Unexplained Hypokalemia in a Patient With Obesity Harboring an Armadillo Repeat-Containing 5 (ARMC5) Gene Variant: A...

Hypokalemia of unknown cause can often be challenging to diagnose. Although armadillo repeat-containing 5 (ARMC5) gene mutations are primarily associated with primary bilateral macronodular adrenal hyperplasia and Cushing's syndrome, their potential role in other endocrine disorders remains largely unexplored. A 50-year-old man presented with limb weakness and persistent hypokalemia. Comprehensive screening tests, including imaging and endocrinological evaluations, ruled out primary aldosteronism, Cushing's syndrome, and other common causes of hypokalemia. Genetic analysis revealed a heterozygous ARMC5 variant. As the patient also presented with obesity, and given that previous mouse and in vitro studies suggest possible interactions between ARMC5 and mineralocorticoid pathways, we hypothesize that the mechanism of hypokalemia may involve adipose tissue function. This case describes an association between an ARMC5 variant, unexplained hypokalemia, and obesity. Although a direct causal relationship cannot be established from a single case, the systematic exclusion of common causes and known ARMC5 functions in mineralocorticoid pathways suggest potential mechanistic links. This observation warrants further investigation, particularly through comprehensive screening of electrolyte disorders in patients with ARMC5 variants, analysis of mineralocorticoid activity in adipose tissue samples from these patients, and molecular studies examining ARMC5's direct role in the regulation of mineralocorticoids in adipose tissue.