What labs and imaging studies are used to diagnose an insulinoma?

Diagnostic Approach for Insulinoma

The definitive diagnostic workup for insulinoma should include serum insulin, proinsulin, and C-peptide measurements, followed by a 48-72 hour supervised fast and multiphasic CT or MRI imaging. 1

Laboratory Evaluation

• The initial laboratory evaluation should include serum insulin, proinsulin, and C-peptide levels, which are critical for diagnosing endogenous hyperinsulinism 2, 1
• Diagnostic criteria during hypoglycemia include insulin level >3 mcIU/mL (usually >6 mcIU/mL), C-peptide ≥0.6 ng/mL, and proinsulin levels ≥5 pmol/L when blood glucose is <55 mg/dL 2, 1
• A supervised 48-72 hour fast is the gold standard test for diagnosing insulinoma, continued until hypoglycemia occurs or the time limit is reached 2, 1
• Elevated C-peptide levels during hypoglycemia help differentiate endogenous hyperinsulinemia (insulinoma) from exogenous insulin administration 1

Imaging Studies

• Multiphasic CT or MRI scans should be performed as first-line imaging to localize the tumor and rule out metastatic disease 2
• Endoscopic ultrasound (EUS) is highly sensitive (approximately 82%) for detecting pancreatic NETs and is particularly valuable for localizing small insulinomas 2, 1
• Somatostatin receptor scintigraphy (octreoscan) has limited utility for insulinomas as they are less consistently octreotide-avid than other pancreatic NETs 2
• Somatostatin scintigraphy should only be performed if octreotide or lanreotide treatment is being considered for metastatic disease 2

Advanced Diagnostic Techniques

• For difficult-to-localize insulinomas, selective arterial calcium stimulation testing (Imamura-Doppman procedure) may be necessary 2, 3
• This procedure involves injecting calcium into selective pancreatic arteries and measuring insulin levels in the hepatic vein 1
• Most experts recommend this test only for patients with persistent or recurrent insulinoma or when other localization tests are equivocal or negative 2
• Newer functional imaging with 68Ga-DOTA-exendin-4 PET-CT can help confidently diagnose and localize insulinoma when prior biochemical or endoscopic biopsy results are ambiguous 4

Important Caveats and Pitfalls

• Some insulinomas may present with postprandial hypoglycemia rather than fasting hypoglycemia, making diagnosis challenging 5
• A "normal" 72-hour fast does not definitively rule out insulinoma, especially if clinical symptoms are strongly suggestive 6
• Repeated episodes of hypoglycemia can lead to "hypoglycemia unawareness," which can be dangerous and requires early detection 5
• Continuous glucose monitoring (CGM) systems can be useful for evaluating treatment course, monitoring hypoglycemic episodes during the diagnostic period, and detecting unconscious hypoglycemia 5
• Proton pump inhibitors can cause spuriously elevated chromogranin A levels, potentially complicating diagnosis 2, 1

Treatment Considerations

• Surgical resection is the optimal treatment for localized insulinomas, with a cure rate of approximately 90% 2, 1
• Before surgery, glucose levels should be stabilized with dietary management, diazoxide, or everolimus 2
• Somatostatin analogs should be used with extreme caution in insulinoma patients as they can suppress counterregulatory hormones and potentially worsen hypoglycemia 2, 1
• For patients who are not surgical candidates, medical management with diazoxide or EUS-guided radiofrequency ablation may be considered 1, 4