From the Guidelines
The workup for insulinoma should begin with biochemical confirmation of hypoglycemia with inappropriate insulin secretion, followed by localization studies, as outlined in the most recent guidelines 1. The first step in the workup for insulinoma is to obtain a 48- to 72-hour observed or inpatient observed fast with measurements of plasma glucose, insulin, C-peptide, and proinsulin when the patient becomes symptomatic or glucose falls below 55 mg/dL, as recommended by the Journal of the National Comprehensive Cancer Network 1. Diagnostic criteria include:
- Hypoglycemia (plasma glucose <55 mg/dL)
- Inappropriately elevated insulin (≥3 μU/mL)
- Elevated C-peptide (≥0.6 ng/mL)
- Elevated proinsulin (≥5 pmol/L) After biochemical confirmation, localization studies should include:
- Contrast-enhanced CT or MRI of the abdomen as first-line imaging
- Endoscopic ultrasound if CT or MRI are negative, as it has high sensitivity for pancreatic lesions 1
- Selective arterial calcium stimulation testing for difficult cases to help regionalize the tumor
- Somatostatin receptor scintigraphy (Octreoscan) or Gallium-68 DOTATATE PET/CT may be useful for detecting metastases, but should only be performed if octreotide or lanreotide is being considered as a treatment for metastatic disease 1. Genetic testing should be considered to rule out MEN1 syndrome, especially in younger patients or those with family history. This systematic approach helps confirm the diagnosis biochemically before proceeding to invasive localization procedures, as insulinomas are typically small (less than 2 cm) and can be challenging to locate.
From the Research
Insulinoma Workup
- Insulinoma is typically diagnosed using a supervised fasting test to demonstrate Whipple's triad, which includes symptoms of hypoglycemia, low plasma glucose, and relief of symptoms with glucose administration 2.
- The traditional 72-hour fasting test has been the cornerstone for diagnosis, but studies have shown that a 48-hour fast may be sufficient for diagnosis 2, 3.
- A 48-hour fasting test was successful in diagnosing insulinoma in 94.5% of patients in one study, with only 7 patients requiring fasting beyond 48 hours 2.
- An alternative diagnostic approach is the use of a 5-hour oral glucose tolerance test (OGTT) to evaluate insulin and C-peptide to glucose ratios, which may provide a more convenient and cost-effective outpatient test 4.
- The homeostasis model assessment of β-cell function (HOMA-B) has also been shown to be a useful diagnostic tool, with high sensitivity and specificity for insulinoma diagnosis when calculated at the end of a fasting test 5.
- In some cases, insulinoma may be diagnosed in patients with hypoglycemia without obvious hyperinsulinemia, highlighting the importance of a comprehensive diagnostic workup 6.
- Diagnostic criteria for insulinoma include: