Bilateral Adrenalectomy for Primary Bilateral Macronodular Adrenocortical Hyperplasia With a Novel <i>ARMC5</i> Mutation Site

Primary bilateral macronodular adrenocortical hyperplasia (PBMAH) is a heterogeneous disorder, with clinical spectrum ranging from subclinical to severe overt Cushing syndrome (CS). Armadillo repeat containing 5 (<i>ARMC5</i>) mutations, found in 20-55% of cases, are often associated with more severe disease, and specific genotypes may correlate with distinct phenotypes. A 60-year-old woman was admitted with a 1-year history of progressive weight gain and hypokalemia, alongside a 13-year history of refractory hypertension. She exhibited classic CS features and metabolic complications, including hypertension and diabetes. Laboratory tests revealed elevated cortisol, suppressed adrenocorticotropic hormone (ACTH), and positive low- and high-dose dexamethasone suppression tests. Contrast-enhanced computed tomography (CT) showed bilateral irregular macronodular adrenal masses. Adrenal venous sampling (AVS) demonstrated no lateralization (lateralization index < 4). Whole-exome sequencing of peripheral blood leukocytes identified a novel <i>ARMC5</i> mutation (c.534_555dup, p.Ser186Profs*19). A right adrenalectomy was performed in 2023. Although symptoms improved, cortisol levels remained significantly elevated. Consequently, a left adrenalectomy was performed 15 months later in 2024, which led to marked improvement in her CS symptoms, biomarker levels, and metabolic complications. This case report describes a novel <i>ARMC5</i> mutation site in a PBMAH patient who ultimately required bilateral adrenalectomy. While AVS combined with CT can help determine the dominant side for surgery, patients with <i>ARMC5</i> mutations and symmetrically sized tumors often require bilateral adrenalectomy for cure.