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Submitted on April 5, 2005
Accepted on August 3, 2005
Department of Public Health and Cell Biology, Tor Vergata University, Rome (SC, AL, DG); Division of Nuclear Medicine, S. Eugenio Hospital, Rome (S.B.); Departments of Pediatrics, IRCCS Policlinico San Matteo, University of Pavia (MM), University of Modena and Reggio Emilia (LI), University of Messina (MW), University of Parma (MES), University of Bologna (SZ); Department of Internal Medicine, University of Turin (GA), Italy
* To whom correspondence should be addressed. E-mail: stefano.cianfarani{at}uniroma2.it.
Context. Poor sensitivity of 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. To determine the IGF-II GH-dependency and IGFBP-3 proteolysis in patients with GHD from childhood to young adulthood.
Design. Cross sectional study.
Setting. National multicenter study performed in University Hospitals.
Patients. 131 subjects (chronological age, 1.3-25 yr), 72 patients with GHD and 59 subjects with idiopathic short stature (ISS) were studied.
Interventions. IGF-I, IGF-II and IGFBP-3 serum concentrations were measured by IRMA. IGFBP-3 circulating forms were assessed by western immunoblot analysis (WIB).
Main Outcome Measures. 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 kD fragment in both GHD and subjects with ISS. In patients with GHD, WIB showed the presence of an additional smaller IGFBP-3 fragment migrating at approximately 18 kD.
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 kD fragment, concur to reduce the sensitivity of IGFBP-3 assessment, ultimately making it too inaccurate as screening test in the work-up of GHD.
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