Bilateral macronodular adrenocortical disease with isolated primary aldosteronism and normocortisolemia: a case...

Primary aldosteronism (PA) is a common cause of secondary hypertension. Bilateral macronodular adrenocortical disease (BMAD) with ARMC5 mutations is classically associated with hypercortisolism. This report describes a 54-year-old female with hypertension and hypokalemia, biochemically confirmed as PA, and imaging showing bilateral adrenal macronodules. Postoperative peripheral blood genetic testing identified a germline ARMC5 frameshift insertion (c.337dup). Whole-exome sequencing of the resected adrenal tissue revealed an additional somatic frameshift deletion (c.277_316del, p. P93fs, VAF 43.1%) absent in blood, demonstrating biallelic ARMC5 inactivation. Following unilateral adrenalectomy, the patient's aldosterone levels normalized. This case shows that ARMC5 mutations can cause isolated mineralocorticoid excess without hypercortisolism, expanding the known phenotypic spectrum. Genetic testing for ARMC5 should be considered in patients with bilateral adrenal enlargement regardless of steroid hormone profile.