OR05-05 Origins of aldosterone and cortisol production in patients with primary aldosteronism and autonomous cortisol secretion

Abstract Disclosure: E.Z. Kawahara: None. J. Okubo: None. T.S. Goldbaum: None. F.L. Ledesma: None. J.L. Chambo: None. L.A. Bortolotto: None. A. Pio-Abreu: None. G.V. Silva: None. L.F. Drager: None. M.C. Fragoso: None. W.C. Nahas: None. M.N. Zerbini: None. A. Latronico: None. B.B. Mendonca: None. M.Q. Almeida: None. Background: Approximately 25% of patients with primary aldosteronism (PA) exhibit mild autonomous cortisol secretion (MACS). Patients with PA and MACS have an increased incidence of cardiovascular events compared to patients with PA without MACS. However, the characterization of aldosterone lateralization, histopathology, and outcomes among patients with PA and MACS is not well established. Aims: To evaluate the origins of aldosterone and cortisol secretion in patients with PA and MACS who underwent adrenalectomy, and to compare clinical and biochemical aspects, histology and outcomes between PA patients with and without MACS. Methods: We conducted a cohort study including 197 patients with PA who underwent investigation for MACS using a 1 mg dexamethasone suppression test at a single tertiary center. MACS was characterized by cortisol ≥ 1.8 mcg/dL with dexamethasone levels > 130 ng/dL. Histology was investigated using CYP11B2 and CYP11B1 immunostaining in adrenal lesions. Results: MACS was diagnosed in 52 (26.4%) out of 197 patients with PA. Among the 52 patients with MACS, 29 (55.8%) underwent adrenal venous sampling (AVS) under cosyntropin stimulation, and 25 (48.1%) underwent surgical treatment. Patients with PA and MACS were statistically significantly older at the time of PA diagnosis compared to patients with isolated PA (57.15 [33 - 74] vs. 52.58 [20 - 76] years; p = 0.014). Other clinical and biochemical features at diagnosis and PASO outcomes were not different between the two groups. Moreover, the frequency of unilateral and bilateral PA was 48,3% and 51,7% in patients with PA and MACS, respectively. Interestingly, aldosterone and cortisol were produced by different adrenal lesions in 6 (33.3%) out of 18 cases. This included five cases with a unilateral cortisol-producing adenoma (negative for CYP11B2) and bilateral aldosterone-producing nodules or micronodules (positive only for CYP11B2), and one case with bilateral adenomas (one was positive for CYP11B1 and the contralateral was positive for CYP11B2). The remaining 12 (66.6%) patients had a unilateral adenoma producing both aldosterone and cortisol. Conclusion: For the first time, we demonstrate that aldosterone and cortisol originate from distinct adrenal lesions one-third of patients with PA and MACS. This finding has critical implications for the interpretation of AVS and the planning of surgical treatment. Support: Sao Paulo Research Foundation (FAPESP) grant 2019/15873-6 (to M.Q.A.) Presentation: Saturday, July 12, 2025