Endocrine Abstracts

Context: Patients with primary bilateral macronodular adrenocortical hyperplasia (PBMAH) usually present with bilateral benign adrenocortical macronodules at imaging and variable levels of cortisol excess. There is anecdotal evidence that, besides cortisol, other adrenal steroids, like mineralocorticoids, can be oversecreted.

Objective: To assess the prevalence, clinical, biochemical characteristics and imaging features of aldosterone excess leading to primary aldosteronism (PA) in patients with PBMAH.

Methods: We conducted a systematic review according to the PRISMA guidelines. We reviewed single case reports and case series of patients with PBMAH and coexistence of PA, in Pubmed, Embase and Cochrane from database inception to 17 December 2023. Two independent reviewers performed screening and data extraction. PBMAH was defined based on radiological features with ≥1 bilateral adrenal nodule ≥10 mm. We compared our findings to patients with PBMAH and PA derived from the LMU hospital Munich.

Results: 1018 articles were screened, of which 36 articles were assessed for eligibility. We identified 18 articles (8 single case reports and 10 case series), resulting in 68 cases with PBMAH with PA. Of those, 14 had concomitant secretion of aldosterone and cortisol. The prevalence of a PA phenotype in patients with PBMAH in six studies with 166 patients ranged from 2 to 44%. The median age at diagnosis was 51.5 (47.5–56.2) with more male patients (18/26, 69%). Most patients were hypertensive, and the median duration of hypertension at referral was 108 months (48–135). 69.6% (16/23) of the patients were hypokalemic. The baseline aldosterone serum concentration and plasma renin activity (PRA) were 253 ng/l (159.8–436) and 0.25 ng/ml per hour (0.2–0.4), respectively. Treatment modality was reported in 30 cases: 28 patients underwent adrenalectomy (two bilateral, two subtotal, and 15 unilateral, 9 not reported) and two received mineralocorticoid receptor antagonists (MRA). In comparison, in the LMU cohort, fewer patients underwent adrenalectomy (12/20, P=0.0088) whereas 8/20 received MRAs. Outcome following surgery or MRA therapy was only described in eight cases derived from the literature (6 treated with surgery and 2 with MRA). Complete biochemical remission was obtained in 4 cases while complete clinical remission in 1 case. In the LMU cohort, 9 surgically treated patients went into complete biochemical remission and 2 obtained complete clinical remission.

Conclusion: Autonomous secretion of aldosterone in PBMAH appears to be more frequent than previously thought. Larger multicenter studies will help to clarify the association between these conditions as well as the most appropriate treatment modality.