What are the diagnostic investigations for insulinoma (a type of pancreatic tumor)?

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Last updated: March 27, 2025View editorial policy

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From the Guidelines

Investigations for insulinoma should begin with biochemical testing to confirm hypoglycemia with inappropriate insulin secretion, followed by localization studies, as recommended by the most recent guidelines 1. The initial diagnostic test is a supervised 72-hour fast with serial measurements of plasma glucose, insulin, C-peptide, and proinsulin levels.

  • Hypoglycemia (blood glucose <45 mg/dL or 2.5 mmol/L) with inappropriately elevated insulin (≥3 μU/mL), C-peptide (≥0.2 nmol/L), and proinsulin levels confirms endogenous hyperinsulinism.
  • Once biochemically confirmed, localization studies should be performed, starting with non-invasive imaging such as contrast-enhanced CT or MRI of the pancreas, which can detect 70-80% of insulinomas.
  • If these are negative, endoscopic ultrasound (EUS) should be considered, which has a sensitivity of 75-95% 1.
  • For occult insulinomas, more specialized techniques may be needed, including 68Ga-DOTATATE PET/CT scanning or selective arterial calcium stimulation testing with hepatic venous sampling (SACST) 1.
  • Intraoperative ultrasound is often used during surgery to confirm tumor location. These investigations are essential because insulinomas are typically small (less than 2 cm) and can be difficult to localize, yet accurate localization is crucial for successful surgical resection, which is the definitive treatment for these tumors.
  • The use of somatostatin scintography may be less useful as an imaging technique for insulinomas than for other tumor subtypes, and should only be performed if octreotide or lanreotide is being considered as a treatment for metastatic disease 1.
  • CT or MRI scans should be performed to rule out metastatic disease, as 90% of insulinomas pursue an indolent course and can be cured surgically 1.

From the Research

Diagnostic Investigations for Insulinoma

The diagnostic investigations for insulinoma, a type of pancreatic tumor, involve a combination of biochemical tests, imaging studies, and other modalities. The key diagnostic criteria include:

  • Demonstration of hypoglycemia and elevated plasma levels of insulin or C-Peptide 2
  • Plasma concentrations of glucose <55 mg/dl with corresponding insulin level >3.0 μU/ml (18 pmol/L) and C-peptide of >0.6 ng/ml (0.2 nmol/L) 3
  • Prolonged (72 h) fast, which is a robust standard test for establishing a biochemical diagnosis 4, 5

Imaging Modalities

Various imaging modalities can be used to localize the tumor, including:

  • Computerized tomography (CT) scans 2, 3
  • Magnetic resonance imaging (MRI) 2, 3
  • Positron emission tomography (PET)/CT 2, 3
  • Intra-operative ultrasonography (IOUS) 3
  • Transhepatic portal venous sampling (THPVS) 3
  • Selective arterial calcium stimulation and hepatic venous sampling 6
  • Somatostatin receptor scintigraphy 2

Other Diagnostic Tools

Other diagnostic tools that may be used include:

  • Oral glucose tolerance test to demonstrate induction of severe hyperinsulinemia followed by significant hypoglycemia 4
  • Pro-insulin measurements as a valuable supplementary tool 5

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Insulinoma case series: Experience of a tertiary care center.

Indian journal of endocrinology and metabolism, 2014

Research

The clinical diagnosis of insulinoma.

Scandinavian journal of gastroenterology. Supplement, 1979

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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