Growth hormone treatment in children with idiopathic short stature: correlation of growth response with peripheral thyroid hormone action

Clin Endocrinol (Oxf). 2011 Mar;74(3):346-53. doi: 10.1111/j.1365-2265.2010.03924.x.

Abstract

Objective: Idiopathic short stature (ISS) describes short children with normal GH secretion. Although GH treatment increases their heights, growth response to the therapy differs among patients. Thyroid hormones (TH) are essential for longitudinal growth acting mainly through TH receptors (TR) α and β. We have previously reported that GH treatment reduced peripheral TH action in Turner Syndrome by TR down-regulation. The aims of the study were to assess the effect of GH treatment to ISS on peripheral TH action and the correlation between thyroid status and growth response to the therapy. SUBJECTS, DESIGN AND MEASUREMENTS: Eighteen normal (control) and twenty-five ISS children were enrolled and evaluated before and after 12 months of life time (control) or 12 months of GH therapy (ISS). Fasting blood was used for serum biochemical evaluations, peripheral blood mononuclear cells for TR mRNA determination by QRT-PCR and growth parameters by standard methods.

Results: GH treatment modified neither TR mRNA levels nor serum markers of TH action in ISS evaluated as a whole group. However, the individual change in TRβ mRNA levels correlated to the change in sex hormone-binding globulin (SHBG) levels after GH therapy. The growth response to GH correlated positively with the change in TRα mRNA level and negatively with that in TRβ mRNA, TSH and SHBG levels. The change in each TR mRNA isoform after GH treatment correlated negatively with its own basal level.

Conclusions: GH therapy induced individual changes in TR expression in ISS that correlated with their growth response. The basal TR mRNA level could predetermine the change in TR expression and therefore the sensitivity to GH treatment.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Growth Disorders / blood*
  • Growth Disorders / drug therapy*
  • Growth Disorders / genetics
  • Human Growth Hormone / therapeutic use*
  • Humans
  • Immunoassay / methods
  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor Binding Proteins / blood
  • Insulin-Like Growth Factor I / metabolism
  • Osteocalcin / blood
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sex Hormone-Binding Globulin / metabolism
  • Thyroid Hormone Receptors beta / genetics
  • Thyroid Hormones / blood
  • Thyrotropin / blood
  • Time Factors
  • Treatment Outcome

Substances

  • IGFBP3 protein, human
  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor Binding Proteins
  • RNA, Messenger
  • Sex Hormone-Binding Globulin
  • Thyroid Hormone Receptors beta
  • Thyroid Hormones
  • Osteocalcin
  • Human Growth Hormone
  • Insulin-Like Growth Factor I
  • Thyrotropin