Searching for peripheral proteomic markers of primary aldosteronism.

Metabolic syndrome (MetS) is a frequent clinical condition in hypertension patients and is more frequently reported in primary aldosteronism (PA). This study is aimed at investigating the prevalence of MetS and its components in the two major types of patients with adrenal venous sampling (AVS)-confirmed unilateral PA and bilateral PA. This was a retrospective cross-section study. We analysed metabolic parameters from 169 PA patients subtyped by AVS, including 85 unilateral PA patients and 84 bilateral PA patients, and we also included 169 non-PA patients matched for age and sex. Patients with unilateral PA had higher concentrations of aldosterone and lower serum potassium than patients with bilateral PA. However, patients with bilateral PA had higher prevalence of MetS (79.8% vs 64.7%, P=.029), obesity (40.5% vs 24.7%, P=.029), dyslipidemia (72.6% vs 55.3%, P=.019) and hyperglycaemia (29.8% vs 16.5%, P=.040) than those with unilateral PA. Meanwhile, bilateral PA had higher BMI (27.55±4.58 vs 25.57±3.28kg/m2 , P=.001), waist circumference (98.54±11.44 vs 93.32±10.64cm, P=.003) and fasting plasma glucose (4.98±1.16 vs 4.64±0.93mmol/L, P=.034). The logistic regression analysis also showed that bilateral PA was associated with the presence of MetS after adjustment for age, sex and duration of hypertension. Patients with bilateral PA have a higher prevalence of MetS than those with unilateral PA, despite unilateral PA patients exhibiting higher concentrations of aldosterone and lower serum potassium, suggesting that unilateral PA and bilateral PA may have differing mechanisms of MetS.

Introduction Primary aldosteronism (PA) is common, clinically elusive, and causes considerable morbidity and mortality. The current praxis of diagnosing PA is cumbersome, invasive, and depends on arbitrary thresholds. Very few cases are clinically discovered; new diagnostic methods are needed. Method Hypertensive patients were evaluated for PA in accordance with the current guidelines. Those diagnosed with PA underwent adrenal vein catheterization and/or adrenocortical positron emission tomography. Three groups were included: primary hypertension (HT), lateralized or unilateral PA (uPA), and bilateral PA (bPA). Serum from 11 HT, 16 uPA, and 12 bPA patients was subjected to microRNA extraction and sequencing. Serum from 29 HT, 26 uPA, and 29 bPA was subjected to a proximity extension assay on a cardiometabolic 384 protein panel (Olink® Explore 384). Result Several differentially expressed miRNAs were identified between the groups HT versus PA, but also uPA versus bPA. To validate our results in an external cohort, a machine learning model was developed and applied to an earlier published primary aldosteronism dataset (Decmann et al., 2019). This model could discriminate uPA from bPA successfully in 83% of the cases. Numerous significantly different proteins were observed between the groups. Interestingly, one of the coagulation factors had a distinct elevated expression in both uPA and bPA versus HT, which could be confirmed by an ELISA assay. Validation using an external cohort is underway. Discussion Further studies of serum biomarkers as a tool for identifying PA and discriminating between uPA and bPA may aid in the diagnosis and subsequently improve the treatment outcomes of PA.

Disclosure: M.A. Grytaas: None. P. Methlie: None. I. Marinelli: None. E. Zavala: None. M. Øksnes: None. T. Upton: None. K. Simunkova: None. D.A. Vassiliadi: None. K. Løvås: None. S. Bensing: None. I. Botusan: None. K. Berinder: None. G.M. Russell: None. G. Ueland: None. O. Kampe: None. S. Tsagarakis: None. S.L. Lightman: None. E.S. Husebye: None. Background: Primary aldosteronism (PA) is the most common cause of secondary hypertension but is grossly underdiagnosed. Early detection, accurate discrimination between unilateral and bilateral PA and appropriate treatment are vital to prevent cardiovascular and renal complications. The current workup however is a cumbersome, multistep process that may not detect dynamic aldosterone variability or nocturnal hypersecretion. Furthermore, subtype determination with adrenal venous sampling is invasive and technically challenging. Novel dynamic 24-hour steroid profiling may represent a major step forward in the diagnostics and subtyping of PA. Aim: To assess 24-hour rhythmicity of aldosterone and metabolites in PA, and to develop a novel dynamic diagnostic tool to discriminate PA from healthy subjects (HS), using tissue microdialysis. Material and methods: Twenty-minute frequency microdialysis fractions were collected over 24 hours from 64 ambulatory patients with PA (26 bilateral, 24 unilateral, 14 with undetermined subtype) using the U-Rhythm sampler followed by multiplex hormone assay liquid chromatography tandem mass spectrometry (LC-MS/MS). Sixteen patients subsequently treated with adrenalectomy for unilateral PA had additional postoperative samplings. Microdialysis samplings from 214 HS were used as controls. We calculated statistical distributions of dynamic biomarkers of abnormality, and developed a machine learning classifier that discriminates PA from HS. Results: Although there were large interindividual variations, PA patients did show a disturbed circadian rhythmicity of aldosterone compared with HS, including some with multiple very high ultradian spikes. Unilateral PA had higher aldosterone spikes and more disturbed rhythmicity compared with bilateral PA. A profound reduction of aldosterone levels and normalisation of rhythmicity was seen post adrenalectomy. Applying a Random Forest classifier in a subgroup of 20 PA patients, 82% specificity and 85% sensibility were achieved to discriminate PA from HS. Our analysis also suggests 18-hydroxycortisol as the most discriminative dynamic biomarker. Conclusions: We demonstrate for the first time circadian and ultradian rhythms of aldosterone in a large cohort of PA compared with HS. Based on our preliminary results, dynamic 24-hour samplings may provide a novel method for diagnosing and subtyping PA, and assess biochemical cure after adrenalectomy. Presentation: Thursday, June 15, 2023

Background and Aims Primary aldosteronism (PA) is one of the most frequent causes of secondary hypertension. Patients with PA are at higher risk for cardiovascular and renal complications than those with essential hypertension. Screening for PA is rarely considered in the assessment of a hypertensive patient, in part because of difficulties in the diagnostic process. Nevertheless, identification of PA is crucial to guide patients towards optimal management, either by mineralocorticoid receptor blockade or by unilateral adrenalectomy, with the latter offering potential cure for patients with aldosterone-producing adenomas (APAs). Numerous studies show inadequate diagnostic accuracy of the aldosterone:renin ratio (ARR) for screening for PA, particularly in females, who have higher ARR variability and lower renin compared to males. Women have a higher risk of false-positive screening results leading to unnecessary confirmatory tests. Use of oral contraception (OC) or hormone replacement therapy (HRT) may also confound the ARR. The aim of this study was to develop improved screening tools for PA, including adjustments for sex-specific differences. Method PROSALDO is a multicenter prospective cohort study designed to test new diagnostic procedures for patients with suspected PA. Medication that interfere with the renin-angiotensin-aldosterone system are withdrawn before laboratory measurements. For screening, the routine ARR is calculated along with additional probability scores based on a peripheral venous steroid hormone profile (PVSP). The latter allows for identification of potentially false-negative ARR results. After a positive screening result of the ARR and/or a high probability score based on the PVSP, PA is confirmed or excluded with a saline infusion test (SIT). PA confirmation is followed by adrenal venous sampling (AVS) to identify patients with unilateral PA. We compared aldosterone, renin and ARR levels between females and males with and without PA. Renin- and sex dependent formulas for aldosterone screening cut-offs were derived from the study population. Logistic regression and the corresponding receiver operating characteristic (ROC) curves were used to determine and compare diagnostic accuracies. Results PA was confirmed in 159 (24.5%) of 649 (328 (50.5%) females and 321 (49.5%) males). Lateralization was shown in 58 out of 117 patients who underwent AVS. In hypertensive patients without PA, ARR was higher in females vs. males (26.4 vs. 11.7 pmol/mU, P < 0.0001), mainly due to a lower renin (9.2 vs. 16.2 mU/L, P < 0.0001). Furthermore, ARRs in patients with vs. without PA showed more overlap in females compared to males. Areas under ROC curves (AUROCs) for the ARR were 0.857 (CI 95%: 0.797-0.902) vs. 0.912 (CI 95%: 0.876-0.938) for females and males respectively. Using liquid chromatography mass spectrometry measurements (LC-MS/MS) of aldosterone, an ARR cut-off of 21.75 pmol/L yielded a sensitivity of 93% with only 45% specificity in females, while for males, a specificity of 66% was obtained for a sensitivity of 97.7%. This meant for females having a higher risk of false-positive screening results (OR 2.36 (CI 95%: 1.65-3.41)), even after excluding patients on OC or HRT (OR 2.17 (CI 95%: 1.5-3.17)). We derived a renin- and sex-dependent formula for the calculation of aldosterone cut-offs, which improved diagnostic accuracy for both males and females (ΔAUROC = 0.05 and 0.045, P < 0.0001 and 0.02 respectively): for a diagnostic sensitivity of 94-95%, specificity was improved to 61% in females and 82% in males. Conclusion Lower renin in females without PA leads to higher ARRs and thus a higher risk of false-positive screening results. Higher overlap of the ARR between females with and without PA compared to their male counterparts weakens utility of the ARR for discrimination of patients with and without PA. Sex- and renin-specific aldosterone cut-offs for screening for PA offer improved diagnostic accuracy. Diagnostic accuracy remains however superior in males, which highlights the need for further optimization of diagnostic procedures specifically in women.

Primary aldosteronism (PA) adversely affects cardiovascular and renal health and has been linked to increased urinary calcium excretion, elevated parathyroid hormone (PTH) levels, and reduced bone mineral density. Although adrenalectomy and mineralocorticoid receptor antagonists (MRAs) are established treatments, their differential effects on calcium dynamics across PA subtypes remain unclear. We conducted a retrospective observational study, analyzing a large, well-characterized cohort on calcium metabolism in PA. A total of 352 patients with PA and 57 controls were evaluated. Clinical and biochemical parameters, including intact PTH (iPTH) and urinary electrolyte levels, were retrospectively assessed. Comparative analyses were performed before and after treatment in 43 patients with unilateral PA (UPA) and 131 patients with bilateral PA (BPA), with a direct comparison of adrenalectomy and MRAs in UPA. Patients with PA had higher urinary fractional excretion of calcium (FECa) (1.28% vs 1.04%, P < .001) and iPTH (60.0 vs 57.0 pg/mL, P = .047) than controls, with more pronounced abnormalities in UPA (FECa, 1.50%, iPTH 73.1 pg/mL). Both treatments reduced FECa and iPTH levels, but adrenalectomy resulted in greater improvement than MRAs in the UPA (FECa, 0.68% post-MRA vs 0.36% post-adrenalectomy). In the BPA group, MRAs decreased FECa, irrespective of disease severity. Adrenalectomy was associated with greater improvements in calcium abnormalities than MRAs in patients with UPA, consistent with its cardiovascular benefits. These findings underscore the importance of subtype-specific strategies and suggest that adrenalectomy may offer additional benefits beyond cardiovascular outcomes.

Current guidelines recommend adrenal venous sampling (AVS) to identify unilateral primary aldosteronism (UPA) before offering adrenalectomy. However, AVS is costly and technically challenging, limiting its use to expert centres. To establish a model to predict UPA, and therefore, bypass the need for AVS prior to surgery. The model was developed in a Chinese cohort and validated in an Australian cohort. Previously published prediction models of UPA were also tested. primary aldosteronism patients with a definite subtyping diagnosis based on AVS and/or surgery. Diagnostic value of the model. In the development cohort (268 UPA and 88 bilateral primary aldosteronism), combinations of different levels of low serum potassium (≤3.0 or 3.5 mmol/l), high PAC (≥15-30 ng/dl), low PRC (≤2.5-10 μIU/ml) and presence of unilateral nodule on adrenal CT (>8-15 mm in diameter) showed specificity of 1.00 and sensitivity of 0.16-0.52. The model of serum potassium 3.5 mmol/l or less, PAC at least 20 ng/dl, PRC 5 μIU/ml or less plus a unilateral nodule at least 10 mm had the highest sensitivity of 0.52 (0.45-0.58) and specificity of 1.00 (0.96-1.00). In the validation cohort (84 UPA and 117 bilateral primary aldosteronism), the sensitivity and specificity of the model were 0.13 (0.07-0.22) and 1.00 (0.97-1.00), respectively. Ten previous models were tested, and only one had a specificity of 1.00 in our cohorts but with a very low sensitivity [0.07 (0.04-0.10) and 0.01 (0.00-0.06) in our development and validation cohorts, respectively]. A combination of high PAC, low PRC, low serum potassium and unilateral adrenal nodule could accurately determine primary aldosteronism subtype in 13-52% of patients with UPA and obviate the need for AVS before surgery.

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

Analysis of left ventricular hypertrophy in patients with unilateral and bilateral primary aldosteronism

Primary aldosteronism (PA), a common cause of secondary hypertension, has a higher risk of cardiovascular complications than essential hypertension. To determine specific treatment for PA, subtype classification by adrenal venous sampling (AVS) is used. Sometimes, bilateral adrenal vein cannulation cannot be successfully performed. Previous studies have tried to use the data from unilateral adrenal vein cannulation, namely ipsilateral ratio (IR) and contralateral ratio (CR) in terms of aldosterone level, to interpret lateralization of aldosterone secretion. However, the cut-off values are still inconclusive. The objective of our study was to determine diagnostic performance using IR and CR in terms of adenoma location to identify functioning adrenal adenoma in patients with PA. Methods: The PA patients with unilateral adrenal adenoma who underwent AVS were included. The exclusion criteria were unsuccessful bilateral AVS or equivocal lateralization index (LI), i.e., values between 3 and 4. Successful AVS was assessed by sensitivity index, defined by adrenal vein/inferior vena cava (IVC) cortisol ratio of more than 5. The LI was calculated by dividing the higher aldosterone/cortisol ratio (dominant side) by the lower aldosterone/cortisol ratio (non-dominant side) obtained from adrenal vein samples. The LI of more than 4 indicated unilateral PA and those of less than 3 indicated bilateral PA. The IR was aldosterone/cortisol ratio at the side of adenoma divided by aldosterone/cortisol ratio at IVC. The CR was aldosterone/cortisol ratio at the side contralateral to the adenoma divided by aldosterone/cortisol ratio at IVC. Area under the receiver operating characteristic (ROC) curve was used to determine the diagnostic performance. The cut-off values giving the best sensitivity and specificity were determined. Results: Forty-three patients were included for analysis. Most patients (69.8%) were female with mean onset of hypertension at the age of 40.8±8.8years (SD). Median plasma aldosterone concentration and plasma aldosterone/renin activity ratio were 59.0 (IQR 44.2, 97.4) ng/dL and 1,020 (IQR 235, 4257), respectively. Thirty-five patients had unilateral PA, 7 patients had bilateral adrenal hyperplasia and 1 patient had unilateral adrenal hyperplasia. The area under ROC curve for identifying patients with functioning adrenal adenoma was 0.92 (95% CI; 0.81-1.00) when using IR and 0.78 (95% CI; 0.56-0.98) when using CR. The IR with the cut-off value of 1.2 had 89% sensitivity and 88% specificity. The CR with the cut-off value of 0.3 had 80% sensitivity and 75% specificity. Conclusion: The IR could be used to identify the functioning adrenal adenoma in PA patients with high accuracy.

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.

Primary aldosteronism (PA) is a major cause of hypertension and cardiovascular disease; however, diagnosing PA remains challenging. We investigated whether deep proteomic analyses could be used to diagnose unilateral PA in hypertensive patients. We enrolled 52 patients with unilateral PA and 46 with essential hypertension (EH) and divided them into training and validation cohorts. Plasma samples were collected at baseline from all patients and again from PA patients after adrenalectomy. Deep proteomic analysis was performed to identify peptide signatures used to develop a classification model distinguishing PA from EH in the training cohort. The classification model was subsequently tested in the validation cohort and post-adrenalectomy PA patients. After proteomic analysis, six peptide features including HBB, FIBA, Complement CO7, ALBU, C4BPA, and A2AP were selected to generate risk scores and develop a classification model for distinguishing unilateral PA from EH. Risk scores were significantly higher in PA patients compared to those with EH. The classification model had a sensitivity and specificity of 80.5% and 83.3%, respectively, for diagnosing unilateral PA in the training cohort, and 81.8% and 80.0% in the validation cohort. The model demonstrated strong performance with an area under the curve of .92 for distinguishing hypertensive patients with or without PA. Post-unilateral adrenalectomy, the risk scores showed a significant decrease. Proteomic analysis can identify peptide signatures that effectively distinguish unilateral PA from EH. These findings underscore the potential utility of proteomics as an adjunct diagnostic and monitoring tool in the clinical management of PA.

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: S. Rolak: None. N. Venkatesan: None. R. Gregg Garcia: None. W.F. Young: None. I. Bancos: None. Background: Bilateral primary hyperaldosteronism (PA) is treated with mineralocorticoid receptor antagonist (MRA) therapy. However, the best way to monitor the success of MRA therapy is unclear. Aims: To compare the impact of curative adrenalectomy versus MRA therapy in patients with PA on plasma renin activity (PRA), renal function, and hypertension control. Methods: Single center retrospective study of patients with unilateral PA treated with adrenalectomy or bilateral PA treated with MRAs, 2017-2021. Patients underwent adrenal vein sampling to confirm laterality. Hypertension control was defined based on blood pressure measurements and the standardized hypertension daily dose (HDD). Minimum follow-up was defined as first nonsuppressed PRA or &amp;gt;1 month from therapy. Results: Of 73 patients, 53 underwent unilateral adrenalectomy for unilateral PA (median age 57, range 25-71 years, 36% women) and 20 had bilateral PA treated with MRA (median age 49, range 30-70 years, 70% women). At baseline, when compared to the bilateral PA, patients with unilateral PA had higher plasma aldosterone concentrations (median 31 ng/dL vs 19 ng/dL, P= 0.001), similarly suppressed PRA, and similar estimated glomerular filtration rate (eGFR). Uncontrolled hypertension (&amp;gt;130/90 mmHg) was seen in 40 (75%) of patients with unilateral PA and 14 (70%) patients with bilateral PA, despite a more intensive antihypertensive regimen in unilateral PA (median HDD 5, range 1-18 vs median HDD 3.5 in bilateral PA, range 0.5-9; P=0.016). Hypokalemia was present in 50 (94%) patients with unilateral PA and 15 (75%) in bilateral PA, P = 0.02.Following treatment, hyperkalemia developed in 10 (19%) patients post-adrenalectomy and in 2 (10%) patients treated with MRAs, P = 0.36. At a median follow up of 108 days, 24 (45%) patients treated with adrenalectomy and 16 (80%) patients treated with MRAs demonstrated PRA &amp;gt;1.5 ng/mL/hr, P = 0.008. eGFR decreased by at least 10 points in 15 (30%) patients treated with adrenalectomy vs in 11 (59%) patients treated with MRAs (P=0.033). Post-adrenalectomy, antihypertensive management lessened by a median of 2.5 HDD, while HDD increased in patients treated with MRAs by a median of 1.25, P&amp;lt;0.0001. Hypertension control improved, with a mean decrease in systolic blood pressure of -11 mmHg (95%CI -16.5-(-5.5)) without between group differences. Diastolic blood pressure decreased by a mean of -4.7 mmHg (95%CI -8.7-(-0.7)) in the adrenalectomy group but did not change in those treated with MRAs. Conclusions: Following curative adrenalectomy in unilateral PA, more than half of patients continue to have suppressed PRA. Despite less severe PA at baseline, patients treated with MRAs, as compared to those treated with adrenalectomy, demonstrate a higher prevalence of non-suppressed PRA, lower eGFR, similar hypertension control, and a more intense antihypertensive regimen during follow up. Presentation: Thursday, June 15, 2023

Background: Correct subtyping of primary aldosteronism (PA) is critical for guiding clinical management. Adrenal imaging is less accurate than adrenal vein sampling (AVS); nonetheless, AVS is invasive, technically challenging and limited to specialty centers. Objective: We aimed to identify predictors of concordance between computed tomography (CT) and AVS in patients with unilateral PA, which could circumvent the need for AVS in a subset of PA patients. Methods: We retrospectively studied all patients with confirmed PA who underwent AVS in our institution between 2009-2018. Simultaneous AVS samples were obtained both before and 10-30 minutes after cosyntropin stimulation. Only patients with unilateral (U) PA, based on a lateralization index (LI) ≥ 4 pre- and/or post-cosyntropin were included from this study. Demographic, laboratory and imaging data were collected. Aldosterone synthase (CYP11B2)-guided targeted next generation sequencing was performed in available cases. Chi-square test was used to compare proportions between two groups. Logistic regression was performed to identify predictors of CT-AVS lateralization concordance. Results: In total, 177 patients, 107 (60.5%) men, with a mean age of 52 years (range 25-79), met our study requirements. Of these, 124 (73%) patients were Caucasian (CA), 41 (24%) African American (AA) and 5 (3%) Asian (AS). AVS subtyping was concordant both pre- and post-cosyntropin (UU) in 118 (67%) patients and discordant in 59 (23%) patients (UB, 36; BU, 23). The mutation status was analyzed in 62 patients who underwent adrenalectomy and identified: 30 KCNJ5, 18 CACNA1D, 8 ATP1A1, 5 ATP2B3 and 1 CTNNB1 mutations. AVS-CT agreement was higher in patients with KCNJ5 than in those with other aldosterone-driver somatic mutations (90% vs. 59%, p<0.01); in AS and CA than in AA patients (80%, 70% and 32%, respectively); in UU patients than in the discordant group (69% vs. 44%, p<0.01); and for single left vs. right adrenal mass on CT (74% vs 46%, p<0.01). After adjusting for sex, LI, contralateral suppression, aldosterone concentrations, and dominant side, the size of the lesion and young age were also associated with a higher likelihood of AVS-CT agreement. Two patients age <40 y (25 y and 36 y) had CT-AVS discrepancy. LI, aldosterone concentrations in the dominant adrenal vein and periphery, contralateral suppression, and sex did not predict concordance of CT- and AVS-based PA lateralization. Conclusions: Agreement between AVS and CT for lateralizing PA is higher with young age, CA and AS race, larger adrenal lesions, and CT abnormalities in the left adrenal gland. Nonetheless, CT-based predictors remain poor compared to AVS, even in young patients with U PA.

Current clinical guidelines of primary aldosteronism recommend adrenalectomy (AdX) for unilateral primary aldosteronism based on the studies showing the potential superiority of AdX over the medical treatment. However, since most medically treated cases consisted of bilateral primary aldosteronism and all surgically treated cases consisted of unilateral primary aldosteronism, the different subtype of primary aldosteronism could be a bias for their effects. This study compared the effects of AdX and medical therapy in patients with unilateral primary aldosteronism confirmed by adrenal vein sampling. Of the 339 patients with unilateral primary aldosteronism in the Japan Primary Pldosteronism Study data base, unilateral AdX and treatment with mineral corticoid receptor antagonists (MRAs) was done in 276 patients (AdX group) and in 63 patients (MRAs group), respectively. The effects were compared by the clinical (improvement of blood pressure) and biochemical outcomes (improvement of hypokalemia). At baseline, use of potassium replacement, plasma aldosterone concentration, aldosterone-to-renin ratio, estimated glomerular filtration rate, and prevalence of adrenal mass on imaging were higher in the AdX group than in the MRAs group. At 6 months after commencement of specific treatment for primary aldosteronism, clinical outcome and biochemical outcome in the AdX group were superior than those in the MRAs group. The difference of the outcome between the two groups were the case even after adjusting for the different clinical backgrounds in the two groups before the specific treatment. Our study provides evidence that AdX is the first choice of treatment in the patients with unilateral primary aldosteronism in terms of clinical and biochemical outcome.