How do I diagnose an insulinoma?

Diagnosing Insulinoma

The diagnosis of insulinoma requires a supervised 48-72 hour fast demonstrating Whipple's triad with inappropriately elevated insulin, C-peptide, and proinsulin levels when blood glucose falls below 55 mg/dL. 1

Clinical Presentation and Initial Evaluation

• Look for symptoms of hypoglycemia:
  • Neuroglycopenic symptoms: confusion, lethargy, periodic numbness
  • Adrenergic symptoms: sweating, palpitations, anxiety
  • Symptoms typically occur during fasting or exercise

Diagnostic Algorithm

Step 1: Laboratory Testing

• Measure serum insulin, proinsulin, and C-peptide levels 1
• Diagnostic criteria during hypoglycemia (blood glucose <55 mg/dL):
  • Insulin level >3 mcIU/mL (usually >6 mcIU/mL)
  • C-peptide concentrations ≥0.6 ng/mL
  • Proinsulin levels ≥5 pmol/L 1

Step 2: Supervised Fast (Gold Standard)

• Perform a supervised 48-72 hour fast 1
  • 48-hour fast is now considered sufficient and should replace the traditional 72-hour fast 2
  • Monitor blood glucose, insulin, C-peptide, and proinsulin levels
  • Test is terminated when hypoglycemia occurs or at completion of time period
  • Most insulinomas (94.5%) can be detected within 48 hours of fasting 2

Step 3: Imaging for Localization

• Endoscopic ultrasound (EUS): best initial imaging modality (localizes ~82% of pancreatic NETs) 1
• Multiphasic CT or MRI: should be performed to rule out metastatic disease 1
• Consider selective arterial calcium stimulation test (Imamura-Doppman procedure) only when:
  • Other localization tests are equivocal or negative
  • For persistent or recurrent insulinoma 1

Important Diagnostic Considerations

Whipple's Triad

Confirm all three elements:

1. Symptoms of hypoglycemia
2. Low blood glucose (<55 mg/dL) when symptoms occur
3. Relief of symptoms after glucose administration

Alternative Testing Methods

• For outpatient settings or when prolonged fast is not feasible:
  • 5-hour oral glucose tolerance test (OGTT) with measurement of insulin-to-glucose and C-peptide-to-glucose ratios 3
  • Short fasting test (24-hour) initiated overnight at home and continued in outpatient setting 4
  • Recent research shows 91.7% of insulinomas can be diagnosed within 24 hours of beginning a fast 4

Pitfalls to Avoid

1. False negatives: Some insulinomas may present with normoglycemia after prolonged fasting but glucose-stimulated hypoglycemia 5

   • Consider OGTT if clinical suspicion is high despite negative fast

2. Factitious hypoglycemia: Test urinary sulfonylurea to rule out factitious causes 1

3. Premature termination of fast: Ensure proper monitoring of subtle neuroglycopenic symptoms

4. Somatostatin analogs: Avoid administering octreotide or lanreotide before diagnosis as they can profoundly worsen hypoglycemia in patients with insulinoma 1

5. Insulin-to-glucose ratio: An insulin-to-glucose ratio ≥0.3 reflects inappropriate insulin secretion during hypoglycemia 1

By following this diagnostic approach, insulinoma can be accurately diagnosed, allowing for appropriate surgical management which can cure 90% of these tumors that typically follow an indolent course 1.