A Rare and Aggressive Case of Malignant Insulinoma

Insulinomas are rare pancreatic neuroendocrine tumors (NETs) characterized by autonomous insulin secretion leading to hypoglycemia. Malignant insulinomas are defined by the presence of metastases and present significant therapeutic challenges due to limited treatment options. We report the case of a 69-year-old woman with a two-month history of neuroglycopenic symptoms, including morning headaches, blurred vision, palpitations, and sweating, which were alleviated by sugar intake. An episode of severe hypoglycemia-induced unconsciousness necessitated intramuscular glucagon administration, resulting in regained consciousness. The combination of neuroglycopenic symptoms relieved by carbohydrate and documented hypoglycemia fulfilled Whipple's triad, prompting evaluation for an insulin-secreting tumor. Laboratory findings revealed elevated endogenous insulin and C-peptide levels, indicating hyperinsulinemia. Imaging studies, including contrast-enhanced computed tomography (CT) and magnetic resonance imaging (MRI), identified a 25 mm solid lesion in the pancreatic body and multiple hepatic metastases. A ⁶⁸Ga-DOTA-NOC positron emission tomography (PET) scan demonstrated high somatostatin receptor expression in both the pancreatic lesion and hepatic metastases. Ultrasound-guided liver biopsy revealed a high-grade (G3) neuroendocrine carcinoma with a Ki-67 proliferation index exceeding 30%, confirming the diagnosis of malignant insulinoma. Multidisciplinary consultation recommended initiation of systemic chemotherapy with cisplatin and etoposide. Despite optimized medical management, including dextrose infusion, diazoxide, octreotide, and corticosteroids, the patient experienced persistent severe hypoglycemia. Transarterial chemoembolization (TACE) of the tumor vasculature was performed to mitigate hypoglycemia by reducing tumor burden. Post-procedure, the patient developed a cerebellar hemorrhage leading to coma and subsequent death. This case underscores the aggressive nature and poor prognosis associated with malignant insulinomas, particularly those with high proliferative indices. It highlights the complexities of managing refractory hypoglycemia in the context of widespread metastatic disease and emphasizes the urgent need for effective therapeutic strategies to improve patient outcomes.