Inaccuracy of insulin-like growth factor (IGF) binding protein (IGFBP)-3 assessment in the diagnosis of growth hormone (GH) deficiency from childhood to young adulthood: association to low GH dependency of IGF-II and presence of circulating IGFBP-3 18-kilodalton fragment.
BACKGROUND
Poor sensitivity of IGF binding protein (IGFBP)-3 assessment in the work-up of GH deficiency (GHD) has been ascribed to the equal affinity of IGFBP-3 for IGF-I and IGF-II and to IGFBP-3 proteolysis.


OBJECTIVE
The objective of this study was to determine the IGF-II GH dependency and IGFBP-3 proteolysis in patients with GHD from childhood to young adulthood.


METHODS
This study was cross-sectional.


METHODS
This was a national multicenter study performed in university hospitals.


METHODS
One hundred thirty-one subjects (chronological age, 1.3-25 yr), 72 patients with GHD and 59 subjects with idiopathic short stature, were studied.


METHODS
IGF-I, IGF-II, and IGFBP-3 serum concentrations were measured by immunoradiometric assay. IGFBP-3 circulating forms were assessed by Western immunoblot (WIB) analysis.


METHODS
Main outcome measures were sensitivity and specificity of IGF-I, IGF-II, and IGFBP-3 measurements.


RESULTS
Sensitivity and specificity of IGFBP-3 measurement were 27 and 100%, respectively. IGFBP-3 sensitivity was 46% in young adulthood. Sensitivity and specificity of IGF-I were 69 and 81%, respectively. Sensitivity and specificity of IGF-II assessment were 23 and 97%, respectively. IGFBP-3 WIB revealed the presence of the intact form and the major 29-kDa fragment in both GHD and subjects with idiopathic short stature. In patients with GHD, WIB showed the presence of an additional smaller IGFBP-3 fragment migrating at approximately 18 kDa.


CONCLUSIONS
Our results suggest that in children and young adults with GHD, the low GH dependency of IGF-II together with IGFBP-3 proteolytic activity yielding the 18-kDa fragment concur to reduce the sensitivity of IGFBP-3 assessment, ultimately making it too inaccurate as a screening test in the work-up of GHD.
Cianfarani
Stefano
S
Rina Balducci Center of Pediatric Endocrinology, Department of Public Health and Cell Biology, Room E-178, Tor Vergata University, Via Montpellier 1, 00133 Rome, Italy. stefano.cianfarani@uniroma2.it
Liguori
Alice
A
Boemi
Sergio
S
Maghnie
Mohamad
M
Iughetti
Lorenzo
L
Wasniewska
Malgorzata
M
Street
Maria E
ME
Zucchini
Stefano
S
Aimaretti
Gianluca
G
Germani
Daniela
D
D000293:Adolescent; D000328:Adult; D002648:Child; D003430:Cross-Sectional Studies; D005260:Female; D019382:Human Growth Hormone / Q000172:deficiency*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007335:Insulin-Like Growth Factor II / Q000032:analysis*; D008297:Male; D010446:Peptide Fragments / Q000097:blood*
D018972:Insulin-Like Growth Factor Binding Protein 3; D010446:Peptide Fragments; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II