Abstract
The efficacy of growth hormone (GH) treatment in children with idiopathic growth failure has been the subject of controversy because of ethical concerns (1,2), financial considerations (3) and variable adult height outcomes (4,5). Much of the disagreement about the benefits of GH treatment relates to the heterogeneity of the study populations receiving therapy. Ideally, the efficacy of GH therapy should be based on the height outcomes of homogeneous populations of pathologically short children rather than the adult heights of children with variable shortness of differing etiologies. Published studies have sometimes combined children who had constitutional delay of growth and adolescence with subjects who had either severe genetic short stature or significant growth failure growth failure based on abnormal heights and growth rates for chronological age. These short children have been classified by various terminologies: Normal Variant Short Stature (NVSS), Idiopathic Short Stature (ISS), Constitutional Delay of Growth and Puberty (CGDP), GH neurosecretory dysfunction, idiopathic growth failure, and non-GH deficient short stature. Without treatment, the height outcomes in most studies have failed to reach mid-parental target height. In contrast, GH therapy has resulted in mixed height outcomes; some patients reached or exceeded genetic target height whereas others did not. Given the high cost and potential risk of adverse events, some authors have criticized the use of GH in healthy very short children without a documented endocrine disorder (1). Some of this disagreement may be resolved as we improve our ability to identify mutations in various growth regulating genes such as SHOX, GHRH, Ghrelin, GHRP, Pit-1, Prop-1, GH and their receptors.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Underwood LE, Rieser PA. Is it ethical to treat healthy short children with growth hormone? Acta Paediatr Scand 1989; 362: 18–23.
Lantos J, Siegler M, Cutler L. Ethical issues in growth hormone therapy. JAMA 1989; 261 (7): 1020–1024.
Finklestein BS, Silvers JB, Marrero U, Neuhauser D, Cuttler L. Insurance coverage, physician recomendations and access to emerging treatments. JAMA 1998; 279 (9): 663–668.
Guyda HJ. Four Decades of growth hormone therapy: what have we achieved? J Clin Endocrinol Metab 1999; 84 (12): 4307–4316.
Buchlis JG, Irizarry L, Crotzer BC, Shine BJ, Allen L, MacGillivray MH. Comparison of Final Heights of growth hormone-treated vs Untreated Children with Idiopathic Growth Failure. J Clin Endocrinol Metab 1998; 83 (4): 1075–1079.
Genentech Collaborative Study Group. Idiopathic Short Stature 2. J Pediatr 1989; 115: 713–719.
Loche S, Cambiaso P, Setzu S, et al. Final height after growth hormone therapy in non-deficient children with short stature. J Pediatr 1994; 125 (2): 196–200.
Ranke MB. Toward a consensus on the definition of short stature. Horm Res 1996; 45: 64–66.
Kelnar CJH, Albertsson-Wikland K, Hintz RL, Ranke MB, Rosenfeld RG. Should we treat children with idiopathic short stature? Horm Res 1999; 52: 155–157.
Bierich JR, Nolte K, Drew K, Brugman G. Constitutional delay of growth and adolescence. Result of a short term treatment with growth hormone. Acta Endocrinol (Copenh) 1992; 127: 392–396.
Zadik Z, Mira U, Landau H. Final height after growth hormone therapy for peripubertal boys with a subnormal integrated concentration of growth hormone. Horm Res 1992; 37 (4–5): 104–105.
Wit JM, Kamp GA, Rikken B, et al. Spontaneous growth and response to growth hormone in children with growth hormone deficiency or idiopathic short stature (review). Pediatr Res 1996; 39 (2): 295–302.
Witt JM, Boersma B, de Muink, et al. Long term results of growth therapy in children with short stature, subnormal growth rate and normal growth hormone response to secretagogues. Dutch growth hormone working group. Clin Endocrinol 1995; 42 (4): 365–372.
Albanese A, Standhope R. Does constitutional delayed puberty cause segmented disproportion and short stature. Eur J Pediatr 1993; 152: 293–296.
Zadik Z, Chalew S, Lhlekrhzk A. Effect of long term growth hormone therapy on bone age and pubertal maturationin boys with and without classic growth hormone deficiency. J Pediatr 1994; 125 (2): 189–195.
Sperlich M, Butenandt O, Schwarz HP, Butenandt O. Final height and predicted height in boys with untreated constitutional growth delay. Eur J Pediatr 1995; 154 (8): 627–632.
Rekers-Mombarg LT, Wit JM, Massa GG, et al. Spontaneous growth in idiopathic short stature. European Study Group. Arch Dis Child 1996; 75 (3): 175–180.
Tanaka T, Horikawa R, Mari S, et al. Increased pubertal height in non-GHD short children treated with combined GH and GnRH analogs. Abstract presented at the 6th joint meeting of the LWPES, and ESPE, Montreal, Canada July 6–10, 2001.
Kaplowitz PB. If gonadotropin-releasing hormone plus growth hormone (GH) really improves growth outcomes in short non-GH-deficient children, then what? (Editorial). J Clin Endocrinol Metab 2001; 86 (7): 2695–2698.
Hintz RL, Attie KM, Baptista J, Roche A. Effect of growth hormone treatment on adult height of children with idiopathic short stature. N Engl J Med 1999; 340 (7): 502–507.
Leshek EW, Rose SR, Yanovski JA, et al. Effect of growth hormone treatment on the final height of children with non-growth hormone-deficient short stature: a randomized, double-blind, placebo-controlled trial. abstract presented at the 6th joint Meeting of the LWPES and ESPE, Montreal Canada, July 6–10, 2001.
Guyda HJ. Growth Hormone treatment of Non-Growth hormone deficient Children with Short Stature. Clin Pediatr Endocrinol 1996; 5: 11–18.
Stabler B, Clopper RR, Stoppani C, Compton PG, Underwood LE. Academic achievement and psychological adjustment in short children. The National Cooperative Growth Study. J Dev Behav Pediatr 1994; 15 (1): 1–6.
Sandberg DE. Should short children who are not deficient in growth hormone deficient be treated? West J Med 2000; 172: 186–189.
Zimet GD, Cutler M, Litvene M, Dahms W, Owns R, Cuttler L. Psychosocial Adjustment of Children Evaluated for short stature: a preliminary report. J Dev Behav Pediatr 1995; 16 (4): 264–270.
Downie B, Mulligan J, McCaughey ES, Stratford RJ, Betts PR, Voss LD. Psychological response to growth hormone treatment in short normal children. Arch Dis Child 1996; 75 (32): 35.
Sandberg DE, Michael P. Psychosocial stresses related to short stature: does their presence imply psychiatric dysfunction? In: Drotar D, ed. Assessing pediatric health-related quality of life and functionnal status: implication for research, practice and policy. Lawrence Erlbaum, New Jersey 1998, pp. 287–312.
Sandberg DE, Brook AE, Campos SP. short stature: A psychosocial burden requiring growth hormone therapy? Pediatr 1994; 94 (6): 832–840.
Rekers-Mombarg, Busschbach JJ, Dicke J, Wit JM. Quality of life of young adults with idiopathic short stature: effect of growth hormone treatment. Dutch Growth Hormone Working Group. Acta Paediatrica 1998; 87 (8): 865–870.
Wilton P. Adverse events during GH treatment: 10 years’ experience in KIGS, a pharmacoepidemiological survey. Growth hormone therapy in KIGS- 10 years’ experience. Johann Ambrosius Barth Verlag, 1999; 349: 364.
Saenger P, Attie KM, DiMartino-Nardi J, Frahm L, Frane JW. Metabolic consequences of 5 year growth hormone (GH) therapy in children treated with GH for idiopathic short stature. J Clin Endocrinol Metab 1998; 83 (9): 115–120.
Giustina A, Veldhuis JD. Pathophysiology of the Neuroregulation of growth Hormone Secretion in Experimental Animals and the Human. Endocrine Rev 1998; 19 (6): 717–797.
Salvatori R, Hayashida CY, Aguiar-Oliveira MH, et al. Familial dwarfism due to a novel mutation of the growth hormone-releasing hormone receptor gene. J Clin Endocrinol Metab 1999; 84 (3): 917–923.
Bowers CY. Growth hormone releasing peptides (GHRP). Cellular and molecular life sciences. 1998; 54 (12): 1316–1329.
Howard AD, Feighner SD, Cully DF, et al. A Receptor in pituitary and hypothalamus that functions in growth hormone release. Science 1996; 273: 974–977.
Takaya K, Ariyasu H, Kanamoto N, et al. Ghrelin strongly stimulates growth hormone (GH) release in humans. J Clin Endocrinol Metab 2000; 85: 4908–4911.
Takahashi Y, Hidesuke K, Okimura Y, Goji K, Abe H, Chihara K. Brief report:Short stature caused by a mutant growth hormone 29. N Engl J Med 1996; 334 (7): 432–436.
Carlsson LM, Attie K, Compton PG, Vitangcol RV, Merimee TJ. Reduced concentration of growth hormone binding protein in children with idiopathic short stature J Clin Endocrinol Metab 1994; 78: 1325–1330.
Woods KA, Camacho-Hubner C, Savage MO, Clark AJL. Brief report: intrautrine growth retardation and post-natal growth failure asssociated with deletion of the insulin-like growth factor 1 gene. N Engl J Med 1996; 335 (18): 1363–1367.
Camacho-Hubner C, Woods KA, Miraki-Moud F, et al. Effects of recombinant human insulin-like growth factor (IGF-1) therapy on the growth hormone-IGF system of a patient with partial IGF-1 deletion. J Clin Endocrinol Metab 1999; 84 (5): 1611–1616.
Ranke MB, Aronson AS. Adult height in children with constitutional short stature. Acta Paediatr Scand 1989; 362: 27–31.
Blethen SL, Gaines S, Weldon V. Comparison of predicted and adult heights in short boys: effect of androgen therapy. Pediatr Res 1984; 467: 469.
Crowne ED, Shalet SM, Wallace WHB, Eminson DM, Price DA. Final height in boys with untreated constitutional delay of growth and puberty. Arch Dis Child 1990; 65: 1109–1112.
Crowne ED, Shalet SM, Wallace WHB, Eminson DM, Price DA. Final height in girls with untreated constitutional delay of growth and puberty. Eur J Pediatr 1990; 150: 708–712.
Bramswing JH, Frasse M, Holthoff ML, Von Lengerke HJ, Petrykowski W, Schellong G. Adult height in boys and girls with untreated short stature and constitutional delay of growth and puberty: accuracy of five different methods of height prediction. J Pediatr 1990; 117: 886–891.
LaFranchi S, Hanna C, Mandel S. Constitutional delay of growth: expected vs final adult height. Pediatr 1991; 87: 82–86.
Lopez-Siguerro JP, Garcia-Garcia E, Carralero I, Martinez-Aedo MJ. Adult height in children with idiopathic short stature treated with growth hormone 9. J Pediatr Endocrinol Metab 2000; 13 (9): 1595–1602.
McCaughey ES, Mulligan J, Voss LD, Betts PR. Randomised trial of growth hormone in short normal girls. Lancet 1998; 351: 940.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2003 Springer Science+Business Media New York
About this chapter
Cite this chapter
Desmangles, JC., Buchlis, J., MacGillivray, M.H. (2003). Growth Hormone Treatment of Children with Idiopathic Short Stature or Growth Hormone Sufficient Growth Failure. 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_3
Download citation
DOI: https://doi.org/10.1007/978-1-59259-336-1_3
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-61737-268-1
Online ISBN: 978-1-59259-336-1
eBook Packages: Springer Book Archive