Primary aldosteronism (PA) is the most common cause of endocrine arterial hypertension, and the suggested screening test for case detection is the aldosterone-to-renin ratio (ARR) or aldosterone-to-direct renin ratio (ADRR) based on radio-immunoassay (RIA) and chemiluminescence assay (CLIA), respectively. The objective of our study was to evaluate the reliability of CLIA for aldosterone and renin measurement and the diagnostic performance of ADRR. A prospective cohort of 1110 patients referred to a single laboratory medicine center underwent measurement of aldosterone and direct renin concentration (DRC) by CLIA and measurement of aldosterone and plasma renin activity (PRA) by RIA. Of 1110 patients, 640 obtained a final diagnosis of hypertension, and 90 of these patients were diagnosed with PA. Overall, between-method correlation was highly significant for aldosterone concentrations (R = 0.945, p < 0.001) and less strong but significant for DRC/PRA (R = 0.422, p < 0.001). Among hypertensive patients, in PA cases, the areas under the receiver operator characteristics (ROC) curves were 0.928 (95% confidence interval 0.904–0.954) for ADRR and 0.943 (95% confidence interval 0.920–0.966) for ARR and were comparable and not significantly different. The highest accuracy was obtained with an ADRR cut-off of 25 (ng/L)/(mIU/L), displaying a sensitivity of 91% and a specificity of 85%. The chemiluminescence assay for aldosterone and DRC is a reliable method for PA diagnosis compared to the classical RIA method.

Context: Perioperative use of mineralocorticoid receptor antagonists (MRA) in patients with unilateral primary aldosteronism (PA) awaiting surgery is not well standardized. Objective: The aim of this study was to compare the risk of postoperative complications and surgical outcomes between PA patients treated with MRA prior to adrenalectomy and those not pretreated. Methods: Adrenalectomized patients for unilateral PA from the SPAIN-ALDO registry, with clinical, hormonal, and treatment information before and after adrenalectomy, were analyzed. Results: A total of 355 surgically treated patients were included; 76.9% (n = 273) received presurgical treatment with MRA (spironolactone [64.5%], eplerenone [35.5%]). Adrenalectomy was guided by lateralization at adrenal venous sampling in 33.5% of the overall cohort, and by imaging in all the other cases. Patients pretreated with MRA had longer duration of hypertension, higher prevalence of hypokalemia, and greater aldosterone concentrations than those not pretreated (n = 82). No differences in the rate of postsurgical hyperkalemia, hypoaldosteronism, renal function impairment, blood pressure changes, and biochemical outcomes were detected between groups in the immediate (≤30 days) and short-term (≤90 days) follow-up evaluations after surgery. At long-term follow-up (≥6 months), patients pretreated with MRA exhibited better postsurgical biochemical outcomes (81.7% had complete biochemical response vs 57.1% of non-pretreated patients; P = .004). In the multivariable analysis, the use of MRA prior to adrenalectomy was independently associated with a successful postsurgical biochemical response. Conclusion: Preoperative MRA therapy can be safely introduced to control blood pressure and potassium levels in patients with PA awaiting surgery, without increasing the risk of postoperative hyperkalemia, hypoaldosteronism, renal impairment, or hypotension.

Objective: This study aims to analyze current medical management of primary aldosteronism (PA) in Spain, including doses, adverse events (AEs), and efficacy. Methods: SPAIN-ALDO is a national, multicenter, retrospective registry of patients with PA in Spain. For this study, information about medical treatment with mineralocorticoid receptor antagonist (MRA) as first-line or postsurgical therapy and about antihypertensive medications used before PA targeted treatment (MRA or adrenalectomy) was included. We reported surgically and medically treated patients at baseline and at last available follow-up and evaluated clinical and biochemical responses according to Primary Aldosteronism Surgical Outcome (PASO) and Primary Aldosteronism Medical treatment Outcome (PAMO) criteria. Results: A total of 997 patients with PA were included. Before PA diagnosis, the classes of antihypertensive drugs most used were calcium-channel blockers (66%) and angiotensin II receptor blockers (48.4%). Of the initial cohort, 880 patients had at least 1 visit available after initiation of MRA (N = 511 as first-line therapy, N = 47 postsurgery) or adrenalectomy (N = 322). The median defined daily dose of MRA therapy was 1.33. Spironolactone was more prescribed than eplerenone (58% vs 42%). Eplerenone was better tolerated than spironolactone (AEs in 4% vs 18%), particularly among males. After a median follow-up of 35 and 17 months for medically and surgically managed patients, the latter achieved a complete biochemical (68.1%) or clinical (33.6%) response more frequently than people under MRA as first-line therapy (48.6% and 15.7%; P < .001). Conclusion: This study underscores the need to optimize PA medical management in Spain to improve patient clinical and biochemical outcomes, since currently the proportion of patients achieving complete clinical and biochemical response with MRA is quite low.

Objective: To evaluate the efficacy and safety of osilodrostat in patients with Cushing’s disease (CD). Methods: A retrospective, multicenter, real-world study of patients with CD. The main efficacy endpoint was the proportion of patients who were complete responders (urinary free cortisol [UFC] < the upper limit of normal and/or with adrenal insufficiency development). Results: Thirty-seven CD patients were enrolled. There were 33 patients who initially received osilodrostat in monotherapy and 4 in combination. However, 3 patients of the monotherapy group were switched to combination therapy. The median duration of osilodrostat treatment was 5 months (range 1–93). All the patients were classified as responders: 33 (89.2%) had complete response and 4 partial response. A positive correlation was detected between the percentage of UFC decrease and the maximum (r = 0.481, p = 0.006) and the maintenance doses (r = 0.440, p = 0.011). The initial doses of osilodrostat were a predictor of complete response (vs. partial) (Odds ratio [OR] 2.82, p = 0.030). The median time to UFC normalization in the group of complete responders was 4 weeks (range 1–20) and UFC normalized before or at month 1 in 67% (n = 20/30) of the patients. Osilodrostat led to a significant decrease in systolic and diastolic blood pressure in parallel with a reduction of antihypertensive medications. Conclusions: Osilodrostat leads to a complete UFC normalization in up to 90% of the patients with CD, in parallel with an improvement in the cardiometabolic profile. A proper titration of osilodrostat is important to achieve a complete response since a positive correlation between the doses and the UFC reduction was observed.

Aims: Bariatric surgery (BS) reduces obesity-associated systemic inflammation leading to multiple cardiovascular (CV) and metabolic benefits. Here, we tested whether measuring vaso-inflammatory cytokines, gut hormones, and circulating extracellular vesicles (EV) provide vaso-inflammatory-metabolic signatures that better correlate to CV-metabolic outcomes after BS, compared to a standard clinical assessment including body weight (BW) loss and traditional CV risk factors. Methods and results: In 111 patients with severe obesity, conventional clinical-biochemical parameters and non-conventional vaso-inflammatory-metabolic markers were analysed at baseline, after 1- (T12) and 3-years (T36) post-BS and were associated to post-surgical BW loss and improvement of patients’ CV-metabolic profile. Body weight decreased from a median of 111 to 77 Kg at T36 (30 Kg and 32.8% BMI cumulative reduction), and all traditional CV risk factors improved after BS. However, the baseline evaluation of these parameters was unable to discriminate patients according to their CV-metabolic outcome, after BS. This objective was achieved combining the decrease in circulating serum amyloid associated protein, IL-6, TNF-α, and insulin after BS, together with the increase of GLP-1, ghrelin, PYY and bile acids, and changes in EV profiling. Of note, a specific signature given by the reduced expression of several surface antigens carried by EVs and specific single EV markers (i.e. derived from endothelium, platelets, inflammatory cells), successfully discriminated patients at baseline according to their CV-metabolic post-surgical outcome. Conclusion: Non-conventionally measured vaso-inflammatory-metabolic signatures, and in particular EV profiling, are associated with CV-metabolic outcome after BS and may be integrated to conventional parameters to improve the management and risk stratification of these patients.

BACKGROUND: Primary aldosteronism (PA) is a common and treatable cause of hypertension, yet data on the durability of medical treatment response beyond the first year are limited. Using the PA medical treatment outcomes framework, we evaluated long-term biochemical and clinical outcomes and factors associated with treatment response. METHODS: We conducted an international, multicenter, observational cohort study across 27 centers on 4 continents. Adults with PA treated with mineralocorticoid receptor antagonists and/or epithelial sodium channel blockers between 2016 and 2021 were included if follow-up data were available at ≥12 months. Biochemical and clinical responses were classified as complete, partial, or absent using PA medical treatment outcomes criteria. Ordinal logistic regression identified determinants of a favorable treatment response. RESULTS: The cohort included 1292 patients (47.5% women, mean age 52 years) with a median follow-up of 34 months (interquartile range, 21–51). At ≥12 months, 58.3% achieved a complete biochemical response, and 20.8% achieved a complete clinical response, with only 5% showing no response. Determinants of a favorable biochemical response included lower aldosterone and lateralization index, and higher renin and potassium levels at baseline. In those taking spironolactone, a higher daily dose was also associated with a favorable biochemical response. Determinants of a favorable clinical response included female sex, lower body mass index, shorter duration of hypertension, and absence of hypertension-mediated organ damage. CONCLUSIONS: Targeted medical therapy for PA can deliver sustained biochemical and clinical benefits. Early disease detection and adequate dose titration are highly actionable determinants of long-term treatment success.