Tag Archives: idiopathic short stature

Why some kids are short & understanding linear growth

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If you want to explore the biological basis for short stature, then an excellent review (YH Jee, J Bacon. J Pediatr 2016; 173: 32-7) is worthwhile.

The article begins by explaining the reasons why linear growth is rapid in infancy, slows in childhood and accelerates in adolescence through a process of growth plate chondrogenesis.  In addition, the idea that growth plate fusion causes growth cessation is not accurate.  Fusion of the growth plate occurs because of growth cessation. In addition, in many with “catch-up growth” the “delay in maturation appears to be driven by subtle undernutrition due to diminished appetite.”

Altered Growth Plate Chondrogenesis:

  • Nutritional intake -excess and inadequate nutrient intake affects growth, often through modulation of endocrine hormones.  Overnutrition accelerates linear growth “but the adult height is not substantially affected.”
  • Hormones –thyroid hormones, growth hormone, IGF-1, androgen, and estrogen all positively regulate linear growth.  Glucocorticoids negatively regulate linear growth.
  • Inflammatory cytokines –these cytokines (including TNF-α, IL-6, IL-1β) negatively regulate chondrogenesis
  • Paracrine growth factors, Extracellular Matrix, Intracellular Proteins –local growth factors can be deficient in those with specific genetic mutations:  FGFR3 -achondroplasia, GNAS -Albright hereditary osteodystrophy, PTH1R -Blomstrand chrondrodysplasia, PTPN11 (& others) -Noonan, SHOX -Langer mesmeric dysplasia.  SHOX mutations accounts for 2-5% of children with formerly idiopathic short stature.  SHOX gene is also involved in Turner syndrome short stature. More listed in their Table (pg 35).

My take: It is cool to see the evolved understanding of the various factors affecting stature.  While the authors conclude that exome sequencing will alter the diagnostic approach to children with severe short or tall stature, it seems that a genetic panel would be quite practical and less expensive than many endocrinological evaluations.

Related blog post: Here’s Why Biologic Therapy for Crohn’s Helps Adolescents …

Imodium

Treatment of Short Stature

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While gastroenterology focuses more on being skinny than being short, understanding the current treatment approach to short stature is important.  Certainly, this is a common condition in a pediatric gastroenterology practice.  An update is available: NEJM 2013; 368: 1220-8.

This article presents the case of an 11-year-old with probable constitutional delay of growth and puberty (CDGP) who is projected to achieve an adult height of 5 ft 5 in.  It asks the question of the optimal management but does not answer this definitively.

Background:  Most children with short stature have either CDGP or familial short stature and are generally healthy.  The FDA has approved human growth hormone therapy for children with idiopathic short stature and height below the 1st percentile.  In the U.S. this amounts to more that 500,000 children (1% of children 4-13 years).  However, growth hormone is expensive $10,000-60,000 per year and achieves modest results, 1.2-2.8 inches in added final stature.

Key Recommendations:

  • Thorough evaluation of short stature especially if child’s height deficit is severe (<1st percentile for age), the growth rate is abnormal (<10% for bone age), predicted height is significantly different from midparental height, or body proportions are abnormal.
  • History of intrauterine growth retardation is important since 15% remain short throughout life.
  • Screening labs (according to the authors) include measurement of thyroid assays, checking for renal dysfunction (BUN, creatinine), assessing for inflammatory conditions (eg. sedimentation rate), checking tissue transglutaminase antibody, and assessing hematologic conditions (eg. complete blood count).  In addition, examination should look for evidence of Turner syndrome.
  • The authors discuss growth hormone testing.  IGF-1 serves as a screen but even provocative testing can miss mild cases of growth hormone deficiency.
  • Psychosocial well-being has not predictably improved with growth hormone treatment.
  • Treatment options: observation, growth hormone, or androgen use (eg. oxandrolone).  The latter will expedite growth but not significantly impact long-term height.

Are there risks to growth hormone therapy?

Yes.  There have been occurrences of intracranial hypertension, glucose intolerance, and slipped capital femoral epiphysis. The absolute risks are considered low.  Long-term risks are not entirely clear.  One study suggested a slight increased mortality rate with increased mortality from bone cancer and circulatory disorders.  A similar study did not confirm these findings.

What are the costs?

For idiopathic short stature, the cost has been estimated to be $35,000-50,000 per inch of height.

Who benefits the most?

Predictors of growth hormone response in idiopathic short stature include younger age at baseline, delay in skeletal maturation, and taller parents.  Also, daily administration achieves superior results to less frequent administration.

Related reference:

  • -J Clin Endocrinol Metab 2008; 93: 4210-7.  Consensus statement on the diagnosis and treatment of children with idiopathic short stature.