Bilateral Macronodular Adrenocortical Disease with Isolated Primary Aldosteronism and Normocortisolemia: A Case Report
Primary aldosteronism (PA) is a common cause of secondary hypertension, yet its etiology in the context of bilateral adrenal lesions presents a significant diagnostic challenge. Bilateral macronodular adrenocortical disease (BMAD), particularly the genetic subtype PBMAH2 driven by ARMC5 mutations, is classically associated with hypercortisolism. This report details an exceptionally rare case of a 54-year-old female with severe hypertension and hypokalemia, biochemically confirmed as PA, and imaging revealing bilateral adrenal macronodules. Comprehensive genetic testing identified a heterozygous ARMC5 mutation, confirming PBMAH2, despite the patient exhibiting entirely normal cortisol dynamics. Following unilateral adrenalectomy, the patient's aldosterone levels normalized, resolving the hyperaldosteronism. This case is of considerable clinical and scientific significance as it dramatically expands the recognized phenotypic spectrum of ARMC5-related disease, demonstrating that these mutations can manifest as an isolated mineralocorticoid-excess disorder. It underscores a critical diagnostic pitfall, highlighting that genetic etiologies like PBMAH2 must be considered in patients with bilateral adrenal enlargement regardless of the steroid hormone profile, and it challenges the pathophysiological paradigm linking ARMC5 dysfunction exclusively to glucocorticoid pathway dysregulation.