Abstract
OBJECTIVE: Mild autonomous cortisol secretion (MACS) is associated with increased cardiometabolic risk factors including hypertension, type 2 diabetes and dyslipidaemia. By using evening doses of metyrapone, a short-acting 11-β hydroxylase inhibitor, it has been shown that it is possible to reset the abnormal circadian cortisol rhythm in MACS. This study aimed to evaluate the tolerability and impact of this approach on cardiometabolic outcomes in patients with MACS. DESIGN: We conducted a single-centre retrospective, longitudinal review of patients with MACS who received evening metyrapone (250-500 mg at 6 PM and 250 mg at 10 PM) to evaluate adverse events, tolerability, and cardiometabolic outcomes (systolic and diastolic blood pressure, HbA1c, weight and non-HDL cholesterol) at 6 months, compared to controls. Age and sex-matched controls were identified from patients with adrenal incidentalomas and non-suppressed serum cortisol following 1 mg overnight dexamethasone suppression testing. RESULTS: Fifteen patients and 15 matched controls were identified. Over 6 months there were no adrenal crises. Metyrapone was stopped in 2/15 patients in view of side effects. In the metyrapone group compared to controls, there were significant decreases in systolic blood pressure (-17.7 (SE 5.8) vs. +8.7 (5.7)mmHg, p = 0.008, n = 9) and diastolic blood pressure (-9.9 (4.2) vs. +3.0 (3.6)mmHg, p = 0.024). The differences between groups for HbA1c, weight and non-HDL cholesterol were not statistically significant. CONCLUSION: Evening metyrapone was associated with significant reductions in systolic and diastolic blood pressure in patients with MACS, without causing adrenal insufficiency, indicating its potential safe clinical utility. A well-powered, controlled, prospective study is needed to validate these findings and comprehensively investigate the broader metabolic outcomes.