A 28-year-old man is evaluated for a 2-month history of recurrent confusion, palpitations, and diaphoresis occurring whenever he misses breakfast. The symptoms are relieved with eating. His medical history is otherwise unremarkable, and he takes no medications.

On physical examination, vital signs are normal, and BMI is 26. The results of the general physical examination are normal.

Results of laboratory studies show a fasting plasma glucose level of 52 mg/dL (2.9 mmol/L) and an insulin level of 18 µU/mL (129.9 pmol/L) (normal range, 2 to 20 µU/mL [14.4 to 144.3 pmol/L]).

Which of the following is the most appropriate next step in diagnosis?


Answer and Critique (Correct Answer: E)

Educational Objective:Evaluate a suspected insulinoma.

Key Point

  • The supervised 72-hour fast is the gold standard for diagnosing insulinoma.

This patient most likely has an insulin-producing tumor and should be admitted to the hospital for a supervised 72-hour fast. Because symptoms of hypoglycemia are nonspecific, it is important to clearly document the presence of an abnormally low level of blood glucose. The biochemical diagnosis of insulinoma is made when the fasting glucose level falls below 45 mg/dL (2.5 mmol/L), accompanied by inappropriate hyperinsulinemia (insulin level higher than 5-6 µU/mL [36.1-43.3 pmol/L]), after exogenous factors have been eliminated. To best evaluate the patient for insulinoma, a prolonged fast (up to 72 hours) under strict medical observation is often necessary. Serum glucose, insulin, C-peptide, and proinsulin levels are measured at 4- to 6-hour intervals throughout the supervised fast. The fast is discontinued once the glucose value falls below 45 mg/dL (2.5 mmol/L) with associated symptoms of hypoglycemia and appropriate blood tests (measurement of plasma glucose, insulin, and C-peptide levels) are obtained. More than 95% of patients with insulinoma will have hypoglycemia within 72 hours. Insulin and C-peptide levels will generally be elevated, as will the proinsulin level, which suggests a greater tumor release of immature insulin.

Once the diagnosis of insulinoma is confirmed biochemically, imaging studies of the pancreas are obtained, beginning with an abdominal CT scan. Although these typically benign lesions are usually too small to be detected on a CT scan, this imaging modality is an important first step to exclude larger lesions or lesions already metastatic to the liver. If there are no significant findings, further evaluation may include endoscopic ultrasonography, MRI, hepatic venous sampling with arterial calcium stimulation, arteriography, and intraoperative ultrasound. Octreotide scans are usually not helpful for small, localized tumors. After the lesion is identified, surgical resection should follow.

The measurement of glucose should involve whole blood or plasma samples, collected in specialized tubes that inhibit glycolysis. “Fingerstick” capillary readings using home glucose meters are inaccurate in the hypoglycemic range, and results should be interpreted cautiously.


  • Khoo TK, Service FJ. Hyperinsulinemic hypoglycemia. Endocr Pract. 2007;13(4):424-426. [PMID:17669722] - See PubMed

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