Skip to main content
SpringerLink
Log in

Long-term auxological and pubertal outcome of patients with hereditary insulin-like growth factor-I deficiency (Laron and growth hormone-gene deletion syndrome) treated with recombinant human insulin-like growth factor-I

  • Original Articles
  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

Background: GH-IGF-I axis is mainly involved in the complex process of somatic growth but emerging evidence suggests that it also influences hypothalamic-pituitary-gonadal (HPG) function. Subjects: We report some data regarding long-term auxological and pubertal outcome of five female patients with hereditary forms of GH-IGF-I deficiency (Laron and GH-gene deletion syndrome) and a mean age of 23.4±5.3 yr (range 19–32). Methods: All the patients received recombinant human IGF-I (rhIGF-I, Pharmacia and Upjohn, Stockholm, Sweden, and rhIGF-I, Genentech, San Francisco, CA, USA) from a mean age of 8.6 yr (range 3.2–14.2) up to the final height. Results: Final height was very disappointing (≤ − 5.0 SD scores) and lower than target height in all the patients. Pubertal onset was delayed in most of them but menarche occurred spontaneously in all the patients. Median age at menarche was 15.1 yr. Menstrual cycles were regular for several years. Median duration of gynecological follow-up was 8.3 yr with the longest span of 17.2 yr. Conclusion: We can assert that GH-IGF-I axis has an essential role in promoting linear growth in humans and its physiological action cannot be replaced by pharmacological treatment in most patients with hereditary forms of IGF-I insufficiency as demonstrated by their subnormal final height. Our clinical observations can also support an essential role of IGF-I in genitalia growth but not in the function of HPG axis as demonstrated by the maintenance of regular menstrual cycles in the presence of subnormal levels of IGF-I after treatment discontinuation.

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

References

  1. Chandrashekar V, Bartke A. The role of insulin-like growth factor-I in neuroendocrine function and the consequent effect on sexual maturation: inferences from animal models. Reprod Biol 2003, 3: 7–28.

    PubMed  Google Scholar 

  2. Vendola K, Zhon J, Wang J, Bondy CA. Androgens promote insulin-like growth factor-I and insulin-like growth factor-I receptor gene expression in the primate ovary. Hum Reprod 1999, 14: 2328–32.

    Article  PubMed  CAS  Google Scholar 

  3. Bondy C, Werner H, Roberts CT, Le Roith D. Cellular pattern of type-I insulin-like growth factor receptor gene expression during maturation of the rat brain: comparison with insulin-like growth factor I and II. Neuroscience 1992, 46: 909–23.

    Article  PubMed  CAS  Google Scholar 

  4. Daftary SS, Gore AC. IGF-1 in the brain as a regulator of reproductive neuroendocrine function. Exp Biol Med 2005, 230: 292–306.

    CAS  Google Scholar 

  5. Laron Z. Development and biological function of the female gonads and genitalia in IGF-I deficiency — Laron syndrome as a model. Pediatr Endocrinol Rev 2006, 3 (Suppl 1): 188–91.

    PubMed  Google Scholar 

  6. Messina MF, D Luca F, Wasniewska M, Valenzise V, Lombardo F, Ghizzoni L. Final height in isolated GH deficiency type 1 A: effects of 5-year treatment with IGF-I. Eur J Endocrinol 2001, 144: 379–83.

    Article  PubMed  CAS  Google Scholar 

  7. Zucchini S, Scarano E, Baldazzi L, Mazzanti L, Pirazzoli P, Cacciari E. Final height in a patient with Laron syndrome after long-term therapy with rhIGF-I and short term therapy with LH-RH analogue and oxandrolone during puberty. J Endocrinol Invest 2005, 28: 274–9.

    Article  PubMed  CAS  Google Scholar 

  8. Merz E, Miric-Tesanic D, Bahlmann F, Weber G, Wellek S. Sonographic size of uterus and ovaries in pre and post menopausal women. Ultrasound Obstet Gynecol 1996, 7: 38–42.

    Article  PubMed  CAS  Google Scholar 

  9. Tanner JM, Whithouse RH. Clinical longitudinal standards for height, weight, height velocity, weight velocity and the stages of puberty. Arch Dis Child 1976,51: 170–9.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  10. Cacciari E, Milani S, Balsamo A, et al. Italian cross-sectional growth charts for height, weight and BMI (6–20 y). Eur J Clin Nutr 2002, 56: 171–80.

    Article  PubMed  CAS  Google Scholar 

  11. Vnencak-Jones CL, Phillips JA, De-Fen W. Use of polymerase chain reaction in detection of growth hormone gene deletions. J Clin Endocrinol Metab 1990, 70: 1550–3.

    Article  PubMed  CAS  Google Scholar 

  12. Laron Z. The essential role of IGF-I: lessons from the long-term study and treatment of children and adults with Laron syndrome. J Clin Endocrinol Metab 1999, 84: 4397–404.

    Article  PubMed  CAS  Google Scholar 

  13. 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.

    PubMed  CAS  Google Scholar 

  14. Chernausek SD, Backeljauw PF, Frane J, Kuntze J, Underwood LE; GH insensitivity Syndrome Collaborative Group. 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 

  15. Christoforidis A, Maniadaki I, Stanhope R. Growth hormone/insulin-like growth factor-1 axis during puberty. Ped Endocrinol Rev 2005, 3: 5–10.

    Google Scholar 

  16. Danilovich N, Wernsing D, Coschigano KT, Kopchick JJ, Bartke A. Deficits in female reproductive function in GH-R-KO mice: role of IGF-I. Endocrinology 1999, 140: 2637–40.

    Article  PubMed  CAS  Google Scholar 

  17. Chandrashekar V, Zaczek D, Bartke A. The consequence of altered somatotropic system on reproduction. Biol Reprod 2004, 71: 17–27.

    Article  PubMed  CAS  Google Scholar 

  18. Zaczek D, Hammond J, Suen L, et al. Impact of growth hormone resistance on female reproductive function: new insights from growth hormone receptor knockout mice. Biol Reproduct 2002, 67: 1115–24.

    Article  CAS  Google Scholar 

  19. Yoshimura Y, Iwashita M, Karube M, et al. Growth hormone stimulate follicular development by stimulating ovarian production of insulin-like growth hormone factor-I. Endocrinology 1994, 135: 887–94.

    PubMed  CAS  Google Scholar 

  20. Silva JR, Figueiredo JR, van den Hurk R. Involvement of growth hormone (GH) and insulin-like growth factor (IGF) system in ovarian folliculogenesis. Theriogenology 2009, 71: 1193–208.

    Article  PubMed  CAS  Google Scholar 

  21. Su PH, Wang SL, Chen JY, Chen SJ, Ke JC. A study of anthropomorphic and biochemical characteristics in girls with central precocious puberty and thelarche variant. J Pediatr Endocrinol Metab 2008, 21: 213–20.

    Article  PubMed  CAS  Google Scholar 

  22. Utriainen P, Voutilainen R, Jaaskelainen J. Girls with premature adrenarche have accelerated early childhood growth. J Pediatr 2009, 154: 882–7.

    Article  PubMed  Google Scholar 

  23. Dor J, Ben-Shlomo I, Lunenfeld B, et al. Insulin-like growth factor-I (IGF-I) may not be essential for ovarian follicular development: evidence from IGF-I deficiency. J Clin Endocrinol Metab 1992, 74: 539–42.

    PubMed  CAS  Google Scholar 

  24. Laron Z, Sarel R, Pertzelan A. Puberty in Laron-type dwarfism. Eur J Pediatr 1980, 134: 79–83.

    Article  PubMed  CAS  Google Scholar 

  25. Laron Z. Laron syndrome (primary growth hormone resistance or insensitivity): the personal experience 1958–2003. J Clin Endocrinol Metab 2004, 89: 1031–44.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pediatrics, University of Messina, Messina

    M. F. Messina MD, T. Arrigo, M. Valenzise, G. Crisafulli, G. Zirilli & F. De Luca

  2. Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Turin

    L. Ghizzoni

  3. Department of Pediatrics, University of Catania, Catania

    M. Caruso-Nicoletti

  4. Department of Pediatrics, University of Bologna, Bologna

    S. Zucchini

  5. Division of Pediatric Endocrinology, Regina Margherita Children’s Hospital, Turin, Italy

    P. Chiabotto

Authors
  1. M. F. Messina MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. Arrigo
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Valenzise
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L. Ghizzoni
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Caruso-Nicoletti
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S. Zucchini
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. P. Chiabotto
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. G. Crisafulli
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. G. Zirilli
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. F. De Luca
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. F. Messina MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Messina, M.F., Arrigo, T., Valenzise, M. et al. Long-term auxological and pubertal outcome of patients with hereditary insulin-like growth factor-I deficiency (Laron and growth hormone-gene deletion syndrome) treated with recombinant human insulin-like growth factor-I. J Endocrinol Invest 34, 292–295 (2011). https://doi.org/10.1007/BF03347088

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03347088

Key-words

Search

Navigation