SUN-LB068 Ectopic Cushing Syndrome Due to a Metastatic Neuroendocrine Tumor Treated with Metyrapone

Abstract

Introduction: We describe a patient with a non-secretory low grade neuroendocrine tumor that transformed into a high grade carcinoma causing Cushing syndrome that was medically managed with metyrapone. Clinical Case: A 53 year old woman with a history of widely metastatic neuroendocrine tumor for 5 years was treated with somatostatin analogues, multiple chemotherapeutic agents, radiation therapy, and recently peptide receptor radionuclide therapy (PRRT). Some of her tumors were responding to PRRT, except that 1 month after her 3rd round of PRRT, she presented with profound muscle weakness, confusion, hypokalemia (K = 3.1 meq/L), and new onset of diabetes mellitus (glucose 319 mg/dL). Ectopic Cushing syndrome was diagnosed by ACTH of 748 pg/mL (n 7.2 - 63 pg/mL), a serum cortisol of 127 mcg/dL (n 6.7 - 22.6 mcg/dL), and a 24 hour urine free cortisol of 20,328 mcg/L (n 0 - 50 ug/24 hr). Her labs also showed pancytopenia including platelet count of 47 E3/ul (n 150 - 450 x10E3/uL). Imaging revealed growing necrotic liver metastases and thickened adrenal glands. Biopsy of the liver lesions revealed a high grade metastatic small cell neuroendocrine carcinoma with a mitotic rate of 49/10 HPF and Ki-67 of 70%. Interestingly, the neuroendocrine tumor cells in the liver biopsy did not stain for ACTH. This diverged greatly from pathology on initial diagnosis which revealed a low-grade well differentiated neuroendocrine tumor with a mitotic rate 2/10 HPF and Ki-67of 4-5%. It was clear from the patient’s clinical presentation and pathology results that her tumor had evolved into a poorly differentiated tumor secreting either ACTH and/or CRH resulting in Cushing syndrome. She was deemed a poor surgical candidate for adrenalectomy due to critical illness and advanced cancer. Elevated transaminases related to necrotic liver lesions precluded use of ketoconazole. Thus, medical therapy was initiated using metyrapone as well as spironolactone, potassium supplements, and insulin. Serum cortisol improved rapidly to 20 mcg/dl. 24 hour urine free cortisol improved to 1,129 mcg/ 24 hours with metyrapone 250mg twice daily and to 429 mcg/ 24 hours with metyrapone 250 mg every 6 hours. Her thrombocytopenia worsened with a nadir of 5 E3/ul but recovered to 127 E3/ul with continuation of metyrapone. Bone marrow biopsy performed at that time found low grade neuroendocrine tumor cells that did not stain for ACTH. Conclusion: The transformation of an indolent low grade neuroendocrine tumor to a high grade neuroendocrine carcinoma was accompanied by an ectopic Cushing syndrome. The cortisol excess was controlled rapidly and effectively with metyrapone. Thrombocytopenia was temporally related to the severe hypercortisolism and platelets improved to near normal with correction of cortisol. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.