Prevalence and main characteristics of primary aldosteronism in bilateral macronodular adrenal disease: a systematic review of the literature

Context: Bilateral macronodular adrenal disease (BMAD) typically presents with bilateral benign adrenocortical macronodules and variable cortisol excess. Anecdotal evidence suggests oversecretion of other adrenal steroids, including mineralocorticoids. Hypothesis: We hypothesized that primary aldosteronism (PA) can occur in BMAD, resulting in a distinct, more severe phenotype compared to BMAD with isolated cortisol hypersecretion or unilateral PA (uPA). Objective: To assess the prevalence and characteristics of PA in BMAD. Methods: We systematically reviewed case reports and series of BMAD patients with PA, following PRISMA guidelines. BMAD was defined by bilateral adrenal nodules ≥10 mm. PA diagnosis followed US or Japanese Endocrine Society guidelines. We compared these findings with 2 cohorts from LMU Hospital Munich: BMAD with isolated cortisol hypersecretion and uPA. Conclusion: This review highlights the need for increased screening for PA in younger, hypertensive BMAD patients. Larger multicenter studies are needed to determine the association between these conditions, cardiovascular risk, and optimal treatment.