MON-332 Metastatic Pancreatic Neuroendocrine Tumor: A Very Rare Cause of Ectopic ACTH Production (ACTHoma)

Abstract

Introduction Ectopic ACTH syndrome (EAS)is responsible for 10% of Cushing’s syndrome. Multiple tumors, most commonly small cell carcinoma of lung are associated with EAS. Pancreatic neuroendocrine tumors (pNETs) are usually associated with secretion of pancreatic polypeptide, gastrinomas, insulinomas, glucagonomas and vasoactive intestinal peptide (VIPomas). EAS or “ACTHomas” are rarely associated with pNETs. Case 76y/o man with ah/o hairy cell leukemia, bladder cancer (both in remission), and stage M1 unresectable pNET tumor with liver metastases presented with generalized weakness. Discovery of his pNET was incidentally noted during routine surveillance with CT monitoring following successful bladder cancer treatment six years ago. Treatment of his pNET initially began with Everolimus and then switched to Lanreotide injections. No evidence of Cushing’s Syndrome at the time of diagnosis. The lesions remained stable in size and patient was doing well. Physical exam was notable for lethargy, frailty, and absence of Cushingoid features. Labs showed serum glucose 231mg/dl, sodium 141mEq/L, potassium 2.4mEq/L, AM cortisol 116 ug/dL (range 6.7-22.6ug/dl) and ACTH was 209.6pg/mL (range 7.2-63.3pg/mL). Renin-aldosterone levels were normal. Cortisol level did not suppress with low dose or high dose dexamethasone. His hospital course was significant for persistent hypokalemia despite aggressive supplementation, difficult to control blood glucose, and worsening kidney function. EAS with pNET is very refractory to management and may be rapidly progressive. They occasionally demonstrate classic manifestations of Cushingoid features. However, they often lack the traditional phenotypic features of Cushing syndrome. Treatment options for EAS in the setting of an unresectable tumor include medical management versus bilateral adrenalectomy. Metyrapone, a cortisol synthesis inhibitor, can be an effective therapy. Ketoconazole, an antifungal that inhibits cortisol production can be an alternative, but may need weeks to achieve control. Etomodate can rapidly reduce cortisol levels, but requires intensive care monitoring. Somatostatin analogs may be effective by reducing ectopic ACTH production and stabilize tumor growth. Medical versus surgical management of Cushing’s syndrome was discussed with the patient and family, but they opted for hospice care. Conclusion We present a case of pNET associated with late onset EAS without obvious signs of Cushing’s syndrome. To our knowledge this late presentation of ACTH secretion in the setting of a stable pNET has not been previously reported in the literature. EAS due to pNET is rare and metabolic abnormalities can occur rapidly without other Cushingoid manifestations which can pose significant management challenges. High index of suspicion is required for early diagnosis. Due to the aggressive nature, the 5 years survival rate is 16%.