MON-494 Severe Ectopic Acth Syndrome From Metastatic Neuroendocrine Carcinoma: Medical Rescue Without Surgery

Abstract Disclosure: A. Ezici: None. H. Abdelrahman: None. K. Chen: None. Introduction: Ectopic ACTH syndrome (EAS) accounts for 10-15% of Cushing syndrome (CS) cases and is most often caused by intrathoracic neuroendocrine tumors (NETs). Mortality is high due to profound hypercortisolism and tumor burden, and timely intervention is critical. We report a case of EAS secondary to high-grade metastatic neuroendocrine carcinoma (HGNEC) with a favorable response to chemotherapy and steroidogenesis inhibitors, despite poor surgical candidacy and an unidentified primary tumor. Case Narrative: A 73-year-old man with a remote history of microprolactinoma presented with rapid weight gain, edema, and hypertension. Labs revealed hypokalemia (K 2.6 mmol/L), hypernatremia (Na 148 mmol/L), metabolic alkalosis (HCO₃ 41 mmol/L), and elevated cortisol (59.3 and 67.4 μg/dL). ACTH was 362 pg/mL, and cortisol remained unsuppressed at 74.4 μg/dL after 8 mg dexamethasone. MRI showed no pituitary lesion. Chromogranin A was elevated (392 ng/mL). CT and 68Ga-DOTATATE PET/CT revealed diffuse osseous metastases and bilateral adrenal thickening. Biopsy of a pelvic lymph node confirmed HGNEC (Ki-67 95%), while the primary tumor remained unknown. A 24-hour urine steroid profile demonstrated marked elevation of tetrahydrocortisone, B-cortolone, and 11 beta-OH-etiocholanolone. His course was complicated by new-onset diabetes, lactic acidosis, and ketosis requiring insulin. Hypercortisolism was persistently resistant to ketoconazole and spironolactone, prompting consideration of bilateral adrenalectomy. However, given his poor surgical candidacy and the marked biochemical response after initiating metyrapone and chemotherapy (carboplatin and etoposide), surgery was ultimately deferred. Cortisol levels decreased by nearly half within one week (from 96 to 57.8 μg/dL). Discussion: This case was notable for severe hypercortisolism, diffuse metastatic disease, and an unknown primary tumor, complicating diagnosis and limiting treatment options. Despite the poor prognosis of HGNEC, our patient showed marked clinical and biochemical improvement with steroidogenesis blockade and chemotherapy. Although bilateral adrenalectomy is often recommended for resistant hypercortisolism in EAS, this case illustrates that combined medical therapy can achieve adequate cortisol control and may delay or avoid surgery in select patients. Given that markedly elevated ACTH (>200 pg/mL) and 24-hour urinary free cortisol (>5× ULN) strongly suggest EAS in the presence of a negative brain MRI, inferior petrosal sinus sampling (IPSS) was appropriately deferred to expedite treatment. This case highlights the management of severe EAS secondary to high-grade metastatic neuroendocrine carcinoma and the role of timely medical therapy when surgery is not an option. Presentation: Monday, July 14, 2025