Insulin

Insulin is a hormone secreted by the beta cells that are located in the islets of the pancreas. Insulin regulates uptake and metabolism glucose. Insulinoma is a rare tumor that produces excess insulin and causes hypoglycemia. 

Hypoglycemia can cause palpitations, tremulousness, and diaphoresis. Severe hypoglycemia can lead to blurred vision, slurred speech, confusion, seizures, behavioral changes, or loss of consciousness. 

Eighty percent of patients have a single benign tumor, usually <2-cm in diameter, that is 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. The remaining 10% of patients have metastatic malignant insulinoma.  

Fasting hypoglycemia is the most common finding in patients with  insulinoma, occurring in approximately 73% of cases. About 20% of patients experience both fasting and postprandial hypoglycemia. A minority of patients experience only postprandial hypoglycemia.

The diagnosis of insulinoma should be considered in patients presenting with Whipple’s triad, which comprises symptoms of hypoglycemia, documented low plasma glucose levels, and resolution of symptoms following glucose administration.

Laboratory tests play an important role in the initial diagnosis. The diagnosis depends on demonstrating elevated serum insulin and C-peptide levels when the patient has symptoms of hypoglycemia and plasma glucose concentration is low. 

Diagnostic criteria include: 

• Glucose concentration of <55 mg/dL
• Insulin level ≥3 µU/mL
• C-peptide level ≥0.6 ng/mL
• Proinsulin level ≥5 pmol/L
• Beta-hydroxybutyrate level ≤2.7 mmol/L
• Sulfonylurea screen negative 

Altogether, these findings indicate that hypoglycemia is mediated by hyperinsulinemia. 

A 72-hour fasting test is considered the gold standard for diagnosing insulinoma. This test is useful when Whipple’s triad is not clinically evident or when laboratory tests could not be drawn during a spontaneous hypoglycemic episode.

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.  C-peptide is not present in pharmaceutical insulin.  Serum C-peptide level is low in patients who are surreptitiously injecting insulin and elevated in patients with insulinoma.  

Insulin antibodies may be present in diabetic patients who have been treated with beef or pork insulin. They may interfere with the accuracy of 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 also may have elevated insulin levels.

The reference range for insulin is 2.6 – 25 mIU/mL. 

Specimen requirement for insulin is one SST tube of blood.

Reference

Zhuo F, Menon G, and Anastasopoulou C. Insulinoma, 2025. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK544299/.