Endocrine Abstracts

Background: Although surgery is considered the first-line treatment for patients with endogenous Cushing’s syndrome (CS), medical therapy is often required to control severe hypercortisolism. Metyrapone and osilodrostat are inhibitors of 11β-hydroxylase that have not been directly compared yet.

Methods: Retrospective analysis of patients with adrenocorticotropin (ACTH)-dependent and ACTH-independent CS treated with metyrapone or osilodrostat (as monotherapy) for at least one month. Serum cortisol and 24h-urinary free cortisol (24h-UFC) were analyzed at baseline (T0), after 2 weeks (T1), 1 month (T2) and 3 months (T3) of therapy. Furthermore, serum potassium and blood pressure were evaluated.

Results: 16 patients with CS (8 under metyrapone and 8 under osilodrostat) were identified. Despite heterogeneity, both groups showed comparable mean 24h-UFC levels at T0 (757.8 μg/24h under metyrapone vs 816.9 μg/24h under osilodrostat; n.s.). From T0 to T1, the decrease of 24h-UFC was less pronounced under metyrapone than osilodrostat (-21.3% vs -68.4%; median drug dose: 1000 mg vs 4 mg). This tendency persisted at T2 (-37.3% vs -50.1%; median drug dose: 1250 mg vs 6 mg). A substantial difference in potassium levels at T3 was identified (-10.9% under metyrapone vs +14.5% under osilodrostat from T0). Furthermore, a more prolonged QTc-interval was observed under osilodrostat than under metyrapone (455.3 ms vs 432.5 ms). From T0 to T2, the number of antihypertensive drugs decreased under osilodrostat.

Conclsion: Although both of the drugs are efficient in reducing cortisol levels, osilodrostat seems to induce a faster reduction of cortisol levels and a faster control of blood pressure.