Patients with insulinoma develop profound hypoglycemia during fasting or after exercise. The clinical picture includes the signs and symptoms of neu-roglycopenia (anxiety, tremor, confusion, and obtundation) and the sympathetic response to hypoglycemia (hunger, sweating, and tachycardia). These bizarre complaints initially may be attributed to malingering or a psychosomatic etiology unless the association with fasting is recognized. Many patients eat excessively to avoid symptoms, causing significant weight gain. Whipple triad refers to the clinical criteria for the diagnosis of insulinoma: (a) hypoglycemic symptoms during fasting, (b) blood glucose levels less than 50 mg/dL, and (c) relief of symptoms after administration of glucose. Factitious hypoglycemia (excess exogenous insulin administration) and postprandial reactive hypoglycemia must be excluded. A supervised, in-hospital 72-h fast is required to diagnose insulinoma. Patients are observed for hypoglycemic episodes and have 6-h measurement of plasma glucose, insulin, proinsulin, and C-peptide. Nearly all patients with insulinoma develop neuroglycopenic symptoms and have inappropriately elevated plasma insulin (greater than 5 pU/mL) associated with hypoglycemia (glucose less than 50 mg/dL).
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