From the Guidelines
Diagnosing insulinoma requires a systematic approach combining clinical evaluation, laboratory tests, and imaging studies, with the most recent and highest quality study recommending a 48- to 72-hour observed or inpatient observed fast as a helpful diagnostic tool 1. To diagnose insulinoma, clinicians should first suspect the condition in patients presenting with Whipple's triad: hypoglycemic symptoms, documented low blood glucose levels (typically <50 mg/dL), and relief of symptoms after glucose administration.
Initial Diagnostic Testing
Initial diagnostic testing includes:
- A 48- to 72-hour observed or inpatient observed fast, which can help determine the insulin/glucose ratio and is considered a helpful diagnostic tool 1
- Measuring serum insulin, proinsulin, and C peptide levels during the fast
- Diagnostic criteria include:
- Hypoglycemia with inappropriately elevated insulin (≥3 μU/mL)
- Elevated C-peptide (≥0.6 ng/mL)
- Elevated proinsulin levels
Additional Laboratory Tests
Additional laboratory tests may include:
- Measuring beta-hydroxybutyrate (which is suppressed in insulinoma)
- Screening for sulfonylurea use to rule out factitious hypoglycemia
Localization Studies
Once biochemical diagnosis is established, localization studies are necessary, including:
- CT scan
- MRI
- Endoscopic ultrasound (EUS), which has been shown to localize approximately 82% of pancreatic NETs 1
- Sometimes selective arterial calcium stimulation testing with hepatic venous sampling
Imaging Techniques
Somatostatin receptor scintigraphy or PET scans may also be helpful in some cases, but their use should be limited to patients with suspected metastatic disease or those being considered for treatment with somatostatin analogues 1. The combination of biochemical confirmation and precise tumor localization is essential for proper surgical planning, as surgery remains the definitive treatment for insulinoma.
From the Research
Diagnostic Tests for Insulinoma
To diagnose insulinoma, several tests can be utilized, including:
- A supervised 48-hour fast, which has been shown to be effective in diagnosing insulinoma 2
- A short fasting test, which can be initiated overnight and prolonged up to 24 hours, has been found to be a sensitive method for diagnosing insulinoma 3
- A 5-hour oral glucose tolerance test (OGTT), which measures insulin and C-peptide levels, can help diagnose insulinoma 4, 5
- A 72-hour fasting test, which is the current standard for diagnosing insulinoma, but requires hospitalization due to the risk of severe hypoglycemic episodes 2, 6
Diagnostic Criteria
The diagnosis of insulinoma is based on demonstrating Whipple's triad during a supervised fast, which includes:
- Symptoms known or likely to be caused by hypoglycemia
- A low plasma glucose measured at the time of the symptoms
- Relief of symptoms when the glucose is raised to normal 2 The measurement of insulin, C-peptide, and proinsulin levels during the fast can also help diagnose insulinoma 2, 6
Localization Procedures
Once insulinoma is diagnosed, localization procedures such as MRI can be used to identify the tumor 6 These procedures can help guide surgical resection of the tumor, which is the primary treatment for insulinoma 6