The efficacy and safety of recombinant growth hormone in children with idiopathic short stature (two-year experience)

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This study was designed to evaluate the efficacy and safety of the treatment of children with idiopathic short stature using recombinant growth hormone (rGH); in addition, the factors influencing its therapeutic efficiency were analysed. A total of 93 patients aging from 3 to 12 years were available for the observation. They were divided into three groups. The children in group 1 (n=38 ) were given rGH at a dose of 0.033 mg/kg/24 hours and in group 2 (n=18 ) at 0.05 mg/kg/24 hr; the control group 3 was comprised of 37 children. The duration of therapy was 6 months in 56 children, 12 months in 41, 18 months in 24, and 24 months in 18 children. The end points of the study were bone age variations; dynamics of insulin-like growth factor-1 levels; characteristics of carbohydrate, lipid, and phosphorus-calcium metabolism; hepatic, renal, and thyroid function. The growth rate within the first year after the onset of the treatment increased from 4.5±1.2 to 7.9±1.5 cm/year in group 1 (0.033 mg/kg/24 hours) and from 9.1±1.5 cm/year in group 2 (0.05 mg/kg/24 hr). In the second year, the growth rate under effect of the same GH doses was 7.1±1.4 and 7.9±1.6 cm/year respectively. The total growth rate ΔSDS for the first year of therapy was 0,56±0,28 (0,033 mg/kg/24 hr) and 0,71±0,22 (0,05 mg/kg/24 hr), the respective ΔSDS values in the second year were 0,94±0,29 and 1,06±0,67. Neither the growth rate nor the failure to thrive changed significantly in the control group. The growth rate in the treated children correlated with their age at the onset of therapy (r = –0.28, p= –0.045; n=56) and the dose of GH (r=0.32, p<=0.043; n=41); in addition, there was correlation between the growth rate ΔSDS values and the age at the onset of therapy (r=–0.50, p=0.0002; n=56). 21% of the children reached the normal growth range (>–2ΔSDS) 6 months after the beginning of therapy, 30% and 37% after 1 and 2 years respectively. None of the patients in the control group showed the normal growth. Some of them underwent accelerated bone maturation, and their growth prognosis (calculated according to Bayley-Pinneau) was improved. The IGF-1 level in the treated patients increased within the normal range but did not correlate with the efficacy of therapy. Nor were apparent changes recorded in the characteristics of carbohydrate, lipid, and phosphorus-calcium metabolism. It is concluded that the growth-stimulating treatment of children with idiopathic short stature using rGH at a dose range from 0.033 to 0.05 mg/kg/24 hours significantly increased the growth rate and dynamics. The main factors determining the therapeutic efficacy of rGH are the age of the patients at which the treatment is initiated and the calculated rGH dose.

A N Shandin

E V Nagaeva

V A Peterkova

I I Dedov

  • Consensus Statement on the Diagnosis and Treatment of Children with Idiopathic Short Stature: A Summary of the Growth Hormone Research Society, the Lawson Wilkins Pediatric Endocrine Society and the European Society for Paediatric Endocrinology Workshop. J Clin Endocrinol Metab 2008;93:11:4210-4217.
  • Шандин А.Н., Петеркова В.А. Классификация, диагностика и лечение идиопатической низкорослости. Пробл эндокринол 2009;55:4:36-44.
  • Tanner J.M., Whitehouse R.H. Arch Dis Child 1976;51:3:170-179.
  • Gerver W.J.M., de Bruin R. Paediatric Morphometrics, a reference manual. 2nd ed. University press Maastricht 2001.
  • Niklasson A., Albertsson-Wikland K. Continuous growth reference from 24th week of gestation to 24 months by gender. BMC Pediat 2008;8:8.
  • Ranke M.B. Towards a consensus on the definition of idiopathic short stature. Horm Res 1996;45:Suppl 2:64-66.
  • Wit J.M., Reiter E.O., Ross J.L. et al. Idiopathic short stature: management and growth hormone treatment. Growth Horm IGF Res 2008;18:2:111-135.
  • Greulich W.W., Pyle S.I. Radiographic atlas of skeletal development of the hand and wrist. 2nd ed. Stanford 1959.
  • Marshall W.A., Tanner J.M. Variations in the pattern of pubertal changes in boys. Arch Dis Child 1970;45:239:13-23.
  • Lofqvist C., Andersson E., Gelander L. et al. Reference values for IGF-I throughout childhood and adolescence: a model that accounts simultaneously for the effect of gender, age, and puberty. J Clin Endocrinol Metab 2001;86:12:5870-5876.
  • Bakker B., Frane J., Anhalt H. et al. Height velocity targets from the national cooperative growth study for first-year growth hormone responses in short children. J Clin Endocrinol Metab 2008;93:2:352-357.
  • Bryant J., Baxter L., Cave C.B., Milne R. Recombinant growth hormone for idiopathic short stature in children and adolescents. Cochrane Database Syst Rev 2007;3:CD004440.
  • Finkelstein B.S., Imperiale T.F., Speroff T. et al. Effect of growth hormone therapy on height in children with idiopathic short stature: a meta-analysis. Arch Pediat Adolesc Med 2002;156:3:230-240.
  • Hintz R.L. Growth hormone treatment of idiopathic short stature: clinical studies. Growth Horm. IGF Res 2005;15:Suppl A:S6-S8.
  • Hintz R.L., Attie K.M., Baptista J., Roche A. Effect of growth hormone treatment on adult height of children with idiopathic short stature. Genentech Collaborative Group. N Engl J Med 1999;340:7:502-507.
  • Hopwood N.J., Hintz R.L., Gertner J.M. et al. Growth response of children with non-growth-hormone deficiency and marked short stature during three years of growth hormone therapy. J Pediatr 1993;123:2:215-222.
  • Kemp S.F. Growth hormone treatment of idiopathic short stature: History and demographic data from the NCGS. Growth Horm. IGF Res 2005;15:Suppl A:S9-S12.
  • Kemp S.F., Kuntze J., Attie K.M. et al. Efficacy and safety results of long-term growth hormone treatment of idiopathic short stature. J Clin Endocrinol Metab 2005;90:9:5247-5253.
  • Leschek E.W., Rose S.R., Yanovski J.A. et al. Effect of growth hormone treatment on adult height in peripubertal children with idiopathic short stature: a randomized, double-blind, placebo-controlled trial. J Clin Endocrinol Metab 2004;89:7:3140-3148.
  • Moore W.V., Moore K.C., Gifford R. et al. Long-term treatment with growth hormone of children with short stature and normal growth hormone secretion. J Pediatr 1992;120:5:702-708.
  • Quigley C.A., Gill A.M., Crowe B.J. et al. Safety of growth hormone treatment in pediatric patients with idiopathic short stature. J Clin Endocrinol Metab 2005;90:9:5188-5196.
  • Rekers-Mombarg L.T., Massa G.G., Wit J.M. et al. Growth hormone therapy with three dosage regimens in children with idiopathic short stature. European Study Group Participating Investigators. J Pediat 1998;123:3:Pt 1:455-460.
  • Saenger P., Attie K.M., DiMartino-Nardi J. et al. Metabolic consequences of 5-year growth hormone (GH) therapy in children treated with GH for idiopathic short stature. Genentech Collaborative Study Group. J Clin Endocrinol Metab 1998;83:9:3115-3120.
  • Wit J.M., Rekers-Mombarg L.T. Dutch Growth Hormone Advisory Group. Final height gain by GH therapy in children with idiopathic short stature is dose dependent. J Clin Endocrinol Metab 2002;87:2:604-611.
  • Wit J.M., Rekers-Mombarg L.T., Cutler G.B. et al. Growth hormone (GH) treatment to final height in children with idiopathic short stature: evidence for a dose effect. J Pediat 2005;146:1:45-53.
  • Солтаханов Э.М. Семейная низкорослость: патогенез, оптимизация методов диагностики и лечения: Автореф. дис. ... канд. мед. наук. М 1996.
  • Wit J.M., Clayton P.E., Rogol A.D. et al. Idiopathic short stature: definition, epidemiology, and diagnostic evaluation. Growth Horm. IGF Res 2008;18:2:89-110.
  • Kamp G.A., Waelkens J.J., de Muinck Keizer-Schrama S.M. et al. High dose growth hormone treatment induces acceleration of skeletal maturation and an earlier onset of puberty in children with idiopathic short stature. Arch Dis Child 2002;87:3:215-220.
  • Ranke M.B., Lindberg A., Price D.A. et al. Age at growth hormone therapy start and first-year responsiveness to growth hormone are major determinants of height outcome in idiopathic short stature. Horm Res 2007;68:2:53-62.
  • Crofton P.M., Stirling H.F., Kelnar J.H. Bone alkaline phosphatase and height velocity in short normal children undergoing growth-promoting treatment: longitudinal study. Clin Chem 1995;41:5:672-678.
  • Crofton P.M., Stirling H.F., Schonau E., Kelnar C.J. Bone alkaline phosphatase and collagen markers as early predictors of height velocity response to growth-promoting treatments in short normal children. Clin Endocrinol (Oxf) 1995;44:4:385-394.


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CrossRef     1 citations

  • Samson O, Sprynchuk N, Bolshova O. Actual questions of diagnosis and treatment of idiopathic short stature in children. Reports of the National Academy of Sciences of Ukraine. 2017;(4):96. doi: 10.15407/dopovidi2017.04.096

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