Mild autonomous cortisol secretion in patients with aldosterone-producing adenoma and risk for cardiac remodeling and diastolic dysfunction

Eur J Endocrinol. 2025 Jan 18:lvaf007. doi: 10.1093/ejendo/lvaf007. Online ahead of print.

Abstract

Background: Mild autonomous cortisol secretion (MACS) is common in adrenal adenomas, including patients with primary aldosteronism (PA) with aldosterone-producing adenomas (APA). This study investigated the impact of MACS on cardiac remodeling and diastolic dysfunction in patients with APA.

Methods: We prospectively enrolled 483 patients with APA. MACS was defined as a cortisol level >1.8 μg/dL after an overnight dexamethasone suppression test (DST). Clinical, biochemical, and echocardiographic data were collected at baseline and one-year following targeted treatments.

Results: In this prospective cohort, 21% of patients with APA had concurrent MACS. Patients with MACS were older, had a higher prevalence of diabetes, larger adrenal tumor size, higher left ventricular mass index (LVMI), and worse diastolic function (E/e'). Multivariable linear regression analysis showed that concurrent MACS with APA was an independent risk factor for higher LVMI and worse E/e'. Among patients who underwent adrenalectomy, both those with and without MACS showed significant improvements in LVMI and E/e'. In contrast, among patients who received mineralocorticoid receptor antagonist (MRA) treatment, significant LVMI improvement was only observed in patients without MACS. MRA therapy did not improve E/e' regardless of the presence or absence of MACS.

Conclusions: The presence of MACS in patients with PA was associated with worse cardiac hypertrophy and diastolic dysfunction. Surgical adrenalectomy was able to effectively reverse cardiac remodeling in patients with PA and concurrent MACS; however, MRA therapy was not associated with significant improvements in cardiac function. These findings highlight the independent deleterious effects of cortisol on cardiovascular disease in PA.

Keywords: diastolic dysfunction; hyperaldosteronism; left ventricular remodeling; mild autonomous cortisol secretion.