Skip to main content
SpringerLink
Log in

Recombinant Human IGF-1 (Insulin-Like Growth Factor) Therapy: Where Do We Stand Today?

  • Symposium on Growth Hormone
  • Published:
The Indian Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Recombinant human (rh) IGF-1 has been available for therapy since the 1980s and has been commercially available for over 5 y, yet the role of rhIGF-1 in treating children with short stature remains ambiguous. This is consequent to the inherent difficulty in defining criteria for IGF-1 deficiency, and in determining the outcome of rhIGF-1 therapy in terms of growth rate and adult height. The rationale for its efficacy compared with rhGH (recombinant human growth hormone) for treatment of short stature is still widely debated. Additionally, adverse events such as increased intracranial pressure and hypoglycemia are of therapeutic concern. The goal of this article is to review published data that describes the impact of IGF-1 therapy in treatment of short stature and other growth disorders.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

ALS:

Acid Labile Sub-unit

FDA:

Food and Drug Administration

GHRD:

Growth Hormone Receptor Deficiency

IGF-BP3:

Insulin like Growth Factor Binding Protein 3

IGHD:

Isolated GH Deficiency

ISS:

Idiopathic Short Stature

rhGH:

Recombinant Human Growth Hormone

rh (IGF-1):

Recombinant Human Insulin Like Growth Factor-1

MGH:

Massachusetts General Hospital

MPHD:

Multiple Pituitary Hormone Deficiency

References

  1. Rosenbloom AL. Recombinant human insulin-like growth factor I (rhIGF-I) and rhIGF-I/rhIGF-binding-protein-3: new growth treatment options? J Pediatr. 2007;150:7–11.

    Article  PubMed  CAS  Google Scholar 

  2. Kemp SF, Thrailkill KM. SomatoKine Is there a use in treating growth disorders? Curr Opin Investig Drugs. 2005;6:373–7.

    PubMed  CAS  Google Scholar 

  3. Rosenbloom AL. Is there a role for recombinant insulin-like growth factor-I in the treatment of idiopathic short stature? Lancet. 2006;368:612–6.

    Article  PubMed  CAS  Google Scholar 

  4. Daughaday WH. Endocrinology–the way we were: a personal history of somatomedin. Growth Horm IGF Res. 2006;16:S3–5.

    Article  PubMed  CAS  Google Scholar 

  5. Daughaday WH, Rotwein P. Insulin-like growth factors I and II. Peptide, messenger ribonucleic acid and gene structures, serum, and tissue concentrations. Endocr Rev. 1989;10:68–91.

    Article  PubMed  CAS  Google Scholar 

  6. Yakar S, Courtland HW, Clemmons D. IGF-1 and bone: new discoveries from mouse models. J Bone Miner Res. 2010;25:2267–76.

    Article  CAS  Google Scholar 

  7. Khosravi MJ, Diamandi A, Mistry J, Krishna RG, Khare A. Acid-labile subunit of human insulin-like growth factor-binding protein complex: measurement, molecular, and clinical evaluation. J Clin Endocrinol Metab. 1997;82:3944–51.

    Article  PubMed  CAS  Google Scholar 

  8. Collett-Solberg PF, Cohen P. The role of the insulin-like growth factor binding proteins and the IGFBP proteases in modulating IGF action. Endocrinol Metab Clin North Am. 1996;25:591–614.

    Article  PubMed  CAS  Google Scholar 

  9. Baxter RC. Insulin-like growth factor binding proteins in the human circulation: a review. Horm Res. 1994;42:140–4.

    Article  PubMed  CAS  Google Scholar 

  10. Twigg SM, Baxter RC. Insulin-like growth factor (IGF)-binding protein 5 forms an alternative ternary complex with IGFs and the acid-labile subunit. J Biol Chem. 1998;273:6074–9.

    Article  PubMed  CAS  Google Scholar 

  11. Collett-Solberg PF, Misra M. The role of recombinant human insulin-like growth factor-I in treating children with short stature. J Clin Endocrinol Metab. 2008;93:10–8.

    Article  PubMed  CAS  Google Scholar 

  12. Monzavi R, Cohen P. IGFs and IGFBPs: role in health and disease. Best Pract Res Clin Endocrinol Metab. 2002;16:433–47.

    Article  PubMed  CAS  Google Scholar 

  13. Rosenfeld RG, Wilson DM, Lee PD, Hintz RL. Insulin-like growth factors I and II in evaluation of growth retardation. J Pediatr. 1986;109:428–33.

    Article  PubMed  CAS  Google Scholar 

  14. Buckway CK, Guevara-Aguirre J, Pratt KL, Burren CP, Rosenfeld RG. The IGF-I generation test revisited: a marker of GH sensitivity. J Clin Endocrinol Metab. 2001;86:5176–83.

    Article  PubMed  CAS  Google Scholar 

  15. Blum WF, Cotterill AM, Postel-Vinay MC, Ranke MB, Savage MO, Wilton P. Improvement of diagnostic criteria in growth hormone insensitivity syndrome: solutions and pitfalls. Pharmacia Study Group on Insulin-like Growth Factor I Treatment in Growth Hormone Insensitivity Syndromes. Acta Paediatr Suppl. 1994;399:117–24.

    Article  PubMed  CAS  Google Scholar 

  16. Buckway CK, Selva KA, Pratt KL, Tjoeng E, Guevara-Aguirre J, Rosenfeld RG. Insulin-like growth factor binding protein-3 generation as a measure of GH sensitivity. J Clin Endocrinol Metab. 2002;87:4754–65.

    Article  PubMed  CAS  Google Scholar 

  17. Selva KA, Buckway CK, Sexton G, et al. Reproducibility in patterns of IGF generation with special reference to idiopathic short stature. Horm Res. 2003;60:237–46.

    Article  PubMed  CAS  Google Scholar 

  18. Savage MO, Blum WF, Ranke MB, et al. Clinical features and endocrine status in patients with growth hormone insensitivity (Laron syndrome). J Clin Endocrinol Metab. 1993;77:1465–71.

    Article  PubMed  CAS  Google Scholar 

  19. Rosenfeld RG, Rosenbloom AL, Guevara-Aguirre J. Growth hormone (GH) insensitivity due to primary GH receptor deficiency. Endocr Rev. 1994;15:369–90.

    PubMed  CAS  Google Scholar 

  20. Osio D, Dahlgren J, Wikland KA, Westphal O. Improved final height with long-term growth hormone treatment in Noonan syndrome. Acta Paediatr Suppl. 2005;94:1232–7.

    Article  Google Scholar 

  21. Conchillo M, de Knegt RJ, Payeras M, et al. Insulin-like growth factor I (IGF-I) replacement therapy increases albumin concentration in liver cirrhosis: results of a pilot randomized controlled clinical trial. J Hepatol. 2005;43:630–6.

    Article  PubMed  CAS  Google Scholar 

  22. Saatman KE, Contreras PC, Smith DH, et al. Insulin-like growth factor-1 (IGF-1) improves both neurological motor and cognitive outcome following experimental brain injury. Exp Neurol. 1997;147:418–27.

    Article  PubMed  CAS  Google Scholar 

  23. Rosenbloom AL, Guevara-Aguirre J. Controversy in clinical endocrinology: reclassification of insulin-like growth factor I production and action disorders. J Clin Endocrinol Metab. 2006;91:4232–4.

    Article  PubMed  CAS  Google Scholar 

  24. Cohen P. Controversy in clinical endocrinology: problems with reclassification of insulin-like growth factor I production and action disorders. J Clin Endocrinol Metab. 2006;91:4235–6.

    Article  PubMed  CAS  Google Scholar 

  25. Guevara-Aguirre J, Rosenbloom AL, Vasconez O, et al. Two-year treatment of growth hormone (GH) receptor deficiency with recombinant insulin-like growth factor I in 22 children: comparison of two dosage levels and to GH-treated GH deficiency. J Clin Endocrinol Metab. 1997;82:629–33.

    Article  PubMed  CAS  Google Scholar 

  26. Backeljauw PF, Chernausek SD. Treatment of insulin-like growth factor deficiency with IGF-I: studies in humans. Horm Res. 2006;65:21–7.

    Article  PubMed  CAS  Google Scholar 

  27. Ranke MB, Savage MO, Chatelain PG, Preece MA, Rosenfeld RG, Wilton P. Long-term treatment of growth hormone insensitivity syndrome with IGF-I. Results of the European Multicentre Study. The Working Group on Growth Hormone Insensitivity Syndromes. Horm Res. 1999;51:128–34.

    Article  PubMed  CAS  Google Scholar 

  28. Klinger B, Laron Z. Three year IGF-I treatment of children with Laron syndrome. J Pediatr Endocrinol Metab. 1995;8:149–58.

    Article  PubMed  CAS  Google Scholar 

  29. Chernausek SD, Backeljauw PF, Frane J, Kuntze J, Underwood LE. Long-term treatment with recombinant insulin-like growth factor (IGF)-I in children with severe IGF-I deficiency due to growth hormone insensitivity. J Clin Endocrinol Metab. 2007;92:902–10.

    Article  PubMed  CAS  Google Scholar 

  30. Camacho-Hubner C, Underwood LE, Yordam N, et al. Once daily rhIGF-I/rhIGFBP-3 treatment improves growth velocity in children with severe primary IGF-I defici-ency: results of a multicenter clinical trial. 88th Annual Meeting of The Endocrine Society, Boston, MA. 2006(Abst OR):40–1.

  31. van der Eerden BC, Karperien M, Wit JM. Systemic and local regulation of the growth plate. Endocr Rev. 2003;24:782–801.

    Article  PubMed  Google Scholar 

  32. Midyett LK, Rogol AD, Van Meter QL, Frane J, Bright GM. Recombinant insulin-like growth factor (IGF)-I treatment in short children with low IGF-I levels: first-year results from a randomized clinical trial. J Clin Endocrinol Metab. 2010;95:611–9.

    Article  PubMed  CAS  Google Scholar 

  33. Simpson HL, Jackson NC, Shojaee-Moradie F, et al. Insulin-like growth factor I has a direct effect on glucose and protein metabolism, but no effect on lipid metabolism in type 1 diabetes. J Clin Endocrinol Metab. 2004;89:425–32.

    Article  PubMed  CAS  Google Scholar 

  34. Moller N, Blum WF, Mengel A, Hansen LB, Alberti KG, Schmitz O. Basal and insulin stimulated substrate metabolism in tumour induced hypoglycaemia; evidence for increased muscle glucose uptake. Diabetologia. 1991;34:17–20.

    Article  PubMed  CAS  Google Scholar 

  35. Guler HP, Zapf J, Froesch ER. Short-term metabolic effects of recombinant human insulin-like growth factor I in healthy adults. N Engl J Med. 1987;317:137–40.

    Article  PubMed  CAS  Google Scholar 

  36. Guevara-Aguirre J, Vasconez O, Martinez V, et al. A randomized, double blind, placebo-controlled trial on safety and efficacy of recombinant human insulin-like growth factor-I in children with growth hormone receptor deficiency. J Clin Endocrinol Metab. 1995;80:1393–8.

    Article  PubMed  CAS  Google Scholar 

  37. Vasconez O, Martinez V, Martinez AL, et al. Heart rate increases in patients with growth hormone receptor deficiency treated with insulin-like growth factor I. Acta Paediatr Suppl. 1994;399:137–9.

    Article  PubMed  CAS  Google Scholar 

  38. Klinger B, Anin S, Silbergeld A, Eshet R, Laron Z. Development of hyperandrogenism during treatment with insulin-like growth factor-I (IGF-I) in female patients with Laron syndrome. Clin Endocrinol (Oxf). 1998;48:81–7.

    Article  CAS  Google Scholar 

  39. 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.

    Article  PubMed  CAS  Google Scholar 

  40. Perry JK, Emerald BS, Mertani HC, Lobie PE. The oncogenic potential of growth hormone. Growth Horm IGF Res. 2006;16:277–89.

    Article  PubMed  CAS  Google Scholar 

  41. Laron Z. The GH-IGF1 axis and longevity. The paradigm of IGF1 deficiency. Hormones (Athens). 2008;7:24–7.

    Google Scholar 

  42. Steuerman R, Shevah O, Laron Z. Congenital IGF-I deficiency tends to confer protection against post-natal development of malignancies. Eur J Endocrinol. 2011;164:485–9.

    Article  PubMed  CAS  Google Scholar 

  43. Cuttler L, Silvers JB. Growth hormone and health policy. J Clin Endocrinol Metab. 2010;95:3149–53.

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of Interest

Dr. Levitsky has received a grant from Tercica, Lilly, Novo Nordisk and Pfizer in the past. Dr. Misra has received a grant from Tercica and Genentech in the past.

Role of Funding Source

This review is not supported by a grant from any funding agency in the public, commercial, or not-for-profit sector.

Author information

Authors and Affiliations

  1. Pediatric Endocrine Unit, Massachusetts General Hospital for Children and Harvard Medical School, Room 539, 175 Cambridge Street, Boston, MA, 02114, USA

    Bharti Balhara, Madhusmita Misra & Lynne L. Levitsky

Authors
  1. Bharti Balhara
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Madhusmita Misra
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lynne L. Levitsky
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lynne L. Levitsky.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Balhara, B., Misra, M. & Levitsky, L.L. Recombinant Human IGF-1 (Insulin-Like Growth Factor) Therapy: Where Do We Stand Today?. Indian J Pediatr 79, 244–249 (2012). https://doi.org/10.1007/s12098-011-0608-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12098-011-0608-5

Keywords

Search

Navigation