Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Case Study
  • Published:

Diagnosis of insulinoma in a patient with hypoglycemia without obvious hyperinsulinemia

Nature Reviews Endocrinology volume 5, pages 628–631 (2009)Cite this article

Abstract

Background. A 41-year-old Maltese woman with a 12-month history of severe, morning episodes of confusion, blurred vision and sweating was referred to a specialist center for evaluation of fasting hypoglycemia. She was not taking medication and did not report any prior personal or familial history of endocrinopathy or other relevant pathology.

Investigations. Measurement of plasma glucose, insulin, C-peptide, and β-hydroxybutyrate concentrations during a prolonged supervised fast; sulfonylurea screen; CT, MRI scan and endoscopic ultrasonography of the pancreas; calcium stimulation test; surgical exploration and intra-operative ultrasonography of the pancreas.

Diagnosis. Insulin-secreting lesion (insulinoma) in the tail of the pancreas.

Management. The tumor was resected with cure of symptoms.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Localization of a possible insulinoma in the case patient.

References

  1. Service, F. J. Clinical review 42: Hypoglycemias. J. Clin. Endocrinol. Metab. 76, 269–272 (1993).

    CAS  PubMed  Google Scholar 

  2. Service, F. J., McMahon, M. M., O'Brien P. C. & Ballard, D. J. Functioning insulinoma–incidence, recurrence, and long-term survival of patients: a 60-year study. Mayo Clin. Proc. 66, 711–719 (1991).

    Article  CAS  PubMed  Google Scholar 

  3. Service F. J. & Natt, N. The prolonged fast. J. Clin. Endocrinol. Metab. 85, 3973–3974 (2000).

    Article  CAS  PubMed  Google Scholar 

  4. Service, F. J., Dale, A. J., Elveback, L. R. & Jiang, N. S. Insulinoma: clinical and diagnostic features of 60 consecutive cases. Mayo Clin. Proc. 51, 417–429 (1976).

    CAS  PubMed  Google Scholar 

  5. Service, F. J. Hypoglycemic disorders. N. Engl. J. Med. 332, 1144–1152 (1995).

    Article  CAS  PubMed  Google Scholar 

  6. Vezzosi, D. et al. Insulin levels measured with an insulin-specific assay in patients with fasting hypoglycemia related to endogenous hyperinsulinism. Eur. J. Endocrinol. 149, 413–419 (2003).

    Article  CAS  PubMed  Google Scholar 

  7. Shimizu, T. et al. Assessment of immunoassays for insulin in diagnostic tests for insulinoma. Diabetes Res. Clin. Pract. 26, 149–154 (1994).

    Article  CAS  PubMed  Google Scholar 

  8. Service, F. J. Classification of hypoglycemic disorders. Endocrinol. Metab. Clin. North Am. 28, 501–517 (1999).

    Article  CAS  PubMed  Google Scholar 

  9. Cryer, P. E. et al. Evaluation and management of adult hypoglycemic disorders: an endocrine society clinical practice guideline. J. Clin. Endocrinol. Metab. 94, 709–728 (2009).

    Article  CAS  PubMed  Google Scholar 

  10. Chia, C. W. & Saudek, C. D. The diagnosis of fasting hypoglycemia due to an islet-cell tumor obscured by a highly specific insulin assay. J. Clin. Endocrinol. Metab. 88, 1464–1467 (2003).

    Article  CAS  PubMed  Google Scholar 

  11. Dons, R. F. et al. Anomalous glucose and insulin responses in patients with insulinoma. Caveats for diagnosis. Arch. Intern. Med. 145, 1861–1863 (1985).

    Article  CAS  PubMed  Google Scholar 

  12. Vezzosi, D., Bennet, A., Fauvel, J. & Caron, P. Insulin, C-peptide and proinsulin for the biochemical diagnosis of hypoglycemia related to endogenous hyperinsulinism. Eur. J. Endocrinol. 157, 75–83 (2007).

    Article  CAS  PubMed  Google Scholar 

  13. Kao, P. C., Taylor, R. L. & Service, F. J. Proinsulin by immunochemiluminometric assay for the diagnosis of insulinoma. J. Clin. Endocrinol. Metab. 78, 1048–1051 (1994).

    CAS  PubMed  Google Scholar 

  14. O'Rahilly, S., Burnett, M. A., Smith, R. F., Darley, J. H. & Turner, R. C. Hemolysis affects insulin but not C-peptide immunoassay. Diabetologia 30, 394–396 (1987).

    Article  CAS  PubMed  Google Scholar 

  15. Service, F. J. & O'Brien, P. C. Increasing serum betahydroxybutyrate concentrations during the 72-hour fast: evidence against hyperinsulinemic hypoglycemia. J. Clin. Endocrinol. Metab. 90, 4555–4558 (2005).

    Article  CAS  PubMed  Google Scholar 

  16. Service, F. J., O'Brien, P. C., McMahon, M. M. & Kao, P. C. C-peptide during the prolonged fast in insulinoma. J. Clin. Endocrinol. Metab. 76, 655–659 (1993).

    CAS  PubMed  Google Scholar 

  17. Service, F. J. Proinsulin levels and insulinomas. Diabetes Care 12, 661–663 (1989).

    Article  CAS  PubMed  Google Scholar 

  18. Gutman, R. A., Fink, G., Shapiro, J. R., Selawry, H. & Recant, L. Proinsulin and insulin release with a human insulinoma and adjacent nonadenomatous pancreas. J. Clin. Endocrinol. Metab. 36, 978–987 (1973).

    Article  CAS  PubMed  Google Scholar 

  19. Lazarus, N. R., Tanese, T., Gutman, R. & Recant, L. Synthesis and release of proinsulin and insulin by human insulinoma tissue. J. Clin. Endocrinol. Metab. 30, 273–281 (1970).

    Article  CAS  PubMed  Google Scholar 

  20. Hirshberg, B. et al. Forty-eight-hour fast: the diagnostic test for insulinoma. J. Clin. Endocrinol. Metab. 85, 3222–3226 (2000).

    Article  CAS  PubMed  Google Scholar 

  21. Wiesli, P. et al. Abnormalities of proinsulin processing in functioning insulinomas: clinical implications. Clin. Endocrinol. (Oxf.) 61, 424–430 (2004).

    Article  CAS  Google Scholar 

  22. Gorden, P. et al. Plasma proinsulin-like component in insulinoma: a 25-year experience. J. Clin. Endocrinol. Metab. 80, 2884–2887 (1995).

    CAS  PubMed  Google Scholar 

  23. Wiesli, P. et al. Assessment of hyperinsulinemia at the termination of the prolonged fast. Clin. Chim. Acta 342, 227–231 (2004).

    Article  CAS  PubMed  Google Scholar 

  24. Glauber, H. S. et al. The effects of biosynthetic human proinsulin on carbohydrate metabolism in non-insulin-dependent diabetes mellitus. N. Engl. J. Med. 316, 443–449 (1987).

    Article  CAS  PubMed  Google Scholar 

  25. Alsever, R. N., Roberts, J. P., Gerber, J. G., Mako, M. E. & Rubenstein, A. H. Insulinoma with low circulating insulin levels: the diagnostic value of proinsulin measurements. Ann. Intern. Med. 82, 347–350 (1975).

    Article  CAS  PubMed  Google Scholar 

  26. Kar, P. et al. Insulinomas may present with normoglycemia after prolonged fasting but glucose-stimulated hypoglycemia. J. Clin. Endocrinol. Metab. 91, 4733–4736 (2006).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Written consent for publication was obtained from the patient. C.C. was on an elective placement in the Department funded by the Portuguese endocrinology society and the Study Association for Diabetes and Endocrinology of Almada. We thank Mr Satya Bhattacharya for his contribution to the clinical management of the patient.

Désirée Lie, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the MedscapeCME-accredited continuing medical education activity associated with this article.

Author information

Authors and Affiliations

  1. Endocrinology Department of Garcia de Orta Hospital, Almada, Portugal

    Catarina Coelho

  2. Department of Endocrinology, St. Bartholomew's Hospital, Barts and the London NHS Trust London, UK

    Maralyn R. Druce & Ashley B. Grossman

Authors
  1. Catarina Coelho
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maralyn R. Druce
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ashley B. Grossman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ashley B. Grossman.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Coelho, C., Druce, M. & Grossman, A. Diagnosis of insulinoma in a patient with hypoglycemia without obvious hyperinsulinemia. Nat Rev Endocrinol 5, 628–631 (2009). https://doi.org/10.1038/nrendo.2009.198

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrendo.2009.198

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing