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

CONTEXT AND OBJECTIVE: 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. DESIGN, SETTING AND INTERVENTION: 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.). OUTCOME MEASURES AND METHODS: 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. RESULTS: 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. CONCLUSIONS: Treatment with evening doses of metyrapone improved blood pressure and reduced epicardial adipose tissue.