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Given the heterogeneity and lack of standardization across these tests, the ability to provide general recommendations for their implementation and interpretation is limited. Table 8 de - scribes the 3 most widely used aldosterone suppression tests. Aldosterone suppression testing has traditionally been used to confirm... | 60 | 22 | 22 | 496e8692b08d09af02fe04134f5517e41bc736ac7817530c42403e7acaaa4f9c |
Limitations of using al - dosterone suppression testing as a diagnostic metric include that the numerous protocols are not calibrated against one another, and each has diagnostic thresholds that are not validated against a gold standard. | 40 | 22 | 22 | d30d7bf3ba8ca20d5c04a15569e63cd4bb93ff17c10965d55958257b587b14a7 |
The summary of many studies suggests that a sin - gle optimal threshold for most aldosterone suppression tests does not exist and that over-reliance on these tests may result in erro - neous exclusion of PA cases rather than increased accuracy of diagnosis. | 51 | 22 | 22 | 1d77087cece664360dec0b47ef0968d0a33e5e8751865257dbab960e1399f485 |
The balance of evidence ( 106 , 107 ) suggests that the quality of evidence to support the accuracy of this practice is low, particularly in relation to confidently excluding the diagno - sis. However, if testing results that fall below protocol thresholds are interpreted as implying nonlateralizing PA or low-renin hyp... | 98 | 22 | 22 | a5f95cd7a6b3634218e912c73b34d9aa3e89c35caf6dfa0cccd0284e6f58bf51 |
The caveat for this approach is the implicit assumption that a positive PA screen indicates a high pretest probability for PA. Some studies suggest that the results of aldosterone sup - pression testing predict the general likelihood that an indi - vidual may have lateralizing PA (ie, greater inability to suppress aldo... | 111 | 22 | 22 | 3bd917df3d17db8b31aae793df9f45ec09a7cb17ccecf66ada091ff53f52c50a |
Caveats to this ap - proach include its lack of quantifiable metrics to guide such interpretations, supporting data are not uniformly available for all suppression tests/protocols, and high-quality com - parative effectiveness studies to assess whether other bio - markers may have similar predictive power are also lack... | 62 | 22 | 22 | 40c8dbd9886266e7bba105bb1f29e57eb0ec551b4f02248138047f9daea8186d |
Nevertheless, this approach may help some clini - cians streamline referrals for AVS, especially when this re - source is not readily available, for those who need it and spare those who do not. | 42 | 22 | 22 | ab0c6affe8b4d7992a5156232589095d20f2247d0c7842d5d6ccb16600d8c563 |
Given the low certainty in the trade-offs between benefits and harms of aldosterone suppression testing, along with considera - tions regarding the costs, resource requirements, and expertise needed to perform it, as well as its feasibility, acceptability, and equity implications, the panel suggests conducting aldoster... | 86 | 22 | 22 | 67c973f9801e9ed7ce0f49e33daf28cdf873a12cd1cc21d31a2954db99f21776 |
Aldosterone suppression testing can be performed without stopping or changing antihyperten - sive medications as long as renin is low; when treatment with MRAs has been initiated and renin is no longer low, it is advised that these medications be stopped, and aldosterone suppression testing be performed only when renin... | 68 | 22 | 22 | fa5ac6adeac1ca36d03ce995948e969ba015842611257ef9e5f5396fc8e95650 |
2474 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 | 22 | 22 | 47a5c47dcab931d9320d400b1ad6449000faa2a81ea506c35993a6f915bef825 |
Comments The use of aldosterone suppression testing in individuals with a positive PA screen may best serve individuals and clinicians by providing them with a probabilistic framework to deter - mine the optimal treatment pathway ( Fig. | 42 | 23 | 23 | fc0d1cac207f7cb1a9644049a03c142f408e3f871488f3906a538fb7fe81d9c4 |
The evidence for the outcomes of the percentage of individuals achieving BP control and detection of lateralizing PA following aldoster - one suppression testing was very low. However, conducting relatively safe testing to prognosticate the value of undergoing AVS (and determining the next therapeutic steps) would like... | 63 | 23 | 23 | 0b3ec1c9885ccf8e8de6029d32861133b14a812cc7404c9312a3d6d15320dee5 |
In resource-constrained settings, aldosterone suppression testing may be difficult to implement, considering the lack of evidence for major outcomes. Research Considerations Current gaps in knowledge call for further research in the fol - lowing areas: • Prospective, randomized, comparative outcome studies: | 57 | 23 | 23 | a8832fc71185d02571de35a80915db8580395e3a435f75f039f2768027e639da |
The lack of a gold-standard diagnostic to define PA is one of the main reasons why aldosterone suppression tests are not uniformly calibrated to one another or validated against a central benchmark. As a result, most available evidence provides low-quality information to reliably ad - judicate whether the use of aldost... | 76 | 23 | 23 | 815acd93ab1861a3577de0aaea2e0159fa1ab59afa14e57b8ffab18fcf33c53d |
Prospective studies, employing randomization to each ap - proach, and evaluating clinical efficacy outcomes are needed to robustly assess whether the practice of aldoster - one suppression testing adds value in selecting the correct individuals for localization procedures and targeted treat - ment, and improves outcome... | 56 | 23 | 23 | aaca23c05e8e8899de13b1e4c26cfb2e6f39e755c83ed8518a9a36d980eae414 |
• New diagnostic biomarkers: Novel cutting-edge omics tech - nologies together with the application of artificial intelligence (AI) for disease prediction hold potential for the development of more effective biomarkers to diagnose PA. | 43 | 23 | 23 | 1ca96d9f6c77e36da7792c25bf219580bc191b396e0aa0ef9fc35232ec1a5281 |
Besides the im - proved diagnostic performance of plasma or urinary steroid profiling to diagnose PA ( 82 , 114 ), a recent approach using multi-omics data, including plasma miRNAs, plasma cat - echol O-methylated metabolites, plasma steroids, urinary steroid metabolites, and plasma small metabolites, integrated by mac... | 102 | 23 | 23 | bdc20e7a4204e0394e51bd6664a26d859a654cc9dbf050d50543e35322350f90 |
This and similar approaches, combining clinical data with biologic profiles, may provide better performances to diagnose PA and potentially lateraliz - ing PA, thereby possibly eliminating the need for aldosterone suppression tests in the future. | 43 | 23 | 23 | d7c04cffbedaeb92a4ff97d7115301f28522ea3c2036fa725ee5e213020b5819 |
Medical Therapy vs Surgical Therapy for Individuals With Primary Aldosteronism Background Effective prevention of excess cardiovascular and cerebrovascular risk in individuals with primary aldosteronism (PA) involves tar - geted therapies for lateralizing and bilateral forms of the disease. | 54 | 23 | 23 | 8b23144c16381b3861b9f4839ef2e87434678a6740567f6049390c8751d80e5d |
For individuals with bilateral disease and those who do not desire or are not a candidate for surgery, lifelong pharmacotherapy with a mineralocorticoid receptor antagonist (MRA) is the standard ap - proach. | 43 | 23 | 23 | 2a79c80e2d4c0473d287aadee924f2dab3c682b6ec2ca9683e956a4905de450f |
In contrast, surgical intervention is typically recommended for individuals with lateralizing PA who wish to pursue this op - tion. However, surgical intervention requires adrenal venous sam - pling (AVS) to confirm lateralization, a procedure that demands significant expertise and specialized resources, often limited ... | 65 | 23 | 23 | 8136b1f9543470950de50f35c25d1a6eda9cea2f286a94cf75b2430f7d75e636 |
These challenges highlight the need to balance the benefits and feasibility of medical vs surgical treatments. Considering these factors, the panel formulated this question to de - termine the best management strategy for individuals with PA. | 40 | 23 | 23 | 4a42d928248ccac73c9df82a5373fb220363da7ecf9c7851c38505567e548c4d |
Question 5. Should primary aldosteronism–specific medical therapy vs surgical therapy be used in individuals diag - nosed with primary aldosteronism? Recommendation 5 In individuals with primary aldosteronism (PA), we sug - gest medical therapy or surgical therapy with the choice of therapy based on lateralization of a... | 88 | 23 | 23 | 9c772a7bada23dca1af781f272b2ffe648f40b208af582d441b9e32e7f3b4806 |
Technical remarks ( Fig. • Surgical therapy by total unilateral adrenalec - tomy, usually by the laparoscopic approach, is mainly offered to individuals with lateralizing PA who choose to pursue the surgical option ( Fig. | 46 | 23 | 23 | 560696bbb5b6deaee9c1f2516e339d33e835a9f5c3af682f2292f905680a82c2 |
• Lifelong medical therapy that includes an MRA is usually offered to individuals with bilateral PA or lateralization status unknown (refer to Question 6 for definition of lateralization) and to those who decline the surgical option or who are not surgical candidates ( Fig. | 52 | 23 | 23 | 49f985df835768a2a6dfb76d68687d59a10d4bcd6ab9d6fd3365adc98d6344b0 |
• Individuals with mild PA typically have bilateral disease and may bypass AVS, proceeding directly to medical management ( Fig. • Individuals with multiple comorbidities who may not be good surgical candidates may also proceed directly to medical therapy ( Fig. | 48 | 23 | 23 | e274efb4e0914a21a0b99895a9e75e7cf246e4c6390edcd2babc66bae753e5dc |
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/FT5oNrFmGsY . | 55 | 23 | 23 | 617767a776160e24d69d5841a94e5c5cf931bb7b2b7a622c4b14d855ba87737c |
Benefits and Harms The panel voted for the following patient-important outcomes for Question 5 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 | 23 | 23 | 0e4a1f17d21b1bbbaddf924602f031f8794f2ccda05c3eba636e2c7ab8afff4a |
Systematic review metadata ( 53 ) from 4 randomized con - trolled trials (RCTs) enrolling 669 individuals with PA (mean age 52.6 years, 28.7% females) and from 52 comparative obser - vational studies with 17 893 individuals with PA (mean age 52.6 years, 46.9% females) were included for evidence synthesis. | 77 | 23 | 23 | fc697149662cf3a78f47229794fa768f5b9a99bca1a8d2a29174099fe6f52661 |
The Journal of Clinical Endocrinology & Metabolism , 2025, Vol. 110, No. 9 2475 Downloaded from https://academic.oup.com/jcem/article/110/9/2453/8196671 by University of Wisconsin System user on 20 February 2026 | 62 | 23 | 23 | 63a2f3bcfd914e370fad86fe531cb157b0f725a2811c8c245a364e480a55f129 |
No significant differences between medical and surgical man - agement were identified for hypertension remission. However, a meta-analysis ( 53 ) of 20 observational studies, including 3209 individuals with PA, showed an association of lower long-term efficacy in achieving BP control with PA-specific medical ther - apy... | 342 | 24 | 24 | d9720c53a1a8ff992dd6838b8cc2f7518be5a8ea7678be0e6578cf055171783b |
The systematic review ( 53 ) assessed the comparative efficacy of medical vs surgical management for cardiovascular risk. No statistically significant differences were found between the 2 treatment modalities for ischemic heart disease, atrial fibrilla - tion, MACEs, and cardiovascular mortality. However, com - pared w... | 162 | 24 | 24 | 6e2ee63f265b92491fe01fe5c3ff621999892df1628a782fe9c18c2c63fca2ee |
One cohort study reported that MRA therapy compared with adrenalectomy had a higher risk of mortality, major car - diac or cardiovascular events, and combined new-onset atrial fibrillation with mortality ( 118 ). However, this increased risk might be mitigated with adequate mineralocorticoid receptor blockade based on ... | 73 | 24 | 24 | 6ffb7a8a305fad5fa00fb7107575ad71cd480c4cee48b858c838ae0b4f7f257f |
Due to off-target androgen receptor antagonism and pro - gesterone receptor agonism, spironolactone has dose- dependent side effects of gynecomastia and sexual dysfunction in men and menstrual irregularities in women ( 116 , 119-121 ). The meta-analysis of a systematic review of 2 observational studies estimated signif... | 109 | 24 | 24 | e4eabaf7670585504eaf9aef0afd399f1d2dbdf6fd03d03de0c32f4baa9dfb15 |
Of note, fewer side effects were associated with eplerenone than spir - onolactone, consistent with eplerenone ’ s greater specificity for the mineralocorticoid receptor ( 122 ). While the antihyper - tensive efficacy of eplerenone was lower than that of spirono - lactone, the eplerenone doses studied were about one-th... | 153 | 24 | 24 | bd11f1840ab55402304bbe393673e77af46bf041d21195f3f4418092e8b1026f |
However, in an individual with PA and a remaining life expectancy of 25.4 years or more, surgery was esti - mated as the least costly strategy in the long-term due to the decreased risk of PA-associated adverse events ( 125 ). • MRAs are readily available, including in resource-poor settings, whereas surgery requires a... | 93 | 24 | 24 | 461ada6e9885b70ea3ccdc0ffffcbbdce28533a83d4614bc64d562c7c784ad02 |
• MRA therapy is often preferred by health care clinicians due to its accessibility and low cost. However, individual adherence to spironolactone is lower compared with other antihypertensive medications, possibly related to its anti- androgen and progestogenic side effects. • Adherence may improve with the use of more... | 251 | 24 | 24 | 87f3d664694e2fe8342e0dee3244214a73c9110e9f0c50dfb5f8916b8d073dc2 |
However, individ - uals often favor surgical therapy due to the possibility of avoiding lifelong medical therapy, overall QOL improve - ments, limited pharmacologic treatment options, and side effects of some MRAs (eg, spironolactone). Thus, surgical treatment is generally preferred by individuals with lateral - izing ... | 149 | 24 | 24 | 7a9e3d45f3b5e1bb9c155830a6df2ce07f7b5610028c25db54b9b936d8fae93f |
Postsurgical outcomes partly depend on successful AVS and the availability of skilled adrenal surgeons, which might be limited outside specialized centers. Preoperative morbidity and length of stay are more favorable in high- volume centers ( 130 ). Adrenalectomy is mainly performed by a laparoscopic ap - proach, but o... | 89 | 24 | 24 | 1ec45beecc2c0dffc21738abbb5a79e1d9a862a870c3268c7d6a9ba8e24508d5 |
Individuals with bilateral PA in whom medical therapy is not well-tolerated or effective can be considered for unilateral adrenalectomy although evidence regarding clinical effective - ness in those situations is limited ( 131-133 ). 2476 The Journal of Clinical Endocrinology & Metabolism , 2025, Vol. 110, No. 9 Downlo... | 106 | 24 | 24 | 54a082d6c10949458478cae8337cc1b4ffcf0a679d46798495a044d674604264 |
Research Considerations Further research is necessary to investigate the protective ef - fects of aldosterone synthase – inhibitor therapy as well as oth - er strategies like adrenal ablation and tailored approaches for milder forms of PA. | 49 | 25 | 25 | c6ee3a44af81373fd72779397cb1736681c65632eb2a4982df1a1f2a4b4d725f |
Role of Adrenal Venous Sampling and Computed Tomography Scanning in Determining Lateralization of Primary Aldosteronism Background Cross-sectional imaging (eg, computed tomography [CT] or magnetic resonance imaging [MRI]) has limitations in the evaluation of individuals with primary aldosteronism (PA) because it cannot... | 78 | 25 | 25 | 1f9d74e09be05e678e0fd32ce4d6a4c9b55ee5a87004b28b47bb11dc883b65d6 |
This can result in misclassification as lateralizing or bilateral PA, especially in those with bilateral adrenal hyper - plasia or nonfunctional adrenal nodules. While adrenal ven - ous sampling (AVS) can improve diagnostic accuracy and guide treatment decisions, its limited availability raises the question of whether ... | 111 | 25 | 25 | 3e659ddb1b14b5ecbf5f69eac85ba6db8aff88adef52bcec3a10336fa1fbb45f |
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 | 25 | 25 | bf35ac57bfac6dbaf1f03e0bafee0aac5ac0543b679f0f629754b84e1e537965 |
Recommendation 6 In individuals with primary aldosteronism (PA) con - sidering surgery, we suggest adrenal lateralization with computed tomography (CT) scanning and ad - renal venous sampling (AVS) prior to deciding the treatment approach (medical or surgical) (2 | ⊕⊕ OO). | 70 | 25 | 25 | 2f916068e04191edc8ecc9c34f404ade1ba795500f64769304d55f7422e2ec0b |
Technical remarks • Individuals with PA who desire and are candidates for adrenalectomy should undergo AVS in order to reliably differentiate lateralizing from bilateral forms. • A potential exception is when the diagnosis of uni - lateral aldosterone-producing adenoma (APA) is so likely that AVS could be considered un... | 104 | 25 | 25 | f9ee8f2f03d0b69b8509041dfb42ddd71b38edaf64e2dd97127d0d0375093b58 |
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/FL6i3ZvDYXg . | 56 | 25 | 25 | 9770e540c9b2185c5139e7bff8255b84afdb4c5e6704fac7938f82061bc197ac |
Benefits and Harms The panel voted for the following patient-important outcomes for Question 6 decision making: 1) detection of lateralizing PA, 2) biochemical cure rate post-adrenalectomy, 3) percent of individuals achieving blood pressure (BP) control, 4) num - ber of antihypertensive agents, 5) dosage of antihyperte... | 94 | 25 | 25 | 123402dfc519f11db6cb58acc3eede973b59f02934aaf9b0e1e6f658f264a688 |
A systematic review of 38 studies including 950 individuals reported that when AVS was used as the criterion standard test for the diagnosis of lateralizing PA, CT/MRI misdiag - nosed the cause of PA in 37.8% of individuals ( 134 ). | 52 | 25 | 25 | a380054ac0c54c62f59552e357fab68f61f14c355655f24536a79225c0aebf25 |
Several retrospective studies reported low-level concordance between CT scanning alone and CT scanning plus AVS ( 89 , 135 , 136 ). In individuals who were biochemically cured after surgery with AVS-based management, CT/MRI alone correctly de - tected lateralizing PA in 58.6% ( 135 ) and 64% of cases ( 89 ). | 72 | 25 | 25 | 9262bde8cddebdcf0754cfa382b9ccc759e9915b5d84e0842bd65908a263a8e6 |
These studies highlight the limitations of adrenal CT in the diagnosis of unilateral aldosterone-producing adenomas (APAs). Small unilateral APAs may not be visible on CT, leading to misinterpretation as normal adrenal glands. | 47 | 25 | 25 | bb7ab4ba9a1f1a06a59dbafd1e315e7c1172ca12052d95093e048c51fcb15b95 |
Conversely, appar - ent microadenomas on CT might actually be areas of hyperplasia, making unilateral adrenalectomy inappropriate. Furthermore, nonfunctioning unilateral adrenal macroadenomas, which are common in individuals older than age 35 years, cannot be distin - guished from APAs on CT. | 64 | 25 | 25 | f8bebd7ed76a6c85aa66b90f757da1a03424cdc45e333e9b23e5271dd78e4bb6 |
Therefore, to address the performance of adrenal lateraliza - tion with CT scanning plus AVS vs CT scanning alone for the management of PA, the systematic review ( 53 ) identified one randomized controlled trial (RCT) ( 117 ) enrolling 200 indi - viduals with PA (mean age 53.1 years; 21.7% female) and 29 comparative ob... | 96 | 25 | 25 | 4fc7158f1e61a0f7f5b103e8e971ff4ccdc49dc9d41d3c8981b80f46bae86ab2 |
Data from the RCT alone did not show differences in inten - sity of antihypertensive medications, BP control, or biochem - ical remission after 1-year of follow-up. | 42 | 25 | 25 | 705bab8c8e07f5bafa00c53a6ee089b6f4c29c3eee7b93bf07ffe2667527fa02 |
Meta-analysis of 4 observational studies including 1070 individuals with PA indi - cated that compared with AVS-based management, CT scan - ning alone may be associated with lower postoperative biochemical cure (odds ratio [OR]: | 48 | 25 | 25 | 4d4c84deb8eb6c7d235df55211f8bdc53ce17bf6b37b89ada49e0f1fcfb6592f |
0.266; 95% CI: 0.103-0.690) ( 89 , 137-139 ). Otherwise, comparable out - comes were observed between AVS- and CT-based manage - ment approaches for the detection of lateralizing PA, achieving BP control, number or dosage of antihypertensive medications, and SBP levels. | 70 | 25 | 25 | 4cd0ce7c1caded2f4e3b7296fbeb4714c685a5acbc19a6d5a4a569f4262bb921 |
Additionally, an observational, retrospective, multicenter study reported an overall adrenal vein rupture during 0.61% of AVS procedures, with an inverse correlation between rupture incidence and the radiologist ’ s experience in performing AVS studies ( 140 ). | 50 | 25 | 25 | 56e3ce808844fa2e9d28db1f58405c4675d898f68277ecb4be77eddefa30f36d |
Evidence to Decision Factors • Resource requirements for AVS include training and time of expert interventional radiologists, accurate laboratory measurements, and interpretation of AVS results ( 141 ). • One RCT reported increased average health care costs for individuals undergoing AVS ( 117 ), but decision-tree mod ... | 102 | 25 | 25 | 849b5413cd2b4b63de8e6e2a2d60b2abc6fbf10aceb5311e3027550cab29d626 |
• AVS has low feasibility to implement due to the require - ment for a highly trained interventional radiologist and other additional resources and is probably less acceptable The Journal of Clinical Endocrinology & Metabolism , 2025, Vol. | 47 | 25 | 25 | af57fd811d11efb101a3c48d2ba4e5ae1262fd9c4d4116b096f81c855c30a8ff |
110, No. 9 2477 Downloaded from https://academic.oup.com/jcem/article/110/9/2453/8196671 by University of Wisconsin System user on 20 February 2026 | 46 | 25 | 25 | f73430633d76b17a671c8b43dfa4e302d2eb3193613a9c1c06897cabfeff103a |
to care clinicians who do not have local or regional access to a center that performs AVS with a high bilateral adrenal vein cannulation success rate. • AVS might be unacceptable to some individuals unwilling to undergo an invasive procedure but should be accept - able to individuals who want to achieve hypertension cu... | 76 | 26 | 26 | 3ae1d2f6336315aac9d935e42ddf0c67063565478e189300f571d8285592f968 |
• AVS has higher costs relative to CT-guided care, is not wide - ly available in most countries, and is offered only in highly specialized centers and not at all in resource-poor countries. | 41 | 26 | 26 | 4fc8b3789096cdb7e633d871f499840be6cc0a59687e0e7af3fe927a904851d3 |
• Although AVS is more accurate than cross-sectional imaging, it is substantially more costly and difficult to implement. • Individuals with PA prioritize the accurate detection of surgically treatable forms; therefore, AVS is acceptable and desired by those who favor a cure of PA over lifelong mineralocorticoid recept... | 69 | 26 | 26 | 316eab1c5648541c81fdf91bba158d71b51ea85867d276c7b5de5372f075fbc8 |
Justification for the Recommendation The panel recommended that for individuals diagnosed with PA who are candidates for surgical intervention, the treatment approach should be guided by adrenal lateralization using both CT scanning and AVS. | 41 | 26 | 26 | a161125e82420ef75be14e5f498d61f13d5754a0d55fc8caa41f48b3946614d1 |
This recommendation is based primarily on indirect evidence, and partially supported by dir - ect evidence, highlighting the low detection rate of lateralizing PA with CT scanning alone compared with combined CT scanning and AVS. | 40 | 26 | 26 | ad7accc9dee53c6ff76cefa34fea86eb1769bcdbfa441674455167b733ca2df5 |
Also considered was the value that clini - cians place on the accuracy of aldosterone lateralization be - cause it leads to successful surgical outcomes in those individuals who want to pursue a surgical cure. | 41 | 26 | 26 | 81d56ebdbf96e3f4ddc6c3f3db1ecc9575fbb86e676f8b27db0bf542b7a988a8 |
CT (or MRI) cannot assess the functional activity of adrenal glands and may misclassify individuals, particularly those with bilat - eral adrenal hyperplasia or nonfunctional adrenal nodules. | 42 | 26 | 26 | 1440e270d92bc062c0ee7233bf4b7e16476d05ec495ba9914d92d343f7e2e814 |
Thus, in individuals who are surgical candidates, an addition - al localization step is needed, and the most accurate currently available option is AVS. Although a prospective randomized trial reported no appar - ent outcome differences between CT-based and cosyntropin- stimulated AVS-based management ( 117 ), several ... | 67 | 26 | 26 | 74afd67d56d928e8f3fdb3c797e4c78ef2cdadace3d3459330c7050ce55dc23e |
For example, medication and BP out - come data at 1 year after intervention were pooled from the surgical and medically managed individuals in each arm of the study, which failed to recognize that MRA treatment is a “ surgical equivalent. | 46 | 26 | 26 | 056a5aa81bdd9a8daf74a31fe166edc5053ff45ff39ab275cbcb647b199621a6 |
” The study was not powered to detect outcome differences in those individuals treated only with sur - gery based on CT vs AVS. Additional issues with this study in - cluded the selection bias toward more florid forms of PA, which limited its generalizability, and a suboptimal selectivity index cutoff for AVS ( > 3:1 w... | 109 | 26 | 26 | 7c139454f1ad3f5a9fedbb80dbc668c54f5d0d84b50f570fb78ec2b6d581b75d |
In addition, 5 of the 92 individuals in the CT-based management group had apparent unilateral adrenal disease on CT scan but were not managed surgically. Implementation Strategies AVS success rates depend on the experience of the operators and thus performance in centers with high expertise is recom - mended ( 143 ). | 61 | 26 | 26 | e5552de4e6c1cce519b0957aaee2935014b87bc1485c07dee0f4a082dcdb9e29 |
Most centers use radiographic contrast administration dur - ing AVS to help localize the adrenal veins. Contrast administration carries a risk of a contrast allergy reaction, as does contrast-enhanced adrenal CT. | 42 | 26 | 26 | 50a53fe7362f1c449029af391052fd55c78d70a8361ba0ebd83ac6575bdd3d53 |
A contrast allergy may ne - cessitate the use of cosyntropin for AVS for those individuals treated with exogenous corticosteroids for contrast-associated allergic reaction prevention ( 144 ). Three protocols have been used successfully for AVS: Unstimulated sequential or simultaneous bilateral AVS; 2. Unstimulated sequ... | 107 | 26 | 26 | 8e3631aff58597d9db0af5399480832ecef873c667d8ea1a658f8096c4173dd2 |
Simultaneous bilateral AVS is difficult to per - form and is not used at most centers ( 145,146 ). Many groups advocate the use of continuous cosyntropin infusion during AVS to minimize stress-induced fluctuations in aldosterone secretion during nonsimultaneous (sequential) AVS, maximize the gradient in cortisol from a... | 130 | 26 | 26 | 1354869a7b6f5cd3ec821efca208f99555d441cd6dfd2ed6ab8153419b95eee1 |
However, there is a lack of consensus on the use of cosyntro - pin stimulation to assess for lateralization ( 150 ). Aldosterone and cortisol concentrations are measured in the blood from all 3 sites (right and left adrenal veins and in - ferior vena cava [IVC]). | 60 | 26 | 26 | 474188e1f0e0312a87195a7a36bb4cd5d3ac4e2c71b4866568b9fcfb50984223 |
The IVC sample may be obtained from veins that are even more peripheral (eg, external iliac vein) ( 141 ). All of the blood samples should be assayed at 1:1, 1:10, and 1:50 dilutions; absolute values and accurate la - boratory assays for cortisol and aldosterone are essential for successful interpretation of the AVS da... | 79 | 26 | 26 | 232689154c4b1c0b0b106a9faf1087c0b532447efc359e0abd66354ff7777250 |
The interpretation of AVS results relies on several key indi - ces and their corresponding cutoff values, which help deter - mine the success of the sampling procedure and the lateralization of aldosterone excess ( Table 9 ). | 45 | 26 | 26 | 2465744ff71d2e0f9bf83af0edc7568049dadcc9c98834e03a72943f091918bc |
The cortisol con - centrations from the adrenal veins and IVC are used to confirm successful cannulation of both adrenal veins. With cosyntropin protocols, an adrenal vein to IVC cortisol ratio (referred to as the selectivity index ) of more than 5:1 is required to be confi - dent that the adrenal veins were successful... | 80 | 26 | 26 | 3968f1d754572a79ce57a4e68489b688b90f6eb85a2abd05c2a8a08cfb4a0cb4 |
When cosyntropin is not used, a selectivity index of more than 1.4 to 3.0 is a threshold that has been used to verify successful catheterization ( 150-152 ). | 41 | 26 | 26 | c2612dd45c255f761372adb2a19ac70621fa734c9555a7fb5fc9f4bb8f266302 |
Use of intraprocedural cortisol measurement has been shown to improve bilateral ad - renal vein catheterization success rates ( 153 ). Dividing the right and left adrenal vein aldosterone concentra - tions by their respective cortisol concentrations corrects for dilu - tional effects of the inferior phrenic vein flowin... | 93 | 26 | 26 | 6574779ad8519879f16bdfdeac0718830ed759f6a59e22666e7b50813613ea8d |
These are termed cortisol-corrected al - dosterone ratios . With unstimulated or continuous cosyntropin administration, clinicians use a cutoff of the cortisol-corrected al - dosterone ratio from high-side to low-side of more than 4:1 (re - ferred to as the lateralization index ) to indicate lateralizing aldosterone ex... | 99 | 26 | 26 | 3759ee51a9368b9ccf5151b433df33d5827da5fb41e4d391ac56832d29f95001 |
Individuals with a lat - eralization index between 3:1 and 4:1 may have either lateralizing or bilateral disease, and the AVS results must be cau - tiously interpreted in conjunction with the clinical setting, CT scan, and the contralateral suppression of aldosterone secretion. | 62 | 26 | 26 | ba6ccb908ad7aa09dfcf59d4b65704a50c95b7490b4a03dcc26794878ff4bb15 |
2478 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 | 26 | 26 | 72580a1bb7eea39d0b93eeda12ea01e51b1c9702f4e54a646c02dee0a56c2d81 |
Although the use of cosyntropin clearly improves the selectivity index, there is debate on its impact on accurate lateralization. In a retrospective cohort study of 340 patients with primary al - dosteronism, bilateral simultaneous AVS was performed before and after the administration of cosyntropin ( 154 ). | 62 | 27 | 27 | adf2e745749762237bce00551ca47116af994873efcac2c4d410682f579f815d |
Using a lateral - ization index of > 4:1, there was a 19% discordance rate between pre- and post-cosyntropin data sets. More than half (64%) of the discordance was due to apparent lateralizing adrenal disease prior to cosyntropin administration that was reinterpreted as bilateral disease after cosyntropin ( 154 ). | 76 | 27 | 27 | d0d5ca50db13207ffaf50a3109d920c60eaa2a5b6fafc69b4cedab13bb42b700 |
In the same publication, the au - thors reported that 10 of 11 similar studies that they reviewed demonstrated either no change or a decrease in lateralization rates following cosyntropin stimulation. Most studies have found no difference in post-adrenalectomy outcomes with or without cosyntropin-stimulated AVS ( 151 ,... | 107 | 27 | 27 | ad28357dbeb7d41d034f00e478f6ec9493ca5d1c90a81f7ab5fb49bfe676a5de |
Finally, in most individuals with lateralizing disease, with cosyntropin-stimulated AVS, the aldosterone to corti - sol ratio from the nondominant adrenal vein is lower than the aldosterone to cortisol ratio in the IVC, termed the contralateral suppression index ( 157 ). When AVS is per - formed without cosyntropin sti... | 120 | 27 | 27 | 81df5cbdab7c1afb809d632c41b802fd55233399092e12069c488c5e6acb4a91 |
Use of the contralateral suppression index remains controver - sial and more work is required to validate this and other in - dices of lateralization. Comments For accurate interpretation of AVS, it is important that serum potassium concentration is normal and renin is suppressed. | 55 | 27 | 27 | 1337af921e894b1673c71c3e7d884d7dd49d2cfa8f874560f9f57d5898e905ee |
It is also important that blood pressure is well controlled, and this may necessitate the use of antihypertensive agents. Antihypertensive agents (eg, diuretics, angiotensin-converting enzyme [ACE] inhibitors, angiotensin receptor blockers [ARBs], or MRAs) do not interfere with AVS as long as renin is low ( 159 , 160 )... | 83 | 27 | 27 | 7c6169d31bd805e06ca02e784e8e475e6686efa4b9fc4cbd2740b0f8f10caaa2 |
If renin is not suppressed, changes in the antihypertensive program should be considered before AVS. Drugs that have minimal effect on renin may include selective α 1 -receptor antagonists (eg, doxazosin, terazosin, prazosin) and long-acting dihydropyridine (eg, amlodipine, felodipine) or non-dihydropyridine calcium-ch... | 108 | 27 | 27 | 7e78ab8415e29df9b498acfdc70182728cd447f8aaff5c0b66012801fef7ef34 |
There are 4 exceptions to the suggested requirement for AVS prior to surgery: • Most young individuals (eg, age < 35 years) who have marked PA (eg, spontaneous hypokalemia, plasma aldosterone con - centration > 30 ng/dL [ > 832 pmol/L] by immunoassay or > 22.5 ng/dL [ > 624 pmol/L] by liquid chromatography – tan - dem ... | 133 | 27 | 27 | b886faf9df8f950779bfc250e8fb1a43826d1967030ceb72fc0d9a6bbf5fb95b |
Adrenal in - cidentalomas are very uncommon in individuals aged < 35 years (0.28%) ( 161 ), and marked PA is usually associated with a CT-detectable adrenal nodule ( 162-164 ). | 47 | 27 | 27 | 4f5d97c69c09276f708efb766009c3bf5b6bdd89939c0dd797d0d0698f01be38 |
Thus, in young individuals (eg, age < 35 years) with marked PA and a > 1.0-cm unilateral adrenal nodule on CT, unilateral adre - nalectomy without prior AVS can be considered. | 47 | 27 | 27 | 0398f5773cce60dee1a179ff2bb51b0f72d692256c5938e3909f91a0e191213b |
• Individuals with a unilateral adrenal macroadenoma ( > 1 cm) who have both PA and clinically important corti - sol secretory autonomy. The source of clinically important cortisol secretory autonomy is the unilateral adrenal mac - roadenoma, and a localization study (eg, AVS) is not needed. | 65 | 27 | 27 | 18263f36f7442dc7551ce073545c1ccb0af87e72912b415625affda0c5c5dc6e |
• Individuals with familial hyperaldosteronism (types I-IV). These autosomal-dominant disorders are each linked to specific germline pathogenic variants ( 165 , 166 ). These in - dividuals have bilateral adrenal disease, and AVS is not re - quired (Question 4.) Adrenalectomy is usually not indicated in individuals with... | 75 | 27 | 27 | a37068ead67118858bb466680ca72de382c0d554d689b36a07ffdef2e43a4d10 |
• Individuals with primary bilateral macronodular adrenal hyperplasia (PBMAH) who have excessive production of both cortisol and aldosterone ( 167 ). These individuals have bilateral adrenal disease, and AVS is not required. | 48 | 27 | 27 | 5378388ea182606a21038d3ca6ad6c68ece219e494403c6e3fe084a7884ff382 |
Research Considerations One of the long-term goals for subtype evaluation is to decrease the reliance on specialized interventional radiologists for AVS. Positron emission tomography (PET)-based imaging with aldos - terone synthase – specific molecules is under investigation as a method to identify whether excess adren... | 78 | 27 | 27 | d8812e724481867a15f640797683a0445c2c2ef94f8679d81afd9c7cb9e0f749 |
A recent study showed that pretreatment with dexamethasone converts 11 C-metomidate from a nonselective ligand for CYP11B1 and CYP11B2 into an in vivo selective CYP11B2 ligand ( 171 ). | 54 | 27 | 27 | d21c4b13c0658eb22d0331e43a9d4a13178ba9030ce2f05699dcfeafaec47e9b |
In 93 patients with PA and CT-detected adrenal nodules who were treated surgically, dexamethasone-suppressed 11 C-metomidate PET-CT was nonin - ferior to AVS in diagnosing lateralizing PA ( 171 ). | 55 | 27 | 27 | d273d56b170d48febe6ad76fafc7f6f7fa04b2313bea6c0a93295216adaa12f4 |
In addition, the C-X-C chemokine receptor 4 (CXCR4) is a G protein-coupled transmembrane receptor overexpressed in APAs and exhibits low to undetectable expression levels in normal adrenal tissues and nonfunctional adenomas ( 172 ). | 62 | 27 | 27 | 132da3c5c365acfc230caaf0d791bda109cfa690393076e4b02491f011873e85 |
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