Intermittent Dosing of Etomidate for Hypercortisolism Associated With Ectopic Cushing Syndrome

Introduction: Acute severe hypercortisolism due to Cushing syndrome can be life-threatening if untreated. Initial pharmacotherapy management includes inhibitors of adrenal steroidogenesis, such as ketoconazole. Etomidate, an intravenous (IV) anesthetic that inhibits CYP11B1 synthesis of cortisol, has been used off-label for cortisol suppression. Prior publications have administered etomidate via continuous infusion due to its short half-life.


Description: A 36-year-old female with a diagnosis of Cushing syndrome from an unknown ectopic adrenocorticotropic hormone-secreting focus was admitted for endoscopic duodenal biopsy as a part of her workup. Her outpatient management with ketoconazole was discontinued due to severe diarrhea and hypokalemia. On admission, the patient exhibited signs of severe hypercortisolism, including an elevated cortisol level of 71.4 mcg/dL and persistent hypokalemia below 2.7 mmol/L despite aggressive potassium supplementation. She was transferred to the intensive care unit for etomidate therapy initiation with close respiratory and sedation monitoring. The patient received a novel dosing strategy utilizing intermittent IV bolus etomidate 5 mg every 4 hours. The total daily dose reflects that of continuous infusion 0.02 mg/kg/hr reported in previous literature. Given her high body mass index, adjusted body weight was used for dosing calculation. A profound cortisol reduction to 33.2 mcg/dL was observed immediately after the first two doses. The patient received a total of eight intermittent doses over 28 hours, which resulted in a significant reduction in cortisol level to 17.0 mcg/dL. The patient experienced no adverse effects such as oversedation or respiratory compromise and was discharged two days later with a cortisol level of 10.9 mcg/dL.


Discussion: This case represents the first reported use of intermittent IV etomidate for the management of hypercortisolism. Despite the short sedative duration of etomidate, its adrenal suppression effect persists beyond its anesthetic properties and continuous infusion may not be needed. This approach presents a safe and effective alternative to continuous infusion while mitigating the need for institutional infusion protocols, specialized monitoring, or pharmacy compounding concerns.