Short Stature

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Practice Essentials

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 sign 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: chronic disease (including undernutrition genetic disorders), familial short stature, and constitutional delay of growth and development. Endocrine diseases 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).



View Image

Comparison of the growth patterns between idiopathic short stature and constitutional growth delay.

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).

Diagnosis and management

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.

Background

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 sign 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: chronic disease (including undernutrition genetic disorders), familial short stature, and constitutional delay of growth and development. Endocrine diseases 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).



View Image

Comparison of the growth patterns between idiopathic short stature and constitutional growth delay.

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).

Pathophysiology

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.

Epidemiology

Frequency

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.

Race

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.

Sex

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 amenorrhea, mandates a karyotype to exclude this disorder.

Age

Individuals of any age can be affected.

Prognosis

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]

Patient Education

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

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:

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

History

Key data to obtain for the evaluation of short stature include the child's weight and length at birth; prior growth pattern; and the final (or current) heights and weights of parents, siblings, and grandparents.

Document pubertal timing in first-degree relatives.

Review of symptoms by organ system provides additional clues to the etiology underlying short stature.

Physical

Endocrinologists rely heavily on accurate and reliable height assessment.

Causes

The nonendocrine causes of short stature (see Other Problems to be Considered) can be divided into 3 major categories, as follows:

Genetic causes of short stature are as follows:

Laboratory Studies

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

Other useful tests include the following:

Murray et al estimated that through the use of genetic studies, such as copy number variant analysis, targeted gene panels, and whole-exome sequencing, a molecular diagnosis could be derived for 25-40% of children initially diagnosed with idiopathic short stature.[9]  

Imaging Studies

Perform anteroposterior radiography of left hand and wrist to assess bone age (see image below).



View Image

Bone age comparison between an 8-year-old boy (left) and a 14-year-old adolescent boy (right).

Chondrodysplasia of the distal radial epiphysis (Madelung deformity) suggests Lerí-Weill dyschondrosteosis.

Perform renal and cardiac ultrasonography in all patients with Ullrich-Turner syndrome. The most commonly associated anomalies include horseshoe kidney and bicuspid aortic valve.

Other Tests

Perform hearing tests in all patients with Ullrich-Turner syndrome. Use Bayley-Pinneau or Tanner-Goldstein-Whitehouse methods. These methods are often used to predict final adult height and become more accurate with advancing bone age.

Within 5 years of epiphyseal closure, the predicted height may fall within ±5 cm of the final adult height, with 95% confidence. The Bayley-Pinneau method can be used with a bone age as young as 6 years; however, the prediction is less accurate at the younger ages.

Procedures

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

Perform all GH provocative testing under the supervision of a pediatric endocrinologist. Please refer to Hyposomatotropism for further details of these tests.

Medical Care

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. These reports were flawed because of the following:

A double-blinded, randomized study from the National Institutes of Health suggests GH has a small effect on adult height in children with normal short stature if they are treated with GH injections for many years.[10]

Other randomized studies have shown variable results, with some demonstrating benefit[11]  and others not.[12, 13]  A study by Schena et al indicated that in children with short stature who are not GH deficient (ie, those with idiopathic short stature), long-term treatment with rhGH yields results similar to those in GH-deficient children who undergo this therapy, although this study did not have an untreated control group and pretreatment growth velocity data for the patients was missing.[14]  Thus, the risk-benefit ratio for treatment of children with idiopathic short stature is not well defined.

In a randomized, 1-year, placebo-controlled trial, Shemesh-Iron et al found improved height perception in boys with idiopathic short stature who received growth hormone. By the end of 3 additional years, in which all members of the study received growth hormone, there were improvements in the Rosenberg Self-Esteem Scale (RSES) and Single-Category Implicit Association Test for height (SC-IAT-H) scores but not in the Pediatric Quality-of-Life Inventory (PedsQL) or Child Behavior Checklist (CBCL) scores.[15]

However, a prospective, observational study by González Briceño et al found that PedsQL scores, as well as scores on the Quality of Life in Short Stature Youth (QoLISSY) questionnaire, improved in children with short stature who were treated with GH, indicating significant increases in emotional and social quality of life. The investigators could not rule out a placebo effect, since this was not a placebo-controlled trial. (Time may also have been a factor, since the above scores can improve with increased patient maturity.) Nonetheless, the authors reported that improvement in QoLISSY questionnaire results moderately correlated with increases in height standard deviation scores (SDS).[16]

Along with questions regarding the benefits of GH therapy, there is also controversy regarding GH dosing. Fixed dosing based on weight has long been used. However, a 2-year, open-label, randomized trial that measured the response to somatotropin (rDNA origin) therapy based on serum insulinlike growth factor-I (IGF-I) levels in children with GH deficiency and in children with idiopathic short stature suggested that IGF-based dosing of GH may safely provide superior growth outcome in both groups.[17]

Recombinant human GH has been used for over 4 decades, with a good track record of safety. A preliminary report from the French part of the European Union Safety and Appropriateness of GH treatments in Europe (EU SAGhE) study showed increased overall mortality in adults treated with rhGH during childhood, raising concerns about the long-term safety of this therapy.[18] Data from Belgium, The Netherlands, and Sweden, however, did not show a similar distribution of causes of death.[19] After reviewing information from the EU SAGhE study and other sources, the US Food and Drug Administration (FDA) recommended continued rhGH prescription and use according to the labeled recommendations.[20]

Surgical Care

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.

Consultations

The following consultations are indicated:

Diet

Optimize nutrition in patients with GI disease. Obtain psychologic or psychiatric consultation for patients with eating disorders. Forced energy intake in children with normal variant short stature has not been demonstrated to improve short-term growth or final adult height.

Activity

Do not restrict activity in children with normal variant short stature.

Complications

Short stature may be the harbinger of an occult chronic disease of childhood. Normal variant short stature may be associated with a bone mineral density that is lower than in the remainder of the (taller) population. Whether this healthy subset of the population is at higher risk of osteoporosis remains unclear.

Prevention

Growth evaluation is a useful means of detecting chronic disease in children.

Long-Term Monitoring

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 (see image below).



View Image

Comparison of the growth patterns between idiopathic short stature and constitutional growth delay.

In children younger than 3 years, track length and weight at 3-month intervals. Standing height and weight can be tracked at 6-month intervals in older children.

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.”[21]

Medication Summary

Medication administered depends on the etiology of the short stature.

Somatropin (Humatrope, Nutropin, Genotropin, Saizen, Tev-Tropin, Norditropin)

Clinical Context:  hGH produced via recombinant DNA technology in Escherichia coli; widely available since 1985. Currently, only 1 of the 10 largest reported clinical studies has demonstrated that therapy can increase final adult height in patients with normal variant short stature. This most recent NIH-funded study was randomized, placebo controlled, and took place over 14 y. Investigators demonstrated average gain in height did not exceed 4 cm when rhGH treatment of normal variant short stature began prior to puberty and continued through completion of puberty. They did not identify any clinical feature that, prior to start of therapy, could predict whether an individual patient would respond to rhGH and to what degree. Whether several years of daily injections are worth the potential, but not promised, relatively small increase in final adult height remains a personal and individual decision involving the patient, patient's family, and physician.

Class Summary

These agents improve symptoms associated with growth hormone deficiency (GHD).

Mecasermin (Increlex)

Clinical Context:  Recombinant human insulinlike growth factor-1 (rhIGF-1) indicated for long-term treatment of GF in children with severe primary IGFD (primary IGFD defined as basal serum IGF-I level and height SD scores ≤ -3, normal or elevated serum GH level). IGF-I is essential for normal growth of children's bones, cartilage, and organs by stimulating uptake of glucose, fatty acids, and amino acids into tissues. IGF-I is the principal hormone for linear growth and directly mediates GH actions. Primary IGFD is characterized by absent IGF-I production despite normal or elevated GH release.

Class Summary

Indicated for long-term treatment of severe, primary insulin-like growth factor-I (IGF-I) due to mutations of the growth hormone receptor (GH-R) or GH-R downstream signaling pathways.

What is short stature defined?What is the difference between growth failure (GF) and short stature?What is short stature?Which lab tests are used to assess short stature?Which provocative tests are performed in the evaluation of suspected growth hormone deficiency (GHD)?How is short stature evaluated?What is the role of recombinant human growth hormone (rhGH) in the treatment of short stature?What is the role of surgery in the treatment of short stature?How is short stature defined?What is the difference between growth failure (GF) and short stature?What are causes and hallmarks of short stature?What is the pathophysiology of short stature?What is the prevalence of short stature in the US?What is the global prevalence of short stature?What is the racial predilection of short stature?What is the sexual predilection of short stature?Which age group has the highest prevalence of short stature?What is the prognosis of short stature?Where are patient education resources about short stature found?What is the focus of clinical history in the evaluation of short stature?What are the signs of a GI etiology for short stature?What are the signs of a cardiac disease etiology for short stature?What are the signs of an infectious etiology for short stature?What are the signs of a pulmonary etiology for short stature?What are the signs of a neurologic etiology for short stature?What are signs of a renal etiology for short stature?What are the signs of an environmental etiology for short stature?How is an accurate and reliable height assessment determined in the evaluation of short stature?How is growth velocity over time documented in the evaluation of short stature?How is height assessment performed in suspected short-limb dwarfism?What is included in the physical exam to evaluate short stature?What is the role of arm span in the evaluation of short stature?What is the role of a midface exam in the evaluation of short stature?What causes of short stature?What are the genetic causes of short stature?Which GI conditions are associated with short stature?What are the endocrine causes of growth failure?What are the genetic causes of panhypopituitarism in patients with short stature?Which endocrine conditions are associated with short stature?What are the genetic causes of normal variant short stature?Which conditions are associated with short stature?What are the differential diagnoses for Short Stature?What is the role of lab testing in the evaluation of short stature?What is the role of imaging studies are in the evaluation of short stature?What is the role of a hearing test in the evaluation of short stature?How is the Bayley-Pinneau method of height predication used in the evaluation of short stature?Which provocative tests are performed in the evaluation of short stature?What is the efficacy of medical treatment of short stature?What is the role of surgery in the treatment of short stature?Which specialist consultations are beneficial to patients with short stature?Which dietary modifications are used in the treatment of short stature?Which activity modifications are beneficial in the treatment of short stature?What are the possible complications of short stature?How is short stature prevented?What is included in the long-term monitoring of patients with short stature?What are the Pediatric Endocrine Society guidelines for growth hormone (GH) and insulin-like growth factor-I treatment in patients with short stature?Which medications are used in the treatment of short stature?Which medications in the drug class Insulin-like growth factor-I are used in the treatment of Short Stature?Which medications in the drug class Growth Hormone are used in the treatment of Short Stature?

Author

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

Disclosure: Nothing to disclose.

Specialty Editors

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

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

Disclosure: Nothing to disclose.

Additional Contributors

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

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

References

  1. [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. [View Abstract]
  2. 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. [View Abstract]
  3. 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. [View Abstract]
  4. 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. [View Abstract]
  5. 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. [View Abstract]
  6. 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. [View Abstract]
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  11. 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. [View Abstract]
  12. 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. [View Abstract]
  13. 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. [View Abstract]
  14. 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. [View Abstract]
  15. 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. [View Abstract]
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  17. 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. [View Abstract]
  18. 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. [View Abstract]
  19. 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. [View Abstract]
  20. 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.
  21. [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. [View Abstract]
  22. 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. [View Abstract]
  23. Zayed S, Madlon-Kay DJ. Growth Hormone for Treatment of Idiopathic Short Stature in Children. Am Fam Physician. 2015 Jul 1. 92 (1):64. [View Abstract]
  24. Wit JM, Oostdijk W. Novel approaches to short stature therapy. Best Pract Res Clin Endocrinol Metab. 2015 Jun. 29 (3):353-66. [View Abstract]

Comparison of the growth patterns between idiopathic short stature and constitutional growth delay.

Comparison of the growth patterns between idiopathic short stature and constitutional growth delay.

Proper use of a wall-mounted stadiometer.

Bone age comparison between an 8-year-old boy (left) and a 14-year-old adolescent boy (right).

Comparison of the growth patterns between idiopathic short stature and constitutional growth delay.

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.