Short Stature

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Longitudinal growth assessment is essential in child care. Short stature can be promptly recognized only with accurate measurements of growth and critical analysis of growth data.

Short stature, optimally defined relative to the genetic endowment of the individual, is recognized by comparing an individual child’s height with that of a large population of a similar genetic background and, more particularly, using the mid-parental target height (see History). Adult height is largely genetically predetermined; typically, 80% or more of the variation in height can be explained by genetic factors, although environmental factors also play a pivotal role.

Growth failure (GF) is often confused with short stature. By definition, GF is a pathologic state of abnormally low growth rate over time, whereas short stature is often a normal variant. Regardless of the genetic background, short stature may be a of a wide variety of pathologic conditions or inherited disorders. Thus, accurate longitudinal growth assessment is a fundamental aspect of health maintenance in children. Reviewing the patient’s growth chart is critical to evaluating short stature. Deviation from a prior growth pattern appropriate for the genetic background often heralds new pathology. In addition, analysis of the prior growth pattern helps distinguish normal growth from pathologic variants of short stature.

Compared with a well-nourished, genetically relevant population, short stature is defined as a standing height more than 2 standard deviations (SDs) below the mean (or below the 2.5 percentile) for sex. [1] Skeletal maturation is typically determined by the bone age, which is assessed using anteroposterior radiography of the left hand and wrist. Sex-specific reference data for standing height, head circumference, and weight have been published for most developed countries, most ethnic subpopulations (including Asians and blacks), and the most common genetic disorders (eg, Down syndrome, Ullrich-Turner syndrome, achondroplasia).

The causes of short stature can be divided into 3 broad categories: disease (including undernutrition genetic disorders), familial short stature, and constitutional delay of growth and development. Endocrine are rare causes of short stature (see Frequency). The hallmark of endocrine disease is linear GF that occurs to a greater degree than weight loss. Most short children evaluated by clinicians in developed countries have familial short stature, constitutional growth delay, or both. Short stature and constitutional growth delay are diagnoses of exclusion.

The hallmarks of familial short stature (also referred to as genetic short stature) include bone age appropriate for chronologic age, normal growth velocity, and predicted adult height appropriate to the familial pattern (using the Bayley-Pinneau or Tanner-Goldstein-Whitehouse tables). By contrast, constitutional growth delay is characterized by delayed bone age, normal growth velocity, and predicted adult height appropriate to the familial pattern (see image below).

Patients with constitutional growth delay typically have a first-degree or second-degree relative with constitutional growth delay (eg, menarche reached when older than 15 y, adult height attained in male relatives when older than 18 y).

Laboratory studies used to assess the major causes of short stature in children include the following:

Several provocative tests have been developed for the evaluation of suspected GH deficiency (GHD), including the following:

The proper evaluation of short stature is conducted in an outpatient setting with a calibrated stadiometer. The most useful information in the evaluation of a child with short stature is the child’s growth pattern

Medical care depends on the etiology of the short stature. Recombinant human growth hormone (rhGH) administration has not been proven to remarkably improve final adult height in children with normal variant short stature. [2, 3] Published clinical studies that have focused on this particular issue have been inconclusive.

Surgical care depends on the underlying cause of short stature. Brain tumors that cause hyposomatotropism may require neurosurgical intervention, depending on the tumor type and location (see Hyposomatotropism). Limb-lengthening procedures have been performed but carry enormous morbidity and mortality risks and are not recommended.

Longitudinal growth assessment is essential in child care. Short stature can be promptly recognized only with accurate measurements of growth and critical analysis of growth data.

Short stature, optimally defined relative to the genetic endowment of the individual, is recognized by comparing an individual child’s height with that of a large population of a similar genetic background and, more particularly, using the mid-parental target height (see History). Adult height is largely genetically predetermined; typically, 80% or more of the variation in height can be explained by genetic factors, although environmental factors also play a pivotal role.

Growth failure (GF) is often confused with short stature. By definition, GF is a pathologic state of abnormally low growth rate over time, whereas short stature is often a normal variant. Regardless of the genetic background, short stature may be a of a wide variety of pathologic conditions or inherited disorders. Thus, accurate longitudinal growth assessment is a fundamental aspect of health maintenance in children. Reviewing the patient’s growth chart is critical to evaluating short stature. Deviation from a prior growth pattern appropriate for the genetic background often heralds new pathology. In addition, analysis of the prior growth pattern helps distinguish normal growth from pathologic variants of short stature.

Compared with a well-nourished, genetically relevant population, short stature is defined as a standing height more than 2 standard deviations (SDs) below the mean (or below the 2.5 percentile) for sex. [1] Skeletal maturation is typically determined by the bone age, which is assessed using anteroposterior radiography of the left hand and wrist. Sex-specific reference data for standing height, head circumference, and weight have been published for most developed countries, most ethnic subpopulations (including Asians and blacks), and the most common genetic disorders (eg, Down syndrome, Ullrich-Turner syndrome, achondroplasia).

The causes of short stature can be divided into 3 broad categories: disease (including undernutrition genetic disorders), familial short stature, and constitutional delay of growth and development. Endocrine are rare causes of short stature (see Frequency). The hallmark of endocrine disease is linear GF that occurs to a greater degree than weight loss. Most short children evaluated by clinicians in developed countries have familial short stature, constitutional growth delay, or both. Short stature and constitutional growth delay are diagnoses of exclusion.

The hallmarks of familial short stature (also referred to as genetic short stature) include bone age appropriate for chronologic age, normal growth velocity, and predicted adult height appropriate to the familial pattern (using the Bayley-Pinneau or Tanner-Goldstein-Whitehouse tables). By contrast, constitutional growth delay is characterized by delayed bone age, normal growth velocity, and predicted adult height appropriate to the familial pattern (see image below).

Patients with constitutional growth delay typically have a first-degree or second-degree relative with constitutional growth delay (eg, menarche reached when older than 15 y, adult height attained in male relatives when older than 18 y).

Short stature may be normal. Obtaining the family history of growth patterns and direct measurement of the parents is crucial to determine the genetic potential for growth in the child.

Short stature can also be the sign of a wide variety of pathologic conditions or inherited disorders when it results from GF or premature closure of the epiphysial growth plates. Therefore, pathophysiology depends on the underlying cause. For detailed discussions of the disorders included in the differential diagnoses of short stature, see Differentials.

United States

By definition, 2.5% of the population is short. However, the number of children with poor linear growth is higher given the frequency of chronic diseases of childhood. The Utah Growth Study is the largest population-based survey of growth in children published to date. [4] These investigators assessed height and growth velocity in nearly 115,000 American children. Among the 555 children with short stature (defined as height below the third percentile) and poor growth rate (defined as growth velocity < 5 cm annually), only 5% had an endocrine disorder. In addition, 48% of the children with growth hormone deficiency (GHD) or Turner syndrome (TS) in this large cohort had been undiagnosed or untreated.

Parents often suspect an endocrine disorder (eg, GHD) as the major cause of short stature in their child. In fact, the Utah Growth Study confirms that most (95%) children with poor growth (velocity < 5 cm/y) do not have an endocrine disorder.

International

Unfortunately, malnutrition remains the most common cause of GF worldwide. Supporting lay and professional efforts to reverse this preventable cause of short stature in besieged communities must be a high priority of all governments and health care professionals.

Normal variations in stature are often related to ethnic background. For example, tall for a Cambodian individual may be short for a Norwegian individual. However, the major causes of short stature (ie, malnutrition, recurrent illness, parasites) are not race specific.

Boys who are short are more likely to come to medical attention than girls who are short. Notwithstanding the legitimate debate regarding this ascertainment bias, boys do appear more likely to have idiopathic GHD or constitutional delay of growth and development. Ullrich-Turner syndrome (ie, TS) affects only females. The evaluation of a short female, or a female with primary , mandates a karyotype to exclude this disorder.

Individuals of any age can be affected.

Individuals with normal variant short stature have an excellent prognosis.

Treatment of patients with classic growth hormone deficiency (GHD) with rhGH can be expected to yield a height consistent with genetic potential, provided that therapy is initiated at least 5 years prior to the onset of puberty. Whether cotreatment with rhGH and a gonadotropin-releasing hormone analog (eg, leuprolide) to inhibit puberty results in greater adult height in patients with classic GHD remains controversial.

Treatment of hypothyroidism at least 5 years before the onset of puberty is essential to attain a height consistent with the genetic potential.

Any chronic illness can reduce the adult height achieved if treatment of the condition is initiated late.

A study by Bourgeois et al, using data from the National Health and Nutrition Examination Survey, reported a link between adult short stature and higher blood pressure. It was found that, starting in the fourth decade of life, taller subjects tended to have significantly lower systolic arterial blood pressure and pulse pressure, but higher diastolic arterial pressure, than shorter persons. Moreover, the effects of height on blood pressure were determined to increase with age. [5]

A Japanese study, by Shimizu et al, indicated that short stature in middle-aged men places them at an inflammatory disadvantage. The study, which involved 3016 men aged 30-59 years, found height to be inversely proportional to white blood cell count, particularly in men with a body mass index of 23 kg/m2 or above. [6]

A study by Quitmann et al indicated that children and adolescents with current short stature are more likely to have internalizing problems and a lower self- and parent-reported health-related quality of life than do those who have previously been diagnosed with short stature but who have reached a height greater than -2SDs by the time of evaluation. [7]

Superb resources prepared by health care professionals for lay audiences include the following:

The MAGIC Foundation (Major Aspects of Growth in Children)

The Hormone Foundation of The Endocrine Society

The Turner Syndrome Society

The Human Growth Foundation

In addition, the following are examples of informative Web sites for specific diseases that bring parents and researchers together in the ongoing effort to improve care:

National Organization for Rare Disorders

Shwachman-Diamond Syndrome

For patient education resources, see the Growth Hormone Deficiency Center, as well as Short Stature in ChildrenGrowth Hormone DeficiencyGrowth Failure in ChildrenUnderstanding Growth Hormone Deficiency Medications, and Growth Hormone Deficiency FAQs.

[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. [Medline].

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. [Medline].

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. [Medline].

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. [Medline].

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. [Medline].

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. [Medline].

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. [Medline]. [Full Text].

Dauber A, Rosenfeld RG, Hirschhorn JN. Genetic Evaluation of Short Stature. J Clin Endocrinol Metab. 2014 Jun 10. jc20141506. [Medline].

Murray PG, Clayton PE, Chernausek SD. A genetic approach to evaluation of short stature of undetermined cause. Lancet Diabetes Endocrinol. 2018 Jan 31. [Medline].

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. [Medline]. [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. [Medline]. [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. [Medline].

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. [Medline].

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. [Medline].

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. [Medline].

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. [Medline].

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. [Medline].

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. [Medline].

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. [Medline].

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.

[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. [Medline]. [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. [Medline].

Zayed S, Madlon-Kay DJ. Growth Hormone for Treatment of Idiopathic Short Stature in Children. Am Fam Physician. 2015 Jul 1. 92 (1):64. [Medline].

Wit JM, Oostdijk W. Novel approaches to short stature therapy. Best Pract Res Clin Endocrinol Metab. 2015 Jun. 29 (3):353-66. [Medline].

Sunil Kumar Sinha, MD 

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.

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.

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.

Angelo P Giardino, MD, MPH, PhD Professor and Section Head, Academic General Pediatrics, Baylor College of Medicine; Senior Vice President and Chief Quality Officer, Texas Children’s Hospital

Angelo P Giardino, MD, MPH, PhD 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.

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 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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