Araujo‐Castro, Marta

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.

Abstract Context Most of the patients included in the clinical trials and real-world studies with osilodrostat only include patients with adrenocorticotropic hormone dependent Cushing syndrome (CS), while data on the efficacy and safety of osilodrostat in patients with adrenal CS is scarce. Objective To assess the efficacy and safety of osilodrostat in adrenal CS. Methods International study of patients with adrenal CS: patients treated with osilodrostat at any time were enrolled in the safety evaluation and those treated for longer than 4 weeks, in the efficacy evaluation. Patients were classified as responders if they experienced a reduction in urinary free cortisol (UFC) >50% (complete responders when UFC levels were below the upper limit of normal [ULN] and partial responders if there was a reduction >50% but not normalization). Results Twenty-eight patients with adrenal CS were enrolled: 16 with adrenocortical carcinoma and 12 with benign disease. Osilodrostat was used in monotherapy in 22 patients and in combination with metyrapone in 6 cases. In those patients treated for longer than 4 weeks (n = 21), 66.7% were classified as responders (28.6% with complete response and 38.1% with partial response), and for those treated for longer than 12 weeks, the rate of response increased to 87.5% The use of osilodrostat as a nonfirst-line therapy (odds ratio 15.0, P = .010) was a predictor of response. Osilodrostat led to a significant decrease in systolic blood pressure and body weight (P < .05). Nine patients developed one or more adverse events and in 56% (n = 5) led to osilodrostat discontinuation. Conclusion Osilodrostat controls hypercortisolism in 66.7% of patients with adrenal CS treated for longer than 4 weeks and in 87.5% of cases treated for longer than 12 weeks, with a positive impact on blood pressure and body weight. Patients who received osilodrostat after other previous steroidogenesis inhibitors have a higher probability of response.

Abstract Background Primary aldosteronism (PA) is a common treatable cause of hypertension. When caused by unilateral adrenal disease, it is potentially curable by adrenalectomy. However, specialized tests and other factors may delay definitive treatment. We assessed the time to adrenalectomy (TTA) for patients worldwide. Methods We conducted an international, multicentre retrospective study involving 39 centres from 15 countries to determine the total time taken from the first presentation to adrenalectomy and the intervals between each stage (screening, confirmatory, subtyping, and adrenalectomy). We included patients with PA who underwent adrenalectomy from January 1, 2018, to October 30, 2022. Post-adrenalectomy outcomes were evaluated using the Primary Aldosteronism Surgery Outcome criteria. We performed multivariable quantile and linear regression to identify characteristics associated with longer TTA. Results We included 861 patients, mean age 49.3 ± 11.1 years, and 44.5% were women. Overall median TTA was 13.5 months, IQR: 6.6-24.5. Median intervals were 0.1 months (screening), 1.0 months (confirmatory), 4.1 months (subtyping), and 4.3 months (adrenalectomy). On multivariable analysis, median TTA was increased by 5.4 months for each additional adrenal vein sampling (AVS) procedure. Other factors associated with longer TTA included adrenalectomy post-COVID-19, younger age, and additional screening tests. Compared with countries with routine AVS, those without AVS had a shorter TTA (6.1 vs 15.1 months, P < .001), but greater likelihood of absent/partial biochemical success post-adrenalectomy (27.4% vs 12.4%, P < .001). Conclusion Primary aldosteronism management is time-consuming worldwide, especially for subtyping tests and adrenalectomy. While omitting AVS reduces overall time, patients are less likely to achieve biochemical cure post-adrenalectomy.