Evidence for partial growth hormone insensitivity among patients with idiopathic short stature. The National Cooperative Growth Study.
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.
Attie
K M
KM
Department of Medical Affairs, Genentech, Inc., South San Francisco, CA 94080, USA.
Carlsson
L M
LM
Rundle
A C
AC
Sherman
B M
BM
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
D002352:Carrier Proteins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; C051815:somatotropin-binding protein