Guidelines Summary

A 2016 update to 2003 guidelines for GH and insulinlike growth factor-I treatment in children and adolescents with GH deficiency, idiopathic short stature, or primary insulinlike growth factor-I deficiency, from the Pediatric Endocrine Society, suggests the use of “a shared decision-making approach to pursuing GH treatment for a child with” idiopathic short stature. The update also states that the “decision can be made on a case-by-case basis after assessment of physical and psychological burdens, and discussion of risks and benefits,” and recommends that GH therapy not be used routinely in every child with a height standard deviation score at or below -2.25. It also suggests that, due to response overlap between dosing groups, the GH dose be initiated at 0.24 mg/kg/wk, “with some patients requiring up to 0.47 mg/kg/week.”^[23]

Medication

[Guideline] 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 Nov. 93(11):4210-7. [QxMD MEDLINE Link].
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 Nov. 93(11):4342-50. [QxMD MEDLINE Link].
Collett-Solberg PF, Misra M,. The role of recombinant human insulin-like growth factor-I in treating children with short stature. J Clin Endocrinol Metab. 2008 Jan. 93(1):10-8. [QxMD MEDLINE Link].
Lindsay R, Feldkamp M, Harris D, Robertson J, Rallison M. Utah Growth Study: growth standards and the prevalence of growth hormone deficiency. J Pediatr. 1994 Jul. 125(1):29-35. [QxMD MEDLINE Link].
Bourgeois B, Watts K, Thomas DM, et al. Associations between height and blood pressure in the United States population. Medicine (Baltimore). 2017 Dec. 96 (50):e9233. [QxMD MEDLINE Link].
Shimizu Y, Yoshimine H, Nagayoshi M, et al. Short stature is an inflammatory disadvantage among middle-aged Japanese men. Environ Health Prev Med. 2016 May 10. [QxMD MEDLINE Link].
Quitmann JH, Bullinger M, Sommer R, Rohenkohl AC, Bernardino Da Silva NM. Associations between Psychological Problems and Quality of Life in Pediatric Short Stature from Patients' and Parents' Perspectives. PLoS One. 2016. 11 (4):e0153953. [QxMD MEDLINE Link]. [Full Text].
Karkinen J, Miettinen PJ, Raivio T, Hero M. Etiology of severe short stature below -3 SDS in a screened Finnish population. Eur J Endocrinol. 2020 Nov. 183 (5):481-8. [QxMD MEDLINE Link].
Dauber A, Rosenfeld RG, Hirschhorn JN. Genetic Evaluation of Short Stature. J Clin Endocrinol Metab. 2014 Jun 10. jc20141506. [QxMD MEDLINE Link].
Murray PG, Clayton PE, Chernausek SD. A genetic approach to evaluation of short stature of undetermined cause. Lancet Diabetes Endocrinol. 2018 Jan 31. [QxMD MEDLINE Link].
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 Jul. 89 (7):3140-8. [QxMD MEDLINE Link]. [Full Text].
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 Nov. 93 (11):4342-50. [QxMD MEDLINE Link]. [Full Text].
Rekers-Mombarg LT, Massa GG, Wit JM, et al. Growth hormone therapy with three dosage regimens in children with idiopathic short stature. European Study Group Participating Investigators. J Pediatr. 1998 Mar. 132 (3 Pt 1):455-60. [QxMD MEDLINE Link].
van Gool SA, Kamp GA, Odink RJ, et al. High-dose GH treatment limited to the prepubertal period in young children with idiopathic short stature does not increase adult height. Eur J Endocrinol. 2010 Apr. 162 (4):653-60. [QxMD MEDLINE Link].
Schena L, Meazza C, Pagani S, et al. Efficacy of long-term growth hormone therapy in short non-growth hormone-deficient children. J Pediatr Endocrinol Metab. 2017 Feb 1. 30 (2):197-201. [QxMD MEDLINE Link].
Shemesh-Iron M, Lazar L, Lebenthal Y, et al. Growth Hormone Therapy and Short Stature-Related Distress: A Randomized Placebo-Controlled Trial. Clin Endocrinol (Oxf). 2019 Feb 5. [QxMD MEDLINE Link].
Gonzalez Briceno LG, Viaud M, Beltrand J, et al. Improved General and Height-Specific Quality of Life in Children with Short Stature after One Year on Growth Hormone. J Clin Endocrinol Metab. 2019 Jan 15. [QxMD MEDLINE Link].
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 Mar 5. [QxMD MEDLINE Link].
Carel JC, Ecosse E, Landier F, et al. 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 Feb. 97 (2):416-25. [QxMD MEDLINE Link].
Savendahl L, Maes M, Albertsson-Wikland K, et al. 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. Feb 2012. 97(2):E213-7. [QxMD MEDLINE Link].
US Food and Drug Administration. Recombinant Human Growth Hormone (somatropin): Ongoing Safety Review - Possible Increased Risk of Death. Available at http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm237969.htm?utm_campaign=Google2&utm_source=fdaSearch&utm_medium=website&utm_term=growth hormone&utm_content=4. Accessed: June 2012.
Miller BS, Ross J, Ostrow V. Height outcomes in children with growth hormone deficiency and idiopathic short stature treated concomitantly with growth hormone and aromatase inhibitor therapy: data from the ANSWER program. Int J Pediatr Endocrinol. 2020. 2020:19. [QxMD MEDLINE Link]. [Full Text].
[Guideline] 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 (6):361-397. [QxMD MEDLINE Link]. [Full Text].
Sandberg DE, Gardner M. Short Stature: Is It a Psychosocial Problem and Does Changing Height Matter?. Pediatr Clin North Am. 2015 Aug. 62 (4):963-82. [QxMD MEDLINE Link].
Zayed S, Madlon-Kay DJ. Growth Hormone for Treatment of Idiopathic Short Stature in Children. Am Fam Physician. 2015 Jul 1. 92 (1):64. [QxMD MEDLINE Link].
Wit JM, Oostdijk W. Novel approaches to short stature therapy. Best Pract Res Clin Endocrinol Metab. 2015 Jun. 29 (3):353-66. [QxMD MEDLINE Link].

Media Gallery

Proper use of a wall-mounted stadiometer.
Comparison of the growth patterns between idiopathic short stature and constitutional growth delay.
Bone age comparison between an 8-year-old boy (left) and a 14-year-old adolescent boy (right).
Growth chart for Turner syndrome. Note that the upper limit overlaps the range for girls of normal height.
A single, central, maxillary incisor reflects a defect in midline facial development.

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Author

Sunil Kumar Sinha, MD Clinical Assistant Professor, Division of Pediatric Endocrinology, University of Arizona College of Medicine

Sunil Kumar Sinha, MD is a member of the following medical societies: American Academy of Pediatrics, American Association of Clinical Endocrinologists, Endocrine Society, Pediatric Endocrine Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Lynne Lipton Levitsky, MD Chief, Pediatric Endocrine Unit, Massachusetts General Hospital; Associate Professor of Pediatrics, Harvard Medical School

Lynne Lipton Levitsky, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Diabetes Association, American Pediatric Society, Endocrine Society, Pediatric Endocrine Society, Society for Pediatric Research

Disclosure: Nothing to disclose.

Chief Editor

Robert P Hoffman, MD Professor and Program Director, Department of Pediatrics, Ohio State University College of Medicine; Pediatric Endocrinologist, Division of Pediatric, Endocrinology, Diabetes, and Metabolism, Nationwide Children's Hospital

Robert P Hoffman, MD is a member of the following medical societies: American College of Pediatricians, American Diabetes Association, American Pediatric Society, Christian Medical and Dental Associations, Endocrine Society, Midwest Society for Pediatric Research, Pediatric Endocrine Society, Society for Pediatric Research

Disclosure: Nothing to disclose.

Additional Contributors

Angelo P Giardino, MD, PhD, MPH, FAAP Wilma T Gibson Presidential Professor and Chair, Department of Pediatrics, University of Utah School of Medicine; Chief Medical Officer, Intermountain Primary Children's Hospital

Angelo P Giardino, MD, PhD, MPH, FAAP is a member of the following medical societies: Academic Pediatric Association, American Academy of Pediatrics, American Professional Society on the Abuse of Children, Harris County Medical Society, International Society for the Prevention of Child Abuse and Neglect, Ray E Helfer Society

Disclosure: Nothing to disclose.

Acknowledgements

Robert J Ferry Jr, MD Le Bonheur Chair of Excellence in Endocrinology, Professor and Chief, Division of Pediatric Endocrinology and Metabolism, Department of Pediatrics, University of Tennessee Health Science Center

Robert J Ferry Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Diabetes Association, American Medical Association, Endocrine Society, Pediatric Endocrine Society, Society for Pediatric Research, and Texas Pediatric Society

Disclosure: Eli Lilly & Co Grant/research funds Investigator; MacroGenics, Inc Grant/research funds Investigator; Ipsen, SA (formerly Tercica, Inc) Grant/research funds Investigator; NovoNordisk SA Grant/research funds Investigator; Diamyd Grant/research funds Investigator; Bristol-Myers-Squibb Grant/research funds Other; Amylin Other; Pfizer Grant/research funds Other; Takeda Grant/research funds Other

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