Association between ARMC5 mutation with bilateral macronodular adrenal hyperplasia and primary aldosteronism: A case...

Mutations in the ARMC5 gene are generally associated with bilateral macronodular adrenal hyperplasia (BMAH), whereas primary aldosteronism (PA) is most commonly linked to adrenal cortical adenomas (ACA). Recent studies have identified ARMC5 mutations in certain PA cases; however, it remains unclear whether BMAH associated with ARMC5 mutations can directly contribute to PA.

A patient undergoing evaluation for secondary hypertension was diagnosed with BMAH, an elevated aldosterone/renin ratio (ARR) suggestive of PA, and subclinical Cushing's syndrome (SCS). Adrenal venous sampling (AVS) indicated left-sided dominance. Genetic testing confirmed ARMC5 mutations in the patient and their son. A subsequent partial left adrenalectomy identified a golden-yellow adrenal tumor, which pathological analysis classified as an ACA. However, given the overlapping histological and clinical features of bilateral multifocal ACA and BMAH, the histological findings were reconsidered. The association of ARMC5 mutations with BMAH rather than ACA, in conjunction with imaging findings and a history of meningioma, supports a diagnosis of ARMC5 mutation-associated BMAH.

This case suggests that ARMC5 mutation-associated BMAH may contribute to the development of PA, expanding the understanding of the genetic underpinnings of PA in BMAH.