Abstract
Donohue syndrome (DS) is a severe form of congenital insulin resistance due to mutation(s) in the insulin receptor (INSR) gene. Given the similarities between insulin and insulin-like growth factor 1 (IGF-1) receptors, recombinant human IGF-1 (rhIGF-1) has been used to treat severe insulin resistance due to INSR mutation(s). Traditional subcutaneous therapy may be limited by the shortened IGF-1 half-life in these patients. We report the case of a female with molecularly confirmed DS treated with continuous rhIGF-1 therapy via an insulin pump. With treatment, the patient’s hemoglobin A1c decreased from 9.8% to 8.8%, and her weight increased by 0.8 kg. Development of an ovarian tumor complicated her course, but it was unclear whether this was related to rhIGF-1 therapy. Limited treatment options exist for patients with DS. The use of continuous rhIGF-1 via an insulin pump may be a viable option, although further experience is needed to establish safety and efficacy.
Acknowledgments
The authors would like to express our sincere gratitude to our patient’s parents for their tremendous strength and genuine desire to help other children. We would also like to thank Dr. David Dunger for his expert advice in treating this child.
Conflict of interest statement
Authors’ conflict of interest disclosure: None of the authors has a conflict of interest to disclose.
Funding source: Dr. Weber was supported by NIH grant K12 DK094723.
Financial disclosure: Dr. Magge served on an advisory board for Ipsen Group in December, 2010 on treatment guidelines for severe insulin resistance, after care for this child was completed. The authors have no financial relationships relevant to this article to disclose.
References
1. Donohue WL, Uchida I. Leprechaunism: a euphemism for a rare familial disorder. J Pediatr 1954;45:505–19.10.1016/S0022-3476(54)80113-2Search in Google Scholar
2. Cochran E, Musso C, Gorden P. The use of U-500 in patients with extreme insulin resistance. Diabetes Care 2005;28:1240–4.10.2337/diacare.28.5.1240Search in Google Scholar PubMed
3. Atabek ME, Pirgon O. Some effect of metformin on insulin resistance in an infant with leprechaunism. J Pediatr Endocrinol Metab 2006;19:1257–61.Search in Google Scholar
4. Cochran E, Young JR, Sebring N, DePaoli A, Oral EA, et al. Efficacy of recombinant methionyl human leptin therapy for the extreme insulin resistance of the Rabson-Mendenhall syndrome. J Clin Endocrinol Metab 2004;89:1548–54.10.1210/jc.2003-031952Search in Google Scholar PubMed
5. Kuzuya H, Matsuura N, Sakamoto M, Makino H, Sakamoto Y, et al. Trial of insulinlike growth factor I therapy for patients with extreme insulin resistance syndromes. Diabetes 1993;42: 696–705.10.2337/diab.42.5.696Search in Google Scholar PubMed
6. Nakae J, Kato M, Murashita M, Shinohara N, Tajima T, et al. Long-term effect of recombinant human insulin-like growth factor I on metabolic and growth control in a patient with leprechaunism. J Clin Endocrinol Metab 1998;83: 542–9.10.1210/jcem.83.2.4602Search in Google Scholar PubMed
7. Backeljauw PF, Alves C, Eidson M, Cleveland W, Underwood LE, et al. Effect of intravenous insulin-like growth factor I in two patients with leprechaunism. Pediatr Res 1994;36:749–54.10.1203/00006450-199412000-00012Search in Google Scholar PubMed
8. Longo N, Singh R, Elsas LJ. Decreased half-life of insulin-like growth factor I in Rabson-Mendenhall syndrome. J Inherit Metab Dis 2001;24:546–50.10.1023/A:1012411709972Search in Google Scholar
9. Semple RK, Cochran EK, Soos MA, Burling KA, Savage DB, et al. Plasma adiponectin as a marker of insulin receptor dysfunction: clinical utility in severe insulin resistance. Diabetes Care 2008;31:977–79.10.2337/dc07-2194Search in Google Scholar PubMed
10. 2005 Food and Drug Administration. INCRELEX™ PI In. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2005/021839lbl.pdf . Accessed on May 18, 2014.Search in Google Scholar
11. LeRoith D, Yakar S. Mechanisms of disease: metabolic effects of growth hormone and insulin-like growth factor 1. Nat Clin Pract Endocrinol Metab 2007;3:302–10.10.1038/ncpendmet0427Search in Google Scholar PubMed
12. Moses AC, Young SC, Morrow LA, O’Brien M, Clemmons DR. Recombinant human insulin-like growth factor I increases insulin sensitivity and improves glycemic control in type II diabetes. Diabetes 1996;45:91–100.10.2337/diab.45.1.91Search in Google Scholar PubMed
13. Ranke MB. Insulin-like growth factor-I treatment of growth disorders, diabetes mellitus and insulin resistance. Trends Endocrinol Metab 2005;16:190–7.10.1016/j.tem.2005.03.011Search in Google Scholar PubMed
14. Taniguchi CM, Emanuelli B, Kahn CR. Critical nodes in signalling pathways: insights into insulin action. Nature reviews. Mol Cell Biol 2006;7:85–96.Search in Google Scholar
15. Ullrich A, Gray A, Tam AW, Yang-Feng T, Tsubokawa M, et al. Insulin-like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity. EMBO J 1986;5: 2503–12.10.1002/j.1460-2075.1986.tb04528.xSearch in Google Scholar PubMed PubMed Central
16. Dupont J, LeRoith D. Insulin and insulin-like growth factor I receptors: similarities and differences in signal transduction. Horm Res 2001;55:22–6.10.1159/000063469Search in Google Scholar PubMed
17. Ogilvy-Stuart AL, Soos MA, Hands SJ, Anthony MY, Dunger DB, et al. Hypoglycemia and resistance to ketoacidosis in a subject without functional insulin receptors. J Clin Endocrinol Metab 2001;86:3319–26.10.1210/jcem.86.7.7631Search in Google Scholar PubMed
18. Escribano O, Guillen C, Nevado C, Gomez-Hernandez A, Kahn CR, et al. Beta-Cell hyperplasia induced by hepatic insulin resistance: role of a liver-pancreas endocrine axis through insulin receptor A isoform. Diabetes 2009;58: 820–8.10.2337/db08-0551Search in Google Scholar PubMed PubMed Central
19. Di Cola G, Cool MH, Accili D. Hypoglycemic effect of insulin-like growth factor-1 in mice lacking insulin receptors. J Clin Invest 1997;99:2538–44.10.1172/JCI119438Search in Google Scholar PubMed PubMed Central
20. Regan FM, Williams RM, McDonald A, Umpleby AM, Acerini CL, et al. Treatment with recombinant human insulin-like growth factor (rhIGF)-I/rhIGF binding protein-3 complex improves metabolic control in subjects with severe insulin resistance. J Clin Endocrinol Metab 2010;95:2113–22.10.1210/jc.2009-2088Search in Google Scholar PubMed
21. Grahnen A, Kastrup K, Heinrich U, Gourmelen M, Preece MA, et al. Pharmacokinetics of recombinant human insulin-like growth factor I given subcutaneously to healthy volunteers and to patients with growth hormone receptor deficiency. Acta Paediatr Suppl 1993;82:9–13.10.1111/j.1651-2227.1993.tb12918.xSearch in Google Scholar PubMed
22. Samani AA, Yakar S, LeRoith D, Brodt P. The role of the IGF system in cancer growth and metastasis: overview and recent insights. Endocr Rev 2007;28:20–47.10.1210/er.2006-0001Search in Google Scholar PubMed
23. Petley T, Graff K, Jiang W, Yang H, Florini J. Variation among cell types in the signaling pathways by which IGF-I stimulates specific cellular responses. Horm Metab Res 1999; 31(2-3):70–6.10.1055/s-2007-978701Search in Google Scholar PubMed
24. Grey A, Chen Q, Xu X, Callon K, Cornish J. Parallel phosphatidylinositol-3 kinase and p42/44 mitogen-activated protein kinase signaling pathways subserve the mitogenic and antiapoptotic actions of insulin-like growth factor I in osteoblastic cells. Endocrinology 2003;144:4886–93.10.1210/en.2003-0350Search in Google Scholar PubMed
25. Brisigotti M, Fabbretti G, Pesce F, Gatti R, Cohen A, et al. Congenital bilateral juvenile granulosa cell tumor of the ovary in leprechaunism: a case report. Pediatr Pathol 1993;13: 549–58.10.3109/15513819309048242Search in Google Scholar PubMed
Supplemental Material
The online version of this article (DOI: 10.1515/jpem-2013-0402) offers supplementary material, available to authorized users.
©2014 by De Gruyter
