What are the diagnostic criteria for Insulinoma (Islet Cell Tumor)?

From the Guidelines

Insulinoma diagnosis is primarily based on clinical presentation, biochemical tests, and imaging studies. The diagnostic criteria for Insulinoma include:

• Inappropriate insulin secretion as evidenced by an insulin level greater than 3 mcIU/mL (usually >6 mcIU/mL) when blood glucose is less than 55 mg/dL, with an insulin-to-glucose ratio of 0.3 or greater 1
• Elevated C-peptide and proinsulin levels, with C peptide concentrations of at least 0.6 ng/mL and proinsulin levels of greater than or equal to 5 pmol/L when fasting blood glucose is less than 55 mg/dL 1
• 48- to 72-hour observed or inpatient observed fast may be helpful in diagnosing insulinoma, as it can trigger hypoglycemia within 24 hours 1
• Imaging studies, such as multiphasic CT or MRI scans, should be performed to rule out metastatic disease 1
• Chromogranin A (CgA) measurement may not be useful in diagnosing insulinoma, as it is usually not raised unless the tumor is metastatic 1

Key laboratory tests for diagnosing insulinoma include:

• Serum insulin, proinsulin, and C peptide levels
• Urinary sulfonylurea to rule out factitious hypoglycemia
• Chromogranin A (CgA) measurement, although not always useful in diagnosing insulinoma

Imaging modalities that may be used to localize insulinomas include:

• Endoscopic ultrasonography (EUS)
• Calcium stimulation test (Imamura-Doppman procedure)
• Multiphasic CT or MRI scans
• Somatostatin scintography (Octreoscan), although it may be less useful in diagnosing insulinoma due to variable somatostatin receptor expression 1

From the Research

Diagnostic Criteria for Insulinoma

The diagnostic criteria for insulinoma include:

• Biochemical proof of endogenous hyperinsulinemic hypoglycemia, as stated in 2
• Whipple's triad, which is characterized by symptoms of hypoglycemia, low plasma glucose, and relief of symptoms with glucose administration, as mentioned in 3
• Inappropriately elevated insulin serum concentrations in the presence of hypoglycemia, as noted in 4
• An end of fast insulin concentration ≥ 3 μIU/mL, as suggested in 5
• A proinsulin concentration ≥ 22 pmol/L, which can distinguish cases from controls, as found in 5

Diagnostic Tests

Various tests can be used to diagnose insulinoma, including:

• Fasting test, which can demonstrate inadequate insulin suppression, as mentioned in 6, 5, 3
• C-peptide suppression test, which can be useful if a diagnosis of insulinoma is in doubt, as noted in 6
• Insulin stimulation tests, which may be useful in some patients with insulinoma, but can lead to false-negative results and dangerous levels of hypoglycemia, as warned in 6
• Imaging techniques, such as ultrasonography, computed tomography, and intra-arterial calcium stimulation with venous sampling, which can help localize the tumor, as mentioned in 2, 6, 3

Localization of Insulinoma

Preoperative localization of insulinoma can be performed using:

• Imaging techniques, such as ultrasonography, computed tomography, and magnetic resonance imaging, as mentioned in 2, 4, 3
• Arterial calcium stimulation and/or intraoperative ultrasonography and palpation by the surgeon, as noted in 4
• Percutaneous transhepatic portal catheterization with measurements of radioimmunoreactive insulin concentration, which can be a reliable method for preoperative localization, as mentioned in 6