Reproducibility in patterns of IGF generation with special reference to idiopathic short stature.
OBJECTIVE
Insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein 3 (IGFBP-3) generation tests are both sensitive and specific measures of growth hormone (GH) sensitivity. Recently, the question of reproducibility of IGF generation tests has been raised. We report our analysis of the correlation of low- and high-dose GH IGF-I and IGFBP-3 generation tests among patients with GH deficiency, GH insensitivity, and idiopathic short stature.


METHODS
A total of 198 subjects were randomized to either high- or low-dose GH for 7 days; the alternate dose was received after a 2-week washout period. Samples were collected at baseline and on days 5 and 8 of GH administration.


RESULTS
The serum concentrations of IGF-I and IGFBP-3 correlated significantly from one test to the other, regardless of the diagnosis. In normal subjects and patients with GH insensitivity and GH deficiency, the delta over baseline in IGF-I and IGFBP-3 in the low-dose test was highly predictive of the delta values in the high-dose test. The delta correlation was greatly diminished, however, in the patient population having idiopathic short stature.


CONCLUSIONS
These observations support partial GH insensitivity effecting IGF-I generation specifically, as a possible etiology for idiopathic short stature, and thus such patients may warrant appropriate biochemical and/or molecular evaluation for partial GH insensitivity.
Selva
Karin A
KA
Department of Pediatrics, Oregon Health & Sciences University, Portland, Oreg. 97239, USA. kselva@lhs.org
Buckway
Caroline K
CK
Sexton
Gary
G
Pratt
Katherine L
KL
Tjoeng
Efi
E
Guevara-Aguirre
Jaime
J
Rosenfeld
Ron G
RG
D000328:Adult; D002648:Child; D004305:Dose-Response Relationship, Drug; D005260:Female; D006130:Growth Disorders / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D019382:Human Growth Hormone / Q000008:administration & dosage* / Q000172:deficiency / Q000494:pharmacology; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000096:biosynthesis* / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis*; D008297:Male; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D012016:Reference Values; D012044:Regression Analysis; D015203:Reproducibility of Results; D013997:Time Factors
D018972:Insulin-Like Growth Factor Binding Protein 3; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I