Insulinoma

An insulinoma is a rare pancreatic neuroendocrine tumor that secretes insulin autonomously, leading to hypoglycemia. Most insulinomas are benign (about 90%) and solitary, and they can occur at any age but most commonly present in adults during middle age. A minority are associated with multiple endocrine neoplasia type 1 (MEN1).

Insulinomas arise from pancreatic beta cells and cause hypoglycemia through unregulated insulin release. Histologically they are usually well-differentiated neuroendocrine tumors. Malignant potential exists in a minority, with liver metastases or local invasion signaling a more aggressive course.

Clinically, patients typically present with symptoms of neuroglycopenia (confusion, visual disturbances, seizures) and autonomic symptoms (palpitations, tremor, anxiety) that improve with glucose. This constellation is described as Whipple’s triad: symptoms of hypoglycemia, low plasma glucose, and relief with glucose. Biochemical diagnosis requires demonstrating inappropriately elevated insulin levels during hypoglycemia, with elevated C-peptide and proinsulin, and a glucose level typically below 55 mg/dL during testing.

Localization for surgical cure relies on imaging and sometimes functional studies. Contrast-enhanced CT or MRI localizes most tumors; endoscopic ultrasound is highly sensitive for small lesions. Functional imaging (such as 68Ga-DOTATATE PET/CT) and selective arterial calcium stimulation with hepatic venous sampling are used in difficult cases, and MEN1 patients require comprehensive screening for additional tumors.

Definitive treatment is surgical. Enucleation is favored for small benign tumors; larger or technically challenging lesions may require pancreatic resection. For inoperable or metastatic disease, medical therapies include diazoxide to suppress insulin release and somatostatin analogs (octreotide, lanreotide); everolimus and, less commonly, streptozotocin-based regimens may be used. Acute hypoglycemia should be managed with prompt glucose administration or glucagon.

Prognosis is generally favorable after curative resection, with relapse uncommon in benign cases. Malignant insulinomas with metastases have a poorer outcome and require multidisciplinary management. Regular follow-up is recommended, especially for patients with MEN1.