Work

MON-098 Alternating Therapy with Osilodrostat and Etomidate in Severe Ectopic Cushing’s Syndrome Complicated by Silent Bowel Perforation

Year: 2025

Type: article

Abstract: Disclosure: H. Mejia: None. C.V. Villabona: None. R.R. Savian: None. S. Barreiro Sacco: None. A. Razzeto: None. T. Ferreira: None. K. Virginia: None. S. Arias: None. E. Donna: None. V.S. Lagari-Libhaber: None. Background: Ectopic ACTH syndrome (EAS) is a rare cause of Cushing’s syndrome, due to ACTH-secreting neuroendocrine tumors, leading to severe hypercortisolism with hypokalemia, metabolic alkalosis, and immunosuppression. This case describes alternating high-dose osilodrostat and intravenous etomidate to manage hypercortisolism in a critically ill patient with EAS complicated by bowel perforation and infections. Case Presentation: A 65-year-old woman presented with worsening hyperglycemia (HbA1c: 7.0% to 10.0%), proximal muscle weakness, and unintentional weight loss of 22 lbs. Laboratory evaluation revealed severe hypokalemia (2.1 mEq/L), metabolic alkalosis, serum cortisol (157 µg/dL), and ACTH (508 pg/mL). A 1-mg dexamethasone suppression test (DST) failed to suppress cortisol (118 µg/dL, reference <1.8 µg/dL), and an 8-mg DST confirmed persistent hypercortisolism (148 µg/dL, reference <5 µg/dL). A desmopressin test showed no response in ACTH or cortisol levels, consistent with an ectopic source. Imaging revealed bilateral adrenal hyperplasia and a 1.9 cm paraesophageal mass with mild Ga-68 DOTATATE PET/CT uptake (SUV 2.6). Fine-needle aspiration confirmed a low-grade bronchial carcinoid tumor producing ACTH. Her course was complicated by silent sigmoid colon perforation requiring emergency colectomy and ileostomy. Severe infections, including sepsis from Enterococcus faecium, ARDS, Pneumocystis jirovecii pneumonia, and Herpes simplex virus (HSV-1) infection, arose due to hypercortisolism-induced immunosuppression. Management: Cortisol suppression began with oral osilodrostat (10 mg twice daily), reducing cortisol to 50 µg/dL within three days. Due to NPO status, osilodrostat was discontinued, and intravenous etomidate (0.02 mg/kg/hr) was employed, lowering cortisol to 17 µg/dL within five days. Once oral intake resumed, osilodrostat was titrated to 20 mg twice daily, ensuring consistent cortisol suppression. Alternating therapy was essential to control hypercortisolism. Severe hypokalemia was treated with potassium supplementation and spironolactone. Adrenal insufficiency was managed with high-dose hydrocortisone, tapered as the patient improved. Definitive treatment included robotic-assisted lobectomy of the ACTH-producing tumor, achieving biochemical remission (midnight salivary cortisol <0.03 µg/dL, 24-h urinary free cortisol 8 µg/24 h). Outcome and Follow-Up: Infections resolved, and rehabilitation improved hypercortisolism-induced myopathy. At follow-up, the patient demonstrated clinical and biochemical remission, with improved glycemic control (HbA1c: 6.5%). Conclusion: This case describes a novel therapeutic approach for severe EAS: alternating osilodrostat and etomidate for cortisol suppression before surgery. Individualized strategies are key for managing life-threatening hypercortisolism. Presentation: Monday, July 14, 2025

Source: Journal of the Endocrine Society

DOI: 10.1210/jendso/bvaf149.1428