Advertisement

Journal of Endocrinological Investigation

, Volume 26, Issue 7, pp 623–628 | Cite as

Growth hormone secretion in polytransfused prepubertal patients with homozygous β-thalassemia. Effect of longterm recombinant GH (recGH) therapy

  • Antonio Masala
  • M. M. Atzeni
  • S. Alagna
  • D. Gallisai
  • C. Burrai
  • M. G. Mela
  • P. P. Rovasio
  • P. Gallo
Original Article

Abstract

Growth was monitored in 133 male and 150 female North Sardinian prepubertal patients with homozygous β-thalassemia in order to ascertain the incidence of GH deficiency (GHD) and the effects of long-term recombinant GH (recGH) treatment on growth velocity and bone maturation. A significant reduction in growth velocity and a fall in IGF-I levels was observed in 19 male and 16 female patients (12.3%). Their peak GH responses to GHRH (5.45±0.78 and 4.99±0.86 ng/ml) and clonidine administration (4.21±0.32 and 4.15±0.27 ng/ml in males and females, respectively) were markedly reduced with respect to control subjects (p<0.01). No statistically significant correlation was found between chronological age, number of blood units received, plasma ferritin levels and plasma IGF-I levels as well as with peak GH response to stimulation. Thalassemic patients with GHD had plasma ferritin levels (1382.44±160.34 and 1255.23±139.81 ng/ml in males and females, respectively) significantly lower than those recorded in the other patients (2848.94±283.61 and 3077.82±220.51 ng/ml). Patients with GHD were treated with recGH for an average period of 59 months (range 26–124). Treatment was able to restore growth and to increase significantly plasma IGF-I levels. Growth velocity at the end of the first yr of treatment was 6.78±1.21 and 6.11±0.85 cm/yr in males and females, respectively. Growth velocity values and plasma IGF-I levels remained significantly higher than basal values throughout the period of treatment. However, treatment was unable to normalize bone maturation since bone age values were always reduced with respect to chronological age. No incidence of side effects was observed. These data indicate that GHD, when present, is one but not the sole cause of delayed bone maturation and height deficiency in thalassemia.

Keywords

Growth Hormone Thalassemia Growth Velocity Ferritin Level Desferrioxamine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Danesi L, Scacchi M, De Martin M, et al. Evaluation of hypothalamic- pituitary function in patients with thalassemia major. J Endocrinol Invest 1992, 15: 177–84.PubMedCrossRefGoogle Scholar
  2. 2.
    Masala A, Meloni T, Gallisai D, Alagna S, Rovasio PP, Rassu S. Endocrine functioning in multitransfused prepubertal patients with homozygous β-thalassemia. J Clin Endocrinol Metab 1984, 58: 667–70.PubMedCrossRefGoogle Scholar
  3. 3.
    McIntosh N. Endocrinopathy in thalassemia major. Arch Dis Child 1976, 51: 195.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Italian Working Group on Endocrine Complications in Non-Endocrine Diseases. Multicentre study on prevalence of endocrine complications in thalassemia major. Clin Endocrinol (Oxf) 1995, 42: 581–6.CrossRefGoogle Scholar
  5. 5.
    Tiosano D, Hochberg Z. Endocrine complications of thalassemia. J Endocrinol Invest 2001, 24: 716–23.PubMedCrossRefGoogle Scholar
  6. 6.
    Low LCK, Kwan EYW, Lim YJ, Lee ACW, Tam CF, Lam KSL. Growth hormone treatment of short chinese children with β-thalassemia major without GH deficiency. Clin Endocrinol (Oxf) 1995, 42: 359–63.CrossRefGoogle Scholar
  7. 7.
    Pintor C, Cella SG, Manso P, et al. Impaired growth hormone (GH) response to GH releasing hormone in thalassemia major. J Clin Endocrinol Metab 1986, 62: 263–7.PubMedCrossRefGoogle Scholar
  8. 8.
    Katzos G, Harsoulis F, Papadopoulou M, Athanasiou M, Sava K. Circadian growth hormone secretion in short multitransfused prepubertal children with thalassemia major. Eur J Ped 1995, 154: 445–9.CrossRefGoogle Scholar
  9. 9.
    Scacchi M, Danesi L, De Martin M, et al. Treatment with biosynthetic growth hormone of short thalassemic patients with impaired growth hormone secretion. Clin Endocrinol (Oxf) 1991, 35: 335–9.CrossRefGoogle Scholar
  10. 10.
    Low LCK, Postel-Vinay MC, Kwan EYV, Cheung PT. Serum growth hormone (GH) binding protein, IGF-I and IGFBP-3 in patients with β-thalassemia major and the effect of GH treatment. Clin Endocrinol (Oxf) 1998, 48: 641–6.CrossRefGoogle Scholar
  11. 11.
    Theodoridis C, Ladis V, Papatheodorou A, et al. Growth and management of short stature in thalassemia major. Pediatr Endocrinol Metab 1998, 11: 835–44.Google Scholar
  12. 12.
    Katzsos G, Papakostantinou-Athanasiadou E, Athanasiou-Metaxa M, Harsoulis F. Growth hormone treatment in short children with beta-thalassemia major. J Pediatr Endocrinol Metab 2000, 131: 163–70.Google Scholar
  13. 13.
    Tanner JM, Whitehouse RH. Clinical longitudinal standards for height, weight, height velocity, weight velocity and stages of puberty. Arch Dis Child 1976, 51: 170–9.PubMedCentralPubMedCrossRefGoogle Scholar
  14. 14.
    Vannasaeng S, Fucharoen S, Poutrakul P, Ploybutr S, Yansukon P. Pituitary function in thalassemic patients and the effect of chelation therapy. Acta Endocrinol (Copenh) 1991, 124: 23–30.Google Scholar
  15. 15.
    Vassillopoulou-Sellin R, Ojedeji CO, Foster PL, Thompson MM, Saman NA. Hemoglobin as a direct inhibitor of cartilage growth in vitro. Horm Metab Res 1989, 21: 11–4.CrossRefGoogle Scholar
  16. 16.
    De Virgilis S, Congia M, Frau F, et al. Desferoxamine-induced growth retardation in patients with thalassemia major. J Pediatr 1988, 113: 661–9.CrossRefGoogle Scholar
  17. 17.
    Cavallo L, Gurrado R, Gallo F, Zecchino C, De Mattia D, Tatò L. Growth deficiency in polytransfused ?-thalassemia patients is not growth hormone dependent. Clin Endocrinol (Oxf) 1997, 46: 701–6.CrossRefGoogle Scholar
  18. 18.
    Garcia-Mayor RV, Andrade Olivie A, Fernandez Catalina P, Castro M, Rego Iraeta A, Reparaz A. Linear growth in thalassemic children treated with intensive chelation therapy. A longitudinal study. Horm Res 1993, 40: 189–93.PubMedCrossRefGoogle Scholar
  19. 19.
    Brill PV, Winchester P, Giardina PI, Cunningham-Rundles S. Desferrioxamine induced bone dysplasia in patients with thalassemia major. Am J Roentgenol 1991, 156: 561–5.CrossRefGoogle Scholar
  20. 20.
    Naselli A, Vignolo M, Di Battista E, et al. Long-term follow- up of skeletal dysplasia in thalassemia major. J Pediatr Endocrinol Metab 1998, 11 (Suppl 3): 817–25.PubMedGoogle Scholar
  21. 21.
    Olivieri NF, Koren G, Harris J, et al. Growth failure and body changes induced by desferrioxamine. Am J Pediatr Hematol Oncol 1992, 14: 48–56.PubMedCrossRefGoogle Scholar
  22. 22.
    De Sanctis V, Pinamonti A, Di Palma A., et al. Growth and development in thalassemia major patients with severe bone lesions due to desferroxamine. Eur J Pediatr 1996, 155: 368–72.PubMedCrossRefGoogle Scholar
  23. 23.
    Cavallo L, Licci D, Acquafredda A, et al. Endocrine involvment in children with β-thalassemia major. Transversal and longitudinal studies. I. Pituitary-thyroidal axis function and is correlation with serum ferritin levels. Acta Endocrinol (Copenh) 1984, 107: 49–53.Google Scholar
  24. 24.
    Frasier SD. Human pituitary growth hormone (hGH) therapy in growth hormone deficiency. Endocr Rev 1983, 4: 155–70.PubMedCrossRefGoogle Scholar
  25. 25.
    Chrysis DC, Alexandrides TK, Koromantzou E, et al Novel application of IGF-I and IGFBP-3 generation tests in the diagnosis of growth hormone axis disturbances in children with β-thalassemia. Clin Endocrinol (Oxf) 2001, 54: 253–9.CrossRefGoogle Scholar
  26. 26.
    Masala A, Meloni T, Alagna S, et al. Plasma growth hormone (GH) and somatomedin-C (SM-C) levels in patients with homozygous β-thalassemia. Exp Clin Endocrinol 1988, 7: 161–3Google Scholar
  27. 27.
    Masala A, Meloni T, Gallisai D, et al. The effects of thyrotropin releasing hormone and luteinizing hormone releasing hormone on growth hormone release in patients with homozygous β-thalassemia. J Clin Endocrinol Metab 1982, 54: 1271–74.PubMedCrossRefGoogle Scholar
  28. 28.
    Masala A, Alagna S, Faedda R, et al. Paradoxical growth hormone (GH) release in response to thyrotropin releasing hormone (TRH) in patients with Wilson’s disease. J Nucl Med All Sci 1987, 31: 104–5.Google Scholar
  29. 29.
    Berkovitch M, Bistritzer T, Milone SD, Perlman K, Kucharczyk W, Olivieri NF. Iron deposition in the anterior pituitary in homozygous beta-thalassemia: MRI evaluation and correlation with gonadal function. J Pediatr Endocrinol Metab 2000, 13: 179–84.PubMedCrossRefGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 2003

Authors and Affiliations

  • Antonio Masala
    • 1
  • M. M. Atzeni
    • 1
  • S. Alagna
    • 1
  • D. Gallisai
    • 2
  • C. Burrai
    • 2
  • M. G. Mela
    • 2
  • P. P. Rovasio
    • 1
  • P. Gallo
    • 1
  1. 1.Dipartimento di Struttura Clinica Medica-Patologia MedicaIstituto di Patologia MedicaSassariItaly
  2. 2.Clinica PediatricaUniversity of SassariSassariItaly

Personalised recommendations