Fellow UConn Farmington, Connecticut, United States
Introduction :
Background: Etomidate, an imidazole derivative similar to ketoconazole, is an intravenous hypnotic nonbarbiturate induction agent often used for intubation. It was shown to substantially and rapidly decrease cortisol secretion and to decreases steroidogenesis by inhibiting not only side chain cleavage enzyme but also 11β-hydroxylase, an enzyme that catalyzes the production of cortisol from its immediate precursor, 11-deoxycortisol; hence its use was proposed for acute, short term management of hypercortisolism.
Case(s) Description : Our patient is a 46-year-old man with a refractory functional ACTH-producing pancreatic neuroendocrine tumor (NET; gastrinoma) initially treated with distal pancreatectomy, lanreotide, everolimus and temozolomide.
In spite of treatment, gastrin was > 10000 (0 - 100 pg/mL), cortisol 70 ug/dl and ACTH 800 (7.2 - 63.3 pg/mL); he was clinically showing signs of severe hypercortisolemia.
In preparation for bilateral adrenalectomy, therapy with ketoconazole and osilodrostat was initiated. However, he developed small bowel obstruction and wasunable to take oral medications, requiring transfer to the ICU in order to receive intravenous etomidate at 0.02 mg/kg/h. Other medications included (all intravenously): nicardipine, enalaprilat, insulin, trimethoprim sulfamethoxazole for pneumocystis prophylaxis, proton pump inhibitors, H2 blockers and subcutaneous heparin thromboembolism prophylaxis. Serum cortisol decreased within 12-24 hours based on etomidate pharmacokinetics.
On hospital day 2, exploratory laparotomy with lysis of adhesions and small bowel resection was performed. Etomidate dose was increased to 0.3 and then to 0.4 ml/kg/h. On day 10, cortisol decreased to 10.9 ug/dl with ACTH 205 pg/ml and hydrocortisone was added (“block-and-replace” strategy). By postoperative day 5, significant improvement was noted and he was transitioned to oral medications, including ketoconazole and osilodrostat. One month later, successful bilateral posterior retroperitoneoscopic adrenalectomy was performed. He is now receiving treatment with Lutetium (Lutathera).
Discussion :
Conclusion: A standardized continuous intravenous etomidate infusion protocol is a safe and effective means of achieving a serum cortisol level of 10 to 20 µg/dL in patients with severe hypercortisolemia. Intravenous etomidate was used to treat hypercortisolemia started May 16, 2023 at night, stopped May 31, 2023 at 10 PM
