(10.15) A New Diagnosis of Hypoglycemia: The Progression of a Non-functional Pancreatic Neuroendocrine Tumor to a Metastatic Insulinoma

Neuroendocrine tumors (NETs) of the pancreas are rare, slow growing tumors with capacity to metastasize. NETs are classified as functional or non-functional. The transformation of a non-functional NET to a functional metastatic NET is exceedingly rare. We present a case of a completely resected non-functional NET that recurred as a metastatic insulinoma.


Case(s) Description :

A 63 year-old woman with well-differentiated NET and history of total pancreatectomy five years prior presented to the hospital with acute hypoglycemia. At initial diagnosis, she had no symptoms of hypoglycemia and was not tested for an insulinoma. After pancreatectomy, she was started on insulin. Two years later, she had recurrent disease in the liver and mesentery treated with peptide receptor radionuclide therapy (PRRT) and sunitinib. One year prior to presentation, she noted intermittent hypoglycemia that prompted her to stop exogenous insulin. She reported improvement in hypoglycemia after PRRT sessions. However, symptoms progressed in the months prior to presentation culminating in a severe neuroglycopenic event prompting hospital admission. Biochemical analysis on admission revealed serum glucose 55mg/dL, insulin 16uU/mL, pro-insulin 48.6pmol/L, c-peptide 3ng/mL, beta-hydroxybutyrate < 0.5mg/dL, insulin-like growth factor-2 194ng/mL, and a negative Insulin Antibody. Insulin, pro-insulin and c-peptide were all considered elevated given prior total pancreatectomy and consistent with a metastatic insulinoma. She was started on dextrose fluids, diazoxide 200mg TID, dexamethasone 2mg BID and capecitabine 1g BID. Octreotide was trialed but not tolerated given gastrointestinal side effects. She was not a candidate for further chemotherapy, antihormonal therapy or immunologic therapy. Despite intervention, she had persistent hypoglycemia and ultimately pursued comfort care. 


Discussion :

NETs represent 3% of primary pancreatic neoplasms. Insulinoma is the most common NET. The transformation of a non-functional NET into functional metastatic disease is exceedingly rare. In patients who undergo total pancreatectomy, drastic reductions in insulin therapy (or in our patient, complete discontinuation) without severe hyperglycemia, should raise concern of transformation to an insulinoma. New symptoms of hypoglycemia require biochemical analysis as transformation confers poor prognosis. Early identification can lead to tailored therapy and goals of care conversations.