The Indian Journal of Pediatrics

, Volume 72, Issue 2, pp 159–164 | Cite as

Growth of children with β-thalassemia major

  • Louis C. K. Low
Symposium on Growth and Its Disorders


Hypertransfusion and regular chelation therapy have allowed improved survival in patients with thalassemia major (TM). Despite medical advances, growth failure and hypogonadism remain significant clinical problems in these patients in adolescence. Disproportionate truncal shortening which is common especially among adolescents with thalassemia, is due to platyspondyly resulting from a combination of factors like hemosiderosis, desferrioxamine toxicity or deficiency of trace elements. Although growth hormone (GH) deficiency and GH neurosecretory dysfunction have been described in TM patients, most short TM patients have normal GH reserve. The low serum IGF-1 and IGFBP-3 concentrations in TM patients despite having normal GH reserve and serum GH binding protein levels suggest that a state of secondary GH insensitivity exists. The pubertal growth spurt may be impaired in TM patients going through spontaneous or induced puberty and may have a negative effect on final adult height. GH therapy in dosages ranging from 0.5–1.0 IU/kg/wk has resulted in a significant improvement in growth velocity in short TM children without any adverse effects on skeletal maturation, blood pressure, glucose tolerance and serum lipids. There is limited evidence that GH treatment can result in an improved final adult height in short TM children. Careful and regular clinical and biochemical monitoring should be preformed on these patients while they are treated with GH.

Key words

Thalassaemia major Truncal shortening GH insensitivity 


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  1. 1.
    Olivieri NF, Nathan DG, MacMillan JHet al. Survival in medically treated patients with homozygous thalassemia major.N Engl J Med 1994;331:574–578.PubMedCrossRefGoogle Scholar
  2. 2.
    Kattamis C, Liakopoulou T, Kattamis A. Growth and development in children with thalassemia major.Acta Pediatr Scand 1990;(Suppl)366:111–117.Google Scholar
  3. 3.
    Low LCK. Growth, puberty and endocrine function in betathalassaemia major.J Pediatr Endocrinol Metab 1997;10:175–184.PubMedGoogle Scholar
  4. 4.
    Brittenham GM, Griffith PM, Nienhaus AWet al. Efficacy of desferrioxamine in preventing complications of iron overload in patients with thalassemia major.N Engl J Med 1994;331:567–573.PubMedCrossRefGoogle Scholar
  5. 5.
    Lucarelli G, Galimberti M, Polchi Pet al. Marrow transplantation in patients with thalassemia responsive to iron chelation therapy.New Engl J Med 1993;329:840–844.PubMedCrossRefGoogle Scholar
  6. 6.
    De Simone M, Olioso P, Di Bartolomeo Pet al. Growth and endocrine function following bone marrow transplantation for thalassaemia.Bone Marrow Transplantation 1995;15:227–233.Google Scholar
  7. 7.
    De Simone M, Verrotti A, Iughetti Let al. Final height of thalassemic patients who underwent bone marrow transplantation during childhood.Bone Marrow Transplantation 2001;28:201–205.PubMedCrossRefGoogle Scholar
  8. 8.
    Low LCK. Growth and endocrine function in b-thalassaemia major. In Desai MP, Bhatia V, Menon PSN, eds.Pediatric Endocrine Disorders, India. Orient Longman, India 2001:411–415.Google Scholar
  9. 9.
    Borgna-Pignatti C, Zurlo MG, DeStefano Pet al. Outcome of thalassemic treated with conventional therapy.Bone Marrow Transplantation 1993;12(Suppl):2–4.PubMedGoogle Scholar
  10. 10.
    Kwan EYW, Lee ACW, Li AMCet al. A cross-sectional study of growth, puberty and endocrine function in patients with thalassemia major in Hong Kong.J Pediatr Child Health 1995;31:83–87.Google Scholar
  11. 11.
    Yesipek MA, Bircan I, Oygur N, Ertug H, Yegin O, Guven AG. Growth and sexual maturation in children with thalassemia major.Haematologica 1993;78:30–33.Google Scholar
  12. 12.
    De Sanctis V, Katz M, Vullo C, Bagni B, Ughi M, Wonke B. Effect of different treatment regimes on linear growth and final height in β-thalassemia major.Clin Endocrinol 1994;40:791–798.Google Scholar
  13. 13.
    Bronspiegel-Weintrob N, Olivieri NF, Tyler B, Andrews DF, Freeman MH, Holland FJ. Effect of age at the start of iron chelation therapy on gonadal function in β-thalassemia major.N Engl J Med 1990;323:713–719.PubMedCrossRefGoogle Scholar
  14. 14.
    Caruso-Nicoletti M, De Sanctis V, Capra Met al. Short stature and body proportion in thalassemia.J Pediatr Endocrinol Metab 1998;11(Suppl 3):811–816.PubMedGoogle Scholar
  15. 15.
    Theodoridis C, Ladis V, Papatheodorou Aet al. Growth and management of short stature in thalassemia major.J Pediatr Endocrinol Metab 1998;11(Suppl 3):835–844.PubMedGoogle Scholar
  16. 16.
    Raiola G, Galati MC, De Sanctis Vet al. Growth and puberty in thalassemia major.J Pediatr Endocrinol Metab 2003;16(Suppl 2):259–266.PubMedGoogle Scholar
  17. 17.
    George A, Bhaduri A, Sen S, Choudhry VP. Physical growth parameters in thalassemic children.Indian J Pediatr 1997;64: 861–871.PubMedCrossRefGoogle Scholar
  18. 18.
    Rodda CP, Reid ED, Johnson S, Doery J, Matthews R, Bowden DK. Short stature in homozygous β-thalassemia is due to disproportionate truncal shortening.Clin Endocrinol 1995;42:587–592.Google Scholar
  19. 19.
    Low CK, Kwan YW, Cheung PTet al. The effect of platyspondyly and pubertal growth spurt on the stature of patients with β-thalassaemia major.Chinese Med J 1998;111:731–735.Google Scholar
  20. 20.
    Orzincolo C, Scuttellari PN, Castaldi G. Growth plate injury of the long bones in treated β-thalassemia.Skeletal Radiol 1992; 21:39–44.PubMedCrossRefGoogle Scholar
  21. 21.
    Olivieri NF, Koren G, Harris Jet al. Growth failure and body changes induced by deferoxamine.Am J Pediatr Hematol Oncol 1992;14:48–56.PubMedCrossRefGoogle Scholar
  22. 22.
    Olivieri NF, Weatherall DJ. Recent progress in the management of thalassemia.Hong Kong J Pediatr 1996;1:1–10.Google Scholar
  23. 23.
    Leger J, Girot R, Crosnier H, Postel-Vinay MC, Rappaport R. GH response to GH-RH in children with thalassemia major before puberty: a possible age related effect.J Clin Endocrinol Metab 1989;69:453–456.PubMedGoogle Scholar
  24. 24.
    Chatterjee R, Katz M, Cox T, Bantok H. Evaluation of growth hormone in thalassaemic boys with failed puberty: spontaneous versus provocative test.Eur J Pediatr 1993;152:721–726.PubMedCrossRefGoogle Scholar
  25. 25.
    Oerter KE, Kamp GA, Munson PJ, Nienhaus AW, Cassorla FG, Manasco PK. Multiple hormone deficiencies in children with hemochromatosis.J Clin Endocrinol Metab 1993;76:357–361.PubMedCrossRefGoogle Scholar
  26. 26.
    Grundy RG, Wood KA, Savage MO, Evan JPM. Relationship of endocrinopathy to iron chelation status in young patients with thalassemia major.Arch Dis Child 1994;74:128–132.Google Scholar
  27. 27.
    Soliman AT EI Banna N, Ansari BM. GH response to provocation and circulating IGF-1 and IGF-binding protein-3 concentrations, the IGF-1 generation test and clinical response to GH therapy in children with β-thalassemia.Eur J Endocrinol 1998;138:394–400.PubMedCrossRefGoogle Scholar
  28. 28.
    Chrysis DC, Alexandrides TK, Koromantzouet al. Novel application of IGF-1 and IGFBP-3 generation tests in the diagnosis of the growth hormone axis disturbances in children with β-thalassemia.Clin Endocrinol 2001;54:253–259.CrossRefGoogle Scholar
  29. 29.
    Shehadeh N, Hazani A, Rudolf MC, Peleg I, Benderly A, Hochberg Z. Neurosecretory dysfunction of growth hormone secretion in thalassemia major.Acta Paediatr Scand 1990;79: 790–795.PubMedGoogle Scholar
  30. 30.
    Roth C, Pekrum A, Bartz Met al. Short stature and failure of pubertal development in thalassemia major: Evidence for hypothalamic neurosecretory dysfunction of growth hormone secretion and defective pituitary gonadotropin.Eur J Pediatr 1997;156:777–783.PubMedCrossRefGoogle Scholar
  31. 31.
    Pintor C, Cella SG, Manso Pet al. Impaired growth hormone (GH) response to GH-releasing hormone in thalassemia major.J Clin Endocrinol Metab 1986;62:263–267.PubMedGoogle Scholar
  32. 32.
    Leheup BP, Cisternino M, Bozzola Met al. Growth hormone response following growth hormone releasing hormone injection in thalassaemia major: influence of pubertal development.J Endocrinol Invest 1991;14:37–40.PubMedGoogle Scholar
  33. 33.
    DeLuca G, Maggiolini M, Bria Met al. GH secretion in thalassemic patients with short stature.Horm Res 1995;44:158–163.Google Scholar
  34. 34.
    Low LCK, Postel-Vinay MC, Kwan EYW, Cheung PT. Serum growth hormone (GH) binding protein, IGF-1 and IGFBP-3 in patients with β-thalassaemia major and the effect of GH treatment.Clin Endocrinol 1998;48: 641–646.CrossRefGoogle Scholar
  35. 35.
    Werther GA, Mathews RN, Burger HG, Herrington AC. Lack of response of non-suppressible insulin-like activity in thalassemia major.J Clin Endocrinol Metab 1981;53:806–809.PubMedGoogle Scholar
  36. 36.
    Postel-Vinay MC, Girot R, Leger Jet al. No evidence for a defect in growth hormone binding to liver membranes in thalassemia major.J Clin Endocrinol Metab 1989;68:94–98.PubMedCrossRefGoogle Scholar
  37. 37.
    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 1995; 42:359–363.Google Scholar
  38. 38.
    Italian Working Group on Endocrine Complication in Non Endocrine Disease. Mulicentre study on prevalence of endocrine complications in thalassaemia major.Clin Endocrinol 1995;42:581–586.Google Scholar
  39. 39.
    Berkovitch M, Bistritzer T, Milone SDet al. Iron deposition in the anterior pituitary in homozygous β-thalassemia: MRI evaluation and correlation with gonadal function.J Pediatr Endocrinol Metab 2000;13:179–184.PubMedGoogle Scholar
  40. 40.
    Landau H, Gross V, Dagar I, Palti Z, Rachmilewitz EA, Spitz IM. Growth and sexual development before and after sex steroid therapy in patients with thalassemia major.Arch Int Med 1984;144:2341–2346.CrossRefGoogle Scholar
  41. 41.
    Scacchi M, Danesi L, De Martin Met al. Treatment with biosynthetic growth hormone of short thalassemic patients with impaired growth hormone secretion.Clin Endocrinol 1991; 35:335–339.Google Scholar
  42. 42.
    Masala A, Alagna A, Gallisai Det al. Long-term treatment with biosynthetic growth hormone (GH) of patients with thalassemia major.Eur J Nucl Med 1992;19:682.Google Scholar
  43. 43.
    Cavello L, Gurrado R, Zecchino Cet al. Short-term therapy with recombinant growth hormone in polytransfused thalassemia major patients with growth deficiency.J Pediatr Endocrinol Metab 1998;11(Suppl 3):845–849.Google Scholar
  44. 44.
    Arcasoy A, Ocal G, Kemahli Set al. Recombinant human growth hormone treatment in children with thalassemia major.Pediatr Int 1999;41:655–661.PubMedGoogle Scholar
  45. 45.
    Katzos G, Papakostantinou-Athanasiadou E, Athanasiou-Metaxa M, Harsoulis F. Growth hormone treatment in short children with β-thalassemia major.J Pediatr Endocrinol Metab 2000;13:163–170.PubMedGoogle Scholar
  46. 46.
    Sartorio A, Conte G, Conti Aet al. Effects of 12 months rec-GH therapy on bone and collagen turnover and bone mineral density in GH deficient children with thalassemia major.J Endocrinol Invest 2000;23:356–361.PubMedGoogle Scholar
  47. 47.
    Wu KH, Tsai FJ, Peng CT. Growth hormone (GH) deficiency in patients with β-thalassemia major and the efficacy of recombinant GH treatment.Ann Hematol 2003;82:637–640.PubMedCrossRefGoogle Scholar
  48. 48.
    De Sanctis V, Urso L, Galati MCet al. Growth hormone (GH) treatment in thalassemic patients with short stature, GH insufficiency and different severity of iron overload.Bone Marrow Transplant 1997;19(Supp 2):32–33.Google Scholar
  49. 49.
    Kwan EYW, Tam SCF, Cheung PT, Low LCK. The effect of 3 years of recombinant growth hormone therapy on glucose metabolism in short Chinese children with β-thalassemia major.J Pediatr Endocrinol Metab 2000;13:545–552.PubMedGoogle Scholar
  50. 50.
    Cavallo L, Aquafredda A, Zecchino Cet al. Recombinant growth hormone treatment in short patients with thalassemia major: results after 24 and 36 months.J Pediatr Endocrinol Metab 2001;14:1133–1137.PubMedGoogle Scholar
  51. 51.
    Low LCK, Kwan EYW, Cheung PT. Final height of growth hormone treated non-GH deficient children with β-thalassemia major. Proceedings of the Endocrine Society 81st Annual Meeting, San Diego, California. June 12, 1999.Google Scholar
  52. 52.
    Tam SCF, Pang RWC, Janus ED, Kwan EYW, Low LCK. Growth hormone therapy transiently increases apolipoprotein (a) in short β-thalassemia major children with normal growth hormone reserve.Atherosclerosis 1997;128:175–182.PubMedCrossRefGoogle Scholar
  53. 53.
    Katz M, De Sanctis V, Vullo C, Wonke B, McGarriglo HH, Bagni B. Pharmacokinetics of sex steroids in patients with β-thalassemia major.J Clin Pathol 1993;46:660–664.PubMedCrossRefGoogle Scholar

Copyright information

© Dr. K C Chaudhuri Foundation 2005

Authors and Affiliations

  • Louis C. K. Low
    • 1
  1. 1.Department of Pediatrics and Adolescent MedicineThe University of Hong Kong, Queen Marg HospitalHong Kong SAR, PR China

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