7117 Cushings Conundrum: Taming The Hormone Hurricane

Abstract Disclosure: S. Syed: None. A. Poloju: None. A. Krueger: None. C. O'connor: None. Ectopic ACTH syndrome is a rare disease that presents with severe hypercortisolism that can be challenging to treat. This case reviews a patient with high- grade metastatic neuroendocrine tumor causing ectopic ACTH-related Cushing's syndrome and describes navigating these treatment challenges with an evidence-based and patient centered strategy to try to optimize care.Clinical case: This 32-year-old male, with a history of metastatic pancreatic neuroendocrine tumor and liver metastases, initially presented with dyspnea, hyperglycemia, and metabolic derangements. Agitated, with a systolic blood pressure of 190mm Hg, he exhibited notable hypokalemia (2.5mmol/L), hyperglycemia (508mg/dL), and elevated beta-hydroxybutyrate (3.60mmol/L). Random cortisol was 85.9ug/dL and ACTH 472pg/ml. Urgent cortisol control prompted etomidate infusion, lowering cortisol to 27ug/dL in 24 hours. Ketoconazole was initiated but discontinued later due to rising liver enzymes, Metyrapone and spironolactone were initiated and etomidate infusion titrated off. Hemorrhagic shock, DKA, and mental status changes complicated his course.Interventional radiology-guided hepatic artery embolization was performed. Post-procedure cortisol levels improved, metyrapone and spironolactone were stopped. Dexamethasone was initiated given concern for relative adrenal insufficiency during this time and was later switched to hydrocortisone, and eventually discontinued with normalizing cortisol levels. Octreotide and later lanreotide maintained stability for a year. He was readmitted with uncontrolled diabetes, hypertension, and vertebral compression fractures, requiring rapid control with etomidate infusion again. Metyrapone was reintroduced, facilitating etomidate tapering. Spironolactone was re-initiated. Bilateral adrenalectomy was discussed as definitive treatment for the ectopic ACTH syndrome (neuroendocrine cancer was deemed incurable, however he was considered elevated risk for surgery given other co-morbidities. Even with normalization of cortisol, he intermittently refused cares/medications. Conclusion: Managing ACTH-producing neuroendocrine tumors necessitates a multidisciplinary approach. In severe Cushing’s syndrome, etomidate infusion quickly normalizes cortisol but requires intensive care due to sedation risks. Ketoconazole and levoketoconazole carry a hepatotoxicity risk. Metyrapone and mitotane are alternatives but supply challenges exist. Osilodrostat, studied for short-term use, has limited data in ectopic ACTH syndromes. Bilateral adrenalectomy is an option if surgical risks are acceptable. Patient history influences therapeutic decisions, highlighting the need for a patient-centered approach. Presentation: 6/3/2024