A Novel ARMC5 Germline Variant in Siblings With Primary Bilateral Macronodular Adrenal Hyperplasia and Colonic Adenomas

一对患有原发性双侧肾上腺大结节性增生和结肠腺瘤的兄弟姐妹中发现一种新的ARMC5种系变异

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Abstract

We report 2 siblings with primary bilateral macronodular adrenal hyperplasia (PBMAH). Both case 1, a 61-year-old male, and case 2, his 54-year-old brother, presented with incidentally discovered multiple nodules in bilateral adrenal glands on computed tomography (CT) scan. There was no family history of endocrine disease nor visible signs of Cushing syndrome. Early morning adrenocorticotropic hormone (ACTH) levels were low, and a dexamethasone suppression test revealed unsuppressed cortisol, leading to a diagnosis of PBMAH with mild autonomous cortisol secretion (MACS). Examinations for extra-adrenal lesions detected colorectal adenomas in both patients. Genetic analysis revealed a novel germline pathogenic variant (c.2647del) in the armadillo repeat containing 5 (ARMC5) gene in both cases. Because both patients preferred not to undergo surgery, we opted to follow their condition with periodic imaging studies, including CT and colonoscopy. Our experience suggests that ARMC5 gene pathogenic variants are associated with colorectal tumors as well as PBMAH. Therefore, periodic screening with colonoscopy should be considered in patients with PBMAH.

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