From the Guidelines
For suspected insulinoma, initial laboratory evaluation should include fasting plasma glucose, insulin, C-peptide, and proinsulin levels during a supervised 72-hour fast, which is the gold standard diagnostic test, as recommended by 1 and 1. To diagnose insulinoma, the following labs should be ordered:
- Fasting plasma glucose
- Insulin
- C-peptide
- Proinsulin These tests should be performed during a supervised 72-hour fast, with blood samples drawn every 4-6 hours and when symptoms occur, and the fast terminated when hypoglycemia (glucose <45 mg/dL) develops 1. Additional tests should include:
- Measurement of beta-hydroxybutyrate (low in insulinoma)
- Screening for sulfonylurea use to exclude factitious hypoglycemia Elevated insulin (≥3 μU/mL), C-peptide (≥0.6 ng/mL), and proinsulin levels in the presence of hypoglycemia strongly suggest insulinoma 1. Once biochemical diagnosis is established, localization studies should include:
- Contrast-enhanced CT or MRI of the abdomen as first-line imaging
- Endoscopic ultrasound, which has high sensitivity for pancreatic lesions and can be used if initial imaging is negative 1
- Selective arterial calcium stimulation testing with hepatic venous sampling may help regionalize the tumor in difficult cases 1
- Somatostatin receptor scintigraphy (Octreoscan) or Gallium-68 DOTATATE PET/CT may be useful for detecting metastatic disease, but should be used with caution in patients with insulinoma, as they can worsen hypoglycemia 1.
From the Research
Laboratory Tests for Insulinoma
To diagnose an insulinoma, several laboratory tests can be ordered, including:
- Fasting glucose levels to demonstrate hypoglycemia
- Insulin levels to assess for inappropriate insulin secretion
- C-peptide levels to evaluate for elevated C-peptide, a marker of insulin secretion 2
- Proinsulin levels to assess for elevated proinsulin, which is often elevated in insulinoma 3
- Sulfonylurea screening to rule out factitious hypoglycemia
Imaging Studies for Insulinoma
Imaging studies that can be performed to localize an insulinoma include:
- Computed Tomography (CT) scan to visualize the pancreas and detect any masses 4
- Magnetic Resonance Imaging (MRI) to provide detailed images of the pancreas and detect any tumors
- Endoscopic Ultrasound (EUS) to visualize the pancreas and detect any small tumors
- Somatostatin Receptor Scintigraphy (SRS) to detect any tumors that express somatostatin receptors
Diagnostic Tests for Insulinoma
Diagnostic tests that can be used to diagnose an insulinoma include:
- 48-hour fast test to demonstrate Whipple's triad and assess for inappropriate insulin secretion 3
- 72-hour fast test to demonstrate Whipple's triad and assess for inappropriate insulin secretion 5
- 5-hour oral glucose tolerance test (OGTT) to assess for abnormal insulin and C-peptide secretion 6
- Glucagon stimulation test to assess for exaggerated insulin response and diagnose insulinoma 4