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Insulinoma Differential Diagnoses

  • Author: Zonera Ashraf Ali, MBBS; Chief Editor: Jules E Harris, MD, FACP, FRCPC  more...
Updated: Feb 21, 2016

Diagnostic Considerations

Factitious hypoglycemia can occur in patients who have psychiatric disturbances or a need for attention and access to insulin or sulfonylurea drugs (eg, medical staff).[14] The triad of hypoglycemia, high immunoreactive insulin levels, and suppressed plasma C-peptide immunoreactivity is pathognomonic of exogenous origin. Insulin-induced hypoglycemia can be detected by a ratio of insulin to C-peptide that is greater than 1.0.

Hypoglycemia can occur after inadvertent ingestion of sulfonylurea due to patient or pharmacist error.

Autoimmune hypoglycemia is a rare disorder caused by the interaction of endogenous antibodies with insulin or the insulin receptor.[15] The condition is more common in Japan than in the United States or Europe. The syndrome may produce severe neuroglycopenic symptoms, making immunosuppressive therapy occasionally necessary.[10]

Nesidioblastosis is defined as hyperplasia of the islet cells causing hyperinsulinemic hypoglycemia. It is a predominantly neonatal disorder, although cases in adults have been reported recently.[16]

Noninsulinoma pancreatogenic hypoglycemia syndrome (NIPHS) is a condition in which pancreatic islet hyperplasia is present.[17] This is manifested with postprandial neuroglycopenia, a negative normal fasting test, negative pancreatic imaging results, and positive intra-arterial calcium stimulation of serum insulin.

Familial persistent hyperinsulinemia is manifested with inappropriately high insulin secretions seen in families with mutations in the glucokinase enzymes, glutamate dehydrogenase and short-chain3-hydroxyacyl1-CoA dehydrogenase.

Other causes for hypoglycemia include liver disease, endocrine deficiencies, extrapancreatic insulin-producing tumors (an insulin-secreting small-cell carcinoma of the cervix recently has been described), and pentamidine-induced hypoglycemia.

Contributor Information and Disclosures

Zonera Ashraf Ali, MBBS Consulting Staff, Main Line Oncology Hematology Associates, Lankenau Cancer Center

Zonera Ashraf Ali, MBBS is a member of the following medical societies: American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Jules E Harris, MD, FACP, FRCPC Clinical Professor of Medicine, Section of Hematology/Oncology, University of Arizona College of Medicine, Arizona Cancer Center

Jules E Harris, MD, FACP, FRCPC is a member of the following medical societies: American Association for the Advancement of Science, American Society of Hematology, Central Society for Clinical and Translational Research, American Society of Clinical Oncology

Disclosure: Nothing to disclose.

Additional Contributors

Pradyumna D Phatak, MBBS, MD Chair, Division of Hematology and Medical Oncology, Rochester General Hospital; Clinical Professor of Oncology, Roswell Park Cancer Institute

Pradyumna D Phatak, MBBS, MD is a member of the following medical societies: American Society of Hematology

Disclosure: Received honoraria from Novartis for speaking and teaching.


Klaus Radebold, MD, PhD Former Research Associate, Department of Surgery, Yale University School of Medicine

Disclosure: Nothing to disclose.

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CT scan image with oral and intravenous contrast in a patient with biochemical evidence of insulinoma. The 3-cm contrast-enhancing neoplasm (arrow) is seen in the tail of the pancreas (P) posterior to the stomach (S) (Yeo, 1993).
Endoscopic ultrasonography in a patient with an insulinoma. The hypoechoic neoplasm (arrows) is seen in the body of the pancreas anterior to the splenic vein (SV) (Rosch, 1992).
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