THU528 ACTH-dependent Hypercortisolism From Neuroendocrine Prostate Tumor With Negative ACTH Staining Of The Tumor Cells

Abstract

Abstract Disclosure: M. Fariduddin: None. J. Sanchez Perez: None. U.N. Syed: None. Y. Eisenberg: None. R.M. Sargis: None. Introduction: Ectopic ACTH-dependent Cushing’s syndrome (CS) is a rare entity accounting for 10-20% of hypercortisolism cases. We present a patient with this syndrome. Case Presentation: A 72-year-old man diagnosed with metastatic prostate cancer to the lumbar spine and pelvis was admitted for persistent hypokalemia. Potassium levels were 2.1 mmol/L (ref. range: 3.5-5.2) despite aggressive potassium supplementation. He reported 30-lb weight gain in the previous 2 months, rounding of his face, increased abdominal girth, and proximal muscle weakness. Facial plethora with puffiness was noted on physical exam. Labs were relevant for impaired glucose tolerance with fasting blood glucose of 110 mg/dL and elevated A1c of 6.3% (<5.7%), compared to 5.0% 1 year earlier. 8 AM cortisol was 59 ug/dL (6.7-22.6) and after dexamethasone, cortisol remained elevated at 65.8 ug/dL (<1.8). ACTH level was 312 pg/mL (7.2 - 63.3) and 24-hr urine cortisol was 3586 ug/dL (<= 60.0). Abdominopelvic CT showed new bilateral adrenal thickening without discrete nodularity or mass. Pituitary MRI showed a 1mm microadenoma, inconsistent with the degree of hypercortisolism observed. Patient’s age, known prostate adenocarcinoma with differentiation into neuroendocrine tumor and rapid onset of development of hypercortisolism were all suggestive of ectopic Cushing’s syndrome. Ketoconazole 200 mg BID, Spironolactone 200 mg BID and Amiloride 5 mg daily were started which resolved the hypokalemia. ACTH staining of the prostate tissue biopsy was negative. Patient later died of respiratory failure from Influenza pneumonia. Conclusion: Ectopic ACTH hypercortisolism is a rare but aggressive form of hypercortisolism. Symptoms like proximal muscle weakness, hyperglycemia, hypokalemia, infections, and blood clots develop rapidly, however, these patients rarely have the clinical stigmata of CS. Neuroendocrine tumors of the lung and small cell lung cancer are the most common tumors associated with ectopic ACTH production, but cases of paraneoplastic prostate cancer have been reported. Published case reports demonstrate positive ACTH staining of these tumor cells, but this was not the case in our patient even though his presentation was consistent with ectopic hypercortisolism. The ACTH staining was done on a sample of prostate tissue taken 2 months prior to presentation, at the time of diagnosis of prostate cancer. Neuroendocrine differentiation could have happened within 2 months after the biopsy. This case impresses upon us that ACTH staining can be negative in ectopic ACTH hypercortisolism and patients can still have CS as tumor cells continue to differentiate throughout the course of the malignancy- and this can be especially rapid in neuroendocrine differentiation of tumors. CS increases mortality by 3 times, therefore making it crucial to recognize it early to institute prompt treatment. Presentation: Thursday, June 15, 2023