SUN-321 Rare Case of Hypoglycemia Induced by IGF2 Secreted by an Ovarian Tumor

Abstract

Introduction: Mesenchymal and epithelial tumors can produced un-cleaved IGF-2 molecules known as “big” IGF-2. These tumors are associated with elevated levels of IGF-2, which can mimic hypoglycemic events of insulin-producing islet-cell tumors by binding and activating insulin receptors. Typically plasma levels of insulin, IGF-1, and GH are low. “Big” IGF-2 molecular testing is not commercially available, however diagnosis of IGF-2 mediated hypoglycemia is based on low insulin and proinsulin in association with a IGF-2 to IGF-1 ratio >3. Clinical Case A 62 year old female with no significant past medical problems presented with 20 lb weight loss and a two month history documented symptomatic hypoglycemia episodes . Her PCP palpated a firm, non-painful mass occupying nearly her entire abdomen on physical exam. CT revealed a pelvic mass measuring 23.4 cm thought to originate from the ovary. Biopsy of the mass showed a well-differentiated neuroendocrine tumor grade 3, Ki 67 of 15%. Lab work by Endocrinology was significant for a serum glucose of 46 mg/dl, insulin <5 uIU/ml, C-peptide <1 ng/ml, cortisol 43 ug/dl, IGF-1 18 ng/ml, IGF-2 163 ng/ml (IGF1:IGF2: 9), pro-insulin 1.7 pmol/L, sulfonyl urea screen was negative, Ca 125: 230 U/ml, Ca 19-9: 7 U/ml, CEA <1 ng/ml, and chromogranin-A 598 ng/ml. Ga DOTATE scan revealed a 21 cm intra-abdominal mass with multiple peritoneal soft tissue implants consistent with a neuroendocrine tumor with peritoneal carcinomatosis. Due to persistent episodes of hypoglycemia, the patient was started on octretotide 200 mg q 8 hrs, Dexamethasone 1 mg q 3 hrs and parenteral nutrition. The patient was evaluated by surgery and deemed to inoperable due to multiple metastasis. She was then treated with cepecidobine and temozolomide with significant improvement in her glycemic control. A week later, the patient was able to be weaned off TPN and dexamethasone and was discharged home on oral diet. She was evaluated a month later as outpatient and had infrequent episodes of hypoglycemia. Conclusion This is the first case report of a patient with IGF-2 induced hypoglycemia treated with a combination of cepecidobine, temozolomide, and octreotide. While octreotide helped to improve her glycemic control by generally inhibiting hormonal secretion, likely of both IGF-2 and insulin production, final symptom relief and clinical stabilization occurred with the combination of capecitabine and temozolomide, which in vitro data has is synergistic for induction of apoptosis in neuroendocrine tumor cell lines .