Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Treatment of growth hormone deficiency in children

Alan D Rogol, MD, PhD
Erick J Richmond, MD
Section Editor
Mitchell E Geffner, MD
Deputy Editor
Alison G Hoppin, MD


Recombinant human growth hormone (GH) is the primary treatment for short stature associated with GH deficiency. Challenges to effective treatment include difficulty in establishing a firm diagnosis of GH deficiency and variable responsiveness to GH within the population diagnosed with GH deficiency.

The indications for and efficacy of exogenous GH treatment in children with GH deficiency are reviewed here. The diagnostic approach to the child with short stature and the diagnosis of GH deficiency are discussed separately. (See "Causes of short stature" and "Diagnostic approach to children and adolescents with short stature" and "Diagnosis of growth hormone deficiency in children".)

GH therapy is also prescribed for several other specific indications in children and adolescents, including idiopathic short stature and short stature associated with small for gestational age, chronic kidney disease, Turner syndrome, Prader-Willi syndrome, mutations in the SHOX gene, and Noonan syndrome. These uses are discussed in separate topic reviews:

(See "Growth hormone treatment for idiopathic short stature".)

(See "Growth hormone treatment for children born small for gestational age".)

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Sep 2017. | This topic last updated: Jun 23, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Veldhuis JD, Roemmich JN, Richmond EJ, et al. Endocrine control of body composition in infancy, childhood, and puberty. Endocr Rev 2005; 26:114.
  2. MURPHY WR, DAUGHADAY WH, HARTNETT C. The effect of hypophysectomy and growth hormone on the incorporation of labeled sulfate into tibial epiphyseal and nasal cartilage of the rat. J Lab Clin Med 1956; 47:715.
  3. SALMON WD Jr, DAUGHADAY WH. A hormonally controlled serum factor which stimulates sulfate incorporation by cartilage in vitro. J Lab Clin Med 1957; 49:825.
  4. Kaplan SA, Cohen P. The somatomedin hypothesis 2007: 50 years later. J Clin Endocrinol Metab 2007; 92:4529.
  5. Rosenfeld RG, Albertsson-Wikland K, Cassorla F, et al. Diagnostic controversy: the diagnosis of childhood growth hormone deficiency revisited. J Clin Endocrinol Metab 1995; 80:1532.
  6. Peter F, Savoy C, Ji HJ, et al. Pharmacokinetic and pharmacodynamic profile of a new sustained-release GH formulation, LB03002, in children with GH deficiency. Eur J Endocrinol 2009; 160:349.
  7. Péter F, Bidlingmaier M, Savoy C, et al. Three-year efficacy and safety of LB03002, a once-weekly sustained-release growth hormone (GH) preparation, in prepubertal children with GH deficiency (GHD). J Clin Endocrinol Metab 2012; 97:400.
  8. Zelinska N, Iotova V, Skorodok J, et al. Long-Acting C-Terminal Peptide-Modified hGH (MOD-4023): Results of a Safety and Dose-Finding Study in GHD Children. J Clin Endocrinol Metab 2017; 102:1578.
  9. Luo X, Hou L, Liang L, et al. Long-acting PEGylated recombinant human growth hormone (Jintrolong) for children with growth hormone deficiency: phase II and phase III multicenter, randomized studies. Eur J Endocrinol 2017; 177:195.
  10. de Muinck Keizer-Schrama SM, Rikken B, Wynne HJ, et al. 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.
  11. Blethen SL, Compton P, Lippe BM, et al. Factors predicting the response to growth hormone (GH) therapy in prepubertal children with GH deficiency. J Clin Endocrinol Metab 1993; 76:574.
  12. Albertsson-Wikland K. The effect of human growth hormone injection frequency on linear growth rate. Acta Paediatr Scand Suppl 1987; 337:110.
  13. 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. Genentech Study Group. J Clin Endocrinol Metab 1996; 81:1806.
  14. Grimberg A, DiVall SA, Polychronakos C, et al. Guidelines for Growth Hormone and Insulin-Like Growth Factor-I Treatment in Children and Adolescents: Growth Hormone Deficiency, Idiopathic Short Stature, and Primary Insulin-Like Growth Factor-I Deficiency. Horm Res Paediatr 2016; 86:361.
  15. 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; 95:2089.
  16. Cohen P, Weng W, Rogol AD, et al. Dose-sparing and safety-enhancing effects of an IGF-I-based dosing regimen in short children treated with growth hormone in a 2-year randomized controlled trial: therapeutic and pharmacoeconomic considerations. Clin Endocrinol (Oxf) 2014; 81:71.
  17. Root AW, Kemp SF, Rundle AC, et al. Effect of long-term recombinant growth hormone therapy in children--the National Cooperative Growth Study, USA, 1985-1994. J Pediatr Endocrinol Metab 1998; 11:403.
  18. 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; 91:2047.
  19. Kemp SF. Insulin-like growth factor-I deficiency in children with growth hormone insensitivity: current and future treatment options. BioDrugs 2009; 23:155.
  20. Chernausek SD, Backeljauw PF, Frane J, et al. Long-term treatment with recombinant insulin-like growth factor (IGF)-I in children with severe IGF-I deficiency due to growth hormone insensitivity. J Clin Endocrinol Metab 2007; 92:902.
  21. 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; 9:64.
  22. 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.
  23. 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. BMJ 2002; 325:70.
  24. Conway GS, Szarras-Czapnik M, Racz K, et al. Treatment for 24 months with recombinant human GH has a beneficial effect on bone mineral density in young adults with childhood-onset GH deficiency. Eur J Endocrinol 2009; 160:899.
  25. Saggese G, Baroncelli GI, Bertelloni S, Barsanti S. 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.
  26. Bonjour JP, Theintz G, Buchs B, et al. Critical years and stages of puberty for spinal and femoral bone mass accumulation during adolescence. J Clin Endocrinol Metab 1991; 73:555.
  27. de Boer H, Blok GJ, van Lingen A, et al. Consequences of childhood-onset growth hormone deficiency for adult bone mass. J Bone Miner Res 1994; 9:1319.
  28. Holmes SJ, Economou G, Whitehouse RW, et al. Reduced bone mineral density in patients with adult onset growth hormone deficiency. J Clin Endocrinol Metab 1994; 78:669.
  29. 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.
  30. Saenger P, Attie KM, 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; 83:3115.
  31. 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.
  32. Youngster I, Rachmiel R, Pinhas-Hamiel O, et al. Treatment with recombinant human growth hormone during childhood is associated with increased intraocular pressure. J Pediatr 2012; 161:1116.
  33. Darendeliler F, Karagiannis G, Wilton P. Headache, idiopathic intracranial hypertension and slipped capital femoral epiphysis during growth hormone treatment: a safety update from the KIGS database. Horm Res 2007; 68 Suppl 5:41.
  34. Bourguignon JP, Piérard GE, Ernould C, et al. Effects of human growth hormone therapy on melanocytic naevi. Lancet 1993; 341:1505.
  35. Hansen TK, Møller J, Thomsen K, et al. Effects of growth hormone on renal tubular handling of sodium in healthy humans. Am J Physiol Endocrinol Metab 2001; 281:E1326.
  36. Pitukcheewanont P, Schwarzbach L, Kaufman FR. Resumption of growth after methionyl-free human growth hormone therapy in a patient with neutralizing antibodies to methionyl human growth hormone. J Pediatr Endocrinol Metab 2002; 15:653.
  37. Meazza C, Schaab M, Pagani S, et al. Development of antibodies against growth hormone (GH) during rhGH therapy in a girl with idiopathic GH deficiency: a case report. J Pediatr Endocrinol Metab 2013; 26:785.
  38. Cutfield WS, Wilton P, Bennmarker H, et al. Incidence of diabetes mellitus and impaired glucose tolerance in children and adolescents receiving growth-hormone treatment. Lancet 2000; 355:610.
  39. Giovannucci E, Pollak M. Risk of cancer after growth-hormone treatment. Lancet 2002; 360:268.
  40. Swerdlow AJ, Cooke R, Beckers D, et al. Cancer Risks in Patients Treated With Growth Hormone in Childhood: The SAGhE European Cohort Study. J Clin Endocrinol Metab 2017; 102:1661.
  41. Wilton P, Mattsson AF, Darendeliler F. Growth hormone treatment in children is not associated with an increase in the incidence of cancer: experience from KIGS (Pfizer International Growth Database). J Pediatr 2010; 157:265.
  42. Jenkins PJ, Mukherjee A, Shalet SM. Does growth hormone cause cancer? Clin Endocrinol (Oxf) 2006; 64:115.
  43. Ross J, Czernichow P, Biller BM, et al. Growth hormone: health considerations beyond height gain. Pediatrics 2010; 125:e906.
  44. Banerjee I, Clayton PE. Growth hormone treatment and cancer risk. Endocrinol Metab Clin North Am 2007; 36:247.
  45. Raman S, Grimberg A, Waguespack SG, et al. Risk of Neoplasia in Pediatric Patients Receiving Growth Hormone Therapy--A Report From the Pediatric Endocrine Society Drug and Therapeutics Committee. J Clin Endocrinol Metab 2015; 100:2192.
  46. Fradkin JE, Mills JL, Schonberger LB, et al. Risk of leukemia after treatment with pituitary growth hormone. JAMA 1993; 270:2829.
  47. Nishi Y, Tanaka T, Takano K, et al. Recent status in the occurrence of leukemia in growth hormone-treated patients in Japan. GH Treatment Study Committee of the Foundation for Growth Science, Japan. J Clin Endocrinol Metab 1999; 84:1961.
  48. Allen DB, Rundle AC, Graves DA, Blethen SL. Risk of leukemia in children treated with human growth hormone: review and reanalysis. J Pediatr 1997; 131:S32.
  49. Swerdlow AJ, Reddingius RE, Higgins CD, et al. Growth hormone treatment of children with brain tumors and risk of tumor recurrence. J Clin Endocrinol Metab 2000; 85:4444.
  50. Sklar CA, Mertens AC, Mitby P, et al. Risk of disease recurrence and second neoplasms in survivors of childhood cancer treated with growth hormone: a report from the Childhood Cancer Survivor Study. J Clin Endocrinol Metab 2002; 87:3136.
  51. Ergun-Longmire B, Mertens AC, Mitby P, et al. Growth hormone treatment and risk of second neoplasms in the childhood cancer survivor. J Clin Endocrinol Metab 2006; 91:3494.
  52. Bell J, Parker KL, Swinford RD, et al. Long-term safety of recombinant human growth hormone in children. J Clin Endocrinol Metab 2010; 95:167.
  53. Poidvin A, Touzé E, Ecosse E, et al. Growth hormone treatment for childhood short stature and risk of stroke in early adulthood. Neurology 2014; 83:780.
  54. 8/25/14: Endocrine Society statement on possible association between GH therapy in childhood and later stroke. Available at: https://www.endocrine.org/~/media/endosociety/Files/Advocacy%20and%20Outreach/Position%20Statements/Other%20Statements/GH%20Stroke%20Statement%20Final%20on%20letterhead.pdf (Accessed on September 08, 2014).
  55. Frasier SD. The not-so-good old days: working with pituitary growth hormone in North America, 1956 to 1985. J Pediatr 1997; 131:S1.
  56. Carel JC, Eugster EA, Rogol A, et al. Consensus statement on the use of gonadotropin-releasing hormone analogs in children. Pediatrics 2009; 123:e752.
  57. Mericq MV, Eggers M, Avila A, et al. Near final height in pubertal growth hormone (GH)-deficient patients treated with GH alone or in combination with luteinizing hormone-releasing hormone analog: results of a prospective, randomized trial. J Clin Endocrinol Metab 2000; 85:569.
  58. Saggese G, Federico G, Barsanti S, Fiore L. The effect of administering gonadotropin-releasing hormone agonist with recombinant-human growth hormone (GH) on the final height of girls with isolated GH deficiency: results from a controlled study. J Clin Endocrinol Metab 2001; 86:1900.
  59. Lee PA. Use of GnRH agonists in GH-deficient patients: arguments for and against. The case for GnRH agonists in GH-deficient patients. Pediatr Endocrinol Rev 2008; 5 Suppl 2:744.
  60. Reiter EO. A brief review of the addition of gonadotropin-releasing hormone agonists (GnRH-Ag) to growth hormone (GH) treatment of children with idiopathic growth hormone deficiency: Previously published studies from America. Mol Cell Endocrinol 2006; 254-255:221.
  61. Mauras N, Welch S, Rini A, Klein KO. An open label 12-month pilot trial on the effects of the aromatase inhibitor anastrozole in growth hormone (GH)-treated GH deficient adolescent boys. J Pediatr Endocrinol Metab 2004; 17:1597.
  62. Wickman S, Sipilä I, Ankarberg-Lindgren C, et al. A specific aromatase inhibitor and potential increase in adult height in boys with delayed puberty: a randomised controlled trial. Lancet 2001; 357:1743.
  63. Kreher NC, Eugster EA, Shankar RR. The use of tamoxifen to improve height potential in short pubertal boys. Pediatrics 2005; 116:1513.
  64. Mauras N, Gonzalez de Pijem L, Hsiang HY, et al. Anastrozole increases predicted adult height of short adolescent males treated with growth hormone: a randomized, placebo-controlled, multicenter trial for one to three years. J Clin Endocrinol Metab 2008; 93:823.
  65. Geffner ME. Aromatase inhibitors to augment height: continued caution and study required. J Clin Res Pediatr Endocrinol 2009; 1:256.