What is the best way to diagnose insulinoma?

Best Diagnostic Approach for Insulinoma

The supervised 48-hour fast with measurement of glucose, insulin, C-peptide, and proinsulin levels is the gold standard for diagnosing insulinoma. 1, 2

Diagnostic Algorithm

Step 1: Clinical Suspicion

• Suspect insulinoma in patients presenting with neuroglycopenic symptoms (confusion, lethargy, seizures) and autonomic symptoms (diaphoresis, tremor, palpitations), especially during fasting or in the morning 1
• Weight gain due to frequent eating to avoid hypoglycemia is a common feature 1

Step 2: Supervised Fast (First-line Test)

• Perform a supervised fast for 48 hours (replacing the traditional 72-hour fast) 1, 2
• Monitor blood glucose levels every 4-6 hours and when symptoms occur 1
• Terminate the fast when hypoglycemia occurs or the time limit is reached 1
• Most insulinomas (94.5%) can be diagnosed within 48 hours of fasting 2

Step 3: Diagnostic Criteria at Termination of Fast

• Diagnostic criteria include:
  • Blood glucose <40-45 mg/dL 1
  • Insulin level >3 mcIU/mL 1
  • C-peptide ≥0.6 ng/mL 1
  • Proinsulin levels ≥5 pmol/L 1
  • Insulin-to-glucose ratio of 0.3 or greater 1

Step 4: Tumor Localization

• Endoscopic ultrasound (EUS) is the preferred initial localization method with approximately 82% sensitivity 1
• Perform multiphasic CT or MRI scans to rule out metastatic disease 1
• For difficult cases, consider selective arterial calcium stimulation test (Imamura-Doppman procedure) 1, 3

Important Diagnostic Considerations

Proinsulin Measurement

• Measure proinsulin at the beginning and end of the fast 4
• Even mild elevations in proinsulin can indicate insulinoma when insulin levels are suppressed 4
• Proinsulin is elevated at the beginning of the fast in 90% of insulinoma patients 2

Atypical Presentations

• Some insulinomas may present with normoglycemia after prolonged fasting but glucose-stimulated hypoglycemia 5
• Consider oral glucose tolerance testing in patients with strong clinical suspicion but normal fasting test 5

Selective Arterial Calcium Stimulation Testing (SACST)

• Useful for localizing insulinomas not detected by conventional imaging 3
• Involves injecting calcium into selective pancreatic arteries and measuring insulin levels in the hepatic vein 1, 3
• Particularly valuable in difficult cases or post-bariatric surgery patients 3

Common Pitfalls and Caveats

• Proton pump inhibitors can cause spuriously elevated chromogranin A levels, complicating diagnosis 1
• Some insulinomas may not be detected by the standard fasting test, requiring additional testing such as oral glucose tolerance tests 5
• Blind pancreatic resection should be avoided; accurate preoperative localization is essential 6
• Elevated C-peptide levels help differentiate endogenous hyperinsulinemia (insulinoma) from exogenous insulin administration 1