Effects of short-term metyrapone treatment on glycaemic control in patients with mild autonomous cortisol secretion: a pilot study

Purpose: Mild autonomous cortisol secretion (MACS) is associated with impaired glucose metabolism, but the metabolic effects of adrenostatic therapy in this setting remain unclear. This study aimed to explore whether changes in CGM-derived glycaemic metrics could be observed during timed evening metyrapone administration in patients with MACS. Methods: This prospective, single-centre interventional study included nine patients with MACS due to adrenal adenoma or hyperplasia and coexisting prediabetes or untreated mild type 2 diabetes. Participants underwent continuous glucose monitoring (CGM) for one week at baseline and for one week during treatment with the 11β-hydroxylase inhibitor metyrapone (500 mg at 6:00 PM and 250 mg at 10:00 PM). Morning (8:00 AM) serum cortisol, ACTH levels and parameters of glucose metabolism were assessed. Data distribution was evaluated using the Shapiro–Wilk test; paired comparisons were performed using appropriate parametric or non-parametric tests, with correction for multiple comparisons. Results: After one week of metyrapone treatment, the percentage of time with glucose levels between 70 and 140 mg/dL (time-in-tight-range, TITR) increased from 81% to 84% (p < 0.05). Time in range (70–180 mg/dL) increased from 98.4% to 99.4%, while time above range (> 180 mg/dL) decreased from 1.4% to 0.1% (both p < 0.05). ACTH concentrations increased, while morning cortisol levels remained stable. Conclusions: After short-term evening administration of metyrapone a modest yet statistically significant change in CGM-derived glycaemic metrics was observed in patients with MACS, without altering morning cortisol levels. These findings support the need for further studies to evaluate the long-term metabolic effects of adrenostatic therapy in this population.