From the Guidelines
To diagnose insulinoma, a supervised 72-hour fast with serial measurements of blood glucose, insulin, C-peptide, and proinsulin levels is the most important laboratory test, as it is the gold standard for diagnosis. During the fast, if hypoglycemia occurs (blood glucose <45-50 mg/dL) with inappropriately elevated insulin (≥3 μU/mL), elevated C-peptide (≥0.6 ng/mL), and elevated proinsulin (≥5 pmol/L), this strongly suggests insulinoma 1. Additional helpful tests include measuring beta-hydroxybutyrate levels, which are typically suppressed in insulinoma, and sulfonylurea screening to rule out factitious hypoglycemia.
Key Laboratory Tests
- Serum insulin
- Proinsulin
- C peptide
- Blood glucose
- Beta-hydroxybutyrate levels
- Sulfonylurea screening The 72-hour fast should be conducted in a hospital setting with close monitoring, as dangerous hypoglycemia may occur. Most insulinoma patients develop hypoglycemia within 24-48 hours of fasting. These tests are crucial because insulinomas cause inappropriate insulin secretion independent of blood glucose levels, leading to the paradoxical finding of detectable insulin levels during hypoglycemia, which wouldn't occur in normal physiology where insulin secretion should be suppressed when blood glucose is low. Multiphasic CT or MRI scans should also be performed to rule out metastatic disease 1.
From the Research
Labs to Check for Insulinoma
To diagnose insulinoma, several laboratory tests can be used, including:
- Fasting test: a 48-hour or 72-hour fast to demonstrate Whipple's triad, which consists of symptoms known or likely to be caused by hypoglycemia, a low plasma glucose measured at the time of the symptoms, and relief of symptoms when the glucose is raised to normal 2, 3, 4
- Oral glucose tolerance test (OGTT): a 5-hour OGTT to evaluate the ratios of serum concentrations of insulin and C-peptide to glucose 5
- Glucagon stimulation test: to assess the insulin response to glucagon, which can be useful in diagnosing insulinoma, especially in cases with normal results from prolonged fast 6
- Measurement of serum insulin, C-peptide, and proinsulin levels: to assess the insulin secretion and diagnose insulinoma 2, 3, 4
Diagnostic Criteria
The diagnostic criteria for insulinoma include:
- Demonstration of Whipple's triad during a supervised fast
- Elevated serum insulin, C-peptide, and proinsulin levels during hypoglycemia
- Insulin/C-peptide ratio below 1.0
- Relief of symptoms when glucose is raised to normal
Test Performance
The performance of these tests varies, with: