Comparison of response to 2-years' growth hormone treatment in children with isolated growth hormone deficiency, born small for gestational age, idiopathic short stature, or multiple pituitary hormone deficiency: combined results from two large observational studies

Peter A Lee, Lars Sävendahl, Isabelle Oliver, Maithé Tauber, Oliver Blankenstein, Judith Ross, Marta Snajderova, Viatcheslav Rakov, Birgitte Tønnes Pedersen, Henrik Thybo Christesen, Peter A Lee, Lars Sävendahl, Isabelle Oliver, Maithé Tauber, Oliver Blankenstein, Judith Ross, Marta Snajderova, Viatcheslav Rakov, Birgitte Tønnes Pedersen, Henrik Thybo Christesen

Abstract

Background: Few studies have compared the response to growth hormone (GH) treatment between indications such as isolated growth hormone deficiency (IGHD), born small for gestational age (SGA), idiopathic short stature (ISS), and multiple pituitary hormone deficiency (MPHD). The aim of this analysis of data, collected from two large ongoing observational outcome studies, was to evaluate growth and insulin-like growth factor-I (IGF-I) response data for children of short stature with IGHD, MPHD, SGA, or ISS following two years of treatment with the recombinant GH product Norditropin® (Novo Nordisk A/S, Bagsværd, Denmark).

Methods: Analysis of auxologic data from two ongoing prospective observational studies, NordiNet® International Outcomes Study (NordiNet® IOS) and NovoNet®/American Norditropin®

Studies: Web-enabled Research (ANSWER) Program®.

Results: 4,582 children aged <18 years were included: IGHD, n = 3,298; SGA, n = 678; ISS, n = 334; and MPHD, n = 272. After two years' GH treatment, change in height standard deviation score (SDS) was +1.03 in SGA and +0.84 in ISS vs. +0.97 in IGHD (p = 0.047; p < 0.001 vs. IGHD, respectively). Height gain was comparable between IGHD and MPHD. In pre-pubertal children vs. total population, height SDS change after two years was: IGHD, +1.24 vs. +0.97; SGA, +1.17 vs. +1.03; ISS, +1.04 vs. +0.84; and MPHD, +1.16 vs. +0.99 (all p < 0.001).

Conclusions: After two years' GH treatment, change in height SDS was greater in SGA and less in ISS, compared with IGHD; the discrepancy in responses may be due to the disease nature or confounders (i.e. age). Height SDS increase was greatest in pre-pubertal children, supporting early treatment initiation to optimize growth outcomes.

Figures

Figure 1
Figure 1
Mean height SDS at baseline, one year and two years and change in height SDS at one year and two years by indication.
Figure 2
Figure 2
Mean IGF-I SDS at baseline, one year and two years by indication.

References

    1. Gharib H, Cook DM, Saenger PH. et al.American Association of Clinical Endocrinologists medical guidelines for clinical practice for growth hormone use in adults and children – 2003 update. Endocr Pract. 2003;9(1):64–76.
    1. Cohen P, Rogol AD, Deal CL. et al.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. doi: 10.1210/jc.2008-0509.
    1. Carel JC, Ecosse E, Nicolino M. et al.Adult height after long term treatment with recombinant growth hormone for idiopathic isolated growth hormone deficiency: observational follow up study of the French population based registry. Br Med J. 2002;325(7355):70. doi: 10.1136/bmj.325.7355.70.
    1. Takeda A, Cooper K, Bird A. et al.Recombinant human growth hormone for the treatment of growth disorders in children: a systematic review and economic evaluation. Health Technol Assess. 2010;14(42):1–209. iii–iv.
    1. Maghnie M, Ambrosini L, Cappa M. et al.Adult height in patients with permanent growth hormone deficiency with and without multiple pituitary hormone deficiencies. J Clin Endocrinol Metab. 2006;91(8):2900–2905. doi: 10.1210/jc.2006-0050.
    1. Bannink E, Djurhuus CB, Christensen T. et al.Adult height and health-related quality of life after growth hormone therapy in small for gestational age subjects. J Med Econ. 2010;13(2):221–227. doi: 10.3111/13696998.2010.484323.
    1. Bryant J, Baxter L, Cave CB, Milne R. Recombinant growth hormone for idiopathic short stature in children and adolescents. Cochrane Database Syst Rev. 2007;18(3):CD004440.
    1. Albertsson-Wikland K, Aronson AS, Gustafsson J. et al.Dose-dependent effect of growth hormone on final height in children with short stature without growth hormone deficiency. J Clin Endocrinol Metab. 2008;93(11):4342–4350. doi: 10.1210/jc.2008-0707.
    1. Dahlgren J, Wikland KA. Swedish Study Group for Growth Hormone Treatment. Final height in short children born small for gestational age treated with growth hormone. Pediatr Res. 2005;57(2):216–222. doi: 10.1203/01.PDR.0000148716.71231.81.
    1. Thomas M, Massa G, Bourguignon JP. et al.Final height in children with idiopathic growth hormone deficiency treated with recombinant human growth hormone: the Belgian experience. Horm Res. 2001;55(2):88–94. doi: 10.1159/000049976.
    1. Maiorana A, Cianfarani S. Impact of growth hormone therapy on adult height of children born small for gestational age. Pediatrics. 2009;124(3):e519–e531. doi: 10.1542/peds.2009-0293.
    1. Van Pareren Y, Mulder P, Houdijk M. et al.Adult height after long-term, continuous growth hormone (GH) treatment in short children born small for gestational age: results of a randomized, double-blind, dose–response GH trial. J Clin Endocrinol Metab. 2003;88(8):3584–3590. doi: 10.1210/jc.2002-021172.
    1. Reiter EO, Price DA, Wilton P. et al.Effect of growth hormone (GH) treatment on the near-final height of 1258 patients with idiopathic GH deficiency: analysis of a large international database. J Clin Endocrinol Metab. 2006;91(6):2047–2054. doi: 10.1210/jc.2005-2284.
    1. Rappaport R, Mugnier E, Limoni C. French Serono Study Group. A 5-year prospective study of growth hormone (GH)-deficient children treated with GH before the age of 3 years. J Clin Endocrinol Metab. 1997;82(2):452–456. doi: 10.1210/jc.82.2.452.
    1. Cohen P, Germak J, Rogol AD. et al.Variable degree of growth hormone (GH) and insulin-like growth factor (IGF) sensitivity in children with idiopathic short stature compared with GH-deficient patients: evidence from an IGF-based dosing study of short children. J Clin Endocrinol Metab. 2010;95(5):2089–2098. doi: 10.1210/jc.2009-2139.
    1. Högler W, Briody J, Moore B. et al.Effect of growth hormone therapy and puberty on bone and body composition in children with idiopathic short stature and growth hormone deficiency. Bone. 2005;37(5):642–650. doi: 10.1016/j.bone.2005.06.012.
    1. Centers for Disease Control and Prevention. Percentile data files with LMS values. , ; . Accessed 16 December 2010.
    1. Brabant G, von zur Mühlen A, Wüster C. et al.Serum insulin-like growth factor I reference values for an automated chemiluminescence immunoassay system: results from a multicenter study. Horm Res. 2003;60(2):53–60. doi: 10.1159/000071871.
    1. Ross J, Lee PA, Gut R, Germak J. Factors influencing the one- and two-year growth response in children treated with growth hormone: analysis from an observational study. Int J Pediatr Endocrinol. 2010;2010:494656. doi: 10.1186/1687-9856-2010-494656.
    1. 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. doi: 10.1210/jc.2007-1581.
    1. Ranke MB, Lindberg A, Price DA. 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. doi: 10.1159/000098707.
    1. Clayton PE, Cianfarani S, Czernichow P. et al.Management of the child born small for gestational age through to adulthood: a consensus statement of the International Societies of Pediatric Endocrinology and the Growth Hormone Research Society. J Clin Endocrinol Metab. 2007;92(3):804–810.
    1. Ranke MB, Lindberg A, Ferrández Longás A. et al.Major determinants of height development in Turner syndrome (TS) patients treated with GH: analysis of 987 patients from KIGS. Pediatr Res. 2007;61(1):105–110. doi: 10.1203/01.pdr.0000250039.42000.c9.
    1. de Ridder MA, Stijnen T, Hokken-Koelega AC. Prediction model for adult height of small for gestational age children at the start of growth hormone treatment. J Clin Endocrinol Metab. 2008;93(2):477–483. doi: 10.1210/jc.2007-1381.
    1. Soriano-Guillen L, Coste J, Ecosse E. et al.Adult height and pubertal growth in Turner syndrome after treatment with recombinant growth hormone. J Clin Endocrinol Metab. 2005;90(9):5197–5204. doi: 10.1210/jc.2005-0470.
    1. Cohen P, Rogol AD, Howard CP. et al.Insulin growth factor-based dosing of growth hormone therapy in children: a randomized, controlled study. J Clin Endocrinol Metab. 2007;92(7):2480–2486. doi: 10.1210/jc.2007-0204.
    1. Wit JM, Clayton PE, Rogol AD. et al.Idiopathic short stature: definition, epidemiology, and diagnostic evaluation. Growth Horm IGF Res. 2008;18(2):89–110. doi: 10.1016/j.ghir.2007.11.004.
    1. Bang P. Principles of growth hormone and insulin-like growth factor-I treatment in children with idiopathic short stature. Horm Res Paediatr. 2011;76(Suppl 3):24–26.
    1. Wilson TA, Rose SR, Cohen P. et al.Update of guidelines for the use of growth hormone in children: the Lawson Wilkins Pediatric Endocrinology Society Drug and Therapeutics Committee. J Pediatr. 2003;143(4):415–421. doi: 10.1067/S0022-3476(03)00246-4.
    1. Romano AA, Dana K, Bakker B. et al.Growth response, near-adult height, and patterns of growth and puberty in patients with noonan syndrome treated with growth hormone. J Clin Endocrinol Metab. 2009;94(7):2338–2344. doi: 10.1210/jc.2008-2094.
    1. Bell J, Parker KL, Swinford RD. et al.Long-term safety of recombinant human growth hormone in children. J Clin Endocrinol Metab. 2010;95(1):167–177. doi: 10.1210/jc.2009-0178.

Source: PubMed

Sponsors et collaborateurs

Les conditions médicales

Interventions en matière de drogue

3
S'abonner