Clinical meaning
Insulinoma is the most common functioning pancreatic neuroendocrine tumor, arising from pancreatic beta cells that autonomously secrete insulin independent of blood glucose levels. The incidence is approximately 1-4 per million person-years. Understanding the pathophysiology and diagnostic approach is essential for the NP evaluating recurrent hypoglycemia. Normal insulin secretion is tightly regulated by blood glucose: as glucose falls below 70 mg/dL, insulin secretion is suppressed (essentially turned off) while counterregulatory hormones (glucagon, epinephrine, cortisol, growth hormone) are activated. In insulinoma, neoplastic beta cells continue to secrete insulin autonomously despite hypoglycemia, creating a pathological state of endogenous hyperinsulinism. The ongoing insulin secretion drives glucose into cells, suppresses hepatic gluconeogenesis and glycogenolysis, and inhibits lipolysis — all of which prevent the normal counterregulatory response to hypoglycemia. Whipple's triad is the clinical hallmark used to confirm symptomatic hypoglycemia: (1) symptoms consistent with hypoglycemia (neuroglycopenic — confusion, visual changes, behavioral changes, seizures, loss of consciousness; and adrenergic — tremor, diaphoresis, palpitations, anxiety), (2) documented low blood glucose at the time of symptoms (<55 mg/dL during a monitored fast), and (3) resolution of symptoms upon glucose...