | 7 | 7 | 8d5034c3901b0c3582f5777982ee3dcdfd084be3c4c9c6f45626c91bea7a6c29 |
• Individuals with mild PA typically have bilateral disease and may bypass adrenal venous sampling (AVS), proceeding directly to medical manage - ment, as outlined in the diagnostic algorithm ( Fig. • Individuals with multiple comorbidities who may not be good surgical candidates may also proceed directly to medical th... | 63 | 7 | 7 | e3cf6405415877e74c5fdde756819010b80ea7559c899da6376e143a13d8e353 |
Question 6. 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? | 44 | 7 | 7 | bf35ac57bfac6dbaf1f03e0bafee0aac5ac0543b679f0f629754b84e1e537965 |
Recommendation 6 In individuals with primary aldosteronism (PA) consid - ering surgery, we suggest adrenal lateralization with computed tomography (CT) scanning and adrenal ven - ous sampling (AVS) prior to deciding the treatment ap - proach (medical or surgical) (2 | ⊕⊕ OO). | 74 | 7 | 7 | 5c035d8c50f864d42b6ff222a60b5932811c7d261013d4ead1ad27f84847d08d |
Technical remarks: • Individuals with PA who desire and are candidates for adrenalectomy should undergo AVS in order to reliably differentiate lateralizing from bilateral forms. Figure 2. Algorithm for the management of adults with hypertension in whom PA is likely based on aldosterone, renin, and ARR. | 61 | 7 | 7 | 64c73cea99b0d6886d6f6142c93d93e8962f08d4b8d8c6f3577ccbd082f84ce6 |
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. MRA therapy is highly effective in PA. | 48 | 7 | 7 | 30f78239a52c653a7c81e316b5235d18a0cb5927bba6ddabe22975a8359bbbd0 |
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 ). | 43 | 7 | 7 | ed4c1c736ec75acfd600b2c7c8586fc5e237909d4b4cda277cb97b24b9cd5a7c |
For patients who are interested in the possibility of, and capable of undergoing, unilateral adrenalectomy, probabilistic and shared decision making should be pursued. When the probability of lateralizing PA is low, patients can be offered MRA therapy without further testing. | 52 | 7 | 7 | 10ba3a57779a78f76157856773fd5c2818c98cf43e6cde80a8a804a2a87db243 |
When the probability of lateralizing PA is high, cross-sectional adrenal imaging with CT and AVS can be pursued to adjudicate the possibility of lateralizing PA. When the probability of lateralizing PA is intermediate, or uncertain, shared decision making is advised. | 53 | 7 | 7 | d801996fa5e5a65550e74b5c8036b7c953760395ca48216298b68b61c817be5f |
When possible, aldosterone suppression testing may be considered to steer the direction of management in individuals willing and able to undergo testing. In interpreting the aldosterone suppression test one should consider the possibility of false negatives ( 23 - 27 ). | 47 | 7 | 7 | 58f908f7363f6d5e99b15290c8572cf942fd91a9958b9a1bdb4c301ddfdec171 |
When aldosterone suppression testing is not available or desired, MRA therapy can be initiated. Approximate values for aldosterone and renin are provided for guidance. *See Fig. Initiating and Following MRA Therapy. | 47 | 7 | 7 | 2842dba33bb857dd2066ca62dd28e963273ddc5c6c176e65bee5b64183600b34 |
# False negatives may occur, may be impacted by local study conditions, and should be considered when deciding on whether to proceed to AVS testing. Abbreviations: HTN, hypertension; CVA, cerebrovascular accident; MRA, mineralocorticoid antagonist. | 58 | 7 | 7 | da6862ce24a6c85791712af7a763d7b3c1cc1ed80b5394561272e07d2b4849cb |
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• A potential exception is when the diagnosis of uni - lateral aldosterone-producing adenoma (APA) is so likely that AVS could be considered unnecessary (eg, individual age < 35 years with marked PA with hypokalemia and a > 1.0-cm unilateral adrenal ad - enoma on CT scanning). | 70 | 8 | 8 | d7e6e58bfc37510ae5fd20b2d42a3df6115ee4d7130504a369e370335b946798 |
Question 7. Should suppressed renin vs unsuppressed renin be used in individuals with primary aldosteronism receiv - ing primary aldosteronism–specific medical therapy? Recommendation 7 In individuals with primary aldosteronism (PA) receiv - ing PA-specific medical therapy whose hypertension is not controlled and renin... | 95 | 8 | 8 | ab65fad68a5304e78369f11012a210ca88cfd4a4edca85a466a1a4a0782b3070 |
Technical remarks: • This recommendation applies to individuals with PA receiving aldosterone-directed medical ther - apy whose blood pressure (BP) remains high. Uncertainty remains as to whether titrating aldosterone-directed medical therapy to raise re - nin when BP is controlled is efficacious. | 60 | 8 | 8 | 6ed41a07937da2376e9e8e6df2d91a4de69f155f7fe330e422afdc75d2784e89 |
• The panel does not specify a renin level to target but rather advises titration of aldosterone-directed medical therapy to a rise in renin from pretreat - ment baseline. Question 8. | 41 | 8 | 8 | 7b6e49fcfe8cae0377dd65827d58e5ad1dace987cd0feda36d561f2ece55172f |
Should a dexamethasone suppression test vs no dexamethasone suppression test be used in individuals with primary aldosteronism and adrenal adenoma? Recommendation 8 In individuals with primary aldosteronism (PA) and adrenal adenoma, we suggest a dexamethasone sup - pression test (2 | ⊕ OOO). | 80 | 8 | 8 | c023696b64c746ebb230d2628347df454a68f8257ad561a2c65e4a741effc1ca |
Technical remarks: • A dexamethasone suppression test should be per - formed, and a positive test should prompt further evaluation for Cushing syndrome as detailed in the Endocrine Society Clinical Practice Guidelines. | 41 | 8 | 8 | eeade8cf123500c945870cc417a236d5e49d695e9036fc46aa7670469113715f |
• For the 1-mg overnight dexamethasone suppres - sion 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. | 53 | 8 | 8 | 5fa30271643d972272d1d306048505e890ad4c8f47fde0c7ee1e038413f5392a |
A serum cortisol > 1.8 μ g/dL (50 nmol/L) suggests autonomous cor - tisol secretion (ACS). • For individuals with mild autonomous cortisol se - cretion, measuring plasma metanephrine during adrenal venous sampling may help lateralize both aldosterone and cortisol secretion, although fur - ther research is needed. | 73 | 8 | 8 | 410fb87eddf750a6fa39cdf0c3aca36314691d53420aaac370ede795d432f565 |
It will also be important to measure early morning cortisol following adrenal surgery and prepare for a period of pos - sible glucocorticoid insufficiency. Question 9. Should spironolactone vs other mineralocorticoid receptor antagonists be used for primary aldosteronism– specific medical therapy? | 65 | 8 | 8 | 50462a0eea8821f6ded511df86fcffd6cc9a1ee629989a6a0a4d9d1825f25ba0 |
Recommendation 9 In individuals with primary aldosteronism (PA) receiv - ing PA-specific medical therapy, we suggest spirono - lactone over other mineralocorticoid receptor antagonists (MRAs) due to its low cost and wide - spread availability (2 | ⊕ OOO). | 65 | 8 | 8 | 39d411304e887558c5d584c919dea90c644d7bdafa2e64f29821a8ce5a0f6942 |
Technical remarks: • The recommendation is driven by the availability and low cost of spironolactone vs other MRAs; how - ever, all MRAs, when titrated to equivalent poten - cies, are anticipated to have similar efficacy in treating PA. | 54 | 8 | 8 | 0182bbf47445fd24cdf2e50932004c63269e146d4290a67cb47c68c0f2893567 |
MRAs with greater mineralocorticoid re - ceptor specificity and fewer androgen/progesterone receptor-mediated side effects may be preferred. • When initiating an MRA, consider hypertension severity for dosing and potential discontinuation of other antihypertensive medications ( Fig. | 60 | 8 | 8 | 392552f04773ce9eb4ee8df1daabe263a334b5f738641dee3015e877fcd3956a |
• Monitor potassium, renal function, renin (concen - tration or activity), and blood pressure response during follow-up to guide MRA dose titration. Question 10. Should epithelial sodium-channel inhibitors vs mineralocorticoid receptor antagonists (steroidal and nonsteroidal) be used for medical treatment of primary al... | 74 | 8 | 8 | 4ac50ccf2243cdcc9e38f674fae1e06f5be2b689165622cf9fedbfc465be9500 |
Recommendation 10 For individuals with primary aldosteronism (PA) re - ceiving PA-specific medical therapy, we suggest us - ing mineralocorticoid receptor antagonists (MRAs) rather than epithelial sodium-channel (ENaC) inhibi - tors (amiloride, triamterene) (2 | ⊕ OOO). | 79 | 8 | 8 | db502fde25b4b38958da79f88c4b6d16ace1ab78ecad02ecefd16af6b6cabc60 |
Technical remark: • The recommendation (see Fig. 3 ) does not apply to clinical conditions in which spironolactone is contra - indicated (eg, hyperkalemia, advanced renal impair - ment, or pregnancy) or if a non-spironolactone MRA were indicated for other non-PA indications (eg, heart failure). | 72 | 8 | 8 | db2bff426e742c44fabd9ae96ab1b1bdfa50d88f7855917e29ecd2a5392ba59e |
2460 The Journal of Clinical Endocrinology & Metabolism , 2025, Vol. 110, No. 9 Downloaded from https://academic.oup.com/jcem/article/110/9/2453/8196671 by University of Wisconsin System user on 20 February 2026 | 62 | 8 | 8 | feb152cab39243e15f3183a9b09c85f718bfba088bec486fbec4d8ae81737943 |
Figure 3. Initiating and following MRA therapy. This is a general guide and there is a wide range of inter-patient responsiveness to varying doses of MRA. The process of MRA initiation and titration is expected to be multi-step for many patients; each MRA adjustment is followed by an assessment of both BP and biochemic... | 81 | 9 | 9 | 230f55499ca7fbeec6caad74a1b90d651ef5ffe8f14229ceccc133f92b5c4ec3 |
The primary goal of therapy is control of BP. The secondary goal of therapy is achievement of normokalemia. 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 non-MRA antihypertensive drugs. | 65 | 9 | 9 | 7e7b21487e2bebff8f7c61035b28ad5aaf54bbb410196861840ac757892b857e |
Clinicians may start at a relatively low dose MRA (spironolactone 12.5-25 mg/d or eplerenone 25 mg daily or twice daily). Medically complex or frail individuals and those in whom MRA–drug interactions (eg, with an ACE inhibitor or ARB) are possible may need careful monitoring. | 71 | 9 | 9 | 2bdd651b26838f65d9fd25ccf9eb49a1e91ce1cefe3491a6d566b659341d5fde |
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). | 44 | 9 | 9 | 9e9de7a3c4f3e3ea8865db6e34d0f50a6589bf0ced364e218620219d9a5f6fbf |
All individuals should get routine measurement of serum electrolytes, renal function, and renin within 2 to 3 months of starting MRA therapy; more fre - quent serial measurements may be needed in those with prior severe hypokalemia or renal impairment. | 51 | 9 | 9 | 63106d5b813b558677cb4578c25e2f519e9108476cd45ece550f0c4f1309a640 |
Some panelists recommend enquiring about dietary sodium or measuring 24-hour urine sodium at baseline and periodically throughout follow-up as a means of tracking dietary salt restriction; a target of < 85.5 mmol/d sodium is recommended (representing < 5 g/d salt intake) ( 6 ). | 60 | 9 | 9 | 4e85f216a67861c041d70366141e4eb2ae6795d379596b1e1e43f60cc99552c4 |
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 ). Typical doses required to de-suppress renin are variable and likely higher than doses used as empiric add-on for resistant hypertension ( 29 ) ( 30 ); most indi... | 106 | 9 | 9 | 1799dc7af1ba978dae2c480e90ff28dad87c85131d766f3d38cc99c8848a7df8 |
Spironolactone may be increased in 25- to 50-mg increments, and eplerenone in 25- to 100-mg increments. With each MRA dose change, repeat elec - trolytes, renal function, and renin 2 to 3 months later is recommended. | 60 | 9 | 9 | 8ee45be7fadf7ea565c9b807caffdae49ae5cedcd8024567e3bdfa4ba05c0ac9 |
When possible, consider off-titration of other anti-hypertensives. Once renin is de-suppressed, and if further BP reduction is required, other non-MRA antihypertensives should be added or uptitrated. | 53 | 9 | 9 | ba9d473de25cad919adb29831c8788bff1cc9a21cf588abf4f334bfd768ac3e3 |
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. Normalization of serum potassium usually occurs, even with lower-dose MRAs, in the first 3 to 5 days, so it is reasonable to reduce or discontinue any potassium... | 88 | 9 | 9 | 88bc4c832bb14cf0f9853012c1968847391f560180830b462a77bdf62bb12ac4 |
Individuals who do require ongoing potassium supplementation require frequent careful monitoring of potassium. 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. | 46 | 9 | 9 | 390afcff40de21de50435d83802c6cd1e67e7721130ab45db8ef67cb9c74608d |
An ongoing high-salt diet is a very common reason for apparent nonresponse to MRA therapy. The glomerular filtration rate (GFR) may decrease in individuals with PA on introduction of PA-targeted medical therapy or with successive titration of MRA ( 32 , 33 ). | 61 | 9 | 9 | eb5da16193a0b656051f84d4a61abdacf1c5598e06536a9e1d3a6879417899a7 |
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. The natural history of an appropriate treatment-induced decrease in GFR is usually one of eventual long-term stability, anticipating a renal- sparing effect of effective MRA th... | 68 | 9 | 9 | d661624d898c2ac898e4fab2d1c2efdc69c53cf15c1ed5d3a9707005df4d70bf |
If renal function progressively declines, consider referring to nephrology and discontinuing ACE inhib - itors or ARBs. Gynecomastia from spironolactone is dose-related and may appear as early as 1 to 2 months into therapy but more commonly after ≥ 6 months of treat - ment. | 63 | 9 | 9 | 27c0f0b11a43955d21df0a43785b7588f81d809db22801609543e411f3a93009 |
In some cases (especially in younger males) a dose reduction to ≤ 50 mg per day resolves gynecomastia. 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). | 63 | 9 | 9 | bc44f0058a07bdaf6c8363e6537ad8d0f195fd2f70d97896e04b8a448142d33c |
This almost always allows com - plete resolution of the gynecomastia if it has not already progressed to advanced size. Routine follow-up after MRA dose optimization should generally consist of blood pressure monitoring, along with annual measures of potassium and kidney function. | 54 | 9 | 9 | dff7be9894bfa8a04a684d5b122a2faea0abfef659deeb1ce5656635808f00ae |
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