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Growth Suppression by Glucocorticoids

Mechanisms, Clinical Significance, and Treatment Options

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Pediatric Endocrinology

Part of the book series: Contemporary Endocrinology ((COE))

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Abstract

Long-term treatment with glucocorticoids (GC) frequently results in growth failure in children. While most disorders requiring such treatment (e.g., organ transplantation, inflammatory bowel disease, rheumatoid diseases, severe asthma) are relatively rare, the expanding use of inhaled GC preparations for treatment of mild-to-moderate asthma has greatly increased the numbers of children chronically exposed to exogenous GC. This chapter reviews the mechanisms of GC effects on growth, current information about effects of inhaled corticosteroids (ICS) on growth of children with asthma, and preliminary investigations into reversal of GC-induced growth failure with human growth hormone (GH) therapy.

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References

  1. Allen DB, Julius JR, Breen TJ, Attie KM. Treatment of glucocorticoid-induced growth suppression with growth hormone. J Clin Endocrinol Metab 1998; 83: 2824–2829.

    Article  PubMed  CAS  Google Scholar 

  2. Moore DD, Marks AR, Buckley DI, Kapler G, Payvar F, Goodman HM. The first intron of the human growth hormone gene contains a binding site for clucocorticoid receptor. Proc Natl Acad Sci USA 1985; 82: 699–702.

    Article  PubMed  CAS  Google Scholar 

  3. Wehrenberg WB, Janowski BA, Piering AW, Culler PF, Jones KL. Glucocorticoids: potent inhibitors and stimulators of growth hormone secretion. Endocrinology 1990; 126: 3200–3203.

    Article  PubMed  CAS  Google Scholar 

  4. Miell JP, Corder R, Pralong FP, Gallard RC. Effects of dexamethasone on GHRH, arginine, and dopaminergic stimulated GH secretion and total plasma IGF-I concentrations in normal male volunteers. J Clin Endocrinol Metab 1991; 72: 675–681.

    Article  PubMed  CAS  Google Scholar 

  5. Kaufmann S, Jones KL, Wehrenberg WB, Culler FL. Inhibition by prednisone of growth hormone (GH) response to GH-releasing hormone in normal men. J Clin Endocrinol Metab 1988; 67: 1258–1261.

    Article  PubMed  CAS  Google Scholar 

  6. Gabrielsson BG, Carmignac DF, Flavell DM, Robinson ICAF. Steroid regulation of growth hormone (GH) receptor and GH-binding protein messenger ribonucleic acids in the rat. Endocrinology 1995; 136: 209–217.

    Article  PubMed  CAS  Google Scholar 

  7. Tonshoff B, Mehls O. In: Tejani AH, Fine RN, editors. Pediatric Renal Transplantation. John Wiley and Sons, New York, NY: 1994, pp. 441–459.

    Google Scholar 

  8. Luo J, Reid R, Murphy L. Dexamethasone increases hepatic insulin-like growth factor binding protein-1 (IGFBP- 1) mRNA and serum IGFBP-1 concentrations in the rat. Endocrinology 2000; 125: 165–171.

    Article  Google Scholar 

  9. Unterman TG, Phillips LS. Glucocorticoid effects on somatomedins and somatomedin inhibitors. J Clin Endocrinol Metab 1985; 61: 618–626.

    Article  PubMed  CAS  Google Scholar 

  10. Hokken-Koelega ACS, Stijnen T, deMuinckKeizer-Schrama SMPF, Blum WF, Drop SLS. Levels of growth hormone, insulin-like growth factor I (IGF-I) and -II, IGF binding protein-1 and -3, and cortisol in prednisone-treated children with growth retardation after renal transplantation. J Clin Endocrinol Metab 1993; 77: 932–938.

    Article  PubMed  CAS  Google Scholar 

  11. Sarna S, Sipila I, Vihervuori E, Koistinen R, Holmberg C. Growth delay after liver transplantation in childhood: studies of underlying mechanisms. Pediatr Res 1995; 38: 366–372.

    Article  PubMed  CAS  Google Scholar 

  12. Jux C, Leiber K, Hugel U, et al. Dexamethasone impairs growth hormone (GH)-stimulated growth by suppression of local insulin-like growth factor (IGF)-I production and expression of GH- and IGF-Ireceptor in cultured rat chondrocytes. Endocrinology 2000; 139: 3296–3305.

    Article  Google Scholar 

  13. Robinson ICAF, Gabrielsson B, Klaus B, Mauras N, Holmberg C, Mehls O. Glucocorticoids and growth problems. Acta Paediatr 1995; 411: 81–86.

    Article  CAS  Google Scholar 

  14. Hyams JS, Moore RE, Leichtner AM, Carey DE, Goldberg BD. Relationship of type I procollagen to corticosteroid therapy in children with inflammatory bowel disease. J Pediatr 1988; 112: 893–898.

    Article  PubMed  CAS  Google Scholar 

  15. Morris HG. Growth and skeletal maturation in asthmatic children: effect of corticosteroid treatment. Pediatr Res 1975; 9: 579–583.

    Article  PubMed  CAS  Google Scholar 

  16. Sadeghi-Nelad A, Semor B. Adrenal function, growth, and insulin in patients treated with corticoids on alternate days. Pediatrics 1969; 43: 277–283.

    Google Scholar 

  17. Reimer LG, Morris HG, Ellis EE. Growth of asthmatic children during treatment with alternate-day steroids. J Allergy Clin Immunol 1975; 55: 224–231.

    Article  PubMed  CAS  Google Scholar 

  18. Lam CN, Arneil GC. Long-term dwarfing effects of corticosteroid treatment for childhood nephrosis. Arch Dis Child 1968; 43: 589–594.

    Article  PubMed  CAS  Google Scholar 

  19. Foote KD, Brocklebank JT, Meadow SR. Height attainment in children with steroid responsive nephrotic syndrome. Lancet 1985; 2: 917–976.

    Article  PubMed  CAS  Google Scholar 

  20. Allen DB, Mullen M, Mullen B. A meta-analysis of the effects of oral and inhaled glucocorticoids on growth. J Allergy Clin Immunol 1994; 93: 967–976.

    Article  PubMed  CAS  Google Scholar 

  21. Ryrfeldt A, Edsbacker S, Pouwles R. Kinetics of epimeric glucocorticoid budesonide. Clin Pharmacol Therapeut 1984; 35: 525–530.

    Article  CAS  Google Scholar 

  22. Harding SM. The human pharmacology of fluticasone propionate. Respir Med 1990; 84 (Suppl A): 25–29.

    Article  PubMed  Google Scholar 

  23. Johansson SA, Andersson KE, Brattsand R. Topical and systemic glucocorticoid potencies of budesonide and beclomethasone dipropionate in man. Eur J Clin Pharmacol 1982; 22: 523.

    Article  PubMed  CAS  Google Scholar 

  24. Johnson M. Pharmacokinetics and pharmacodynamics of inhaled glucocorticoids. J Clin Allergy Immunol 1996; 98: 169–176.

    Article  Google Scholar 

  25. Agertoft L, Pedersen S. A randomized, double-blind dose reduction study to compare the minimal effective dose of budesonide Turbuhaler and fluticasone propionate Diskhaler. J Allergy Clin Immunol 1997; 99 (6): 773–780.

    Article  PubMed  CAS  Google Scholar 

  26. Ninan T, Russell G. Asthma, inhaled corticosteroid treatment, and growth. Arch Dis Child 1992; 67: 703–705.

    Article  PubMed  CAS  Google Scholar 

  27. Tinkelman DG, Reed CE, Nelson HS, Offord KP. Aerosol beclomethasone dipropionate compared with theophylline as primary treatment of chronic mild to moderately severe asthma in children. Pediatrics 1993; 92: 64–77.

    PubMed  CAS  Google Scholar 

  28. Doull IJM, Freezer NJ, Holgate ST. Growth of prepubertal children with mild asthma treated with inhaled beclomethasone dipropionate. Am J Respir Crit Care Med 1995; 151: 1715–1719.

    PubMed  CAS  Google Scholar 

  29. Simons FER. A comparison of beclomethasone, salmeterol, and placebo in children with asthma. N Engl J Med 1997; 337: 1659–1665.

    Article  PubMed  CAS  Google Scholar 

  30. Verberne AAPH, Frost C, DipStat MA, Roorda RJ, van der Laag H, Kerribijn KF. One year treatment with salmeterol compared to beclomethasone in children with asthma. Am J Resp Crit Care Med 1997; 156: 688–695.

    PubMed  CAS  Google Scholar 

  31. Agertoft L, Pederson S. Effects of long-term treatment with an inhaled corticosteroid on growth and pulmonary function in asthmatic children. Respiratory Med 1994; 88: 373–381.

    Article  CAS  Google Scholar 

  32. Merkus PJFM, VanEssenZandvliet EEM, Duiverman EJ, VanHouwelingen HC, Kerrebijn KF. Long term effect of inhaled corticosteroids on growth rate in adolescents with asthma. Pediatrics 1993; 91: 1121–1126.

    PubMed  CAS  Google Scholar 

  33. Allen DB, Bronsky EA, LaForce CF, et al. Growth in asthmatic children treated with fluticasone propionate. J Pediatr 1998; 132: 472–477.

    Article  PubMed  CAS  Google Scholar 

  34. Martin AJ, Landau LI, Phelan PD. The effect on growth of childhood asthma. Acta Paediatr Scand 1981; 70: 683–688.

    Article  PubMed  CAS  Google Scholar 

  35. Allen DB. Systemic effects of intranasal steroids: an endocrinologist’s perspective. J Clin Allergy Immunol 2000; 106 (Suppl 4): S179–S190.

    Article  CAS  Google Scholar 

  36. Teper AM, Kofman CD, Maffey AF, Vidaurreta S, Bergadi I, Heinrich J. Effect of inhaled beclomethasone dipropionate on pulmonary function, bronchial reactivity and longitudinal growth in infants with bronchial asthma. Asthma 1995; 95: 13–13.

    Google Scholar 

  37. Reid A, Murphy C, Steen HJ, McGovern V, Shields MD. Linear growth of very young asthmatic children treated with high-dose nebulized budesonide. Acta Paediatr 1996; 85: 421–424.

    Article  PubMed  CAS  Google Scholar 

  38. Skoner DP, Szefler SJ, Welch M, Walton-Bowen K, Cruz-Rivera M, Smith JA. Longitudinal growth in infants and young children treated with budesonide inhalation suspension for persistent asthma. J Allergy Clin Immunol 2000; 105: 259–268.

    Article  PubMed  CAS  Google Scholar 

  39. Pedersen S, Warner JO, Price JF. Early use of inhaled steroids in children with asthma. Clin Exper Allergy 1997; 27: 995–1006.

    Article  CAS  Google Scholar 

  40. Silverstein MD, Yunginger JW, Reed CE, et al. Attained adult height after childhood asthma: Effect of glucocorticoid therapy. J Allergy Clin Immunol 1997; 99: 466–474.

    Article  PubMed  CAS  Google Scholar 

  41. Van Bever HP, Desager KN, Lijssens N, Weyler JJ, Du Caju MVL. Does treatment of asthmatic children with inhaled corticosteroids affect their adult height? Pediatr Pulmonol 1999; 27: 369–375.

    Article  PubMed  Google Scholar 

  42. Lemanske RF, Allen DB. Choosing a long-term controller medication in childhood asthma: the proverbial two-edged sword. Am J Respir Crit Care Med 1997; 156: 685–687.

    PubMed  Google Scholar 

  43. Milgrom H, Bender B, Ackerson L, Bowry P, Smith B, Rand C. Noncompliance and treatment failure in children with asthma. J Allergy Clin Immunol 1996; 98: 1051–1057.

    Article  PubMed  CAS  Google Scholar 

  44. Selye H. Prevention of cortisone overdosage effects with the somatotropic hormone (STH). Am J Physiol 1952; 171: 381–384.

    PubMed  CAS  Google Scholar 

  45. Kovacs G, Fine RN, Worgall S. Growth hormone prevents steroid-induced growth depression in health and uremia. Kidney Int 1991; 40: 1032–1040.

    Article  PubMed  CAS  Google Scholar 

  46. Tomas FM, Knowles SE, Owens PC. Insulin like growth factor I (IGF-I) variants are anabolic in dexamethasone treated rats. Biochemistry 1992; 282: 91–97.

    CAS  Google Scholar 

  47. Ortoft G, Gronbaek H, Oxlund H. Growth hormone administration can improve growth in glucocorticoid-injected rats without affecting the lymphocytopenic effect of the glucocorticoid. J Bone Mineral Res 1999; 14: 710–721.

    Article  CAS  Google Scholar 

  48. Ward WE, Atkinson SA. Growth hormone and insulin-like growth factor-I therapy promote protein deposition and growth in dexamethasone-treated piglets. J Pediatr Gastroenterol Nutr 1999; 28: 404–410.

    Article  PubMed  CAS  Google Scholar 

  49. Morris HG, Jorgensen JR, Elrick H, Goldsmith RE, Subryan VL. Metabolic effects of human growth hormone in corticosteroid-treated children. J Clin Invest 1968; 47: 436–451.

    Article  PubMed  CAS  Google Scholar 

  50. McCaffery TD, Nasr K, Lawrence AM, Kirsner JB. Effect of administered human growth hormone on growth retardation in inflammatory bowel disease. Dig Dis 1974; 19: 411–416.

    Article  Google Scholar 

  51. Allen DB, Goldberg BD. Stimulation of collagen synthesis and linear growth by growth hormone in glucocorticoid-treated children. Pediatrics 1992; 89: 416–421.

    PubMed  CAS  Google Scholar 

  52. Rivkees SA, Danon M, Herrin J. Prednisone dose limitation of growth hormone treatment of steroid-induced growth failure. J Pediatr 1994; 125: 322–325.

    Article  PubMed  CAS  Google Scholar 

  53. Allen DB, Julius JR, Breen TJ, Attie KM. Reversal of glucocorticoid-induced growth failure by human growth hormone. Pediatr Res 1996; 39: 84A.

    Google Scholar 

  54. VanDop C, Jabs KL, Donohoue PA, Bock GH, Fivush BA, Harmon WE. Accelerated growth rates in children treated with growth hormone after renal transplantation. J Pediatr 1992; 120: 244–250.

    Article  CAS  Google Scholar 

  55. Maxwell H, Dalton RN, Nair DR, et al. Effects of recombinant human growth hormone on renal function in children with renal transplants. J Pediatr 1996; 128: 177–183.

    Article  PubMed  CAS  Google Scholar 

  56. Hokken-Koelega ACS, VanZaal MAE, deRidder MAJ, et al. Growth after renal transplantation in prepubertal children impact of various treatment modalities. Pediatr Res 1994; 35: 367–371.

    Article  PubMed  CAS  Google Scholar 

  57. Fine RN, Sullivan EK, Kuntze J, Blethen S, Kohaut E. The impact of recombinant human growth hormone treatment during chronic renal insufficiency on renal transplant recipients. J Pediatr 2000; 136: 376–382.

    Article  PubMed  CAS  Google Scholar 

  58. Tonshoff B, Haffner D, Mehls O. Efficacy and safety of growth hormone treatment in short children with renal allografts. Kidney Int 1993; 44: 199–207.

    Article  PubMed  CAS  Google Scholar 

  59. Mehls O, Tonshoff B, Kovacs G. Interaction between glucocorticoids and growth hormone. Acta Pediatr Suppl 1993; 388: 77–82.

    CAS  Google Scholar 

  60. Hokken-Koelega ACS, Stijnen T, deRidder MAJ, et al. Growth hormone treatment in growth-retarded adolescents after renal transplant. Lancet 1994; 343: 1313–1317.

    Article  PubMed  CAS  Google Scholar 

  61. Horber FF, Haymond MW. Human growth hormone prevents the protein catabolic side effects of prednisone in humans. J Clin Invest 1990; 86: 265–272.

    Article  PubMed  CAS  Google Scholar 

  62. Bennet WM, Haymond MW. Growth hormone and lean tissue catabolism during long-term glucocorticoid treatment. Clin Endocrinol 1992; 36: 161–164.

    Article  CAS  Google Scholar 

  63. Fukagawa NK, Minaker KL, Rowe W. Insulin-mediated reduction of whole body protein breakdown dose-response effects on leucine metabolism in postabsorptive man. J Clin Invest 1985; 76: 2306–2311.

    Article  PubMed  CAS  Google Scholar 

  64. Mauras N, Beaufrere B. rhIGF-I enhances whole body protein anabolism and significantly diminishes the protein catabolic effects of prednisone in humans without a diabetogenic effect. J Clin Endocrinol Metab 1995; 80: 869–874.

    Article  PubMed  CAS  Google Scholar 

  65. Guistina A, Bussie AR, Jacobello C, Wehrenberg WB. Effects of recombinant human growth hormone (GH) on bone and intermediary metabolism in patients receiving chronic glucocorticoid treatment with suppressed endogenous GH response to GH-releasing hormone. J Clin Endocrinol Metab 1995; 80: 122–129.

    Article  Google Scholar 

  66. VanDop C, Donohoue PW, Jabs KL, Bock GH, Fivush BA, Harmon WE. Glucose tolerance in children with renal allografts and effect of growth hormone treatment. J Pediatr 1991; 118: 708–714.

    Article  CAS  Google Scholar 

  67. Hirschberg R, Kopple JD, Blantz RC, Tucker BJ. Effects of recombinant human insulin-like growth factor I on glomerular dynamics in the rat. J Clin Invest 1991; 87: 1200–1206.

    Article  PubMed  CAS  Google Scholar 

  68. Allen DB, El-Hayek R, Friedman AL. Effects of prolonged growth hormone administration on growth, renal function, and renal histology in 75% nephrectomized rats. Pediatr Res 1996; 31: 406–410.

    Article  Google Scholar 

  69. Manredi R, Tumietto F, Azzaroli L. Growth hormone (GH) and the immune system impaired phagocytic function in children with idiopathic GH deficiency is corrected by treatment with biosynthetic GH. J Pediatr Endocrinol 1994; 7: 245–251.

    Google Scholar 

  70. Johansson G, Sietnieks A, Janssens F. Recombinant human growth hormone treatment in short children with chronic renal disease, before transplantation or with functioning renal transplants: an interim report on five European studies. Acta Paediatr Scand 1990; 370 (Suppl): 36–42.

    Article  CAS  Google Scholar 

  71. Broyer M, Guest G, Crosnier H, Berard E. Recombinant growth hormone in children after renal transplantation. Lancet 1994; 343: 539–540.

    Article  PubMed  CAS  Google Scholar 

  72. Guest G, Berard E, Crosnier H, Chevallier T, Rappaport R, Broyer M. Effects of growth hormone in short children after renal transplantation. Pediatr Nephrol 1998; 12: 437–446.

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. David B. Allen MD
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Editors and Affiliations

  1. Section of Pediatric Endocrinology, University of Chicago Medical Center, Chicago, IL, USA

    Sally Radovick MD

  2. Division of Endocrinology, Children’s Hospital of Buffalo, Buffalo, NY, USA

    Margaret H. MacGillivray MD

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Allen, D.B. (2003). Growth Suppression by Glucocorticoids. In: Radovick, S., MacGillivray, M.H. (eds) Pediatric Endocrinology. Contemporary Endocrinology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-336-1_5

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  • DOI: https://doi.org/10.1007/978-1-59259-336-1_5

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-268-1

  • Online ISBN: 978-1-59259-336-1

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