Ectopic Adrenocorticotropic Hormone Syndrome Due to Metastatic Prostate Cancer With Neuroendocrine Differentiation

ABSTRACT Objective: Neuroendocrine differentiation of prostate cancer can result in ectopic adrenocorticotropic hormone (ACTH) secretion (EAS) and Cushing syndrome. The aim of this report is to highlight this unusual mechanism of hypercortisolism and its management. Methods: We report a 73-year-old patient with a history of prostate adenocarcinoma who presented with severe weakness, hyperglycemia, and hypokalemia caused by EAS. Results: Diagnostic workup showed elevated 24-hour urine cortisol and ACTH levels consistent with EAS. Fluorodeoxyglucose positron emission tomography-computed tomography revealed a hypermetabolic mass in the prostate and metastatic lesions to the liver and bones. Liver biopsy was consistent with small cell carcinoma with positive immunostaining for ACTH. Pleural fluid analysis was consistent with high-grade neuroendocrine carcinoma. The patient underwent chemotherapy with carboplatin and etoposide. Hypercortisolism was treated with ketoconazole, metyrapone, mifepristone, and spironolactone. He suffered complications including opportunistic infections, deep venous thrombosis, and delirium. Given his poor prognosis and clinical decline, the patient opted for comfort measures only in a hospice facility. Conclusion: Treatment-related neuroendocrine differentiation of prostate cancer is an emerging entity that may be associated with paraneoplastic syndromes including EAS. Abbreviations: ACTH adrenocorticotropic hormone CS Cushing syndrome CT computed tomography EAS ectopic adrenocorticotrophic hormone syndrome FDG fluorodeoxyglucose SCPC small cell prostate carcinoma