MON-317 Ectopic Cushing's Syndrome Due to Prostate Cancer: A Case Series

Background: The introduction of chemotherapy and androgen receptor signaling inhibitors to patients with newly diagnosed metastatic or castration resistant prostate cancer has resulted in longevity and improved quality of life. However, as the disease transitions to a more resistant clinical state despite multiple agents, there has been, in some patients, the emergence of a more aggressive form of the disease with adrenocorticotropic hormone (ACTH) production due to either small cell or neuroendocrine features. These subtypes of prostate cancer are behaviorally unique and can manifest with clinical symptoms and laboratory abnormalities due to severe hypercortisolemia that portend rapid clinical decline if not death. In order to facilitate early recognition and treatment of this rare clinical syndrome, we describe several cases of ectopic ACTH-dependent Cushing’s syndrome that were associated with this histologic entity and were not easily identified despite refractory hypokalemia and hypertension. Methods: Through a dataline search we identified 10 cases of prostate cancer with ectopic ACTH-dependent Cushing’s syndrome treated at MSKCC over the past 20 years. Data were abstracted from patients' medical records, including clinical course, histopathology and response to therapy. Results: Mean age at presentation was 66 years (range 58 to 80). 9 of 10 patients reported prior tobacco use. 7 of 10 patients had prostate adenocarcinoma prior to diagnosis of ectopic Cushing’s, and 9 of 10 patients had a Gleason score >7. When available, tumor pathology showed small cell or high grade neuroendocrine carcinoma, but despite elevated plasma ACTH levels, not all tumors had immunohistochemistry that was positive for ACTH. Spontaneous hypokalemia was present in all 10 patients, and presenting signs of Cushing’s syndrome were most commonly hypokalemia or resistant hypertension. One patient had hypertensive urgency and two developed psychosis. Median survival was ~2.5 months after the development of Cushing’s syndrome. Four patients died of complications from progressive tumor growth, and three died of complications due to infections, including PCP, aspergillus lung infection, mold lung infection, cellulitis/fasciitis, and mastoiditis. Three died of unclear causes. Conclusions: Prostate cancer that evolves into an ACTH-secreting neuroendocrine phenotype is a rare entity that is associated with high risk for infections, refractory hypokalemia, and poor survival. Further clinical and pathological characterization is needed to ensure early recognition and appropriate treatment interventions for these patients.