An Analysis of the Clinical and Cost Effectiveness of Growth Hormone Replacement Therapy before and during Puberty: Should We Increase the Dose?Howard S.R.a · Butler G.E.a, b
aUCL Institute of Child Health and bUniversity College Hospital, London, UK
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Article / Publication Details
Aim: To investigate the influence of growth hormone (GH) on linear growth before and during puberty in children with GH deficiency. Methods: We analysed the relationship between pubertal growth and GH dose in a large dataset of children (n = 236) with GH deficiency using multiple linear regression and multilevel modelling with repeated measures analysis. Additionally, we examined the cost benefit of increasing doses of GH during puberty. Results: Multilevel modelling revealed a highly significant role for GH dose in the pre-pubertal period (p < 0.001), but a non-significant effect on height gain after pubertal onset (p = 0.32). Important predictors of height gain after puberty onset included gender, age at puberty and number of injections of GH/week. Cost analysis showed that in an average child use of high dose GH, at an extra EUR 5,925 (GBP 4,753/USD 7,538)/year, would produce a height gain of 0.80 cm/year (above baseline growth) pre-pubertally, compared to only 0.20 cm/year post-puberty onset. Conclusions: The influence of GH dose on height gain after puberty onset is at best a modest one. Cost analysis shows use of high doses of GH post-puberty onset has significant cost implications without providing a worthwhile gain in adult height for children with GH deficiency.
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- Ranke M, Lindberg M: Observed and predicted total pubertal growth during treatment with growth hormone in adolescents with idiopathic growth hormone deficiency, Turner syndrome, short stature, born small for gestational age and idiopathic short stature: KIGS analysis and review. Horm Res Paediatr 2011;75:423-432.
- Carel JC: Can we increase adolescent growth? Eur J Endocrinol 2004;151(suppl 3):U101-U108.
- Ranke MB, Lindberg A, Martin DD, Bakker B, Wilton P, Albertsson-Wikland K, Cowell CT, Price DA, Reiter EO: The mathematical model for total pubertal growth in idiopathic growth hormone (GH) deficiency suggests a moderate role of GH dose. J Clin Endocrinol Metab 2003;88:4748-4753.
- Gasser T, Sheehy A, Molinari L, Largo RH: Growth of early and late maturers. Ann Hum Biol 2001;28:328-336.
- Martha P, Rogol A, Veldhius J, Keerigan J, Godman D, Blizzard R: Alterations in the pulsatile properties of circulating growth hormone concentrations during puberty in boys. J Clin endocrinol Metab 1989;69:563-570.
- Cohen P, Rogol AD, Howard CP, Bright GM, Kappelgaard AM, Rosenfeld RG: Insulin growth factor-based dosing of growth hormone therapy in children: a randomized, controlled study. J Clin Endocrinol Metab 2007;92:2480-2486.
- Kriström B, Aronson AS, Dahlgren J, Gustafsson J, Halldin M, Ivarsson SA, Nilsson NO, Svensson J, Tuvemo T, Albertsson-Wikland K: Growth hormone (GH) dosing during catch-up growth guided by individual responsiveness decreases growth response variability in prepubertal children with GH deficiency or idiopathic short stature. J Clin Endocrinol Metab 2009;94:483-490.
- Lenko HL, Leisti S, Perheentupa J: The efficacy of growth hormone in different types of growth failure. An analysis of 101 cases. Eur J Pediatr 1982;138:241-249.
- Tanner JM, Whitehouse TJ, Hughes PCR, Carter BS: Relative importance of growth hormone and sex steroids for the growth at puberty of trunk length, limb length, and muscle width in growth hormone deficient children. J Pediatr 1976;89:1000-1008.
- Ranke MB, Lindberg A, Chatelain P, Wilton P, Cutfield W, Albertsson-Wikland K, Price DA: Derivation and validation of a mathematical model for predicting the response to exogenous recombinant human growth hormone (GH) in prepubertal children with idiopathic GH deficiency. J Clin Endocrinol Metab 1999;84:1174-1183.
- Coelho R, Brook CGD, Preece MA, Stanhope RG, Dattani MT, Hindmarsh PC: A randomized study of two doses of biosynthetic human growth hormone on final height of pubertal children with growth hormone deficiency. Horm Res 2008;70:85-88.
- Mauras N, Attie KM, Reiter EO, Saenger P, Baptista J: High dose recombinant human growth hormone (GH) treatment of GH-deficient patients in puberty increases near-final height: a randomized, multicenter trial. Genentech, Inc, Cooperative Study Group. J Clin Endocrinol Metab 2000;85:3653-3660.
- Riddick L, Alter C, Davis DA, Frane J, Lippe B, Bakker B: A stepwise increase in recombinant human growth hormone dosing during puberty achieves improved pubertal growth: a National Cooperative Growth Study report. J Pediatr Endocrinol Metab 2009;22:623-628.
- Cole TJ: The LMS method for constructing normalized growth standards. Eur J Clin Nutr 1990;44:45-60.
- Peugh JL: A practical guide to multilevel modeling. Sch Psychol 2010;48:85-112.
NICE Guideline: Human growth hormone (somatropin) for the treatment of growth failure in children (review). www.nice.org.uk/guidance/TA188.
- Sävendahl L, Maes M, Albertsson-Wikland K, Borgström B, Carel JC, Henrard S, Speybroeck N, Thomas M, Zandwijken G, Hokken-Koelega A: Long-term mortality and causes of death in isolated GHD, ISS, and SGA patients treated with recombinant growth hormone during childhood in Belgium, The Netherlands, and Sweden: preliminary report of 3 countries participating in the EU SAGhE study. J Clin Endocrinol Metab 2012;97:E213-E217.
- Carel JC, Ecosse E, Landier F, Meguellati-Hakkas D, Kaguelidou F, Rey G, Coste J: Long-term mortality after recombinant growth hormone treatment for isolated growth hormone deficiency or childhood short stature: preliminary report of the French SAGhE study. J Clin Endocrinol Metab 2012;97:416-425.
- Ranke MB: Clinical considerations in using growth hormone therapy in growth hormone deficiency. Endocr Dev 2010;18:83-91.
- Gasser T, Müller HG, Köhler W, Prader A, Largo R, Molinari L: An analysis of the mid-growth and adolescent spurts of height based on acceleration. Ann Hum Biol 1985;12:129-148.
- Russell M, Breggia A, Mendes N, Klibanski A, Misra M: Growth hormone is positively associated with surrogate markers of bone turnover during puberty. Clin Endocrinol (Oxf) 2011;75:482-488.
- Jürimäe J, Mäestu J, Jürimäe T: Bone turnover markers during pubertal development: relationships with growth factors and adipocytokines. Med Sport Sci 2010;55:114-127.
- Bourguignon JP: Linear growth as a function of age at onset of puberty and sex steroid dosage: therapeutic implications. Endocr Rev 1988;9:467-488.
- Ranke MB, Price DA, Albertsson-Wikland K, Maes M, Lindberg A: Factors determining pubertal growth and final height in growth hormone treatment of idiopathic growth hormone deficiency. Analysis of 195 patients of the Kabi Pharmacia International Growth Study. Horm Res 1997;48:62-71.
- Vizmanos B, Martí-Henneberg C, Clivillé R, Moreno A, Fernández-Ballart J: Age of pubertal onset affects the intensity and duration of pubertal growth peak but not final height. Am J Hum Biol 2001;13:409-416.
- Bourguignon JP: Growth and timing of puberty: reciprocal effects. Horm Res 1991;36:131-135.
- Karlberg J, Kwan CW, Gelander L, Albertsson-Wikland K: Pubertal growth assessment. Horm Res 2003;60(suppl 1):27-35.
- Price DA, Shalet SM, Clayton PE: Management of idiopathic growth hormone deficient patients during puberty. Acta Paediatr Scand 1988;347(suppl):44-51.
- Grumbach MM, Bin-Abbas BS, Kaplan SL: The growth hormone cascade: progress and long-term results of growth hormone treatment in growth hormone deficiency. Horm Res 1998;49(suppl 2):41-57.
- Vosahlo J, Zidek T, Lebl J, Riedl S, Frisch H: Validation of a mathematical model predicting the response to growth hormone treatment in prepubertal children with idiopathic growth hormone deficiency. Horm Res 2004;61:143-147.
- De Muinck Keizer-Schrama SM, Rikken B, Wynne HJ, Hokken-Koelega AC, Wit JM, Bot A, Drop SL: Dose-response study of biosynthetic human growth hormone (GH) in GH-deficient children: effects on auxological and biochemical parameters. Dutch Growth Hormone Working Group. J Clin Endocrinol Metab 1992;74:898-905.
- Reiter EO, Price DA, Wilton P, Albertson-Wikland K, Ranke MB: Effect of growth hormone (GH) treatment on the final height of 1258 patients with idiopathic growth hormone deficiency: analysis of a large international database. J Clin Endocrinol Metab 2006;91:795-796.
- Matsumoto K: Secular acceleration of growth in height in Japanese and its social background. Ann Hum Biol 1982;9:399-410.
- Lustig RH: Optimizing growth hormone efficacy: an evidence-based analysis. Horm Res 2004;62(suppl 3):93-97.
- Rachmiel M, Rota V, Atenafu E, Daneman D, Hamilton J: Final height in children with idiopathic growth hormone deficiency treated with a fixed dose of recombinant growth hormone. Horm Res 2007;68:236-243.
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