1562-P: A Rare Case of Metastatic Nonfunctional Pancreatic Neuroendocrine Tumor with Transformation into Insulinoma with Refractory Hypoglycemia Requiring Everolimus Use

Background: Most pancreatic neuroendocrine tumors (pNET) are non-functional and remain so over the course of a patient’s disease. Insulinoma is a form of functional pNET that manifests with hypoglycemia caused by inappropriate autonomous insulin secretion. These rare tumors usually present as a single benign tumor that is treated surgically. Surgery is not possible in patients with metastatic disease which leads to difficult to control often life-threatening hypoglycemia.

Clinical Case: We present a case of a 56 year old woman with a diagnosis of non-functional metastatic pNET that transformed into metastatic insulinoma with subsequent recurrent life-threatening hyperinsulinemic hypoglycemia. At the time of diagnosis, monthly lanreotide and temozolomide/capecitabine chemotherapy was started with initial successful control of disease. Upon disease progression, she was treated with peptide receptor radionuclide therapy (PRRT) during which she began having hyperinsulinemic hypoglycemic episodes refractory to treatment with both long and short acting somatostatin analogue therapy, glucocorticoids, and diazoxide. She received treatment with two cycles of 5-fluorouracil and oxaliplatin chemotherapy but was not well enough to continue. She was eventually started on everolimus in an attempt to control both hypoglycemia and pNET disease burden. This resulted in the resolution of hypoglycemia and later progression into hyperglycemia requiring insulin use. She was unable to tolerate higher doses of everolimus due to mucositis and cytopenias leading to a decreased dose. She passed away several months after initiation of therapy due to progression of malignancy.

Conclusion: This case not only demonstrates the rare ability of pNET to transform into a functional tumor, but also adds to other case reports that propose everolimus use as a potential option for management of hypoglycemia caused by insulinoma.