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. Results: From 1018 articles, 18 representing 68 cases were included. Of these, 66 had BMAD with PA and 2 had BMAD with aldosterone precursor excess. The PA proportion in published BMAD series ranged from 2% to 43%. BMAD patients with PA were predominantly male (75%) and younger (median 51.5 years) than those with isolated cortisol hypersecretion (median 60.5 years, P <. 01). Their median blood pressure was higher (170/100 mm Hg) compared to those with isolated cortisol hypersecretion (138/80 mm Hg) or uPA (153/94 mm Hg, P <. 01). Treatment was only described in 28 cases, with 93% undergoing adrenalectomy. Clinical outcome was similar across groups post-treatment. 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.