title: Evidence for partial growth hormone insensitivity among patients with idiopathic short stature. The National Cooperative Growth Study.
abstract: OBJECTIVE
  To determine whether some patients with idiopathic short stature have partial resistance to growth hormone (GH). Patients with idiopathic short stature have decreased serum levels of the GH receptor-related GH-binding protein (GHBP), and low GHBP levels are associated with complete GH insensitivity (Laron) syndrome. We hypothesized that patients with idiopathic short stature and low GHBP levels may also have a degree of GH insensitivity.
  
  
  METHODS
  Retrospective analysis of patients in a multicenter study.
  
  
  METHODS
  Ninety-six National Cooperative Growth Study centers in the United States and Canada.
  
  
  METHODS
  Five hundred eleven patients with idiopathic short stature who were treated with GH. All patients had a baseline height standard deviation score of less than -2 and a maximum stimulated GH level greater than 10 micrograms/L. Of these, 101 (20%) had a baseline GHBP standard deviation score of -2 or less.
  
  
  RESULTS
  The patients with low GHBP levels, in comparison with those with normal GHBP levels, had a lower mean extracted standard deviation score for insulin-like growth factor I (-3.3 +/- 1.1 vs -2.5 +/- 1.4; p < 0.0001) but mean 12-hour GH values (2.8 +/- 1.1 vs 2.3 +/- 1.1 micrograms/L; p <0.0001). The differences between groups were statistically significant after control for age and weight-for-height standard deviation score. Among prepubertal patients, there was no significant difference between the low and normal GHBP groups in mean pretreatment or first-year growth rate (p = 0.74, 0.61 respectively) with comparable doses of GH.
  
  
  CONCLUSIONS
  Patients with idiopathic short stature and low GHBP levels, compared with those with normal GHBP levels, had significantly lower standardized levels of insulin-like growth factor I, and higher mean 12-hour GH levels, which suggest partial GH insensitivity. There was no significant correlation of GHBP levels with the growth response to exogenous GH.
authors.affiliation: Department of Medical Affairs, Genentech, Inc., South San Francisco, CA 94080, USA.
authors.forename: K M
authors.initials: KM
authors.lastname: Attie
authors.forename: L M
authors.initials: LM
authors.lastname: Carlsson
authors.forename: A C
authors.initials: AC
authors.lastname: Rundle
authors.forename: B M
authors.initials: BM
authors.lastname: Sherman
mesh_terms: D001827:Body Height / Q000187:drug effects; D002352:Carrier Proteins / Q000097:blood*; D016022:Case-Control Studies; D002648:Child; D005260:Female; D006130:Growth Disorders / Q000097:blood / Q000188:drug therapy*; D013006:Growth Hormone / Q000097:blood / Q000172:deficiency / Q000627:therapeutic use*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D016014:Linear Models; D008297:Male; D012016:Reference Values; D012189:Retrospective Studies
chemical_list: D002352:Carrier Proteins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; C051815:somatotropin-binding protein