Tag Archives: constitutional pubertal and growth delay

Here’s Why Biologic Therapy for Crohn’s Helps Adolescents Grow

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It is well-recognized that Crohn’s disease is associated with delays in the onset and progression of puberty with the potential for stunted growth, impaired bone accrual, and diminished quality of life.

Now, a study (MD DeBoer et al. J Pediatr 2016; 171: 146-52) shows that initiation of anti-tumor necrosis factor α (anti-TNFα) treatment results in a rapid increase in sex hormone and gonadotropin levels.

In 72 adolescents, this observational study followed levels of sex hormones, gonadotropin levels, dual-energy x-ray absorptiometry, along with cytokine/inflammatory markers at initiation of anti-TNFα therapy, at 10 weeks and at 12 months.

Key findings:

  • By week 10 , testosterone z scores in males increased from a median of -0.36 to 0.40 (P<0.05)
  • By week 10 , estradiol z scores in females increased from a median of -0.35 to -0.02 (P<0.01)

My take (from the authors): This study suggests that “systemic inflammation suppresses gonadotropin-stimulated production of sex hormones” and that treatment of this inflammation with anti-TNFα agents allows rapid resumption normal production.

Related blog posts:

Law Quad, Univeristy of Michigan

Law Quad, Univeristy of Michigan

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.