Machine Learning Approach for Subtype Prediction in Primary Aldosteronism: A Comprehensive Analysis of Models and Features

Background: Primary aldosteronism (PA) is characterized by excessive, autonomous secretion of aldosterone from one or both adrenal glands. Identification of unilateral disease and surgical resection can lead to cure, and is dependent on accurate criteria for lateralization of excess aldosterone during adrenal vein (AV) sampling (AVS). Current evidence for AVS lateralization cut-offs using plasma aldosterone concentration (PAC) measured by LC-MS/MS and post-surgical outcomes is limited. Aim: To determine optimal cut-off criteria to define lateralization of PA on AVS based on PAC measured by LC-MS/MS post-ACTH stimulation and post-surgical outcomes data. Methods: This study involved 60 subjects with PA who had PAC measured by LC-MS/MS post ACTH-stimulation during bilaterally-cannulated AVS, underwent unilateral adrenalectomy between July 2015-July 2021 and were followed up for ≥6 months. AVS lateralization parameters (lateralization index [LI; dominant PAC/cortisol(AV) ÷ non-dominant PAC/cortisol(AV)], contralateral suppression index [CSI; non-dominant PAC/cortisol(AV) ÷ PAC/cortisol(Peripheral Vein)], lateralization ratio [LR; dominant PAC/cortisol(AV) ÷ PAC/cortisol(Peripheral Vein)] and post-surgical outcome data were examined. Complete biochemical remission (CR) of PA post-surgery was defined using PASO International Consensus Criteria. Receiver operating characteristic (ROC) analysis was performed to determine optimal cut-offs for LI, CSI and LR based on cases who achieved CR of PA post-surgery (n=55) vs those who did not (n=5). Results: Optimal cut-off LI during ACTH-stimulated AVS to identify unilateral PA cases who achieved CR post-surgery was 5.1 (AUC=0.92, P<0.001; 92.7% sensitivity, 80.0% specificity) while the optimal cut-off for CSI was 0.6 (AUC=0.887, P<0.001; 82.1% sensitivity, 100.0% specificity), and for LR was 3.3 (AUC=0.695, P=0.202; 80.0% sensitivity, 80.0% specificity). Cases with LR of 2.0-3.3 also achieved CR post-surgery if it was associated with CSI <0.6. Conclusion: LI of >5.1 provides high sensitivity and CSI <0.6 high specificity for identification of surgically curable unilateral PA during ACTH-stimulated AVS when PAC is analyzed by LC-MS/MS.

It is well known the primary aldosteronism (PA) is most common endocrinological hypertension and accounted for 10% among all hypertension population, and it develops cardiovascular disease more frequently than blood pressure matched essential hypertension. Many literatures have been reported patients with obesity often shows hyperaldosteronism by hyperactivation of sympathetic nerves, over secretion from adipocytes themselves, or aldosterone-secreting factors from adipocytes. Thus, we investigated the impact of BMI on diagnosis of PA in this study. We investigated 328 cases of adrenal venous sampling performed patients with PA in our hospital since 2007, including 125 males and 203 females, and their mean age was 56.1 ± 11.8 years old. We evaluated the relationship of those patients’ body mass index (BMI) with gender, systolic and diastolic blood pressure (SBP and DBP, respectively), serum sodium, serum potassium, plasma renin activity (PRA), plasma aldosterone concentration (PAC), aldosterone-renin ratio (ARR), ACTH, cortisol, and the ratio of patients who showed 1 mg dexamethasone suppression test positive, and none of each showed statistical relationship with BMI. In confirmatory tests, we evaluated those values of PRA at 120 min. in upright furosemide test, either higher values of ARR at 60min. or 90 min. in captopril challenge test, and PAC at 4 hours in saline infusion test (SIT), also positive ratio of those test considered by PRA <2.0 ng/ml/hr, ARR >20, and PAC>6.0 in those tests, respectively. In adrenal venous sampling (AVS), we evaluated lateralized ratio (LR) and contralateral ratio (CR) and those positive ratios considered by LR >4 or CR<1. In our results, only positive ratio of SIT in the confirmatory tests and CR in AVS showed positive relationship with BMI. The ratio of unilateral hyperaldosteronism considered by LR>4 and CR<1 also showed no relationship. Then, we evaluated all consideration above only among 304 patients with bilateral hyperaldosteronism by AVS, suspicious of idiopathic hyperaldosteronism (IHA), because it was reported patients with obesity and hyperaldosteronism are more commonly diagnosed as IHA. Although, all evaluation showed same results. In conclusion, our result revealed the relationship of BMI with positive ratio of SIT and CR, and this means obesity, at least, could affect the diagnosis of PA. We must be very careful to make diagnosis of PA, especially in patients with obesity.

T. Ichijo: None. N. Ikeda: None. H. Ishiodori: None. K. Takuma: None. F. Kasahara: None. K. Ikehara: None. M. Higa: None. It is well known the primary aldosteronism (PA) is most common endocrinological hypertension and accounted for approximately 10% among all hypertension population, and it develops cardiovascular disease more frequently than blood pressure matched essential hypertension. Several confirmatory tests are recommended by Endocrine Society’s guideline including saline infusion test (SIT) and captopril challenge test (CCT). It doesn’t mention how many should be done nor those sequential order to be performed if several tests are planned.Thus, we investigated 576 cases of PA diagnosed by those 2 tests in our hospital since 2007, including 204 males and 372 females, and their mean age was 55.9 ± 11.3 years old. We evaluated the effect of order on those results of the confirmatory tests, comparing 2 groups; patients performed CCT after SIT (SIT-CCT) and those in opposite order (CCT-SIT). We interpreted CCT positive when aldosterone-renin ratio (ARR) after 50mg of captopril administration at 60 or 90 minutes. SIT is performed by 2L of saline infusion for 4 hours in the recumbent position and interpreted SIT positive when plasma aldosterone concentration (PAC) shows more than 60 pg/ml at 4 hours. We evaluated ARR after 60 and 90 minutes in CCT and the positive ratio between 2 groups, SIT-CCT group and CCT-SIT group.In our results, plasma renin activities (PRAs) at 60 and 90 minutes in CCT were significantly lower among SIT-CCT group than CCT-SIT group, 0.50 ± 0.52 vs. 0.68 ± 0.76, p=0.0317; 0.51 ± 0.49 vs. 0.66 ± 0.61ng/ml/hr, p=0.0207, respectively. PACs at basal, 60 and 90 minutes in CCT were also significantly lower among SIT-CCT group than CCT-SIT group, 9.6 ± 5.1 vs. 12.9 ± 8.4, p=0.0002; 8.5 ± 4.7 vs. 11.7 ± 8.4, p=0.004; 8.7±6.2 vs. 12.0±10.0ng/dl, p=0.0002, respectively. In the other hand, the basal PRAs, ARRs at 60 and 90 minutes showed no significant difference, nor the positive ratio of CCT (p=0.0778), either, although it was still tendency to increase to the positive ratio of CCT. The reason of increase the ratio thought to be stronger and longer suppression in PRAs than PAC.In conclusion, our result revealed no significant difference was shown on CCT positive ratio in our patients, though it still showed a tendency to increase the positive ratio with both suppression of PRAs and ARRs. Thus, the order of confirmatory tests may affect the diagnosis of PA, and those should be solved issues what order of confirmatory tests is required and how long should be leaved between the confirmatory tests. Saturday, June 1, 2024

Adrenal venous sampling (AVS) is the gold standard test for distinguishing between unilateral and bilateral primary aldosteronism (PA); however, AVS requires advanced and time consuming technique. The needs for AVS have been increasing due to the increased utilization of screening for PA. An efficient selection of unilateral PA, such as aldosterone-producing adenoma (APA), before AVS is useful to avoid undesirable AVS in bilateral PA, such as idiopathic hyperaldosteronism. In this study, 40 patients who received all three confirmatory tests, including the captopril challenge test, furosemide upright test and adrenocorticotropin (ACTH) stimulation test (AST), and who were diagnosed as having PA by AVS were recruited. Subjects were diagnosed as having unilateral aldosterone excess (n = 22) or bilateral aldosterone excess (n = 18) by AVS. All patients with unilateral PA underwent an operation and were finally diagnosed with APA. Major differences were detected in serum potassium level, basal plasma aldosterone concentration (PAC), presence of adrenal tumor, and AST results between the two groups. The PAC/cortisol ratio at 120 min in the AST showed the highest diagnostic capability for distinguishing the subtypes of PA according to a receiver operating characteristic (ROC) curve analysis (area under the ROC curve was 0.956). At a cutoff value of 1.20 for the PAC/cortisol ratio at 120 min on the AST, the sensitivity was 95.5%, and the specificity was 88.9%. This sufficiently high sensitivity suggests that the PAC/cortisol ratio at 120 min in the AST could be useful for the screening of patients with PA who are suitable for AVS.

Recent studies using the ratio of plasma aldosterone concentration (PAC) to PRA as the screening test for primary aldosteronism in hypertensive populations suggested that the prevalence may be as high as 5-15%, with well over half of the subjects having normal serum potassium concentrations. Despite an increasing clinical awareness of this entity, many clinicians are reluctant to consider routine screening for primary aldosteronism in essential hypertensive patients because there are few community-based prevalence studies of primary aldosteronism in different populations. Furthermore, genetic and environmental differences may affect the prevalence and presentation of primary aldosteronism in distinct populations. This study was designed to determine the prevalence of primary aldosteronism in the predominantly Chinese population in Singapore. Three hundred and fifty unselected adult hypertensive patients attending two primary care clinics had random ambulatory measurements for PAC (nanograms per dL) and PRA (nanograms per mL/h). Serum urea, creatinine, and electrolyte measurements were obtained simultaneously. Subjects with renal insufficiency (serum creatinine, >140 micromol/L) and those treated with glucocorticoids or spironolactone were excluded. Screening was considered positive if the PAC: PRA ratio was more than 20 and the PAC was more than 15 ng/dL (>416 pmol/L). Primary aldosteronism was confirmed with the determination of PAC after 2 L saline administered iv over 4 h. Adrenal computed tomographic (CT) scans were performed in biochemically confirmed cases of primary aldosteronism. Further localization with adrenal vein sampling was carried out in selected patients with equivocal findings on adrenal CT scan. Sixty-three (18%) of the 350 hypertensive patients (215 women and 135 men; age range, 23-75 yr) were screened positive for primary aldosteronism. Only 13 of these 63 subjects (21%) were hypokalemic (serum potassium, <3.5 mmol/L). Confirmatory studies were carried out in 56 (89%) of the subjects with a positive PAC:PRA ratio. Using a PAC above 10 ng/dL (>277 pmol/L) after saline infusion as the diagnostic cut-off, 16 of the 56 patients had biochemically confirmed primary aldosteronism. Hypokalemia was found in 6 of the 16 patients (37.5%) with primary aldosteronism. Subtype evaluation with adrenal CT scan and adrenal vein sampling indicated that half of the patients with primary aldosteronism may have had potentially curable unilateral adrenal adenoma. Our data suggest that primary aldosteronism occurs in at least 5% of the adult Asian hypertensive population, and approximately half of these individuals may have potentially curable, unilateral, aldosterone-producing adrenal adenoma. Our findings also confirm the poor predictive value of hypokalemia in both the diagnosis and the exclusion of primary aldosteronism.

Primary aldosteronism (PA) is a distinct cause of low-renin hypertension (LRH), characterized by inappropriate aldosterone production. We investigated the distinction between LRH and PA by leveraging the physiological effects of angiotensin-converting enzyme inhibition. We conducted a retrospective cohort study including 756 patients with LRH who underwent a captopril challenge test (CCT) for evaluation of PA. The distinction between PA and LRH was assessed using 4 CCT criteria: (1) Post-CCT plasma renin activity <1 ng/mL per hour and plasma aldosterone concentration decrease <30%; (2) Post-CCT aldosterone-to-renin ratio (ARR) >30 ng/dL per ng/mL per hour; (3) Post-CCT plasma renin activity <1 ng/mL per hour; and (4) Post-CCT plasma aldosterone concentration >11 ng/dL. Longitudinal outcomes following aldosterone-targeted therapy were assessed using the Primary Aldosteronism Surgery Outcome and Primary Aldosteronism Medical Outcome criteria. There was a continuous spectrum of nonsuppressible aldosterone production post-CCT. When interpreting CCT results based on both renin and aldosterone responses (criteria 1 or 2), 57.8% to 66.3% of patients were classified as having PA. In contrast, when based on aldosterone or renin responses alone (criteria 3 or 4), 82.5% to 95.1% of patients were classified as having PA. Complete or partial treatment response rates following aldosterone-targeted therapy were high, ranging from 86.5% to 91.7%, regardless of CCT interpretation. These findings highlight the blurred distinction between LRH and PA. Although persistently suppressed renin, or elevated aldosterone, following captopril facilitated the maximum capture of PA cases, the implementation of aldosterone-targeted therapy provided similar benefits to all patints, regardless of CCT interpretation. Empirical aldosterone-directed therapy for patients with LRH suspected of having PA may be an appropriate alternative to laborious diagnostics to confirm PA.

Objective To explore the screening, positive rate and curative effect observation after special treatment for primary aldosteronism (PA) in hypertensive in-patients with diabetes mellitus. Methods One hundred and seventy-eight hypertensive in-patients with diabetes were screened for PA.Patients with aldosterone/renin acrivity ≥554 pmol/L·[μg/(L·h)]-1 were defined the positive screening group, and remains were the negative screening group.PA was considered according on plasma aldosterone concentration (PAC) ≥138.5 pmol/L and PA was defined with PAC≥277.0 pmol/L after saline infusion test in the positive screening group. Results The level of potassium [(3.7±0.4)mmol/L] in the positive screening group was lower than that [(3.9±0.4)mmol/L] in the negative group, and the difference was statistically significant (t=-3.40, P<0.01). The prevalence of PA ranged from 14.0% to 23.0% respectively, due to 41 PA patients with PAC≥138.5 pmol/L and 25 PA patients with PAC≥277.0 pmol/L.Twenty-three patients with PA accepted the adrenal vein sampling (AVS), the operative successful ratio was 91.3%, 6 patients were defined on unilateral adrenal PA, 3 patients accepted adrenalectomy, 2 patients with adrenal producing adenoma and one patient with unilateral nodule hyperplasia were identified via the pathological diagnose after surgery.Twenty-three patients with PA, who had been performed AVS, were followed up 1~2 years after having accepted surgery or mineralocorticoid receptor antagonist.The level of systolic blood pressure [(132.0±7.67)mmHg] after treatment was lower than that [(150.0±14.0)mmHg] before treatment, the difference was statistically significant (t=5.63, P<0.01). The level of diastolic blood pressure [(85.0±7.0)mmHg] after treatment was lower than that [(96.0±5.0)mmHg] before treatment, and the difference was statistically significant (t=5.16, P<0.01). The level of potassium [(4.0±0.3)mmol/L] after treatment was higher than that [(3.5±0.4)mmol/L] before treatment, and the difference was statistically significant (t=-5.45, P<0.01). Conclusion A considerable amount PA patients exist in hypertensive subjects with diabetes mellitus.Screening and management for PA are suggested in these patients and the curative effect is affirmed. Key words: Hypertension; Diabetes mellitus; Primary aldosteronism

Currently, adrenal venous sampling (AVS) is the only reliable method to distinguish unilateral from bilateral hyperaldosteronism in primary aldosteronism (PA). However, AVS is costly and time-consuming compared with simple blood tests. In this study, we conducted a retrospective study to determine whether circadian variation in plasma adrenocortical hormone levels (i.e. aldosterone, cortisol and ACTH) and a 24-h urinary aldosterone could contribute to the clinical differentiation between unilateral hyperaldosteronism (UHA) and bilateral hyperaldosteronism (BHA). In 64 patients who were diagnosed with PA and underwent AVS, 32 and 22 patients were diagnosed with UHA and BHA, respectively. Plasma adrenocortical hormone levels at 0:00, 6:00, 12:00 and 18:00 and 24-h urinary aldosterone under a condition of 6 g daily dietary sodium chloride intake were measured. Baseline plasma aldosterone concentration (PAC) and 24-h urinary aldosterone level in patients with UHA were significantly higher than in patients with BHA, particularly at 6:00. The area under the ROC curve for PAC at 0:00, 6:00, 12:00 and 18:00 and 24-h urinary aldosterone to discriminate UHA and BHA was 0·839 [95% confidence interval (CI); 0·73-0·95], 0·922 (95% CI; 0·85-1·00), 0·875 (95% CI; 0·78-0·97), 0·811 (95% CI; 0·69-0·93), 0·898 (95% CI; 0·81-0·99), respectively. PAC at different blood sampling times and 24-h urinary aldosterone level may be diagnostically helpful in discriminating between UHA and BHA. We believe that these tests could reduce the number of unnecessary AVS procedures.

Background 44.7% adults in China have hypertension but the prevalence of primary aldosteronism (PA) in Chinese hypertensives is unknown. Objective We prospectively investigated the prevalence of PA in newly diagnosed hypertensives and tested the hypothesis that these PA patients have less severe cardiovascular complications and better outcomes when compared to those diagnosed after established (or prolonged) hypertension. Method In a community health center, consecutive hypertensive patients with an aldosterone-renin ratio≥2 (ng∙dL−1/mIU∙L−1) and plasma aldosterone concentration >10ng/dL underwent captopril challenge test and/or saline infusion test for confirmation. Adrenal CT scan and adrenal vein sampling were used for subtyping. PA patients were followed up for one year and clinical outcomes were compared with PA patients from an established hypertensive cohort. Results 1020 newly diagnosed hypertensive patients were screened over 16 months. Forty were diagnosed with PA, 948 with non-PA, resulting in a prevalence of 4.0%. Thirty-two patients were diagnosed as “possible PA” due to positive screening but failure to complete the confirmatory test. Compared to non-PA, PA patients more frequently displayed microalbuminuria (P=0.031), but the incidence of cardiovascular events was not different (P=0.927). For patients treated with surgery, complete clinical success rate was 85.7%, 28% higher than that of PA patients diagnosed after prolonged hypertension. For patients treated with medication, blood pressure control rate was 79.3%, 30% higher than that of PA patients diagnosed after prolonged hypertension. Conclusions The prevalence of PA in patients with newly diagnosed hypertension in China was at least 4.0%. PA screening in newly diagnosed hypertensive patients can lead to better clinical outcomes.

Context: Recent advances in genetic analysis techniques have led to the genetic analysis of adrenal tumors with hormone excess. In pheochromocytomas, many genetic abnormalities have been identified. Furthermore, several causative genes have been also reported in primary aldosteronism. We performed a comprehensive genetic analysis of functional adrenal tumors using next-generation sequencing. We report here a case of pheochromocytoma with KCNJ5 gene abnormality, which is considered to be specific for primary aldosteronism. Case: A 53-year-old woman with high blood pressure since age 48, excessive sweating and weight loss since age 52, and left ventricular hypertension noted on electrocardiogram during a medical checkup presented to her previous physician. A computed tomography scan of the abdomen showed a right adrenal tumor 30 mm in diameter, and an urinary test showed high levels of urinary metanephrine and normetanephrine (1.42 mg/day) and I-123 MIBG scintigraphy showed an accumulation at the tumor. Plasma renin activity was 0.2 ng/mL/hr, plasma aldosterone concentration was 73.9 pg/mL, and a positive captopril challenge test was performed. Adrenal scintigraphy using 131 I-adosterol showed bilateral adrenal accumulation, suggesting bilateral lesions. Laparoscopic right adrenalectomy was performed for pheochromocytoma. Histology showed focal proliferation of enlarged medullary-like cells and calcification of the adjacent adrenal tissue. The tumor tissue was positive for KCNJ5 gene mutation. A postoperative captopril challenge test was performed again, which was negative. Conclusion: KCNJ5 gene abnormality is considered specific for primary aldosteronism, but was also found in pheochromocytoma. However, the contribution of KCNJ5 gene abnormality to catecholamine production is not yet elucidated. This is a case of pheochromocytoma in which coexistence of primary aldosteronism is also suspected based on the captopril challenge test and imaging findings, and the finding of a gene mutation associated with primary aldosteronism in such a case is very interesting and will warrant further investigation.

Introduction: Primary aldosteronism (PA) is defined as a disease in which overproduction of aldosterone causes various complications such as hypertension, cardiovascular disorder and kidney disease. We herein report a case of PA caused by bilateral aldosterone-producing microtumors with a unilateral adrenal mass. Case presentation: A 54-year-old man was referred to our hospital with a clinical suspicion of PA. He had a history of hypertension and chronic kidney disease for 10 years and had experienced paresthesia that was caused by putaminal hemorrhage in the past. In the initial examination, he exhibited hypertension (150/90 mmHg), high aldosterone (pg/mL)-to-renin (ng/mL/h) ratio (1,744), and overt hypokalemia (K, 2.9 mEq/L). The serum creatinine level was 1.89 mg/dL. The captopril challenge test showed no changes in his blood pressure or plasma aldosterone concentration. These results led to a clinical diagnosis of PA. Computed tomography (CT) revealed the presence of left adrenal mass, so that we suspected that the mass should be responsible for overproduction of aldosterone. We performed adrenal venous sampling. Unexpectedly, the adrenal venous sampling highly suggested the presence of aldosterone-producing microtumors in bilateral adrenal glands (lateralized ratio, 1.3; left contralateral ratio, 0.2). After evaluation, we decided that there was no indication for the removal of left adrenal mass. Then, a low dose of a mineralocorticoid receptor (MR) antagonist was started. Although the dose of an MR antagonist could not be increased sufficiently due to poor renal function, he exhibited an improved control of blood pressure and was followed up thereafter. Discussion and Conclusion: Although PA is one of the most common causes of secondary hypertension, making an accurate diagnosis and appropriate treatment is sometimes problematic due to the difficulty in assessing the site of aldosterone overproduction. The Japanese Endocrine Society clinical guideline states that PA with unilateral adrenal tumor in young patients may not require adrenal venous sampling. From the current case, however, we should always consider the possibility of bilateral microtumors or hyperplasia even in the presence of a unilateral adrenal mass.

Disclosure: K. Zekarias: None. J. Kohlenberg: None. M. Xu: None. S. Ma: None.Background: Primary aldosteronism (PA) is a leading, often undiagnosed cause of secondary hypertension. Objective: This study aimed to develop an electronic-health-record (EHR) based machine learning model to predict PA in people with hypertension. Methods: We conducted a retrospective cohort study utilizing EHR data from 1,649 people screened for PA between April 13, 2018, and May 2, 2023 at an academic health system in the upper Midwest, USA. PA screening was conducted using standardized guideline recommended risk factor assessment. PA diagnosis was defined as 1) urine aldosterone > 12 µg/24h after oral salt loading or 2) PAC > 10 ng/dL 4 hours after saline infusion or 3) plasma aldosterone concentration (PAC) > 20 ng/dL with renin < 1 ng/mL/h or 4) Aldosterone to Renin Ratio (ARR) > 50 with PAC ≥ 10 ng/dL. We extracted 74 potential PA predictor variables from EHR data and applied various feature selection and classification methods to develop predictive models. Results: Among 1,649 people screened for primary aldosteronism (PA), 166 (10%) were diagnosed with PA. Compared to people without PA, those with PA were older (mean age 61 ± 13 years vs. 56 ± 17 years, p=0.001). There was no difference in gender (48% male, 52% female, p=0.7). The prevalence of PA among those screened was higher in Black patients (20%) compared to White patients (7%) and other racial groups (5%), with a statistically significant difference (p < 0.001). Those with PA exhibited increased end organ damage (48%) compared to those people without PA (37%, p=0.02).The model selection procedure resulted in a logistic regression model with 13 predictors, with cross validated area under the receiver operating characteristic curve (AUC) 0.7+/-0.021. Key risk factors predicting PA diagnosis were age, race, body mass index, hypokalemia, sodium and bicarbonate concentrations, high-density lipoprotein levels, obstructive sleep apnea, end stage renal disease, uncontrolled blood pressure (B/P >130/80), and prescription of > 4 blood pressure medications, diastolic blood pressure > 80, and Glomerular Filtration Rate (GFR).Discussion/Conclusion: We have developed a predictive model with moderate performance designed to optimize PA screening through risk stratification. Notably, the cohort in this study was screened for PA following current clinical guideline recommendations. The fact that our model achieved AUC=0.7 indicates that additional clinical information not currently included in the screening guideline can enhance screening performance. Following rigorous validation with prospective data, we aim to integrate this prediction tool directly into the clinical workflow as a decision support tool for PA screening. The clinical significance of this approach lies in its potential to enhance targeted screening for PA and to improve screening rates by leveraging a clinical workflow decision support tool.Presentation: Sunday, July 13, 2025

Disclosure: Z. Htut: None. N. Asmar: None. J. Agilinko: None. A. Alsafi: None. F. Wernig: None. Background: The role of adrenal vein sampling (AVS) in younger patients with primary aldosteronism (PA) remains debated. The Endocrine Society (ES) Guidelines suggest that AVS may be omitted in patients ≤35 years with marked PA (aldosterone &amp;gt;831 pmol/L, spontaneous hypokalaemia), and a solitary adrenal lesion consistent with an adenoma. While some centres follow this approach, others, including ours, perform AVS in all PA patients. However, relying solely on imaging may misclassify laterality in a substantial proportion of younger patients, potentially leading to inappropriate management decisions. Aim: To determine the accuracy of imaging alone in differentiating unilateral from bilateral PA in patients ≤35 years and assess the added diagnostic value of AVS. Method: We retrospectively analysed 364 PA patients who underwent AVS between 2011 to 2024, including 39 patients aged ≤35 years. Of these, 38 had pre-AVS imaging (CT/MRI). Two radiologists independently assessed imaging, blinded to AVS results, while two endocrinologists blinded to imaging, analysed AVS. Concordance between imaging and AVS was evaluated. Results: The mean age was 32 years, with 60% female. Median hypertension duration was 1.5 years (IQR: 1-5 years). All had biochemically confirmed PA with spontaneous hypokalaemia and required two to three antihypertensive medications. AVS was technically successful in all cases. Four patients were excluded due to inconclusive AVS results and missing imaging data.Among the remaining 35, imaging suggested unilateral adenomas (6-25 mm) in 82.9% (29/35), bilateral adenomas in 8.6% (3/35), and normal adrenal glands in 8.6% (3/35). However, AVS revealed discordant findings in 13.8% (4/29) of those with unilateral adenomas, indicating bilateral disease. Discordant cases had lateralisation index &amp;lt;2 (range: 1.3-2.0) and/or contralateral suppression index &amp;gt;1, suggesting bilateral PA. Only one discordant case met ES criteria for marked PA, while the remaining three had milder disease. All discordant cases were managed medically, whereas 86.2% (25/29) underwent unilateral adrenalectomy, with histologically confirmed adenoma. Conclusion: Although imaging correctly lateralised PA in 86.2% of cases, 13.8% of patients with apparent unilateral adenomas on imaging had discordant AVS findings, confirming bilateral disease. Notably, only one discordant case met the ES criteria for marked PA, supporting AVS omission in this subset. However, for patients with milder PA, AVS remains critical to prevent misclassification and unnecessary adrenalectomy, reinforcing its continued role in refining treatment decisions. Presentation: Monday, July 14, 2025

The number of centers with established adrenal venous sampling (AVS) programs for the subtype diagnosis of primary aldosteronism (PA) is limited. Aim was to develop an algorithm for AVS based on subtype prediction by computed tomography (CT) and serum potassium. A multi-institutional retrospective cohort study in Japan. A total of 1591 patients with PA were classified into four groups according to CT findings and potassium status. Subtype diagnosis of PA was determined by AVS. Prediction value of the combination of CT findings and potassium status for subtype diagnosis. The percentages of unilateral hyperaldosteronism on AVS were higher in patients with unilateral disease on CT than those with bilateral normal results on CT (50.8% vs 14.6%, P < 0.01), and these percentages were higher in those with hypokalemia than those with normokalemia (58.4% vs 11.5%, P < 0.01). The prevalence and odds ratio for unilateral hyperaldosteronism on AVS were as follows: bilateral normal on CT with normokalemia, 6.2% (reference); unilateral disease on CT with normokalemia, 23.8% and 4.8 [95% confidence interval (CI), 3.1 to 7.2]; bilateral normal on CT with hypokalemia, 38.1% and 9.4 (95% CI, 6.2 to 14.1), and unilateral disease on CT with hypokalemia, 70.6% and 36.4 (95% CI, 24.7 to 53.5). Patients with PA with bilateral normal results on CT and normokalemia likely have a low prior probability of a lateralized form of AVS and could be treated medically, whereas those with unilateral disease on CT and hypokalemia have a high probability of a lateralized form of AVS.

Identification of subsets of Aldosterone-Producing Adenoma (APA) with dynamic Adrenal Vein Sampling (AVS)