Is there still a place for etomidate in the management of Cushing's syndrome? The experience of a single center of low-dose etomidate and combined etomidate-osilodrostat treatment in severe hypercortisolemia.

Purpose: Severe Cushing's syndrome (SCS) is a life-threatening endocrine condition that requires prompt medical intervention. Intravenous etomidate infusion is considered to be the most effective in rapid cortisol overproduction inhibition. This single-center retrospective study aimed to present the safety and effectiveness of intravenous, low-dose, lipid-formulated etomidate infusion in patients with SCS.

Methods: Seven patients with complicated SCS related to ectopic ACTH syndrome (n = 6) or Cushing's disease (n = 1) who received low-dose etomidate infusion as a part of their cortisol-lowering treatment between April 2019 and April 2024 in the Department of Internal Medicine, Endocrinology and Diabetes of Medical University of Warsaw were included in the study. A continuous etomidate infusion was initiated at 0.01-0.02 mg/kg/h.

Results: In all patients, rapid control of hypercortisolemia was achieved with a median time of 30 h (range: 12-48 h). Median serum cortisol concentration reduced from 101.9 μg/dL (range: 78.2-119.6 μg/dL) before etomidate to 19.5 μg/dL (range: 18.3-22.5) after 72 h of etomidate treatment. Etomidate infusion was followed by etomidate and osilodrostat combined treatment and then osilodrostat monotherapy in four patients; one patient underwent adrenalectomy, and two patients died during etomidate infusion due to complications of advanced malignancy.

Conclusions: This study shows that low-dose and short-term lipid formulation etomidate therapy is highly effective in severe hypercortisolemia management. Combined therapy with etomidate and osilodrostat is well tolerated and could serve as a bridge in long-term SCS treatment.