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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. | 40 | 9 | 9 | 7e7274adc2df10986445523de074975a3d30d615b3c7b74a30100a305b6a4c22 |
Routine repeat renin measures are not necessary unless re- entering the MRA titration algorithm due to incomplete BP/potassium control. The Journal of Clinical Endocrinology & Metabolism , 2025, Vol. 110, No. | 48 | 9 | 9 | eec1842fd9e1372eb8af56854a0338024a0d605b91f001466d56ec5959bd44f6 |
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Who Should be Screened for Primary Aldosteronism? Background Primary aldosteronism (PA) is the most common endo - crine cause of secondary hypertension with an estimated prevalence of 5% to 14% of individuals with hyperten - sion seen in primary care ( 34-36 ) and up to 30% in refer - ral centers ( 37-39 ). | 78 | 10 | 10 | 5dd5c77fe5ac07bdbcb8541f1c690a7e2f87a22a4dde4139e964e7176f55e792 |
PA is particularly prevalent in individuals with specific clinical characteristics or co - morbid conditions ( Table 3 ). 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 cardio - vascul... | 67 | 10 | 10 | de373bfff7e96fb1edc6f36e63859216785570e33abeb7c7784751c05d2f4564 |
Detection of PA allows the use of spe - cific treatments — such as mineralocorticoid receptor antagonists (MRAs), or adrenalectomy for those with lateral - izing disease — that can effectively control BP, correct hypo - kalemia, and reduce cardiovascular risk ( 7-9 ) Despite the potential benefits of treatment, PA rema... | 91 | 10 | 10 | 76b23061be3c82f3beed30db7e58523be1970e2dbda70cc9bf656bac040b4a46 |
Many individuals with PA, even those with high-risk features, such as resistant hypertension and hypokalemia ( 52 ), are never identified, leading to subopti - mal management of their hypertension and cardiovascular risk. | 44 | 10 | 10 | a75715036e12f753622fa4494c3133592851389696aaf5e6bf38a33bd9eb0d94 |
Expanding PA screening to all hypertensive individuals could increase the detection rate, allowing more individuals to benefit from targeted therapies and potentially reducing long-term cardiovascular risks. However, the benefits of widespread screening must be weighed against certain challenges. | 46 | 10 | 10 | bbed7351376bc9f6020e95e1b45cbfba91c90cdac63dcaa60c926110b56f9b14 |
The accuracy of screening tests, such as aldosterone concentration, renin concentration or activity, and the aldosterone to renin ratio (ARR), is influ - enced by various factors, including medication use, dietary so - dium intake, and test conditions. | 55 | 10 | 10 | a47b2a7b788f471d53c3efc37b275c326d47f7b833ba80c1be129e3d3aa4c783 |
False positives can occur, resulting in unnecessary aldosterone suppression testing or even inappropriate PA treatment in individuals without the condition. Access to diagnostic and subtyping tests and the availability of specialized treatments may also undermine the feasibility of universal screening unless alternativ... | 55 | 10 | 10 | d2bf85dc13be60c87051213e4cdc4b23cc3f26c34fe9465fbf69be2b1471820a |
Therefore, the guideline addresses the question of whether care with PA screening should be implemented for all individ - uals with hypertension. Question 1. Should care that includes primary aldosteron - ism screening be applied to all individuals with hyperten - sion, compared with care without screening? | 60 | 10 | 10 | 5692228c7e7cc4aaf85671943984ab9191f2d0749e54ca69b900a65d9ed69b09 |
Recommendation 1 In all individuals with hypertension, we suggest screening for primary aldosteronism (PA) (2 | ⊕⊕ OO). 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... | 77 | 10 | 10 | 2681ecaf6e9c8054080e0208399875205a1420d3c9120bdd54e42cead0ffc2c2 |
• 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 | 10 | 10 | d58bbec72c3ec9dfd4fd5b8355515d9a3d85a89306789c4be373961a31ed828f |
Potassium is also assessed—not for screening itself—but to aid in the accurate interpretation of aldosterone (refer to Question 3). Summary of the Evidence The meta-analysis results, a detailed summary of the evidence and Evidence to Decision (EtD) tables can be found online at: | 61 | 10 | 10 | 1371561f47763752445bfe62d4e07f6e001804593fcfd7c40774feb1eb238a95 |
https:/ /guidelines.gradepro.org/profile/goKsLjFSyDQ . Table 3. Prevalence of primary aldosteronism in different subgroups Setting Prevalence Reference Hypertension in Primary Care 5.9% (range, 3.2-14.0) ( 34 - 36 , 39 ) Hypertension in referral centers 7.2% (range, 0.7-21.9) ( 39 ) Hypertension in young adults (ages 1... | 272 | 10 | 10 | f531cabf8ad1db5ca5605671af02012b90a9aeb12984272ba90eb84f2f33048b |
DBP, diastolic blood pressure; SBP, systolic blood pressure. a Grades 1, 2, and 3 hypertension refer to the classification of the 2023 European Society of Hypertension guideline ( 48 ). 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 ≥ 1... | 111 | 10 | 10 | b3fa881b48c24eac76b0f9d96d21915d5735c46a80def5ee7fa85a8378be086d |
b If unexplained by structural heart disease and other conditions like hyperthyroidism. 2462 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 | 78 | 10 | 10 | da8487649b66b763c44a9d9aed56c095d4c77f2de1f20e38ba29e6939a46b227 |
Benefits and Harms The panel voted for the following patient-important outcomes for Question 1 decision making: 1) percent of individuals achiev - ing BP control, 2) number of antihypertensive agents, 3) dosage of antihypertensive agents, 4) systolic BP (SBP) level, 5) major ad - verse cardiovascular events (MACEs), 6)... | 126 | 11 | 11 | f22ed874809c29ae34a6ecbe7a426a132f3318cde54e1750b10ae5f5b17bf4d7 |
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. The authors reported that of 269 010 US veter - ans with apparent treatment-resistant hypertension, only 1.6% were tested for ... | 92 | 11 | 11 | 50c4dce6e33a5afeee76f60fed0d5e658d6d3eb3ea8d824aecb0319bcfbe9a9a |
Testing for PA was associated with a 4-fold higher likelihood of initi - ating treatment with an MRA. Individuals who underwent PA testing also had an average 1.47-mmHg lower SBP over time compared with those not tested. | 50 | 11 | 11 | 792bce4e7b0723b26836d53412f0e68fdacfebf7c64526ba8485818e7a2bb079 |
Certainty of evidence for the outcome of BP control is low due to the nonrandomized nature of the study and indirectness. The panel did not identify any head-to-head studies comparing screening vs no screening for the outcomes of interest. | 49 | 11 | 11 | 75aadcdb899987e18fb3340eb33bd449fcc434f8e744f678e2b55cd6957873a4 |
Due to the limited availability of studies directly evaluating the comparative effectiveness and potential harms of screen - ing, this recommendation relies on indirect evidence. The pan - el used a guideline screening framework that considers multiple factors required to justify screening ( 54 ). | 47 | 11 | 11 | 5038ae3c8621d7d44f50445ff2a1544f8ceedafe8cce6c466b9de98909ef354c |
The panel also adopted a framework based on Wilson and Jungner ’ s principles of screening ( 55 ). This framework, as relevant to screening for PA, is detailed in Table 4 . PA is recognized as an important health problem. | 46 | 11 | 11 | c67678152e9b658f35eab879ae2ed13fac76ed73a9ccb2b0702267baf3c67b55 |
It is com - mon, affecting 5% to 14% of hypertensive individuals in the primary care population and up to 30% in referral centers ( 34 , 38 , 35 , 36 ). Untreated PA confers a higher risk of cardio - vascular complications, with a meta-analysis of 31 studies showing an increased risk of stroke, coronary artery disease,... | 94 | 11 | 11 | f61bf13fd6d8e6201e6dc2a0faeb6ab4dee3d9835e3f6c9e92c1c88d113bc908 |
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 concentra - tion, especially in the presence of low renin concentration or activity, is associated with increased risk of hypertension and cardiovas... | 62 | 11 | 11 | a69b621aeba210c50a996c1727fb565a4156a5904b69df2e0afa30915c5dfaa9 |
For example, data from the Framingham Heart Study demonstrate that individuals with aldosterone levels in the higher quartiles of the normal distri - bution are more prone to develop hypertension or to have an increase in BP during the follow-up period than individuals with lower aldosterone levels ( 56 ). | 61 | 11 | 11 | e254fdd7099a3aa49ac455a01ba9a07931ca593dc3f01082d4892bb670dc1b7f |
Furthermore, higher aldos - terone levels predict the development of chronic kidney disease and microalbuminuria ( 57 ). 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 hypertensi... | 79 | 11 | 11 | fdeb082bc9a31f5800bee108345372c569c8eaf9eb68f0c35ab17ae3df82e30e |
Renin-independent aldos - teronism (with low renin), in contrast to renin-dependent aldosteronism, is associated with higher cardiovascular risk ( 62 ). The ARR in healthy individuals also correlates with vas - cular stiffness ( 63 ). | 56 | 11 | 11 | 0148dc87c71d932799a3979ad89f5ab10c10309c090cdac2164e12e38ea8d08f |
These data were replicated in a Canadian population ( 64 ), which showed that, independent of BP, a bio - chemical phenotype of subclinical PA is negatively associated with cardiovascular health, including greater arterial stiffness, Table 4. | 44 | 11 | 11 | 688756893281b22af2b08fcc9158c713113886d47ba9924c2813282f035a1a87 |
Evidence for the recommendation of primary aldosteronism screening Importance The condition should be an important health problem. PA is a frequent cause of secondary hypertension. PA, independent of blood pressure, is associated with increased mortality and morbidity if untreated. | 50 | 11 | 11 | f5d23aecae2521d0e496b15f2b0a904fbac74af6fc6570bca0409ee6e7d2ad56 |
Natural History The condition being screened for should have a natural history that is understood and a recognized latent period. Individuals with PA develop organ damage and cardiovascular events if left untreated. Difference in Management Individuals with a positive screening test would receive different care than th... | 54 | 11 | 11 | 588f5c82766a4b5258d47299166429df894fe725a98bbaaa4e56a3e0c286b28a |
Individuals with a positive screening test are candidates for PA-targeted therapy. Available Treatment Effective treatment should be available for the condition that improves outcomes if administered earlier than when the condition is clinically apparent. | 40 | 11 | 11 | 446bc14dcd5ebb2b072f00a0a287b4ed052a1cd53c9e5608ad5f3b1672ddf1d5 |
Specific medical therapies are available and effective. Also, adrenalectomy for lateralizing subtypes of PA is effective. PA-specific therapies reduce the rate of cardiovascular complications. Novel therapies are under investigation. | 40 | 11 | 11 | 0a829e503b6f174211a0748807b9d04bcdfcc11d4da9fc7305c1194b75fc1915 |
Difference in Outcomes Improvement in outcomes based on management according to screening results outweighs harms of screening. Individuals with PA display a significant benefit from targeted treatment, with the possibility of cure in those with surgically resectable lateralizing adrenal disease. | 51 | 11 | 11 | 2eeef7f882afca4f2bf4dff62d7313c093ff2fb26b546b275f78e2c4690a9448 |
Individuals with potentially false-positive results are not exposed to harm if treated with aldosterone-blocking drugs since they also proved effective in individuals with primary hypertension. Careful selection for individuals undergoing AVS should be made to avoid unnecessary invasive procedures. | 50 | 11 | 11 | 0f3c28a51ff8f4e6bf6ae3851dcac4ab09cd4f13112bf203e10a168142f83ec3 |
Harms associated with screening are minimal as we provide pathways for screening that involve no or minimal withdrawal of current antihypertensive medications. Accuracy Certainty of evidence for a sufficient accuracy of the test is high or moderate. Screening tests are sufficiently accurate. | 51 | 11 | 11 | 21c50219c9d9ab19d952be25154c5c79d8be65cf18f4520b1432164e7405c7c2 |
False-negative results may be observed in mild forms or may be caused by variability in aldosterone concentration; aldosterone suppression testing can help to confirm PA. Other Considerations Screening should be cost-effective, acceptable to individuals, and feasible to implement. | 53 | 11 | 11 | b9a6c7ae1dffb1d0afa7f6ae3607e4bdcf0bd2998ca062f04bab3c3888dce56f |
Screening for PA is cost-effective, convenient, and accepted by the individuals. Feasibility depends on collaboration between general practitioners, specialists, laboratories, and referral centers. The Journal of Clinical Endocrinology & Metabolism , 2025, Vol. 110, No. | 55 | 11 | 11 | 33a664c78288327f653a947f51a572bf0616b35357d79cdd4c8cd9fe47a8a56a |
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adverse cardiac remodeling, and incident hypertension. In the ARIC study ( 65 ), low renin and high aldosterone levels are as - sociated with cardiac structural and functional alterations. Even in adults as young as 27 years of age, aldosterone concen - trations or the ARR have been found to correlate with left ven - t... | 78 | 12 | 12 | 62543e6ca1c48b274ac1782d3f5dad0298addbb5f2e325c17948e8f12feeb93a |
Management is different if PA screening is incorporated, or not, into the care of individuals with hypertension. In the ab - sence 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 ). | 58 | 12 | 12 | 363ef64119cebe18d417db9fa8627373c5e9e91d2807dc80738798d32b871b05 |
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 1.5 million primary care patient encounters during a 16-year period ( 68 ). | 57 | 12 | 12 | c11f20377a00955732ae2984686d3c4f8e8d7aa4b04d637f1f8f37b55e1bf193 |
Similar rates of low detection have been observed in the United States and Europe ( 50 , 51 ). Without the screening blood test, PA is almost im - possible to diagnose due to the absence of specific symptoms and signs other than high BP. | 47 | 12 | 12 | a5083221b7e4a682d8a1eb7d70eac01fc902ae82de0ab0aa812e033414c1fa11 |
Lack of diagnosis or delayed Table 5. PA screening: ARR cut points according to aldosterone and renin assay and unit measurements Renin Aldosterone concentration measured by immunoassay Aldosterone concentration measured by LC-MS/MS ≥ 10 ng/dL ≥ 277 pmol/L ≥ 7.5 ng/dL ≥ 208 pmol/L Plasma renin activity ≤ 1 ng/mL/h > 20... | 198 | 12 | 12 | 83a347a6c96f27abb639fdceea3d1e726ee7bd78200d5e6430d7e297a286402e |
However, as with many diagnostic tests based on continuous variables, the sensitivity and specificity depend on the selected threshold. Aldosterone and renin levels are further influenced by individual variability, local laboratory assays, and other factors. | 44 | 12 | 12 | 4a8ca65b6809015d8e9dd698f473f96bb7e10c4fd71c08d63f2cad74a8f572c4 |
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. Therefore, results should be interpreted within the context of the patient’s pretest probability for primary aldosteronism (PA), along ... | 73 | 12 | 12 | cb1ef2eb38448522f747caddbc9c964a57bd9f8e106fd4542328a1e0213922c0 |
The AAR values are not bolded. Abbreviations: DRC, direct renin concentration; LC-MS/MS, liquid chromatography–tandem mass spectrometry. Table 6. | 42 | 12 | 12 | e4df3f91a7a0501181095ddaa905d69c60c4eaa3fae6ce69040ca2e53a50d336 |
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 ... | 315 | 12 | 12 | 61a604ebdd1474d731c669340b4da2c765250a50039ab1fdfe572136f2682ae6 |
If repeat is negative, then likely true negative If pretest probability is low, then likely true negative Likely true positive Proceed to algorithm ( Fig. 2 ) β -adrenergic blockers ACE inhibitors ARBs Dihydropyridine CCBs Centrally acting α 2 -agonists (clonidine, α -methyldopa) SGLT2 inhibitors 2 weeks before testing... | 83 | 12 | 12 | 5f2465565a034e0943fbbc15455a8b16272ed7c0fb9cf7f5341298f99954d953 |
ACE, angiotensin-converting enzyme; ARB, angiotensin II–receptor blocker; CCB, calcium-channel blocker; ENaC, epithelial sodium-channel, MRA, mineralocorticoid antagonist; SGLT2, sodium-glucose cotransporter 2. | 68 | 12 | 12 | a5d8343f709b9126c7ddf0d767cfdd0bd7e37bf21cda5fabed913b831a846d1b |
a Ideally individuals receiving hydralazine should also be administered a negative chronotropic agent such as verapamil slow release to avoid reflex tachycardia. 2464 The Journal of Clinical Endocrinology & Metabolism , 2025, Vol. 110, No. | 54 | 12 | 12 | b1a463d6922e91c296c61cbd99ad96791c27dc1bd890b21057600f94d43bccc9 |
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diagnosis of PA is associated with poor BP control, high bur - den of symptoms, and poor quality of life (QOL) ( 3 , 4 ) and re - sults in increased morbidity and mortality ( 1 , 2 , 7 , 69 ). Once diagnosed, PA has specific treatment that differs from that of primary hypertension. The source of excess aldosterone from... | 148 | 13 | 13 | 61162eb574255a334d2029d9c5c84d1daafec022b649a44fe09323abd88a4be3 |
Numerous studies demonstrate that spe - cific treatment is able to improve cardiovascular and renal out - comes in individuals with PA (see Question 2 ( 7-9 , 32 ). This highlights the importance of early detection of individuals with PA who can benefit from targeted medical or surgical treatment that would not be appl... | 100 | 13 | 13 | a4eb4a8d31c7aba2ee1200aeae556f7d6745110a56367ebecb106cbb23487126 |
It is also favored by primary care clinicians ( 73 ) and desired by patients ( 74 ). The screening test for PA has varying diagnostic accuracy, depending on the decision threshold adopted by individual centers. By the nature of screening, the threshold is usually set lower to permit high sensitivity at the expense of l... | 75 | 13 | 13 | 9c69371a1099392db67f789aa28731acb0160c4df744cee6b259a010836be9bd |
A false-positive 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. However, even if the individual is initiated on an MRA on the basis of a false-positive screening test, MRA treatment may still ... | 215 | 13 | 13 | 7aa18d285cbdf05028131410b0e8d61d51956bdddef0d8625a439affb32c0834 |
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 ). Evidence to Decision Factors As described in the Introduction, the panel also used the Evidence to Decision (EtD) framework for this and all subse - quent Questions, to cons... | 139 | 13 | 13 | 165e852c00f3ec7714115fcfe72a078f18e284d78a60c201f08ff2366653e862 |
However, downstream testing — such as aldosterone suppression tests, adrenal imaging, and adrenal vein sampling (AVS) — introduces significant additional costs and is not uni - versally available, particularly in resource-limited settings. While initial screening is affordable at the individual level, im - plementation... | 448 | 13 | 13 | 9b113f59d112fec8956a86ed1b92ecfd7526f7a4bb94b7d0917f597314d262f7 |
ENaC inhibitors (amiloride, triamterene), ARBs, ACE inhibitors, SGLT2 inhibitors Combined estrogen and progesterone-containing 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, β -adrenergic blockers, central α 2 -... | 381 | 13 | 13 | edb86e75bee80c72f271f418d4ec72e48cc9b98b49160a6c63a44b3e8791f4a9 |
panel judged the impact on equity as mixed, taking into ac - count pragmatic treatment pathways provided in Fig. 2 that permit targeted treatment for PA without extensive testing. The panel judged that acceptability of PA screening will vary among providers. | 46 | 14 | 14 | c86f00a3ee750d919ad2fcb4d4ddc693cc5cbd11f4e6dec418957709c1ba89a0 |
Primary care clinicians, in particular, may have lower acceptance due to limited awareness of PA, difficulties interpreting results in patients on interfering med - ications, and concerns about the complexity and availability of subtype testing. | 42 | 14 | 14 | 25f5efe2ce047d9e6fe619c127e47e8fb32f09e37dfc8d5aae7c4dd293b9b4c6 |
Some also view medication washout as burdensome or potentially risky. In contrast, screening is gen - erally well-accepted by patients, especially at the time of initial hypertension diagnosis. However, provider hesitancy could limit implementation, particularly in settings with high work - loads or limited specialist ... | 61 | 14 | 14 | dd68054d026c03b1433cdfe893714560210966d997ac438959eb8483d42fcb35 |
The panel judged that the feasibility of PA screening will vary by setting and stakeholder perspective. While screening relies on simple, widely available biochemical tests and is tech - nically feasible, implementation has remained low. | 41 | 14 | 14 | 2b63c4efc29eb27e3de370d7372e4f3a7475229eb7f0dd980017de1247ed2ff5 |
This is Table 8. | 5 | 14 | 14 | 7cae95a3fc55218385eee406a8870c388c8f232f71236568d81a7f60a6793199 |
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 ... | 450 | 14 | 14 | 4c819262183d02ce54449630c0ff637087aff67289ea1491a1aa6727448970cc |
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 (5.8 ng/dL) via LC-MS/MS assay makes PA unlikely Plasma aldosteron... | 221 | 14 | 14 | fba71dac275d7dfe02393c3994a07b41f2145914f6efdddda658f085324dde9c |
ACE, angiotensin-converting enzyme; ARB, angiotensin II–receptor blocker; IV, intravenous. 2466 The Journal of Clinical Endocrinology & Metabolism , 2025, Vol. 110, No. | 51 | 14 | 14 | bdb9ae440567da1549a8b3795d201105bf0f72722056e73fee124dd768d91221 |
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likely due more to the complexity of prior diagnostic algo - rithms than to challenges with performing the tests them - selves. The current guideline offers suggestions for more pragmatic and feasible approaches to PA testing and treat - ment ( Figs. | 48 | 15 | 15 | 5d416f37f1b0a0f3b72ef06c137b24d37c5fcddfc6c25af064c0f0963f1b74a4 |
1 - 3 ). Justification for the Recommendation The panel suggests PA screening for individuals with hyperten - sion based on the high prevalence of PA, its underdiagnosis, and the potential to reduce cardiovascular morbidity and mortal - ity through targeted treatment. | 53 | 15 | 15 | 538a06d4ce7892c9f843ce2ad43b18f9cf61bda2aee26e0e7972257991b11b80 |
However, this is a conditional recommendation, reflecting important limitations in the evi - dence base. The certainty of evidence for both benefits and harms is low, primarily due to reliance on indirect data and observational studies. | 43 | 15 | 15 | c30856f74fb482a5833883fb8d31ad7b00c02e4f1ac918ddbe24b745dcc35af2 |
While existing evidence suggests improved BP control and reduced long-term complications with screening, the mag - nitude of benefit remains uncertain. No direct comparative studies between screening and no screening were identified for critical clinical outcomes. | 42 | 15 | 15 | f84a618ab05f788d50ac1e3d48bba8d309ca35d3524b9cfb59380e8050454cb6 |
Despite these limitations, the panel judged that the potential benefits of early detection and specific treatment for PA likely outweigh potential harms, including false-positive results and unnecessary downstream testing. In making this decision, the panel placed high value on offering patients the opportunity for eva... | 84 | 15 | 15 | 8c1e4137213a201a37d500484eafb3df30ae38ab3e6eeea5b8bddd1dc8774dc2 |
The panel also acknowledged feasibility concerns, particular - ly the burden on healthcare systems and specialist services, espe - cially in primary care and resource-limited settings. Therefore, the recommendation emphasizes that implementation should be context-sensitive, depending on available resources, local ex - ... | 62 | 15 | 15 | 6e2960b2eafa927a088d3245846d614283c7b8459aabf545e61cb9403231930d |
It also underscores the need for additional guidance to help clinicians interpret and manage screening results, especially when interfering medica - tions are present. Ultimately, this conditional recommendation supports screening to improve PA detection and treatment but leaves room for adaptation based on local resou... | 56 | 15 | 15 | 01cc50bf5e3844a7d4c92c6b6e0c827f0e252262fe91dd05fd7ec279487e0402 |
The panel judged that, on balance, the likely benefits outweigh the harms but that the recommendation should be applied flexibly. Implementation Considerations This is a conditional recommendation, and its implementation will vary depending on contextual factors at both the health - care system and clinician-patient le... | 56 | 15 | 15 | ad989305bd9dbabad13d591c9ff797a5ca366d643c4b2a21bc27536b83576481 |
Health system–level considerations When healthcare systems consider implementing this condi - tional recommendation, they must weigh several intercon - nected factors that will shape feasibility, sustainability, and equity. Expanded PA screening may improve detection but will also introduce system-level demands that va... | 65 | 15 | 15 | dfff4396131299dfb946629122761c761d5cdf192201df211d60b03e45c8e87a |
Key considerations include: Resource availability. 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. | 49 | 15 | 15 | 1e6d90e1679e6422e0e4562e1bf5e63878a956086812c1ad425dd4d76dbfe170 |
In settings where advanced diagnostics or specialist services are limited, al - ternative approaches — such as empiric MRA therapy following a positive screening result — may be appropriate. Table 9. Key indices and cutoffs for adrenal vein sampling interpretation AVS index Index formula Cutoff values Diagnostic signif... | 226 | 15 | 15 | 5292342b82cf352e94c4b3b47314adedb1c6b1113dee1715d79b0219018f97ff |
AV, adrenal vein; highAV, adrenal vein measurement from the dominant adrenal; IVC, inferior vena cava; lowAV, adrenal vein measurement from the nondominant adrenal gland. | 44 | 15 | 15 | b49af2629f94c772e9640c932dab1d02ab1b9cc99e633aa7149eefc4a5fb1378 |
Table 10. Comparisons of MRA and ENaC inhibitors a Drug Typical starting dose in PA Possible maximum dose in PA b Usual cost Spironolactone 12.5-25 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 m... | 136 | 15 | 15 | da3e8cd525bddba0ae6a9a40e6d850abcb290267d042f7219115a7c1eee80fd8 |
b Specialist consultation recommended if doses above these ranges appear to be necessary. c Data are very limited in PA individuals. d Often supplied as combination with hydrochlorothiazide. The Journal of Clinical Endocrinology & Metabolism , 2025, Vol. 110, No. | 55 | 15 | 15 | 82e9c982836c1b882502772661e276dc035f7c1d3446edf6a510da7a23cf222a |
9 2467 Downloaded from https://academic.oup.com/jcem/article/110/9/2453/8196671 by University of Wisconsin System user on 20 February 2026 | 42 | 15 | 15 | e8e11f785fa281d050c5634348ab021b6fc714f45ea43efb4872f8dd22a7eb7f |
Infrastructure and workflow integration. The ability to inte - grate PA screening into existing hypertension care pathways will depend on clinical workflow structures and system-level coordination between primary care and specialty services. This includes managing referrals, follow-up testing, and treat - ment decision... | 79 | 16 | 16 | 0fd2ee117843dbc75c87111282c182a5d7d8abfda8a7df9dd02f30c855137543 |
Equity concerns are particularly relevant in rural and underserved regions, where infrastructure may be lacking and specialist access is limited. Mitigating strategies could include developing regional refer - ral hubs, streamlining diagnostic algorithms, or creating context-sensitive care pathways that balance feasibi... | 55 | 16 | 16 | b8e8b9ede20109540a8ffb175f02e3accd25c61767b9a3aa8b5b1921d9e56367 |
Provider training and system support. Successful implemen - tation requires investment in education for primary care clini - cians and other front-line providers on PA screening protocols, including management of interfering medications and appropriate referral thresholds. | 47 | 16 | 16 | f32983a8ec9c195d5e10063d6c32099c162ca51aa1a549862915a7a00362828a |
Clinician- and patient-level considerations and implementation tools At the clinician and patient level, implementation is shaped by knowledge, attitudes, and available decision-support tools. Clinicians may be hesitant to adopt screening due to limited familiarity with PA, perceived testing complexity, or concerns abo... | 72 | 16 | 16 | 4f6657680709f1cb6c1de57660a413280f881dab6dd46f6e52cea9b14a3e01db |
To address this, the guideline provides practical tools — including Figs. 1 and 2 — to stream - line clinical decision making, guide result interpretation, and clarify pathways for management or referral based on patient characteristics and available resources. | 45 | 16 | 16 | 0e6ea77b554062dfa2144e9e631d0f22dd54abc0c8fcf2e49024bfac9dac02bb |
Additional implementation considerations include: • Some panel members consider every hypertensive individ - ual with low renin levels as affected by PA. 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 sa... | 100 | 16 | 16 | 9390dfd7c664d782e78a0b6bf5919e34978ee5be3a29c63e27a449d9c7374489 |
• The recommendation is applicable to individuals older than age 16 years. Pediatric individuals should be consid - ered to have a positive screening test at an ARR cutoff lower than for adults ( 78 , 79 ). | 43 | 16 | 16 | fe2f976ee1f615ec2c8bf8fdf90805560a4030edd9361f8cc1df1c34b9dbc40d |
The interpretation of aldos - terone and renin levels and the ARR and subsequent man - agement is also different in pregnant individuals due to pregnancy-related changes in the renin – angiotensin – al - dosterone system (RAAS) ( 80 , 81 ). | 59 | 16 | 16 | aae6316e01cbc06fc80fb5eaff0c3d15d32173d6b2398838d4c0ee23df9711f1 |
Individuals with con - comitant heart failure may have unsuppressed renin levels, and diagnosis requires expert input. Elderly pa - tients with hypertension and patients with concomitant renal failure are more likely to have a low renin and in - creased ARR. | 57 | 16 | 16 | c895c8c76328093c40d21e567a16ad95c2f720575da22109be6fbfbad495cad5 |
The approach for subsequent investigations or pragmatic therapy with MRA should be weighed in in - dividual evaluation. • Screening tests should be performed by primary care clini - cians or by specialists in an outpatient setting. | 44 | 16 | 16 | 30bdc53a2f0e0ac51af7d16dd212e31ed459f17f11acffa18aea160084f55951 |
Referral to specialized centers should be considered for aldosterone suppression testing, and, if positive, further subtyping to differentiate lateralizing from bilateral forms of PA. Research Considerations Current gaps in knowledge call for further research in the fol - lowing areas: | 53 | 16 | 16 | 7a542dbe1297aacd1c30e51df7755af9970532a5b94562ac8b06626ef2fda1a6 |
• Determining the benefit of MRA treatment (vs other non - specific antihypertensive treatments) in individuals with an increased ARR but a negative aldosterone suppression test • Determining the efficacy of nonsteroidal MRAs and aldos - terone synthase inhibitors compared with spironolactone in individuals with PA and... | 212 | 16 | 16 | 069d234aa40897ecc3de2c1293678921a92b3c516449ce00d8697e6242fa644a |
Specific vs Nonspecific Therapies Background Specific therapies directed against aldosterone excess are available: treatment with mineralocorticoid receptor antago - nists (MRAs) and, if appropriate, unilateral adrenalectomy ( 84 , 85 ). | 52 | 16 | 16 | 70abc9a0977d39e8a5d6e3742c4f6984bc293fbdbe6e79b211cc6e004bc8a288 |
If those therapies result in better outcomes than non - specific antihypertensive therapy, encouraging their imple - mentation among hypertensive individuals with PA is appropriate. Question 2. Should primary aldosteronism–specific therapy (medical or surgical) vs nonspecific antihypertensive ther - apy be used in indi... | 75 | 16 | 16 | a570ee040c444328f5b74268fd0aa61ec8dd89d61b6612c70517e6398980632b |
Recommendation 2 In individuals with hypertension and primary aldos - teronism (PA), we suggest PA-specific therapy (med - ical or surgical) (2 | ⊕⊕ OO). | 45 | 16 | 16 | 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 MRAs should be considered preferable over non - specific antihypertensive therapy. | 54 | 16 | 16 | 65df59607bf895a932455e6f3b26c29adfdaff5f567fa004d6aabc100420d4aa |
• In individuals with lateralizing PA who are surgical candidates and desire surgery, unilateral adrena - lectomy should be considered preferable over nonspecific antihypertensive therapy. 2468 The Journal of Clinical Endocrinology & Metabolism , 2025, Vol. 110, No. | 57 | 16 | 16 | d6daefba20d130d7852c939712749f1da08710f009d3d0bfac785069300b2231 |
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