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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 https:/ /guidelines.gradepro.org/profile/LGYDlKeCN6A . | 54 | 17 | 17 | a356dbbaab61ef67f8e266f642f1606a3885b53195f0447fbfb1b293da20849a |
Benefits and Harms The panel voted for the following patient-important outcomes for Question 2 decision making: 1) percent of individuals achieving blood pressure (BP) control, 2) number of antihy - pertensive agents, 3) dosage of antihypertensive agents, 4) sys - tolic BP (SBP) level, 5) major adverse cardiovascular e... | 124 | 17 | 17 | 2834f1338d917afe55c7f696bec9c100f0896c48cb3393754c51f6d7910b0437 |
Our systematic review yielded only 2 studies, both of which were observational in nature. One ( 4 ) showed that (a) all indi - viduals who underwent unilateral adrenalectomy displayed complete biochemical resolution of PA at 6-month follow-up assessment; (b) individuals receiving an MRA showed a reduc - tion of SBP and... | 128 | 17 | 17 | 723e14c00939c757d796bec80cb511264f11a3a813203b4c5470b3b04226bcc3 |
Due to the limited availability of studies directly evaluating the comparative effectiveness and potential harms of PA-specific treatment vs nonspecific hypertension management, this recom - mendation also relies on indirect evidence. This indirect evidence derived from noncomparative observational studies. | 51 | 17 | 17 | b86decd9df761eb13ce1259e2590b285f7ca259f5438f7180e8927edde80c2cb |
Individuals with PA who are not receiving PA-specific therapy demonstrate higher rates of cardiovascular, cerebrovascular, and renal com - plications than do individuals with primary hypertension and an otherwise similar risk profile ( 1 , 2 ). | 46 | 17 | 17 | 01539a10db24d36fdc717cf1643c0d6f0744228d68034e176b5f9a1fbc180c3c |
This excess risk is abro - gated, and quality of life (QOL) improved following the institu - tion of PA-specific medical or surgical treatment ( 7 , 86 ). Individuals with PA who undergo surgery demonstrate a lower rate of cardiovascular and cerebrovascular complications than do matched individuals (based on BP and car... | 75 | 17 | 17 | a5311fddfde7d715e200d52444a2df36aecb453a4df2f5d64af74f7c0a352f63 |
Individuals with bilateral PA undergoing sufficient MRA therapy to unsuppress renin, dis - play a similar (rather than higher) risk to matched individuals with primary hypertension, whereas individuals treated with MRA therapy in doses that are insufficient to unsuppress renin still display increased risk ( 7 ). | 60 | 17 | 17 | 64c88d03c0d9e692f6ea89bdc1dc763871ea4c29d8de2ba9f6bb90d0f61e4150 |
PA-specific treatment is associated with significant BP re - duction ( 7 , 86 ), which, in turn, is expected to result in a re - duced rate of cerebrovascular, cardiovascular, and renal events. | 46 | 17 | 17 | d0999eadc18c5fa8496e7ef82831c5dda4142fce06bc3fa8bc3fd91762813fa5 |
Furthermore, individuals with PA display lower rates of adverse events after diagnosis and initiation of PA-specific treatment than before diagnosis when the treatment is with general antihypertensive drugs ( 87 , 88 ). In summary, this indirect evidence shows that institution of specific treatment (medical or surgical... | 72 | 17 | 17 | 5324c19a209298b2996c68a2d8692b206da3a3f0e677a0d4621a7bc017bb9560 |
BP normalization occurs in a significant proportion of those who undergo surgery for lateralizing forms of PA ( 89 ). Furthermore, therapies (medical or surgical) that directly target the increased al - dosterone in PA reduce the excess cardiovascular, cerebrovascu - lar, and renal complications associated with PA. | 61 | 17 | 17 | 2806b17da6afe88f550a313eb93e4c540e019214a56f27554f470035f0c47a95 |
Spironolactone ’ s dose-dependent side effects (including gyne - comastia, erectile dysfunction, and menstrual irregularities) limit the efficacy and tolerability of this medication in PA. | 42 | 17 | 17 | 686ec4ebf28f5622082420134497793eddc6d645cdbf2ca11249bb8600876022 |
However, newer MRAs, such as eplerenone, have a much lower side effect profile (see Recommendation 9). Surgical therapy re - quires skilled surgeons and adequate postsurgical care to minim - ize surgical complications. | 48 | 17 | 17 | 6d118c6933fef2ba4feedfde43fba7437eb99935034187c71f4861e1df000a3e |
Evidence to Decision Factors • Costs of medical therapy are minor (in the case of spirono - lactone) to moderate depending on the medication used, whereas costs of surgical therapy vary. • Three health economic studies in Japan, Australia, and China demonstrated cost-effectiveness of screening for PA in the general hyp... | 66 | 17 | 17 | e8396f5fa201220357597aac860093fdf6ac137971c5469e5cd2dfaaf333dee1 |
Cost-effectiveness was mainly due to a decrease in lifelong complications and their associated costs in individuals with PA who re - ceived PA-specific therapy compared with those who did not receive therapies targeting PA ( 70-72 ). | 45 | 17 | 17 | b1ec7b7b26550b8ca5cdf824e1be69444c8a3c7d8879763d1823baaf5334c865 |
• Surgical therapy requires skilled surgeons and adequate postsurgical care and has economic consequences for individuals. • Medical therapy requires individualized titration and sur - veillance through regular follow-up visits. In areas where these resources are available, the intervention should be feasible. | 53 | 17 | 17 | 762a7e0876a8239b4379589caa3414368263be4dbd0cf1df2355a649879e53c4 |
• Specific medical or surgical treatment of PA should be ac - cepted by individuals since it represents targeted therapy, improved hypertension control (and sometimes cure), im - proved QOL, and a reduction in the complications associ - ated with PA. | 50 | 17 | 17 | d2440c80c240fd3c0838f1eb8537b2e5ac38cf737826f2f2f09713960c050fe6 |
• While PA-specific therapy is likely to be acceptable to pri - mary care clinicians, the steps required to identify individ - uals with PA who are candidates for specific surgical or medical treatment may reduce acceptance (and, hence, up - take) because of: | 55 | 17 | 17 | 79cceda27862b530a3e7dede3b947e8b9a08bcbaf684a0bd0379e1934ad4d581 |
lack of knowledge of prevalence and complications of PA; 2. lack of familiarity with implementing and interpreting screening tests; 3. lack of familiarity with using MRAs; and 4. costly, invasive, and challenging procedures associated with subtype diagnosis (lateralizing vs bilateral adrenal aldosterone production) for... | 70 | 17 | 17 | c9ddaa104caf8a88f06060fd550e61b8c79e95c114ff5781aa5f912a20e858dc |
• Finally, the diagnosis of PA and treatment with MRA should be affordable in most clinical settings. Subtype diagnosis, especially when using adrenal vein sampling (AVS), and access to surgical intervention may be limited in some settings. | 47 | 17 | 17 | e7b09da3094417df94bebaf07e0090ef523f97ebeb557ab894e97c7109025f04 |
After years of implementation with high fidelity, equity will probably be increased. Justification for the Recommendation Aldosterone excess has adverse cardiovascular and renal effects that go above and beyond the effects of hypertension, leading to a higher rate of cardiovascular and renal complications in indi - vid... | 72 | 17 | 17 | da39cd658cee1761eabb7d12f8176898103f9dd6c57fc3065c0b204fc34dcc46 |
Unilateral adrenalectomy in individuals with lateralizing forms of PA often leads to cure of hypertension, and surgically treated individuals demonstrate a lower rate of cardio- and cerebrovascular complications than do matched (for BP and cardiovascular risk profile) individuals with primary hypertension. | 54 | 17 | 17 | cd10b45a9de4bb0ebd8a801ac1baadb0acff58e46bf8dcfe325c84f26b92ddb1 |
Individuals with PA treated with MRAs in sufficient doses to unsuppress renin demonstrate a similar (rather than higher) risk to matched individuals with pri - mary hypertension. While the certainty of evidence is low, indir - ect data from noncomparative cohorts support the intervention, The Journal of Clinical Endocr... | 75 | 17 | 17 | a433acd764e8a440c6c6ab994c9ff00e5824536bb0aa6f831ceb1be8245ad7e9 |
110, No. 9 2469 Downloaded from https://academic.oup.com/jcem/article/110/9/2453/8196671 by University of Wisconsin System user on 20 February 2026 | 46 | 17 | 17 | 91835c40a1d339a40d79d14167a0850fc2b83d48b2294533f66766dea59ec75c |
as the benefits observed with all therapies for PA are likely to outweigh the associated harms. The panel also considered the economic implications of PA-specific therapies. While medical therapy has negligible costs, surgical treatment is associated with higher and variable costs depending on the country and health ca... | 281 | 18 | 18 | d719863b37f755eb4e2aae46f2f49a00611637877525e5f36669b8f1513383ff |
Research Considerations Current gaps in knowledge call for further research in the fol - lowing areas: • Assessing health equity after implementation of this recommendation • Assessing efficacy and safety of newer nonsteroidal MRAs and aldosterone synthase inhibitors in the medical treat - ment of PA and developing new... | 306 | 18 | 18 | 9bdb4e1a5b68a110415e1eb181d140f5c0a314e07f4fdc0b3a8b6db1bc9791cc |
This method may be more sensitive than relying solely on hypokalemia, as hypo - kalemia is present in only a minority of PA individuals (9%-37%), and many individuals with PA have normal potas - sium levels ( 90 ). Aldosterone and renin testing can identify normokalemic individuals with PA, expanding detection to a bro... | 348 | 18 | 18 | c6c5da43979150a8ba4873096ae0c290dd3a89d9e5e823563b004b6874c8013e |
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. Potassium should be measured alongside renin and aldosterone— not for screen ... | 300 | 18 | 18 | ec1bfb80dedded74790ab5c09328f27c1c3758eceb01f393440fad641fa67c2a |
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 immuno - assay or ≥ 7.5 ng/dL ( ≥ 208 pmol/L) when meas - ured by liquid chromatography–tandem mass spectrometry (LC-MS/MS) 2. | 107 | 19 | 19 | 173d0d7654d0b7406c35e2eac718a79ed5ddd2b8f190c7094e74ffc7e58b010b |
Elevated aldosterone to renin ratio (ARR): indi - cative 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 indica - tive of PA is about 25% lower when aldosterone is measured by LC-MS/MS) ( Fig. | 110 | 19 | 19 | 900fa82f6a697d5dfdef908baf41be4d08e180b9c48cd126fb14ed8eac29dd4f |
1 and Table 5 show 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. | 60 | 19 | 19 | a2085468391323eb450b53b04019640a2dc33426a8af5a39dcb07ecf074935ed |
Aldosterone and renin levels are further influenced by individual variability, local la - boratory assays, and other factors. Where pos - sible, clinicians should rely on local laboratory cut points, as assays may vary. | 48 | 19 | 19 | d28e1d3d916edc301b653541145bcaa7474e5ef358ce9d0eeadf77518d9ec9e1 |
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 pa - tient’s pretest probability for PA, along with poten - tial interfering medications and conditions. | 55 | 19 | 19 | 8b40a75ef0ccda792d156a59cdd73bc0cb9443aec225d1b74dc284d49265f714 |
• 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 medications), the test should be repeated on a different day, pref - erably after correcting hypokalemia (where pre - sent) and withdrawing interfering medications if it is saf... | 160 | 19 | 19 | 65edf2b04cf544b8e3378d048268129f625b61b79325c0cf5651054dae2ff3d3 |
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 | 19 | 19 | ccb330deddfa1246fab2137c9d87ecef50173c8b0754f964e4402dff21e566c0 |
During collection, avoid fist clenching, wait at least 5 sec - onds after tourniquet release (if used) to achieve insertion of needle, and ensure separation of plas - ma from cells within 30 minutes of collection. | 48 | 19 | 19 | be84b08e6246e9c8fa89975f7c97e0f0d8a153180bd6a6363756b81ebac1173a |
• 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 renin is suppressed with aldosterone of 5 to 10 ng/dL (138 to 277 pmol/L) by immunoassay, the test should be repeated on a different day. | 76 | 19 | 19 | a99c199acb147a6f5bd955552b9840efc7f289138869efe0bebdf64af9405a95 |
• If the individual’s initial screen is positive, but they are receiving medications (eg, β -adrenergic block - ers 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 week... | 82 | 19 | 19 | 32971f19ac23c08f01d00e6c7c97418ff7dd108a44eede0ce58d867571275bef |
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 | 19 | 19 | 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 | 19 | 19 | 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 | 19 | 19 | 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 Summary of the Evidence The meta-analysis results, a detailed summary of the evidence and Evidence to Decision (EtD) ... | 106 | 19 | 19 | 102597128c546e801a62df180c898f1ed39328c8baee9f7d6521349c30267781 |
Benefits and Harms The panel voted for the following patient-important outcomes for Question 3 decision making: 1) accuracy of PA detection, 2) detection of lateralizing PA, and 3) adverse events. | 42 | 19 | 19 | 7bf92f9153f278bfdb4cae0bca2db76d3699596ec8fe84bd46acb169d5877e1d |
The systematic review found no studies that directly com - pared detection rates for PA among individuals screened by serum or plasma potassium levels vs those screened by meas - uring serum/plasma aldosterone and renin. | 44 | 19 | 19 | ffc24a7a5ef858bb0c2d228a35530aef953305104c54cf37da39e6d7085dc358 |
Therefore, we relied on indirect evidence on the frequency and accuracy of PA detection from observational studies among those with hypertension and hypokalemia vs hypertension and normokalemia. In a retrospective evaluation of the diagno - sis of PA from 5 continents, after the widespread use of the ARR as a screening... | 83 | 19 | 19 | f115ab1c66a47aa8b24454faa010b49d247dae6f9240955830773fcdf69ced41 |
Only be - tween 9% and 37% of individuals had hypokalemia. Three other prospective studies totaling 5797 individuals re - ferred to hypertension centers or from primary care settings reported that only 25% to 30% of those with confirmed PA had hypokalemia ( 34 , 37 , 91 ). | 63 | 19 | 19 | 07b0aadba35060217c7fc4df9e441f7070d735bccbba92cf6274dc118e0f6bcb |
The ARR was effective at screening for PA, and most cases were ultimately diagnosed with bilateral PA. The presence of hypokalemia is associated with more severe forms of PA and is more common in the lat - eralizing subtype. | 49 | 19 | 19 | eeb6e7734bc14f99854e620db67d61628a63620547241ea6f3a0c4ffbbe54274 |
Nevertheless, in a study of 95 individuals with lateralizing PA, more than 90% had suppressed renin preoperatively ( 92 ). In contrast, 62% to 67% had hypokal - emia requiring potassium supplementation preoperatively, suggesting that relying on hypokalemia to detect PA would miss a substantial percentage of individuals... | 74 | 19 | 19 | be3d6703ae7ca189a76c6a940e0e0ce3a0a8cb0fda3f1b7a48d6abf86b86fa7f |
The Journal of Clinical Endocrinology & Metabolism , 2025, Vol. 110, No. 9 2471 Downloaded from https://academic.oup.com/jcem/article/110/9/2453/8196671 by University of Wisconsin System user on 20 February 2026 | 62 | 19 | 19 | 456a8f714cb83fb3b428d780aced61e80808f3dd368fa779fd3391a1f1a1643c |
Although the evidence demonstrated that a large proportion of individuals with PA do not have hypokalemia, and thus the ARR would be more sensitive than the presence of hypokal - emia, these data were indirect and were mostly derived from selected populations of individuals referred to hypertension centers. | 58 | 20 | 20 | d7f4c6d1bcd026555c65f04005524894041147330b1a61c1b723a11b2f406c6d |
Therefore, the level of certainty was low. In addition to increasing case detection, the ability of the ARR to limit false positives and negatives was another import - ant consideration. The accuracy of detection of PA using ARR has inherent variability as assays, screening conditions, and pa - tient populations are he... | 79 | 20 | 20 | aa9c30f2dfeb106f2c20d862e0df909323f508c97938c579158b220f25789613 |
A meta-analysis of 9 studies (974 individuals) determined that the sensitivity and specificity of the aldosterone to PRA and aldosterone to DRC ratios were reasonable and improved when interfering medications were withdrawn ( 93 ). | 46 | 20 | 20 | ddf6286c0d2b07d92d311f92dc011804af8b76e94660d20da5f54febd28177ce |
Regarding false negatives, in a study of 216 in - dividuals with PA with at least 2 aldosterone levels drawn (MRAs were withdrawn prior to testing, but other interfering medications permitted), a lower aldosterone concentration cut point of 10 ng/dL was associated with false-negative rates for PA screening of 14.3% for... | 92 | 20 | 20 | 73822c7de2bb5bef238ba2b4527e0c8bb3c155ba1a9366eeb9104ed5905c892d |
Although one meta-analysis ( 95 ) demonstrated good overall ac - curacy, significant variability precludes a single standard cutoff for detecting PA, and false negatives may result. Evidence to Decision Factors • The GDP considered that measuring aldosterone and re - nin has low cost and resource implications, making t... | 68 | 20 | 20 | d7d0199e179991d461bab0cab8350d5015b30cc91483ca1e93dd42873860262d |
• Cost studies across multiple countries indicate low cost of the aldosterone, renin, and potassium measurements. • Three health economic studies in Japan, Australia, and China demonstrated cost-effectiveness of screening for PA in the general hypertensive population, mainly due to reduced costs of lifelong complicatio... | 71 | 20 | 20 | 195147b3df2d1f2a486fc4359082b6e9ab0a2aed5d13a19641975879cceb1f77 |
• The GDP expects that measuring aldosterone and renin should not have a significant impact on health equity, with the caveat that current access to PA screening and to specialists in PA to interpret findings for manage - ment varies. | 45 | 20 | 20 | 99d3f8fc75eba52c14c94223081269eef7d7fa34f7fee7482d973a40ca117dc8 |
• Although not well studied, available evidence suggests that those living in rural areas and far from tertiary care centers are less likely to be screened with aldosterone and renin ( 51 , 96 ). | 40 | 20 | 20 | fe651bdf28251aa015dfa01b814536e976dd593946a39491bea0898ca12c6699 |
With increased clinician and public awareness, testing should increase in these areas. • A significant barrier to screening is the lack of feasibility of aldosterone and renin testing by clinicians. Complex test - ing requirements, in particular withdrawal of interfering medications prior to testing and selecting speci... | 75 | 20 | 20 | 0da733d5940af28ddb50d1568739eae2378d7f1378db7a61175d23970cac017e |
Although withdrawing interfering medications is associated with more consistent and increased accuracy of the ARR, several studies indicated that the ARR re - tained reasonable accuracy with minimal withdrawal or no withdrawal of interfering medications ( 98 , 99 ). | 44 | 20 | 20 | 5fb3a932bf4836196ebfb98a3be07e2bc413c1a0129c42df2a9a3f694d68ea1b |
• The GDP considered that screening for PA in individuals with newly diagnosed hypertension with an estimated prevalence of PA of 2% to 6% prior to medication initi - ation would be feasible, facilitate widespread screening, and limit false negatives or positives. | 48 | 20 | 20 | 177998048dbab35d79addcc69ed46b22cb0a3b6251822deb978f16da71e66571 |
• As described in technical remarks, Fig. 1 , and Tables 5 and 6 , the GDP created a pathway for clinicians to test individuals on antihypertensive medications with minimal or no withdrawal of interfering medications. | 42 | 20 | 20 | 8995330ca034248b6229144b6e7ae5c435e5de9b6cf5d77751c4c880a3b0f9ad |
Justification for the Recommendation Screening with serum/plasma aldosterone and renin was se - lected over hypokalemia as the global screening tool for de - tecting PA based on indirect evidence that PA is more common than previously appreciated and that most individu - als with PA do not have hypokalemia. | 72 | 20 | 20 | 6b1eabd09edb38b00dac707f8eb0f4674a661cd3d65cf08310c96c1ca0feb5b3 |
Limiting screening to individuals with hypokalemia would miss many cases requir - ing PA-specific therapy, some with potential for cure, and they would remain at increased risk of cardiovascular and renal events. | 42 | 20 | 20 | 3e7983c971c13913546c6664c06b1ae8cf3a6dc5380bb56a638deb5ccde8e348 |
However, screening with serum/plasma aldosterone and renin has notable limitations. The accuracy is variable and depends on assay type; can be influenced by individual so - dium intake/volume status, medications ( Tables 6 and 7 ), and other factors; and has inherent intra-individual variability. | 61 | 20 | 20 | c64168c6bfa09a259029a1bfd7e4c726634a47529ca705f32d3105ce055f70b6 |
Despite these limitations, it is a more sensitive screening tool than hypokalemia, has reasonable accuracy overall with or without interfering medications, and is widely available across regions at low cost. Given the poor uptake of screening for PA and missed op - portunity to provide targeted treatment for individual... | 81 | 20 | 20 | 02a494bec08ce474ebc66c39970c6f9ba604c138b598642a73b82b9b3e43acae |
Screening with aldosterone and renin in individuals with newly diagnosed hypertension prior to medication start is highly feasible with a more straightforward interpretation. Withdrawing a minimum set of interfering medications or not withdrawing them are also screening options for individ - uals on antihypertensive th... | 79 | 20 | 20 | de7755f8a76daa0cd045aacb44988ac0acc56fe281297fa7bb9b5709f4a68867 |
Other approaches for screening include only screening renin or measuring 24-hour urinary excretion of aldosterone. However, these strategies do not have sufficient evidence or cost-effectiveness data to justify their use for widespread screening. | 45 | 20 | 20 | 097c33155e28c87f923b258b0c96aaaca9ee8904c9c92aa25f24d72068dcd398 |
Also, some individuals with low renin do not have PA (ie, those with high sodium diet or Liddle syndrome); thus, to be diagnosed with PA, individuals should have both a suppressed renin and a nonsuppressed aldosterone. | 50 | 20 | 20 | 550eebabe30e87f7da2b5f44dcd6ea3decf3b3872863b6528f2c45b0e1ba6e5b |
Implementation Considerations Given that case detection is currently so low ( 67 ), and detect - ing cases of PA would lead to targeted therapy that would im - prove BP control and cardiovascular morbidity, and cure hypertension in some cases, high priority was given to increas - ing the sensitivity of case detection w... | 67 | 20 | 20 | 5b7b3473bbfedb79c2b522efd4982689bd46b581f2195fa8551a966641b62c57 |
Research Considerations Current gaps in knowledge call for further research in the fol - lowing areas: • Conducting prospective studies to refine the thresholds for the ARR and absolute aldosterone concentration across diverse patient populations and laboratory assays, par - ticularly those using LC-MS/MS for aldostero... | 81 | 20 | 20 | 21c020b1945af70a7c763e28dbe483abfb8ae2db073d700b1b61767a2d4e04cc |
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 | 44 | 20 | 20 | 838dd5eb379613452959448b60e11bc1b5cf46655c5056a0432c7ee39628472d |
• Investigating novel or other methods of screening for PA, including development of new biomarkers (see Question 4) and assessing 24-hour urine aldosterone • Investigating the impact of medication withdrawal proto - cols on false-positive and false-negative rates and develop - ing standardized approaches for testing u... | 212 | 21 | 21 | a7ce6c8343f8e2bbffa7555cd8684347b42da86131ab4075d001f513285076e6 |
It is also unclear whether this additional step has any direct impact on important clinical outcomes, such as im - proved BP control or reduced cardiovascular risk, after treat - ment with either medical or surgical interventions for PA, and prediction of lateralizing PA. | 49 | 21 | 21 | 643b65ac2e7258f5048edd2e0d2240515a9c1c39177bf0abbca37ff7240a5bb5 |
Given these uncertainties, the guideline addresses whether care guided by aldosterone sup - pression testing should be used in individuals with a positive PA screening result, before initiating further diagnostic steps and/or specific treatment for PA, or if treatment can proceed without confirmatory testing. | 54 | 21 | 21 | 3bfc66ae435d2577ea0d1167e94650d3445f83d2d03eccf94f4e4384f38ab708 |
Question 4. Should care guided by aldosterone suppression testing vs no aldosterone suppression testing be used in individuals with a positive primary aldosteronism screen before initiating primary aldosteronism–specific therapy (medical or surgical)? | 49 | 21 | 21 | 73d6a5ac1b3656053e114101bdc3382fa90130c116133a94fe2e6ffd1f4bab09 |
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 | 21 | 21 | 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... | 66 | 21 | 21 | 120c98894e5d12c74596610de354081d4c38d8fd2c46bc1837c740f89e1b6d9b |
• In individuals with resistant hypertension or hyper - tension with hypokalemia and overt biochemical evi - dence of renin-independent aldosterone production (direct renin concentration [DRC] < 2 mU/L or plasma renin activity [PRA] < 0.2 ng/mL/h and plasma aldos - terone concentration > 20 ng/dL [ > 554 pmol/L] via im... | 165 | 21 | 21 | a2d71d7184e955afcb6274634cd9b29f90ed9a911a5cc77872e6ca02042b007c |
• Individuals unwilling or unable to pursue adrenal venous sampling (AVS) and adrenalectomy can be empirically treated with mineralocorticoid receptor antagonists (MRAs) based on screening results with - out aldosterone suppression testing. | 50 | 21 | 21 | cde7aa3572a4c0f7e41c0cd608bf962d9d06060fb089f23efb8688941d33609d |
Aldosterone suppression testing may still provide value in some cases for further documenting the diagnosis. • Aldosterone suppression testing is unnecessary in individuals from families with germline mutations associated with familial hyperaldosteronism. | 42 | 21 | 21 | e05c3b06adace2cf93908d504bae861d3b0b12d3d28a0f15b88dbcb47bae31e1 |
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 | 21 | 21 | 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 <∼ 11 ng/dL [ <∼ 305 pmol/L] [immuno - assay] or <∼ 8 ng/dL [ <∼ 222 pmol/L] [LC-MS/MS]). | 95 | 21 | 21 | 26d8030b48c02b4256c01b896ddcae7e5335b55b759efb41e1624be30e0fbe21 |
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 https:/ /guidelines.gradepro.org/profile/DF0l5-vIoxI . | 55 | 21 | 21 | 9afcd6fce234d0b4f807aad579e5a184e51410b657b74144c001b12f68a8eeca |
Benefits and Harms The panel voted for the following patient-important outcomes for Question 4 decision making: 1) accuracy of PA detection, 2) detection of lateralizing PA, 3) percent of individuals achieving blood pressure (BP) control, 4) number of antihy - pertensive agents, 5) dosage of antihypertensive agents, 6)... | 105 | 21 | 21 | 5047cd91cbd72e6779e7782c2b3660be8131ea7ef3d1fcc9aaa0c7c67fd18544 |
We found no RCTs that addressed this question. Likewise, no prospective and head-to-head studies are available evaluat - ing the value of aldosterone suppression testing, in addition to screening results, on treatment outcomes in PA. | 50 | 21 | 21 | 987272c9380e70869293ad25e69b0b6ea0536ef1bf6b9057b99f030046ffe512 |
Therefore, the panel ’ s recommendation relied primarily on evidence derived from retrospective observational studies. The systematic re - view found only one study (retrospective observational study) that was included ( 24 ). | 40 | 21 | 21 | 89b90bc03506bdc19e1bc7ce63761e4635f219c660ae9a27528eb6796e72bc1e |
Cornu et al showed that when con - ducting the saline suppression test (performed in the supine position) in individuals with high-probability features of PA, all of whom underwent AVS, even very low post-saline aldos - terone levels ( < 139 pmol/L or 5 ng/dL) could not definitively exclude lateralizing PA ( 24 ). Simi... | 154 | 21 | 21 | cee0cd04c68afe1a35ee0b1f4f8e0ba8a22e8d4ec0bedde323dbafeab1b4b25f |
110, No. 9 2473 Downloaded from https://academic.oup.com/jcem/article/110/9/2453/8196671 by University of Wisconsin System user on 20 February 2026 | 46 | 21 | 21 | c58ad43e4cf60bf2f65c31815691b519687c86a93c4c892e8e692703ab5f8688 |
AVS, thereby providing a desirable prognostic value. However, the choice of protocol and aldosterone assay are factors that can modify the interpretation of the results. For example, the sensitivity of the saline suppression test at pre - dicting the fludrocortisone suppression test has been shown to be superior when c... | 78 | 22 | 22 | c6d672eb6e18a5db58cb5987e4ae1c4f824f1c986cf0c93f7336d0f71de1bfba |
Moreover, the use of modern LC-MS/MS aldosterone assays yield lower aldosterone values than trad - itional immunoassays, thereby warranting a re-assessment of aldosterone interpretations for virtually all aldosterone suppression tests ( 101-105 ). | 58 | 22 | 22 | 4b6e2f02beb54158aecaa40229a12ad88366fa2b0c067ad0f60b7634285cfdcd |
Two systematic reviews and meta-analyses ( 106 , 107 ), in - cluding 55 and 31 studies respectively, concluded that the ac - curacy of aldosterone suppression tests in confirming PA was overestimated and that the number of missed cases (false- negative interpretations) may exceed the number of overdiag - noses (false-p... | 74 | 22 | 22 | 21e489b98d1f174dc0bff45d65a1ad1b750c68e0195a935a28241f93f1b47133 |
These results were attributed to inflation of diagnostic accuracy due to biased se - lection of individuals with very high probabilities of having PA. One study reported the anecdotal experience of a hyper - tension referral center abandoning the use of aldosterone sup - pression tests entirely from the diagnostic casc... | 102 | 22 | 22 | 0a6505eb87ac75b7e361c5496f065ee95448b99a3735c2a5e2774974fa84c775 |
When using just the screening aldosterone and renin values to guide subsequent decisions, the authors estimated that less than 3% of individ - uals were at risk of a false-positive diagnostic interpretation. | 42 | 22 | 22 | 9885ae4328751b730430021561b0bd1306c480c76d2cb38aa1fe496dbaa926db |
False-negative determinations after an aldosterone suppres - sion test in individuals with high-probability features of PA is considered to be a substantial undesired effect ( 23-26 ). | 41 | 22 | 22 | 96596093b8dd6b6616bdfc9be15c4a10c00ea492d554748c22ce783352862486 |
If al - dosterone suppression testing is used to enhance knowledge of lateralization and AVS use, the risk of undesirable effects is low. However, a negative aldosterone suppression test does not preclude the option of commencing specific medical therapy for PA, which has shown to be effective in individuals with low-r... | 97 | 22 | 22 | 52cacdf3c6b6a34a98410ce4017dadf3d163d996c248fb6465ae0960accb442b |
For example, in one study evaluating the captopril challenge test, aldosterone-directed therapy was highly effective at improving biochemical and clinical outcomes even for patients that did not meet the for - mal diagnostic criteria for PA ( 26 ). | 47 | 22 | 22 | 8d399496cef27c08e077fc94145d7a5b08c2b445994bcaad83aa166cb51136c2 |
Evidence to Decision Factors • An aldosterone suppression test is cost-effective in the long term, particularly if it assists in identifying lateralizing forms of PA that might guide curative surgery. The cost and resources will depend on the test used. | 49 | 22 | 22 | c44bac75af70c22211c5ab15b55be1ac8cb1f1848f4e0b08140472b7f7de06bd |
• Although no specific studies address this aspect, aldoster - one suppression testing appears acceptable by clinicians with expertise in PA, as well as by patients. In a limited-resource setting, conducting aldosterone suppres - sion testing may be less acceptable. • Aldosterone suppression testing can be prohibitivel... | 124 | 22 | 22 | fd69c031793a7c2d5e2f4ce82ee6d5574585392dec371415d8b4308ab9c9ade3 |
This discrepancy further adds to implications for equitable health care delivery. Justification for the Recommendation At least 10 aldosterone suppression testing protocols have been described and used to confirm or exclude PA, 4 of which are wide - ly recommended by prior major society guidelines ( 84 , 109-111 ), and... | 81 | 22 | 22 | 7c38883ec153915c88963e5c415c3fc794e553afe2502378d4df60d360997caa |
These tests include, but are not limited to, fludrocortisone suppression, oral sodium suppres - sion, supine and seated saline infusion, captopril challenge, losar - tan, dexamethasone-captopril-valsartan, intravenous (IV) furosemide upright, oral furosemide, and posture stimulation tests. | 79 | 22 | 22 | f8b3d50bc6f4644eaf32b9bc2efea1bd584d91334d3025dc1b81f3dabb440650 |
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