Insulinomas

An insulinoma is a rare pancreatic neuroendocrine tumor that arises from beta cells and secretes insulin. Most insulinomas are benign and solitary, typically small (about 1–2 cm). The annual incidence is approximately 1–4 cases per million people. Many cases occur sporadically, but insulinomas can be associated with multiple endocrine neoplasia type 1 (MEN1).

Patients typically experience episodes of hypoglycemia, especially during fasting, exercise, or stress. Symptoms are neuroglycopenic or autonomic and may include confusion, dizziness, sweating, tremor, palpitations, or loss of consciousness. Whipple’s triad describes the combination of hypoglycemic symptoms, low plasma glucose, and relief with glucose.

Pathophysiology involves autonomous insulin secretion that persists or increases as glucose falls, leading to recurrent hypoglycemia. Diagnosis requires demonstrating endogenous hyperinsulinemic hypoglycemia and localizing the tumor. A supervised 72-hour fast with measurements of glucose, insulin, C‑peptide, and proinsulin is commonly used, along with screening to exclude surreptitious sulfonylurea use. Imaging studies such as contrast-enhanced computed tomography or magnetic resonance imaging, endoscopic ultrasound, and functional imaging with Ga-68 DOTATATE PET can aid localization.

Treatment is most often surgical. Enucleation is preferred for small, benign tumors; segmental or distal pancreatectomy may be needed for larger or more regional lesions. Lymph node assessment is important if malignancy is suspected. For unresectable or metastatic insulinomas, medical therapies include diazoxide to inhibit insulin release, somatostatin analogs, everolimus, and, in select cases, chemotherapy. Dietary measures and careful monitoring of glucose are used to control hypoglycemia.

Prognosis is favorable after complete resection, with long-term survival common. Malignant insulinomas or those associated with MEN1 require ongoing surveillance for recurrence or additional tumors.