1. 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
- Author
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Stefano Zucchini, Gianluca Aimaretti, Alice Liguori, Maria E. Street, Daniela Germani, Mohamad Maghnie, Stefano Cianfarani, Malgorzata Wasniewska, Sergio Boemi, and Lorenzo Iughetti
- Subjects
Adult ,Male ,medicine.medical_specialty ,Adolescent ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Clinical Biochemistry ,Context (language use) ,Biochemistry ,Insulin-like growth factor-binding protein ,Insulin-like growth factor ,Endocrinology ,Insulin-Like Growth Factor II ,Internal medicine ,IGFBP-3 ,GHD ,IGF-I ,IGF-II ,child ,adolescent ,multicenter study ,medicine ,Humans ,Insulin-Like Growth Factor I ,Young adult ,Child ,GH deficiency ,Immunoradiometric assay ,biology ,Human Growth Hormone ,Binding protein ,Biochemistry (medical) ,medicine.disease ,Peptide Fragments ,Idiopathic short stature ,IGF-2 ,Cross-Sectional Studies ,Insulin-Like Growth Factor Binding Protein 3 ,IGF-1 ,Insulin-like growth factor 2 ,biology.protein ,Female - Abstract
Context: 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. Design: This study was cross-sectional. Setting: This was a national multicenter study performed in university hospitals. Patients:One hundred thirty-one subjects (chronological age, 1.3–25 yr), 72 patients with GHD and 59 subjects with idiopathic short stature, were studied. Interventions: 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. MainOutcomeMeasures:Mainoutcomemeasuresweresensitivity and specificity of IGF-I, IGF-II, and IGFBP-3 measurements. Results:SensitivityandspecificityofIGFBP-3measurementwere27 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. (J Clin Endocrinol Metab 90: 6028–6034, 2005)
- Published
- 2005