Ampullary Neuroendocrine Carcinoma Presenting with Clinically Confirmed Endogenous Hyperinsulinemic Hypoglycemia.

A 65-year-old man without diabetes presented with fasting hypoglycemia. During a fasting test, plasma glucose decreased to 46 mg/dL with inappropriately elevated insulin (11.1 μU/mL) and C-peptide (8.7 ng/mL) levels, confirming endogenous hyperinsulinemic hypoglycemia. Imaging revealed a tumor of the ampulla of Vater with multiple liver metastases but no pancreatic lesions. An endoscopic biopsy revealed poorly differentiated small cell-type NEC with a Ki-67 index >90% and complete loss of RB1 expression. Despite negative insulin immunostaining, dynamic endocrine testing confirmed endogenous hyperinsulinemic hypoglycemia. These findings were clinically consistent with ectopic insulin secretion from the NEC, although pathological confirmation was not obtained in this case. This case highlights the importance of integrating physiological, radiological, and pathological findings when evaluating suspected ectopic insulin secretion.