Transformation of metastatic nonfunctioning pancreatic neuroendocrine tumor into insulinoma-two case reports

Background: Pancreatic neuroendocrine tumors (PanNETs) are rare neoplasms that are characterized by hormonal symptoms. While most PanNETs are nonfunctional, there have been a few reported cases of patients with previously nonfunctional PanNETs developing significant hormonal symptoms, indicating transformation into a functional PanNET. Case Description: We describe two rare cases of transformation of metastatic non-functional PanNET into a metastatic functional insulinoma. The clinical presentations were significant for severe symptomatic hypoglycemia with symptoms of seizures and loss of consciousness. The diagnoses of insulinoma were confirmed by inappropriately elevated insulin, pro-insulin, C-peptide levels drawn in the setting of documented hypoglycemia, which improved with dextrose supplementation. Given the highly refractory nature of the disease, a multimodal approach of cytotoxic chemotherapy, metabolic suppression of insulin secretion through somatostatin analogs and diazoxide, and glucose supplementation was utilized to treat the insulinoma. Novel somatostatin analogues with higher binding affinity for multiple somatostatin receptor subtypes such as pasireotide demonstrated some effectiveness as an adjunctive agent after transformation. Conclusions: This report highlights the need for clinicians to be aware of the possibility of transformation of non-functional PanNETs. Additionally, there remains a need for further research to understand the mechanism of transformation in PanNETs and for the development of additional therapies for treatment of metastatic PanNETs.