Partial growth hormone insensitivity--idiopathic short stature is not always idiopathic

Heterozygous growth hormone receptor (GHR) gene defects are not a common cause of idiopathic short stature. Although some of these GHR mutations may result in relative insensitivity to growth hormone (GH) in other studies, obligate heterozygotes did not present any clinical manifestations. Although patients with GH insensitivity and elevated GH binding protein (GHBP) levels have been described, it may be a reasonable approach to screen children who have growth failure, low levels of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3, and low levels of GHBP. Whether the sensitivity of this screening approach can be increased by administering pharmacological doses of GH for a few days and measuring the resultant increase in serum IGF-I concentration remains to be determined by ongoing studies.