MON-333 Failure of Medical Therapy to Control Marked Hypercortisolemia by a Metastatic ACTH Producing Neuroendocrine Tumor

Objective: We present a young woman with rapidly progressive Cushing’s syndrome due to ectopic ACTH production from a pancreatic NET. We describe severe neurological and immunosuppressive sequalae of marked hypercortisolemia associated with chemotherapy and reconsider our therapeutic strategy. Case: A previously active and healthy 28 year old woman was admitted with weakness and leg swelling. Two months prior she noticed a petechial rash on her face, back and arms. One week prior she was found to have DM and elevated liver chemistries prompting an abdominal US showing abnormal liver architecture. An outpatient CT showed a 3.7 cm pancreatic mass with liver lesions. Pertinent findings: BP 118/74, rounded facies, acneiform rash and leg edema, WBC 9400/ul, Glucose 173mg/dl, A1C 8.1%, K 2.3meql/L, random cortisol 114ug/dl, ACTH 830pg/ml, Calcitonin 1135 pg/mL, Chromogranin A 1482 ng/mL and Glucagon 276 pg/mL. After a 2 mg DST, 8 AM cortisol was 123 mcg/dL. We planned to reduce her ectopic ACTH production and hypercortisolemia with ketoconazole and chemotherapy followed by bilateral adrenalectomy. FOLFOX protocol reduced ACTH to 76 pg/mL and Cortisol to 73 mcg/dL but she clinically deteriorated, delaying adrenal surgery. She began having muscle weakness, aphasia, and other polyneuropathies. Blood cultures were positive for K. pneuomoniae and she received antibiotics. Cultures were negative for fungemia. Brain MRI showed extensive subcortical changes suggestive of PRES. Cortisol levels increased to 635 mcg/dL! In addition to ketoconazole and spironolactone, mifepristone was started with improvements in her hypokalemia and glucose. Mental status did not improve and repeat MRI showed findings suggestive of multiple abscesses. She was no longer a candidate for further chemotherapy or surgery and died within 40 days of admission. Discussion: Autopsy showed NET with hepatic metastases and multiple organs with fungal hyphae indicating Aspergillus. Both hypercortisolemia and chemotherapy predisposes to opportunistic infections. This patient’s remarkably elevated cortisol levels raised the consideration of urgent adrenalectomy prior to chemotherapy to limit steroid related complications and the polypharmacy required to control this. Both cortisol and chemotherapy impair cell mediated immunity and down regulate pro-inflammatory cytokines providing the opportunity for fungal and other uncommon infections to develop. This patient’s outcome could not have been worse if we elected adrenalectomy as the first therapeutic option to preclude the marked immunosuppressant effects of persisting hypercortisolemia together with chemotherapy. Otherwise, in a patient so profoundly immunosuppressed by endogenous steroids, a multitude of fungi and other atypical infections which are difficult to detect, need be considered when sepsis develops in association with chemotherapy.