Skip to main content
Log in

Symptomatic hypoglycemia during imatinib mesylate in a non-diabetic female patient with gastrointestinal stromal tumor

  • Case Report
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Imatinib mesylate is a selective competitive inhibitor of the bcr-abl tyrosine kinase and c-KIT. Other kinases, such as phosphatidylinositol 3′-kinase (PI-3K) involved in insulin signaling, have also been shown to be indirectly affected by imatinib. A recent report described a lowering of blood glucose levels in Type 2 diabetic patients treated with imatinib resulting in a reduction of oral antidiabetic medication or insulin dosage. We present a female non-diabetic patient with a resected gastrointestinal stromal tumor with an increased insulin response following an oral glucose challenge and hypoglycemic episodes following imatinib therapy. In addition to a rise in insulin sensitivity, the patient showed inappropriately high insulin secretion rates in relation to the actual blood glucose concentrations during and after the completion of imatinib treatment. The symptoms suggestive of hypoglycemia such as dizziness and shivering formerly observed in patients treated with imatinib may be related to hypoglycemic glucose concentrations. Physicians treating patients with imatinib should be aware of the possible occurrence of hypoglycemic episodes in non-diabetic patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Kantarjian H, Sawyers C, Hochhaus A, et al. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med 2002, 346: 645–52.

    Article  PubMed  CAS  Google Scholar 

  2. Druker BJ, Sawyers CL, Kantarjian H, et al. Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med 2001, 344: 1038–42.

    Article  PubMed  CAS  Google Scholar 

  3. Druker BJ, Talpaz M, Resta DJ, et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 2001, 344: 1031–7.

    Article  PubMed  CAS  Google Scholar 

  4. Kharas MG, Fruman DA. ABL oncogenes and phosphoinositide 3-kinase: mechanism of activation and downstream effectors. Cancer Res 2005, 65: 2047–53.

    Article  PubMed  CAS  Google Scholar 

  5. Marley SB, Lewis JL, Schneider H, Rudd CE, Gordon MY. Phosphatidylinositol-3 kinase inhibitors reproduce the selective antiproliferative effects of imatinib on chronic myeloid leukaemia progenitor cells. Br J Haematol 2004, 125: 500–11.

    Article  PubMed  CAS  Google Scholar 

  6. Krause DS, Van Etten RA. Tyrosine kinases as targets for cancer therapy. N Engl J Med 2005, 353: 172–87.

    Article  PubMed  CAS  Google Scholar 

  7. Demetri GD, von Mehren M, Blanke CD, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 2002, 347: 472–80.

    Article  PubMed  CAS  Google Scholar 

  8. Bauer S, Lang H, Schütte H, Hartmann JT. Complete remission with imatinib in metastastic gastrointestinal stromal tumors. J Clin Oncol 2005, 23: 6800–1.

    Article  PubMed  Google Scholar 

  9. Breccia M, Muscaritoli M, Aversa Z, Mandelli F, Alimena G. Imatinib mesylate may improve fasting blood glucose in diabetic Ph+ chronic myelogenous leukemia patients responsive to treatment. J Clin Oncol 2004, 22: 4653–5.

    Article  PubMed  CAS  Google Scholar 

  10. Veneri D, Franchini M, Bonora E. Imatinib and regression of type 2 diabetes. N Engl J Med 2005, 352: 1049–50.

    Article  PubMed  CAS  Google Scholar 

  11. Couzin J. Diabetes research. Researchers puzzle over possible effect of Gleevec. Science 2005, 307: 1711.

    Article  PubMed  CAS  Google Scholar 

  12. Lassila M, Allen TJ, Cao Z, et al. Imatinib attenuates diabetes-associated atherosclerosis. Arterioscler Thromb Vasc Biol 2004, 24: 935–42.

    Article  PubMed  CAS  Google Scholar 

  13. Schmidt-Arras DE, Böhmer A, Markova B, Choudhary C, Serve H, Böhmer FD. Tyrosine phosphorylation regulates maturation of receptor tyrosine kinases. Mol Cell Biol 2005, 25(9): 3690–703.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  14. Böhmer FD, Karagyozov L, Uecker A, et al. A single amino acid exchange inverts susceptibility of related receptor tyrosine kinases for the ATP site inhibitor STI-571. J Biol Chem 2003, 278: 5148–55.

    Article  PubMed  CAS  Google Scholar 

  15. Sanz-Gonzalez SM, Castro C, Perez P, Andres V. Role of E2F and ERK1/2 in STI571 -mediated smooth muscle cell growth arrest and cyclin A transcriptional repression. Biochem Biophys Res Commun 2004, 317: 972–9.

    Article  PubMed  CAS  Google Scholar 

  16. Pink D, Schoeler D, Lindner T, et al. Severe hypoglycemia caused by paraneoplastic production of IGF-II in patients with advanced gastrointestinal stromal tumors: a report of two cases. J Clin Oncol 2005, 20: 6809–11.

    Article  Google Scholar 

  17. Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 1999, 22: 1462–70.

    Article  PubMed  CAS  Google Scholar 

  18. Stumvoll M, Mitrakou A, Pimenta W, et al. Assessment of insulin secretion from the oral glucose tolerance test in white patients with type 2 diabetes. Diabetes Care 2000, 23: 1440–1.

    Article  PubMed  CAS  Google Scholar 

  19. Yoon KH, Ko SH, Cho JH, et al. Selective beta-cell loss and alpha-cell expansion in patients with type 2 diabetes mellitus in Korea. J Clin Endocrinol Metab 2003, 88: 2300–8.

    Article  PubMed  CAS  Google Scholar 

  20. Vilsball T, Krarup T, Sonne J, et al. Incretin secretion in relation to meal size and body weight in healthy subjects and people with type 1 and type 2 diabetes mellitus. J Clin Endocrinol Metab 2003, 88: 2706–13.

    Article  CAS  Google Scholar 

  21. Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC. Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes 2003, 52: 102–10.

    Article  PubMed  CAS  Google Scholar 

  22. Ferrannini E, Camastra S, Gastaldelli A, et al. beta-cell function in obesity: effects of weight loss. Diabetes 2004, 53 (Suppl 3): S26–33.

    Article  PubMed  CAS  Google Scholar 

  23. Service FJ, Natt N, Thompson GB, et al. Noninsulinoma pancreatogenous hypoglycemia: a novel syndrome of hyperinsulinemic hypoglycemia in adults independent of mutations in Kir6.2 and SUR1 genes. J Clin Endocrinol Metab 1999, 84: 1582–9.

    PubMed  CAS  Google Scholar 

  24. Gottschalk S, Anderson N, Hainz C, Eckhardt SG, Serkova NJ. Imatinib (STI571)-mediated changes in glucose metabolism in human leukemia BCR-ABL-positive cells. Clin Cancer Res 2004, 10: 6661–8.

    Article  PubMed  CAS  Google Scholar 

  25. Boren J, Cascante M, Marin S, et al. Gleevec (STI571) influences metabolic enzyme activities and glucose carbon flow toward nucleic acid and fatty acid synthesis in myeloid tumor cells. J Biol Chem 2001, 276: 37747–53.

    PubMed  CAS  Google Scholar 

  26. Bentley J, Walker I, Mcintosh E, Whetton AD, Owen-Lynch PJ, Baldwin SA. Glucose transport regulation by p210 BcrAbl in a chronic myeloid leukaemia model. Br J Haematol 2001, 112: 212–5.

    Article  PubMed  CAS  Google Scholar 

  27. Hamberg P, de Jong FA, Boonstra JG, van Doorn J, Verweij J, Sleijfer S. Non-islet-cell tumor induced hypoglycemia in patients with advanced gastrointestinal stromal tumor possibly worsened by imatinib. J Clin Oncol 2006, 24: e30–1.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to J. T. Hartmann MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Haap, M., Gallwitz, B., Thamer, C. et al. Symptomatic hypoglycemia during imatinib mesylate in a non-diabetic female patient with gastrointestinal stromal tumor. J Endocrinol Invest 30, 688–692 (2007). https://doi.org/10.1007/BF03347451

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03347451

Key-words

Navigation