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Insulin is a hormone secreted by the islet cells of the pancreas that regulates carbohydrate metabolism. Measurement of plasma insulin levels is helpful in the diagnosis of insulinoma. Eighty percent of patients have a single benign tumor, usually <2-cm in diameter, located about equally in the head, body or tail of the pancreas. About 10% of patients have multiple tumors associated with multiple endocrine neoplasia type 1 and the remaining 10% have metastatic malignant insulinoma.

Patients with insulinomas usually present with fasting hypoglycemia, but occasionally may present with postprandial hypoglycemia.The diagnosis depends on demonstrating elevated serum insulin and C peptide levels when the patient has symptoms of hypoglycemia and plasma glucose is low. One third of patients with insulinoma have an insulin level within the normal range, so it must be shown that the insulin level is high for the patient’s glucose level. Inappropriate elevation of insulin can occur in two conditions; insulinoma and exogenous administration of insulin. This distinction can be made by measuring C peptide, which is created by the cleavage of proinsulin to insulin within the beta cell. It is not present in pharmaceutical insulin. Serum C peptide level is low with surreptitious injection of insulin and increased with insulinoma.

Diagnostic criteria of insulinoma include:

  • hyperinsulinemia (6uU/mL) associated with hypoglycemia (plasma glucose<60 mg/dL)
  • elevated insulin C peptide during hypoglycemia (plasma glucose <40 mg/dL)
  • persistent hyperinsulinemia (>20 uU/mL) and hypoglycemia (plasma glucose <60 mg/dL) between 2 and 3 hours after injection of tolbutamide.

Insulin antibodies in diabetic patients who have been treated with beef or pork insulin may interfere with insulin quantitation. A test for insulin antibody should be included in the work-up of these patients.

Insulin levels are increased in obesity, Cushing’s syndrome, and acromegaly. Patients taking oral contraceptives, exogenous corticosteroids, or L dopa have elevated insulin levels.

Reference range is 3–25 uIU/mL.

Specimen requirement is one SST tube of blood.

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