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Objective To assess the usefulness of the upright posture stimulation test (UPT) in the confirmation of primary aldosteronism (PA) in patients in whom saline tests (ST) were inconclusive. Methods One hundred eighty-seven adult patients with possible PA were retrospectively included and compared to 25 control subjects. Blood samples were obtained after a 1-hour supine posture and during 2 hours of ambulation. An increase in plasma aldosterone concentration (PAC) ≥ 50% with a suppressed renin (≤10.1 ng/L; ≤1 ng/mL/hour) and a cortisol increase ≤50% were considered abnormal. Results PA patients had higher basal PAC and lower basal direct renin concentration (DRC) (P <.0001) and a higher maximal PAC (P =.0025) and lower maximal DRC (DRCmax) (P <.0001) during UPT compared to controls. PA was confirmed in 145 patients (77.5%), based on either oral/IV ST or UPT. DRCmax ≤12 ng/L during UPT was a predictor of PA (receiver operating characteristic curve sensitivity 93.8%, specificity 88%), and 95.6% of PA patients increased PAC ≥50% on UPT (median 222.2%), while renin remained suppressed. All 41 PA patients with false-negative IV ST (PAC < 162 pmol/L) and 88.9% with borderline response (162-240 pmol/L) had a DRCmax ≤12, while, respectively, 97.6% and 100% increased aldosterone by ≥50%. Similar responses to UPT were found in lateralized (28/63) and bilateral PA source (35/63). PA diagnosis increased from 23.6% to 88.8% using UPT results instead of IV ST and were confirmed at pathology and clinical outcome after adrenalectomy (n = 22). Conclusion UPT can be useful to confirm PA, particularly in patients with suspected false-negative ST. [ABSTRACT FROM AUTHOR]

Objective: Primary aldosteronism (PA) is one of the most frequent causes of secondary hypertension. Although clinical practice guidelines recommend a diagnostic process, details of the steps remain incompletely standardized. Design: In the present SCOT-PA survey, we have investigated the diversity of approaches utilized for each diagnostic step in different expert centers through a survey using Google questionnaires. A total of 33 centers from 3 continents participated. Results: We demonstrated a prominent diversity in the conditions of blood sampling, assay methods for aldosterone and renin, and the methods and diagnostic cutoff for screening and confirmatory tests. The most standard measures were modification of antihypertensive medication and sitting posture for blood sampling, measurement of plasma aldosterone concentration (PAC) and active renin concentration by chemiluminescence enzyme immunoassay, a combination of aldosterone-to-renin ratio with PAC as an index for screening, and saline infusion test in a seated position for confirmatory testing. The cutoff values for screening and confirmatory testing showed significant variation among centers. Conclusions: Diversity of the diagnostic steps may lead to an inconsistent diagnosis of PA among centers and limit comparison of evidence for PA between different centers. We expect the impact of this diversity to be most prominent in patients with mild PA. The survey raises 2 issues: the need for standardization of the diagnostic process and revisiting the concept of mild PA. Further standardization of the diagnostic process/criteria will improve the quality of evidence and management of patients with PA. [ABSTRACT FROM AUTHOR]

Context: In primary aldosteronism (PA), aldosterone secretion is relatively independent of the renin-angiotensin system, but can be regulated by several other stimuli.Objective: To evaluate aldosterone response to several stimuli in a series of patients with PA secondary either to bilateral adrenal hyperplasia (BAH) or unilateral aldosterone-producing adenoma (APA).Design and Setting: Prospective cohort study conducted in a university teaching hospital research center.Patients: Forty-three patients with confirmed PA and subtyped by adrenal vein sampling (n = 39) were studied, including 11 with BAH, 28 with APA, and 4 with undefined etiology. We also studied 4 other patients with aldosterone and cortisol cosecretion.Interventions: We systematically explored aberrant regulation of aldosterone using an in vivo protocol that included the following stimulation tests performed over 3 days under dexamethasone suppression: upright posture, mixed meal, adrenocorticotropin (ACTH) 1-24, gonadotropin-releasing hormone (GnRH), vasopressin, and serotonin R4 agonist.Main Outcome Measures: Positive response was defined as >50% renin or ACTH-independent increase in plasma aldosterone/cortisol concentration following the various stimulation tests.Results: Renin-independent aldosterone secretion increased in response to several aberrant stimuli (upright posture, GnRH) in up to 83% of patients with APA or BAH in whom ACTH 1-24 and HT4R agonists also produced aldosterone oversecretion in all patients. The mean significant aberrant responses per patient was similar in BAH (4.6) and in APA (4.0).Conclusions: Aldosterone secretion in PA is relatively autonomous from the renin-angiotensin system, but is highly regulated by several other stimuli, which contributes to the large variability of aldosterone levels in PA patients. [ABSTRACT FROM AUTHOR]

Context: Previous studies suggested that plasma aldosterone (PAC) response to ACTH stimulation could predict the subtypes of primary aldosteronism (PA) and avoid adrenal venous sampling (AVS). Objective: Assess the usefulness of peripheral (P) PAC response to ACTH stimulation during AVS to identify the source of aldosterone in patients with PA. Methods: Two hundred and fifteen patients were assigned to four different lateralization ratio (LR) groups based on different combinations of basal (≥ or <2) and post‐ACTH LR (≥ or <4). The P vein parameters analysed included as follows: mean basal PAC, maximal PAC (PACmax), and PAC/C ratio (PACmax/C), PAC absolute increase, PAC relative increase following ACTH bolus (250 mcg IV) and maximal variation of PAC/C ratio between post‐ACTH and basal measures. Results: Mean basal PAC was significantly higher in group 1 (basal LR > 2 and post‐ACTH > 4) than in group 2 (basal LR > 2, post‐ACTH < 4) or group 4 (basal LR < 2 post‐ACTH < 4) (P <.001). PACmax, PACmax/C and PAC absolute increase following ACTH were higher in group 1 than the others (P <.017). Using receiver operating characteristic (ROC) curves analysis of groups 1 and 4, best AUC were obtained with mean basal PAC (AUC: 0.757 95% IC: 0.653‐0.861), PACmax (AUC: 0.753 95% IC: 0.646‐0.860) and PACmax/C (AUC: 0.750 95% IC: 0.646‐0.853). Conclusion: P mean basal PAC and PACmax and PACmax/C are higher in basal and ACTH lateralized PA than in other groups. Peripheral PAC cut‐off values fail to adequately distinguish all groups and cannot replace the requirement to conduct AVS. [ABSTRACT FROM AUTHOR]

Context: Renin-angiotensin-aldosterone system (RAAS) activation is closely linked to obesity; however, the sex-specific associations between RAAS activity and body composition among individuals without obesity are not well understood., Objective: To investigate the associations of aldosterone and renin with body composition according to sex in the general population., Design: Population-based cohort study., Setting: Québec (Canada)., Participants: Adults aged 40 to 69 years enrolled in CARTaGENE between 2009 and 2010 (N = 3687)., Exposures: Plasma aldosterone and renin concentrations., Main Outcome Measures: Body composition assessed via anthropometrics (waist circumference and waist-to-hip ratio), bioelectrical impedance (lean body mass, fat mass, and muscle mass), and cardiac magnetic resonance imaging (epicardial and pericardial adipose tissue volumes)., Results: The mean (SD) age and body mass index were 55 (8) years and 27.3 (4.8) kg/m2, respectively. Among males, higher aldosterone and renin were associated with increased waist circumference, increased waist-to-hip ratio, increased fat mass, decreased lean body mass, and decreased muscle mass (P < .05). Aldosterone (P = .02), but not renin (P = .43), was associated with increased ectopic cardiac adiposity in males. In contrast, higher renin (P < .05), but not aldosterone (P ≥ .05), was associated with increased waist circumference, increased waist-to-hip ratio, and increased cardiac adiposity in females. Among females, higher renin and aldosterone were associated with increased fat mass (P < .05) but were not associated with lean body mass or muscle mass (P ≥ .05). All aforementioned associations were independent of body weight., Conclusion: Independent of body weight, increased RAAS activity is associated with unfavorable differences in body composition; however, the strength and pattern of association varies by sex., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Context: Primary aldosteronism (PA), a frequent but underdiagnosed cause of hypertension, is associated with a significant burden of cardiovascular and renal complications. Studies have reported divergent results regarding the diagnostic performance of seated saline infusion test (SSIT) and oral sodium loading test (OSLT), 2 confirmatory tests recommended by the Endocrine Society Clinical Practice Guidelines. To our knowledge, no study directly compared the results of SSIT and OSLT to diagnose overt PA., Objective: We assessed the diagnostic performance of SSIT and OSLT in a group of patients with hypertension and elevated screening aldosterone-renin ratio (ARR). The diagnostic standard was defined as hypertension with or without hypokalemia with an elevated screening ARR and at least 1 abnormal confirmation test including OSLT and SSIT., Methods: A monocentric retrospective study was conducted, including 87 patients with hypertension with a positive screening who underwent both SSIT and OSLT. A diagnostic performance analysis was conducted using urinary aldosterone at a threshold of 27 nmol/day as the criterion for OSLT, in comparison to a plasma aldosterone concentration (PAC) exceeding 140 pmol/L following the saline infusion., Results: A statistically significant difference in sensitivity was observed between OSLT and SSIT, with OSLT demonstrating superior performance ( P = .025). The aforementioned test exhibited concordance in 59 cases (65.5%), indicating that these methods are not equivalent (McNemar test P = .036)., Conclusion: OSLT demonstrated a significantly higher sensitivity for diagnosing overt PA in comparison with the SSIT in our cohort of patients with hypertension with an abnormal screening ARR., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)