Cardiovascular effects of metyrapone treatment in patients with mild autonomous cortisol secretion: a secondary analysis.

Abstract

Mild autonomous cortisol secretion (MACS) is associated with increased mortality, mainly because of cardiovascular disease. Here we investigated the effects of cortisol-lowering medical treatment on blood pressure regulation, cardiac fat depots, heart function and morphology, and other cardiovascular risk factors. In this secondary analysis of our prospective, open-label, single-center study at the Medical University of Vienna, we investigated 15 patients with MACS (12 females; age 59 [53-64] years) before and after 12 weeks of treatment with evening doses of metyrapone (500 mg at 6 p.m. and 250 mg at 10 p.m.). Cardiac fat stores, morphology and myocardial function were evaluated using cardiac magnetic resonance imaging and spectroscopy. Orthostatic blood pressure regulation was measured by standardized protocols. Lipidomics, renin-angiotensin-aldosterone-system activity and branched-chain amino acid (BCAA) concentrations were assessed. Mean supine systolic (137[121-139] vs 122[115-129] mmHg; p=0.041) and diastolic (89[80-93] vs 75[71-86] mmHg; p=0.045) blood pressure decreased after treatment in patients without changes in concomitant antihypertensive medication. Epicardial fat was lower at follow up compared to baseline (1032.70[894.23-1482.90] vs 929.37[736.12-1317.15]mm2; p=0.022). No changes in paracardial- and intramyocardial fat, as well as in cardiac function and morphology were observed. The aldosterone-to-angiotensin II ratio was lower at follow up (1.56[0.87-2.82] vs 1.21[0.98-1.92]; p=0.042) and alterations in lipid profiles, but not in BCAA levels were identified. Treatment with evening doses of metyrapone improved blood pressure and reduced epicardial adipose tissue.