Treatment of short stature and growth hormone deficiency in children with somatotropin (rDNA origin)

Dana S Hardin, Dana S Hardin

Abstract

Somatotropin (growth hormone, GH) of recombinant DNA origin has provided a readily available and safe drug that has greatly improved management of children and adolescents with GH deficiency (GHD) and other disorders of growth. In the US and Europe, regulatory agencies have given approval for the use of GH in children and adults who meet specific criteria. However, clinical and ethical controversies remain regarding the diagnosis of GHD, dosing of GH, duration of therapy and expected outcomes. Areas which also require consensus include management of pubertal patients, transitioning pediatric patients to adulthood, management of children with idiopathic short stature and the role of recombinant IGF-1 in treatment. Additionally, studies have demonstrated anabolic benefits of GH in children who have inflammatory-based underlying disease and efficacy of GH in overcoming growth delays in people treated chronically with corticosteroids. These areas are open for possible new uses of this drug. This review summarizes current indications for GH use in children and discusses areas of clinical debate and potential anabolic uses in chronic illness.

Keywords: children; growth hormone deficiency; short stature; somatotropin.

References

    1. Alemzadeh R, Upchurch L, McCarthy V. Anabolic effects of growth hormone treatment in young children with cystic fibrosis. J Am Coll Nutr. 1998;17:419–24.
    1. Allen DB, Carrel AL. Growth hormone therapy for Prader-Willi syndrome: a critical appraisal. J Pediatr Endocrinol Metab. 2004;17(Suppl 4):1297–306.
    1. Allen DB, Fost N. hGH for short stature: ethical issues raised by expanded access. J Pediatr. 2004;144:648–52.
    1. Allen DB, Julius JR, Breen TJ, et al. Treatment of glucocorticoid-induced growth suppression with growth hormone. National Cooperative Growth Study. J Clin Endocrinol Metab. 1998;83:2824–9.
    1. Arends NJ, Boonstra VH, Mulder PG, et al. GH treatment and its effect on bone mineral density, bone maturation and growth in short children born small for gestational age: 3-year results of a randomized, controlled GH trial. Clin Endocrinol Oxf. 2003;59:779–87.
    1. Arpadi SM, Cuff PA, Kotler DP, et al. Growth velocity, fat-free mass and energy intake are inversely related to viral load in HIV-infected children. J Nutr. 2000;130:2498–502.
    1. Asokan S, Muthu MS, Rathna Prabhu V. Noonan syndrome: a case report. J Indian Soc Pedod Prev Dent. 2007;25:144–7.
    1. Bechtold S, Ripperger P, Bonfig W, et al. Growth hormone changes bone geometry and body composition in patients with juvenile idiopathic arthritis requiring glucocorticoid treatment: a controlled study using peripheral quantitative computed tomography. J Clin Endocrinol Metab. 2005;90:3168–73.
    1. Bell JJ, Bolar K, Swinford RD, et al. Long-term safety of recombinant human growth hormone: the National Cooperative Growth Study Experience [poster]. 87th Annual Meeting of the Endocrine Society; June 4–7, 2005; San Diego, CA. 2005. pp. 2–450.
    1. Blethen SL, Allen DB, Graves D, et al. Safety of recombinant deoxyribonucleic acid-derived growth hormone: The National Cooperative Growth Study experience. J Clin Endocrinol Metab. 1996;81:1704–10.
    1. Boguszewski CL, Meister LH, Zaninelli DC, et al. One year of GH replacement therapy with a fixed low-dose regimen improves body composition, bone mineral density and lipid profile of GH-deficient adults. Eur J Endocrinol. 2005;152:67–75.
    1. Boonstra V, Van Pareren Y, Mulder P, et al. Puberty in growth hormone-treated children born small for gestational age SGA. J Clin Endocrinol Metab. 2003;88:5753–8.
    1. Carrel AL, Moerchen V, Myers SE, et al. Growth hormone improves mobility and body composition in infants and toddlers with Prader-Willi syndrome. J Pediatr. 2004;145:744–9.
    1. Carrel AL, Myers SE, Whitman BY, et al. Growth hormone improves body composition, fat utilization, physical strength and agility, and growth in Prader-Willi syndrome: A controlled study. J Pediatr. 1999;134:215–21.
    1. Carrel AL, Myers SE, Whitman BY, et al. Sustained benefits of growth hormone on body composition, fat utilization, physical strength and agility, and growth in Prader-Willi syndrome are dose-dependent. J Pediatr Endocrinol Metab. 2001;14:1097–105.
    1. Carrel AL, Myers SE, Whitman BY, et al. Benefits of long-term GH therapy in Prader-Willi syndrome: a 4-year study. J Clin Endocrinol Metab. 2002;87:1581–5.
    1. Chernausek SD, Attie KM, Cara JF, et al. Growth hormone therapy of Turner syndrome: the impact of age of estrogen replacement on final height. Genentech, Inc., Collaborative Study Group. J Clin Endocrinol Metab. 2000;85:2439–45.
    1. Clayton PE, Cuneo RC, Juul A, et al. Consensus statement on the management of the GH-treated adolescent in the transition to adult care. Eur J Endocrinol. 2005;152:165–70.
    1. Codner E, Mericq V, Cassorla F. Optimizing growth hormone therapy during puberty. Horm Res. 1997;48(Suppl 5):16–20.
    1. Colao A, Di Somma C, Pivonello R, et al. The cardiovascular risk of adult GH deficiency GHD. improved after GH replacement and worsened in untreated GHD: a 12-month prospective study. J Clin Endocrinol Metab. 2002;87:1088–93.
    1. Dahlgren J, Wikland KA. Final height in short children born small for gestational age treated with growth hormone. Pediatr Res. 2005;57:216–22.
    1. Davenport ML, Crowe BJ, Travers SH, et al. Growth hormone treatment of early growth failure in toddlers with Turner syndrome: a randomized, controlled, multicenter trial. J Clin Endocrinol Metab. 2007;92:3406–16.
    1. Davenport ML, Quigley CA, Bryant CG, et al. Effects of early growth hormone GH. treatment in very young girls with Turner Syndrome TS. Presented at 7th Join ESPE/LWPES Meeting; Lyon, France. 2005.2005.
    1. Drake WM, Howell SJ, Monson JP, et al. Optimizing GH therapy in adults and children. Endocr Rev. 2001;22:425–50.
    1. Eiholzer U. Deaths in children with Prader-Willi syndrome. A contribution to the debate about the safety of growth hormone treatment in children with PWS. Horm Res. 2005;63:33–9.
    1. Ferreira LV, Souza SA, Arnhold IJ, et al. PTPN11 protein tyrosine phosphatase, nonreceptor type 11. mutations and response to growth hormone therapy in children with Noonan syndrome. J Clin Endocrinol Metab. 2005;90:5156–60.
    1. Fine RN, Kohaut EC, Brown D, et al. Growth after recombinant human growth hormone treatment in children with chronic renal failure: report of a multicenter randomized double-blind placebo-controlled study. Genentech Cooperative Study Group. J Pediatr. 1994a;124:374–82.
    1. Fine RN, Yadin O, Moulton L, et al. Five years experience with recombinant human growth hormone treatment of children with chronic renal failure. J Pediatr Endocrinol. 1994b;7:1–12.
    1. Finkelstein BS, Imperiale TF, Speroff T, et al. Effect of growth hormone therapy on height in children with idiopathic short stature: a meta-analysis. Arch Pediatr Adolesc Med. 2002;156:230–40.
    1. Goldstone AP. Prader-Willi syndrome: advances in genetics, pathophysiology and treatment. Trends Endocrinol Metab. 2004;15:12–20.
    1. Growth Hormone Research Society Consensus guidelines for the diagnosis and treatment of growth hormone GH. deficiency in childhood and adolescence: summary statement of the GH Research Society. J Clin Endocrinol Metab. 2000;85:3990–3.
    1. Growth Hormone Research Society Critical evaluation of the safety of recombinant human growth hormone administration: statement from the Growth Hormone Research Society. J Clin Endocrinol Metab. 2001;86:1868–70.
    1. Gunay-Aygun M, Schwartz S, Heeger S, et al. The changing purpose of Prader-Willi syndrome clinical diagnostic criteria and proposed revised criteria. Pediatrics. 2001;108:E92.
    1. Haffner D, Schaefer F, Nissel R, et al. Effect of growth hormone treatment on the adult height of children with chronic renal failure. German Study Group for Growth Hormone Treatment in Chronic Renal Failure. N Engl J Med. 2000;343:923–30.
    1. Haqq AM, Stadler DD, Jackson RH, et al. Effects of growth hormone on pulmonary function, sleep quality, behavior, cognition, growth velocity, body composition, and resting energy expenditure in Prader-Willi syndrome. J Clin Endocrinol Metab. 2003;88:2206–12.
    1. Hardin DS, Adams-Huet B, Brown D, et al. Growth hormone treatment improves growth and clinical status in prepubertal children with cystic fibrosis: results of a multicenter randomized controlled trial. J Clin Endocrinol Metab. 2006;91:4925–9.
    1. Hardin DS, Ellis KJ, Dyson M, et al. Growth hormone improves clinical status in prepubertal children with cystic fibrosis: results of a randomized controlled trial. J Pediatr. 2001;139:636–42.
    1. Hardin DS, Rice J, Ahn C, et al. Growth hormone treatment enhances nutrition and growth in children with cystic fibrosis receiving enteral nutrition. J Pediatr. 2005a;146:324–8.
    1. Hardin DS, Rice J, Doyle ME, et al. Growth hormone improves protein catabolism and growth in prepubertal children with HIV infection. Clin Endocrinol Oxf. 2005b;63:259–62.
    1. Hardin DS, Stratton R, Kramer JC, et al. Growth hormone improves weight velocity and height velocity in prepubertal children with cystic fibrosis. Horm Metab Res. 1998;30:636–41.
    1. Hardin DS, Woo J, Butsch R, et al. Current prescribing practices and opinions about growth hormone therapy: results of a nationwide survey of paediatric endocrinologists. Clin Endocrinol Oxf. 2007;66:85–94.
    1. Harris M, Hofman PL, Cutfield WS. Growth hormone treatment in children: review of safety and efficacy. Paediatr Drugs. 2004;6:93–106.
    1. Hintz RL. The prismatic case of Creutzfeldt-Jakob disease associated with pituitary growth hormone treatment. J Clin Endocrinol Metab. 1995;80:2298–301.
    1. Hintz RL, Attie KM, Baptista J, et al. Effect of growth hormone treatment on adult height of children with idiopathic short stature. Genentech Collaborative Group. N Engl J Med. 1999;340:502–7.
    1. Hokken-Koelega A, Mulder P, De Jong R, et al. Long-term effects of growth hormone treatment on growth and puberty in patients with chronic renal insufficiency. Pediatr Nephrol. 2000;14:701–6.
    1. Hokken-Koelega AC, De Ridder MA, Lemmen RJ, et al. Children born small for gestational age: do they catch up? Pediatr Res. 1995;38:267–71.
    1. Johann-Liang R, O’Neill L, Cervia J, et al. Energy balance, viral burden, insulin-like growth factor-1, interleukin-6 and growth impairment in children infected with human immunodeficiency virus. Aids. 2000;14:683–90.
    1. Juul A, Bang P, Hertel NT, et al. Serum insulin-like growth factor-I in 1030 healthy children, adolescents, and adults: relation to age, sex, stage of puberty, testicular size, and body mass index. J Clin Endocrinol Metab. 1994;78:744–52.
    1. Kelnar CJ. Growth hormone therapy for syndromic disorders. Clin Endocrinol Oxf. 2003a;59:12–21.
    1. Kelnar CJ. The role of somatropin therapy in children with Noonan syndrome. Treat Endocrinol. 2003b;2:165–72.
    1. Kemp SF, Kuntze J, Attie KM, et al. Efficacy and safety results of long-term growth hormone treatment of idiopathic short stature. J Clin Endocrinol Metab. 2005;90:5247–53.
    1. Kirk JM, Betts PR, Butler GE, et al. Short stature in Noonan syndrome: response to growth hormone therapy. Arch Dis Child. 2001;84:440–3.
    1. Kuizon BD, Salusky IB. Growth retardation in children with chronic renal failure. J Bone Miner Res. 1999;14:1680–90.
    1. Lanes R, Paoli M, Carrillo E, et al. Cardiovascular risk of young growth-hormone-deficient adolescents. Differences in growth-hormone-treated and untreated patients. Horm Res. 2003;60:291–6.
    1. Lee PA, Chernausek SDHokken-Koelega AC, et al. International Small for Gestational Age Advisory Board consensus development conference statement: management of short children born small for gestational age, April 24-October 1, 2001. Pediatrics. 2003;111:1253–61.
    1. Leschek EW, Rose SR, Yanovski JA, 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;89:3140–8.
    1. Levy RA, Connelly K. Diagnostic growth hormone deficiency testing practices among patients in the NCGS/NCSS databases. J Pediatr Endocrinol Metab. 2003;16(Suppl 3):619–24.
    1. Lindgren AC, Ritzen EM. Five years of growth hormone treatment in children with Prader-Willi syndrome. Swedish National Growth Hormone Advisory Group. Acta Paediatr Suppl. 1999;88:109–11.
    1. Lindsay R, Feldkamp M, Harris D, et al. Utah Growth Study: growth standards and the prevalence of growth hormone deficiency. J Pediatr. 1994;125:29–35.
    1. MaCgillivray MH, Baptista J, Johanson A. Outcome of a four-year randomized study of daily versus three times weekly somatropin treatment in prepubertal naive growth hormone-deficient children. Genen-tech Study Group. J Clin Endocrinol Metab. 1996;81:1806–9.
    1. MaCgillivray MH, Blethen SL, Buchlis JG, et al. Current dosing of growth hormone in children with growth hormone deficiency: how physiologic? Pediatrics. 1998;102:527–30.
    1. Maneatis T, Baptista J, Connelly K, et al. Growth hormone safety update from the National Cooperative Growth Study. J Pediatr Endocrinol Metab. 2000;13(Suppl 2):1035–44.
    1. Mauras N, Attie KM, Reiter EO, et al. 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;85:3653–60.
    1. Mauras N, George D, Evans J, et al. Growth hormone has anabolic effects in glucocorticosteroid-dependent children with inflammatory bowel disease: a pilot study. Metabolism. 2002;51:127–35.
    1. Mills JL, Schonberger LB, Wysowski DK, et al. Long-term mortality in the United States cohort of pituitary-derived growth hormone recipients. J Pediatr. 2004;144:430–6.
    1. Park P, Cohen P. The role of insulin-like growth factor I monitoring in growth hormone-treated children. Horm Res. 2004;62(Suppl 1):59–65.
    1. Reiter EO, Blethen SL, Baptista J, et al. Early initiation of growth hormone treatment allows age-appropriate estrogen use in Turner’s syndrome. J Clin Endocrinol Metab. 2001;86:1936–41.
    1. Rekers-Mombarg LT, Kamp GA, Massa GG, et al. Influence of growth hormone treatment on pubertal timing and pubertal growth in children with idiopathic short stature. Dutch Growth Hormone Working Group. J Pediatr Endocrinol Metab. 1999;12:611–22.
    1. Roelfsema V, Clark RG. The growth hormone and insulin-like growth factor axis: its manipulation for the benefit of growth disorders in renal failure. J Am Soc Nephrol. 2001;12:1297–306.
    1. Rosenfeld RG, Attie KM, Frane J, et al. Growth hormone therapy of Turner’s syndrome: beneficial effect on adult height. J Pediatr. 1998;132:319–24.
    1. Saavedra JM, Henderson RA, Perman JA, et al. Longitudinal assessment of growth in children born to mothers with human immunodeficiency virus infection. Arch Pediatr Adolesc Med. 1995;149:497–502.
    1. Saenger P. Dose effects of growth hormone during puberty. Horm Res. 2003;60:52–7.
    1. Saggese G, Baroncelli GI, Bertelloni S, et al. The effect of long-term growth hormone GH. treatment on bone mineral density in children with GH deficiency. Role of GH in the attainment of peak bone mass. J Clin Endocrinol Metab. 1996;81:3077–83.
    1. Sas TC, De Muinck Keizer-Schrama SM, Stijnen T, et al. Normalization of height in girls with Turner syndrome after long-term growth hormone treatment: results of a randomized dose-response trial. J Clin Endocrinol Metab. 1999;84:4607–12.
    1. Savendahl L, Davenport ML. Delayed diagnoses of Turner’s syndrome: proposed guidelines for change. J Pediatr. 2000;137:455–9.
    1. Schnabel D, Grasemann C, Staab D, et al. A multicenter, randomized, double-blind, placebo-controlled trial to evaluate the metabolic and respiratory effects of growth hormone in children with cystic fibrosis. Pediatrics. 2007;119:e1230–8.
    1. Seguy D, Vahedi K, Kapel N, et al. Low-dose growth hormone in adult home parenteral nutrition-dependent short bowel syndrome patients: a positive study. Gastroenterology. 2003;124:293–302.
    1. STUDY, N. A. P. R. T. C 2005. Annual Report.
    1. Tonshoff B, Tonshoff C, Mehls O, et al. Growth hormone treatment in children with preterminal chronic renal failure: no adverse effect on glomerular filtration rate. Eur J Pediatr. 1992;151:601–7.
    1. Underwood LE, Attie KM, Baptista J. Growth hormone GH. dose-response in young adults with childhood-onset GH deficiency: a two-year, multicenter, multiple-dose, placebo-controlled study. J Clin Endocrinol Metab. 2003;88:5273–80.
    1. Van Dyck M, Gyssels A, Proesmans W, et al. Growth hormone treatment enhances bone mineralisation in children with chronic renal failure. Eur J Pediatr. 2001;160:359–63.
    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;88:3584–90.
    1. Van Vliet G, Deal CL, Crock PA, et al. Sudden death in growth hormone-treated children with Prader-Willi syndrome. J Pediatr. 2004;144:129–31.
    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;143:415–21.
    1. EMD Serono, Inc; Zorbtive® somatotropin rDNA origin. for injection. .

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren