Heterogeneity of Multiple Pancreatic Neuroendocrine Tumors Identified by ⁶⁸Ga-DOTANOC and ⁶⁸Ga-Exendin-4 PET/CT in a Patient with Endogenous Hyperinsulinemic Hypoglycemia and Multiple Endocrine Neoplasia 1

Abstract

Insulinomas are the most frequent functional neuroendocrine tumors of pancreas. In about 10% cases, insulinomas are associated with hereditary syndrome including multiple endocrine neoplasia 1 (MEN1). Herein, we presented a case of 44-year-old female with recurrent hypoglycemia. In December 1998, this patient has undergone resection of two pancreatic lesions due to hypoglycemia and diagnosed as insulinoma. After operation, the symptom of hypoglycemia disappeared. However, from 2021, hypoglycemic symptoms reappeared frequently and even coma. In June 2023, enhanced CT showed multiple pancreatic lesions abundant with blood supply. Fasting serum blood glucose and insulin were 1.73mmol/L and 15.2U/L (2.6-11.8U/L). Germline genes suggested MEN1 pathogenic mutations. 68Ga-DOTANOC PET/CT indicated there were multiple lesions located in the pancreas and duodenum with high expression of somatostatin receptor (SSTR). 68Ga-exendin-4 PET/CT were added to localize the insulinoma. Most lesions with high expression of SSTR in body and tail of pancreas manifested part of them with high uptake of 68Ga-exendin-4, and an additional lesion with high expression of glucagon-like peptide 1 receptor was only detected by 68Ga-exendin-4 PET/CT. It showed highly heterogeneity. From the distal pancreatectomy, a total 5 tumors were found in the body and tail of pancreas, which were diagnosed as neuroendocrine tumors (NETs). After the operation, all the symptoms related to hypoglycemia disappeared. Immunohistochemical results of SSTR2 and insulin were consistent with the imaging finding of dual tracer PET/CT. From this case, combination of 68Ga-DOTANOC and 68Ga-exendin-4 PET/CT was recommended in the patients of MEN1 and insulinoma to estimate the heterogeneity of multiple neuroendocrine tumors that contributing to detect all the NET lesions and locate the tumors with secretion of insulin.