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.