Endocrine Abstracts

Background: Mild autonomous cortisol secretion (MACS) in patients with adrenal incidentalomas has been associated with elevated cortisol levels during the nocturnal period resulting in a disturbed cortisol rhythm. We hypothesised that administration of nocturnal metyrapone, an 11-beta-hydroxylase inhibitor, previously shown to restore cortisol rhythm in MACS patients, could reduce metabolic complications in this patient group.

Methods: In this controlled, retrospective, longitudinal study we evaluated the tolerability and metabolic effects of nocturnal metyrapone administration in MACS. The study included all patients (n =15) who were initiated on metyrapone treatment, 250mg-500mg at 6pm and 250mg at 10pm, for MACS at a tertiary endocrinology centre between 2015 and 2022. Age and sex-matched controls were selected from patients with adrenal incidentalomas and non-suppressed overnight dexamethasone suppression tests (ONDST). Metabolic risk factors, including mean arterial blood pressure (MAP), HbA1c, non-HDL cholesterol, and weight, were assessed at baseline and after 1 year.

Results: Metyrapone was well tolerated by 82% of patients, with no occurrences of adrenal crises. Among the metyrapone-treated group (n =6), MAP decreased from 106 mmHg to 92 mmHg after 1 year, demonstrating a statistically significant difference in improvement compared to the control group (P=0.041). There were 4 patients on metyrapone in whom MAP improved by greater than 10mmHg as opposed to only one control patient.

Conclusion: Our findings highlight the potential of metyrapone in controlling metabolic risk factors associated with MACS, as evidenced by the decrease in MAP compared to the control group. This study, albeit small, provides data to power a larger controlled clinical trial for further investigation into the broader metabolic outcomes of metyrapone administration in MACS. Importantly, the well-tolerated nature of metyrapone and the absence of significant events such as adrenal crises support its clinical utility.