Cardiometabolic Burden in Bilateral Macronodular Adrenal Disease With Primary Aldosteronism

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BACKGROUND: Bilateral macronodular adrenocortical disease is often linked to autonomous cortisol secretion, but may also present with primary aldosteronism (PA). METHODS: This international (Europe, United States, Asia) retrospective cohort study included adults with radiological evidence of bilateral macronodular adrenocortical disease and biochemically confirmed PA. The primary endpoints was major adverse cardiovascular events (MACE); secondary end points included cardiometabolic comorbidities and surgical outcomes per PA surgical outcome criteria. RESULTS: Two hundred forty-nine patients from 41 centers in 12 countries were included (median age, 55 years; 62% male). Median hypertension duration at PA diagnosis was 9.9 years. Among 178 tested, 52% had cortisol cosecretion and 47% isolated PA. At baseline, 56% had metabolic comorbidities, and 16% had ≥1 MACE. Patients with MACE were older, more often male, had longer hypertension duration, and higher diabetes rates. Eighty-nine patients underwent adrenalectomy: 50 without MRA (mineralocorticoid receptor antagonists), 38 with MRA, and 1 with steroidogenesis inhibitors. One hundred twenty-four patients received continued MRA without adrenalectomy or steroidogenesis inhibitors. Adrenal venous sampling showed lateralized PA in 89% of surgical versus 19% of MRA-treated patients ( P <0.001). Over a median follow-up of 36 (MRA) and 18 months (surgery; P =0.2), MACE occurred in 8% and 6%, respectively ( P =1.0). Blood pressure and organ damage were similar, but more MRA-treated patients needed ≥3 antihypertensives (MRA: 48% versus adrenalectomy: 14%; P <0.001). Among operated patients, complete clinical and biochemical success was 26% and 71%, respectively. CONCLUSIONS: Bilateral macronodular adrenocortical disease with PA carries a high cardiometabolic burden. Early detection and precise subtyping are key to optimizing management and preventing target organ damage.

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