Etomidate in severe hypercortisolism: early cortisol kinetics and clinical outcomes in a real-world cohort.

Abstract

Purpose: Severe hypercortisolism is a life-threatening endocrine emergency requiring rapid cortisol reduction. Oral steroidogenesis inhibitors may be limited in critically ill patients due to delayed onset, impaired absorption, and toxicity. Intravenous etomidate enables rapid, titratable suppression of cortisol synthesis, but data on early treatment response and real-world safety remain limited.

Methods: We conducted a retrospective study of consecutive patients with severe endogenous hypercortisolism treated with intravenous etomidate at a tertiary care centre over a 3-year period. Serum cortisol was measured at baseline and at 12 and 24 h to assess early response. Biochemical control was defined as serum cortisol < 500 nmol/L (< 18.1 µg/dL). Clinical, biochemical, and safety outcomes were analysed.

Results: Ten patients [median baseline cortisol 1285 nmol/L (46.6 µg/dL)] received etomidate infusion. Serum cortisol declined early, with median reductions of 45% at 12 h and 58.5% at 24 h. Biochemical control was achieved within 24 h in 80% of patients. Response categories included rapid (30%), intermediate (50%), and delayed (20%). Patients with < 25% cortisol reduction at 12 h tended to have delayed biochemical control. Serum potassium improved during treatment and normalized before discontinuation of infusion in all patients with available serial data, while clinical stabilization was achieved in 90%. Etomidate was well tolerated; one death due to sepsis was not related to therapy.

Conclusions: In this real-world cohort of patients with severe hypercortisolism, low-dose intravenous etomidate was associated with early cortisol reduction and clinically useful biochemical control in most patients. Early cortisol trajectories may help guide dose titration, but these findings should be interpreted as descriptive and hypothesis-generating because of the small sample size and retrospective design.