Unexplained Hypoglycemia in a Diabetic Patient Unveiling Insulinoma: A Case Report

Background: Insulinomas are rare, typically benign, insulin-secreting neuroendocrine tumors with an incidence of 1–4 cases per million annually. They commonly present with Whipple’s triad: symptoms of hypoglycemia, low plasma glucose, and resolution of symptoms with glucose administration. The coexistence of insulinoma with type 2 diabetes mellitus (T2DM) is extremely uncommon and often results in diagnostic delays due to overlapping clinical features and misattribution of hypoglycemia to antidiabetic therapy. Case Presentation: We describe the case of a 65-year-old obese woman with a 16-year history of T2DM and hypertension, who presented with persistent symptomatic hypoglycemia despite discontinuation of insulin therapy. Her HbA1c ranged between 5.7% and 8.4% over the past year, and she was previously managed with 40 units/day of premixed insulin. Hypoglycemic episodes continued after insulin cessation, prompting inpatient evaluation. During hospitalization, she exhibited documented plasma glucose of 33 mg/dL with concurrent inappropriately elevated insulin (74.4 µIU/mL) and C-peptide (8.5 ng/mL) levels, confirming endogenous hyperinsulinemia. Chromogranin A was markedly elevated (350 ng/mL). Imaging via contrast-enhanced CT revealed a 14-mm hypervascular lesion in the pancreatic tail. The patient underwent successful laparoscopic distal pancreatectomy. Histopathology confirmed a 17-mm, well-differentiated, grade 3 pancreatic neuroendocrine tumor, positive for chromogranin and synaptophysin. Postoperatively, she developed persistent hyperglycemia requiring resumption of premixed insulin at 0.6 U/kg/day. At 3-month follow-up, she remained insulin-dependent but was free of further hypoglycemic episodes. Discussion: This case underscores the diagnostic complexity when insulinoma coexists with long-standing T2DM. In patients with continued hypoglycemia after insulin withdrawal, endogenous causes such as insulinoma must be considered. High clinical suspicion, biochemical profiling during hypoglycemic episodes, and timely imaging are essential. Notably, this case involved a well-differentiated grade 3 tumor; an uncommon histological finding in insulinomas which may have implications for surveillance due to its potential for more aggressive behavior. The persistence of diabetes post-resection highlights the ongoing insulin resistance associated with long-standing T2DM, despite tumor removal. Conclusion: Insulinoma should remain a differential in diabetic patients presenting with unexplained or worsening hypoglycemia, particularly after insulin discontinuation. Early diagnosis, appropriate imaging, and surgical resection are crucial for favorable outcomes. Postoperative metabolic monitoring remains essential due to the dual risk of hyperglycemia and hypoglycemia.