MON-902 Etomidate - an Under Utilized but Safe and Efficacious Drug to Treat Acute Severe Cushing’s Syndrome- Case Reports of Ectopic ACTH Syndrome from Neuroendocrine Malignancies

Abstract

Background: Intravenous etomidate infusion, in non-hypnotic doses, rapidly lowers cortisol levels by blocking 11-beta hydroxylation of deoxycortisol to inhibit cortisol production. It is an underutilized drug due to concerns of excess sedation and ICU monitoring. Clinical Case 1: A 44 year-old female with HTN, diabetes, and recently diagnosed pancreatic neuroendocrine tumor with liver metastases presented with altered mentation. Labs showed severe hypokalemia, metabolic alkalosis, serum AM cortisol >60.2 ug/dL (n 6.7-22.6 ug/dL), ACTH of 698.1 pg/mL (n 7.2-63.3 pg/mL), 24-hour urine free cortisol (UFC) of 5791 ug/24hr (n 5-64 ug/24hr), midnight salivary cortisol of 8.04 ug/dL (n <0.01-0.09), and abnormal low dose (LDDST) and high dose (HDDST) dexamethasone suppression tests each with cortisol >60.2 ug/dL. She developed worsening psychosis, likely secondary to hypercortisolism. After ICU transfer, etomidate infusion was initiated at 2.5 mg/hr and titrated upward, leading to rapid drop in cortisol levels and concomitant improvement in mentation. No respiratory or airway difficulties developed. Ketoconazole and metyrapone were started and etomidate was weaned off. Steroids were added once cortisol levels fell below 10 ug/dL as part of “block and replace.” The patient eventually underwent bilateral adrenalectomy with improvement in hemodynamic and blood glucose parameters. She was discharged on physiologic replacement doses of hydrocortisone and fludrocortisone, with no reported issues two months later. Clinical Case 2: A 51 year-old man with one month of hematochezia presented with hypertension, severe hypokalemia, metabolic alkalosis, and QTc prolongation. Colonoscopy was unremarkable; however, labs revealed a cortisol of 43.1 ug/dL, ACTH of 83.6 pg/mL, and 24-hour UFC of 7,494 ug/L, with an abnormally elevated LDDST. Imaging showed a pancreatic mass and multiple hypodense liver lesions. The overall presentation was suggestive of ectopic ACTH syndrome due to metastatic neuroendocrine carcinoma, which was confirmed on biopsy. Chemotherapy, ketoconazole, and metyrapone inadequately lowered cortisol. Etomidate drip was initiated at 3 mg/hr in the ICU, with rapid reduction in cortisol levels to <20 ug/dL without respiratory compromise. Attempts to wean off etomidate were unsuccessful and the patient underwent bilateral adrenalectomy. The surgery was compromised due to extensive liver and pancreatic enlargement, and follow up imaging revealed incomplete resection. 8am cortisol level (off etomidate) was >60.0 ug/dL. Metyrapone and ketoconazole were resumed and hydrocortisone was later initiated for “block and replace”. The patient remains in critical condition. Conclusion: Etomidate-in non- hypnotic doses is useful for the rapid lowering of cortisol levels.