Growth Failure

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Short stature may be the normal expression of genetic potential, in which case the growth rate is normal, or it may be the result of a condition that causes growth failure with a lower-than-normal growth rate. [1] Growth failure is the term that describes a growth rate below the appropriate growth velocity for age (see image below).

A child is considered short if he or she has a height that is below the fifth percentile; alternatively, some define short stature as height less than 2 standard deviations below the mean, which is near the third percentile. Thus, 3-5% of all children are considered short. Many of these children actually have normal growth velocity. These short children include those with familial short stature or constitutional delay in growth and maturation, which are normal nonpathologic variants of growth. In order to maintain the same height percentile on the growth chart, growth velocity must be at least at the 25th percentile. When considering all children with short stature, only a few actually have a specific treatable diagnosis. Most of these are children with a slow growth velocity.

The most rapid phase of human growth is intrauterine. Following birth, a gradual decline in growth rate occurs over the first several years of life. The average length of an infant at birth is about 20 inches, the length at age 1 year is approximately 30 inches, the length at age 2 years is approximately 35 inches, and the length at age 3 years is approximately 38 inches. After age 3 years, linear growth proceeds at the relatively constant rate of 2 inches per year (5 cm/y) until puberty.

Normal growth is the result of the proper interaction of genetic, nutritional, metabolic, and endocrine factors. To a large extent, growth potential is determined by polygenic inheritance, which is reflected in the heights of parents and relatives. Secretion of growth hormone (GH) by the pituitary is stimulated by growth hormone–releasing hormone (GHRH) from the hypothalamus. GHRH also stimulates somatotroph proliferation. Another signal, which is stimulated by certain growth hormone–releasing peptides (GHRPs), may be present; the receptor for the GHRPs has been identified, and ghrelin, the natural ligand for these receptors, has been identified. The GHRH receptor is a cell surface-associated seven membrane-spanning domain protein linked to a G protein (Gs). It stimulates intracellular cAMP production after ligand-induced activation.

Ghrelin (from the word ghre, a root word in proto-Indo-European languages meaning grow), is unique in that it is a small polypeptide modified at the third amino acid (serine) by esterification of n-octanoic acid. Ghrelin is a gastrointestinal peptide (synthesized in the stomach) which specifically induces GH secretion. The ghrelin receptor is expressed on the anterior pituitary. Somatostatin secreted by the hypothalamus inhibits growth hormone secretion.

When growth hormone pulses are secreted into the systemic circulation, insulin-like growth factor (IGF)–1 is released, either locally or at the site of the growing bone. Growth hormone circulates bound to a specific binding protein (GHBP), which is the extracellular portion of the growth hormone receptor. IGF-1 circulates bound to one of several binding proteins (IGFBPs). The IGFBP that most depends on growth hormone is IGFBP-3.

United States

In 1994, Lindsay et al studied 114,881 school children in Utah. [2] After 1 year, 79,495 of the original group were available for evaluation. Of these, 555 (0.7%) had heights that were below the third percentile and a growth rate that was less than 5 cm/y. When examined further, causes for short stature within this group of children included familial short stature (37%), constitutional delay (27%), a combination of familial short stature and constitutional delay (17%), other medical causes (10%), idiopathic short stature (5%), growth hormone deficiency (3%), Turner syndrome (3% of girls), and hypothyroidism (0.5%).


Several studies have been conducted to determine the frequency of various causes of short stature. In 1974, Lacey and Parkin evaluated children in Newcastle upon Tyne in England. [3] They studied 2256 children, 111 of whom were below the third percentile in stature. Of the 98 children that they were able to examine, only 16 had evidence of organic disease causing their short stature. Diagnoses included Down syndrome, cystic fibrosis, chronic renal insufficiency, growth hormone deficiency, juvenile rheumatoid arthritis (treated with glucocorticoid), and Hurler syndrome.

Short stature has been thought to have far-reaching effects on psychological well-being, including poor academic achievement (despite normal intelligence, healthy family dynamics, and high socioeconomic status) and behavioral problems (eg, anxiety, attention-seeking actions, poor social skills).

Morbidity related to the underlying cause of the growth failure may also be observed. Some studies involving children who have not been seen in a clinic that treats short stature (and, therefore, may represent a different patient population) have challenged the notion that short stature has psychological implications. At the present time, this issue is not completely resolved.

Mortality rates in children with growth failure relate to the underlying cause of the growth failure. Mortality is not related to growth failure itself; rather, it is related only to the cause of the growth failure.

There is no known racial predilection for growth failure; however, in large databases following children treated with growth hormone, [4] white children appear to be over-represented, compared with children of Asian or African descent. This observation is thought to be probably due to referral bias.

The sex distribution of children treated with growth hormone is about 3 boys for every girl. Recent work in this area suggests that this is mostly due to a referral bias, either from parents themselves or from the referring physician.

[Guideline] New York State Department of Health. Growth, body composition, and metabolism. New York (NY): New York State Department of Health; 2007 Nov. [Full Text].

Lindsay R, Feldkamp M, Harris D. Utah Growth Study: growth standards and the prevalence of growth hormone deficiency. J Pediatr. 1994 Jul. 125(1):29-35. [Medline].

Lacey KA, Parkin JM. Causes of short stature. A community study of children in Newcastle upon Tyne. Lancet. 1974 Jan 12. 1(7846):42-5. [Medline].

Root AW, Kemp SF, Rundle AC, Dana K, Attie KM. Effect of long-term recombinant growth hormone therapy in children–the National Cooperative Growth Study, USA, 1985-1994. J Pediatr Endocrinol Metab. 1998. 11(3):403-12. [Medline].

Rogol AD, Hayden GF. Etiologies and Early Diagnosis of Short Stature and Growth Failure in Children and Adolescents. J Pediatr. 2014 May. 164(5S):S1-S14.e6. [Medline].

Lem AJ, Jobse I, van der Kaay DC, de Ridder MA, Raat H, Hokken-Koelega AC. Health-Related Quality of Life in Short Children Born Small for Gestational Age: Effects of Growth Hormone Treatment and Postponement of Puberty. Horm Res Paediatr. 2012 Mar 21. [Medline].

Rappold G, Blum WF, Shavrikova EP, Crowe BJ, Roeth R, Quigley CA, et al. Genotypes and phenotypes in children with short stature: clinical indicators of SHOX haploinsufficiency. J Med Genet. 2007 May. 44 (5):306-13. [Medline].

Richmond E, Rogol AD. Current indications for growth hormone therapy for children and adolescents. Endocr Dev. 2010. 18:92-108. [Medline].

Grimberg A, DiVall SA, Polychronakos C, Allen DB, Cohen LE, Quintos JB, 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].

Carrel AL, Allen DB. Effects of growth hormone on body composition and bone metabolism. Endocrine. 2000 Apr. 12(2):163-72. [Medline].

Grimberg A, Kutikov JK, Cucchiara AJ. Sex differences in patients referred for evaluation of poor growth. J Pediatr. 2005 Feb. 146(2):212-6. [Medline].

Hindmarsh PC, Brook CG. Short stature and growth hormone deficiency. Clin Endocrinol (Oxf). 1995 Aug. 43(2):133-42. [Medline].

Hintz RL. Growth hormone treatment of idiopathic short stature. Horm Res. 1996. 46(4-5):208-14. [Medline].

Hintz RL. Disorders of growth. Brunwald E, Fauci AS, Isselbacher KJ, et al, eds. Harrison’s Principles of Internal Medicine. 13th ed. New York, NY: McGraw-Hill Medical Publishing Division; 1994.

Horner JM, Thorsson AV, Hintz RL. Growth deceleration patterns in children with constitutional short stature: an aid to diagnosis. Pediatrics. 1978 Oct. 62(4):529-34. [Medline].

Kojima M, Hosoda H, Date Y. Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature. 1999 Dec 9. 402(6762):656-60. [Medline].

Kojima M, Hosoda H, Matsuo H. Ghrelin: discovery of the natural endogenous ligand for the growth hormone secretagogue receptor. Trends Endocrinol Metab. 2001 Apr. 12(3):118-22. [Medline].

Stabler B, Clopper RR, Siegel PT, et al. Academic achievement and psychological adjustment in short children. The National Cooperative Growth Study. J Dev Behav Pediatr. 1994 Feb. 15(1):1-6. [Medline].

Stabler B, Siegel PT, Clopper RR, et al. Behavior change after growth hormone treatment of children with short stature. J Pediatr. 1998 Sep. 133(3):366-73. [Medline].

Tanner JM. Fetus into Man: Physical Growth from Conception to Maturity. Cambridge, Mass: Harvard University Press; 1990.

Tanner JM. Normal growth and techniques of growth assessment. Clin Endocrinol Metab. 1986 Aug. 15(3):411-51. [Medline].

Zemel B. The recognition and treatment of growth disorders – a 50-year retrospective. Ann Hum Biol. 2009 Sep-Oct. 36(5):496-510. [Medline].

Neslihan Gungor, MD Associate Professor of Pediatrics, Division of Endocrinology, Louisiana State University School of Medicine in Shreveport; Pediatric Endocrinologist, LSU Children’s Hospital

Neslihan Gungor, MD is a member of the following medical societies: American Academy of Pediatrics, 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.

George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London) Professor and Chair, First Department of Pediatrics, Athens University Medical School, Aghia Sophia Children’s Hospital, Greece; UNESCO Chair on Adolescent Health Care, University of Athens, Greece

George P Chrousos, MD, FAAP, MACP, MACE, FRCP(London) is a member of the following medical societies: American Academy of Pediatrics, American College of Physicians, American Pediatric Society, American Society for Clinical Investigation, Association of American Physicians, Endocrine Society, Pediatric Endocrine Society, Society for Pediatric Research, American College of Endocrinology

Disclosure: Nothing to disclose.

Sasigarn A Bowden, MD Associate Professor of Pediatrics, Section of Pediatric Endocrinology, Metabolism and Diabetes, Department of Pediatrics, Ohio State University College of Medicine; Pediatric Endocrinologist, Associate Fellowship Program Director, Division of Endocrinology, Nationwide Children’s Hospital; Affiliate Faculty/Principal Investigator, Center for Clinical Translational Research, Research Institute at Nationwide Children’s Hospital

Sasigarn A Bowden, MD is a member of the following medical societies: American Society for Bone and Mineral Research, Central Ohio Pediatric Society, Endocrine Society, International Society for Pediatric and Adolescent Diabetes, Pediatric Endocrine Society, Society for Pediatric Research

Disclosure: Nothing to disclose.

Thomas A Wilson, MD Professor of Clinical Pediatrics, Chief and Program Director, Division of Pediatric Endocrinology, Department of Pediatrics, The School of Medicine at Stony Brook University Medical Center

Thomas A Wilson, MD is a member of the following medical societies: Endocrine Society, Pediatric Endocrine Society, Phi Beta Kappa

Disclosure: Nothing to disclose.

In memory of Stephen Kemp, MD, PhD, a distinguished and beloved mentor, physician, and professor. A unique role model for inspiration, kindness and knowledge.


Growth Failure

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