National Cooperative Growth Study substudy VI: the clinical utility of growth-hormone-binding protein, insulin-like growth factor I, and insulin-like growth factor-binding protein 3 measurements.
OBJECTIVE
To assess the clinical utility of growth-hormone-binding protein (GHBP), along with growth hormone (GH), insulin-like growth factor I (IGF-I), and insulin-like growth factor-binding protein 3 (IGFBP-3), levels in the evaluation of short stature.


METHODS
Prospective substudy of the National Cooperative Growth Study, a multicenter observational study.


RESULTS
A total of 6447 assessable subjects undergoing workup for short stature were enrolled at 197 sites. At baseline the cause of short stature was undefined in 77% of subjects. Mean GHBP levels were lowest in subjects with renal disease and highest in those with Turner syndrome. No cases of complete GH insensitivity syndrome (Laron syndrome) were identified. Subjects with low GHBP levels were among those tested for GH receptor mutations. IGF-I standard deviation scores (SDS) and IGFBP-3 SDS were positively correlated; both increased during GH therapy. There was a weak positive correlation between log peak GH levels and both IGF-I SDS and IGFBP-3 SDS and a weak negative correlation between log peak GH levels and GHBP SDS. Mean changes in GHBP SDS in subjects treated with GH and untreated subjects were not significant. Change in height SDS in subjects treated with GH was negatively correlated with age and IGF-I level but not correlated with baseline GHBP SDS.


CONCLUSIONS
GHBP levels are GH independent and not predictive of responses to GH therapy, although low GHBP levels may indicate GH receptor abnormalities and partial GH insensitivity.
Attie
K M
KM
Department of Medical Affairs, Genentech, Inc., South San Francisco, California 94060, USA.
Julius
J R
JR
Stoppani
C
C
Rundle
A C
AC
D000367:Age Factors; D001827:Body Height / Q000187:drug effects; D002170:Canada; D002352:Carrier Proteins / Q000097:blood*; D002648:Child; D005069:Evaluation Studies as Topic; D005260:Female; D005500:Follow-Up Studies; D005544:Forecasting; D006128:Growth / Q000187:drug effects; D006130:Growth Disorders / Q000097:blood* / Q000188:drug therapy / Q000235:genetics; D019382:Human Growth Hormone / Q000097:blood* / Q000235:genetics / Q000627:therapeutic use; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D007674:Kidney Diseases / Q000097:blood; D008297:Male; D009154:Mutation / Q000235:genetics; D011446:Prospective Studies; D011986:Receptors, Somatotropin / Q000235:genetics; D013577:Syndrome; D014424:Turner Syndrome / Q000097:blood; D014481:United States
D002352:Carrier Proteins; D018972:Insulin-Like Growth Factor Binding Protein 3; D011986:Receptors, Somatotropin; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; C051815:somatotropin-binding protein