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The Characteristics of Insulin-like Growth Factor Binding Protein-3(IGFBP-3) in Serum; The Diagnostic Utility of IGFBP-3 in Growth Hormone Deficiency

Journal of the Korean Pediatric Society 1996;39(11):1594-1599.
Published online November 15, 1996.
The Characteristics of Insulin-like Growth Factor Binding Protein-3(IGFBP-3) in Serum; The Diagnostic Utility of IGFBP-3 in Growth Hormone Deficiency
Ki-Joong Kim, Jeh-Hoon Shin, Young-Ik Lee
Department of Pediatrics, College of Medicine, Hanyang University, Seoul, Korea
혈중에서의 3형 인슐린양 성장인자 결합단백 특성 : 성장 호르몬 결핍증 진단에 인슐린양 성장인자 결합단백-3(IGFBP-3)의 유용도
김기중, 신재훈, 이영익
한양대학교 의과대학 소아과학교실
Abstract
Purpose
: For diagnosis of growth hormone(GH) deficiency in short stature, peak growth hormone levels after pharmacologic stimulation are usually used. In this study, we measured serum IGFBP-3, which is a major binding protein in serum and is considered to be GH-IGF-I axis dependent, levels by radioimmuno assay(RIA) in sera from normal short stature(NSS) children, and patients with GH deficiency children to clarify the utility of IGFBP-3 level as a diagnostic marker for GH deficiency.
Methods
: At the department of Pediatrics, Hanyang University Hospital from November, 1992 to July, 1995, we selected 32 GH deficiency-suspected children on the base of their growth data and bone age. After GH stimulation with clonidine(100-150μg/m2) and L-dopa(200-250 mg/m2), we measured their peak GH levels by the immunoradiometric assay(IRMA) kit(Immunodiagnostic system, UK), IGFBP-3 level by radioimmuno assay(RIA) kit(Diagnostic system labortories, USA).
Results
: 1) The mean IGFBP-3 levels of eight normal short stature(NSS) in Tanner stage I is 2.4±1.5μ g/ml and their stimulated mean peak GH level is 18.7±7.5ng/ml. However, one child in Tanner stage I with nutritional deficiency, IGFBP-3 level is 0.717μg/ml and stimulated peak GH level is 12.2ng/ml. And the mean IGFBP-3 and peak GH levels of two Tanner stage II NSS are 2.2±1.2 μg/ml and 14.3±5.2ng/ml, respectively. 2) The mean IGFBP-3 level of five partial GH deficient(PGHD) children in Tanner stage I is 1.8±1.1μg/ml, and their stimulated mean peak GH level is 8.2±1.3ng/ml. The mean IGFBP-3 level of five PGHDs in Tanner stage II is 2.2±0.8μg/ml, and their stimulated mean peak GH level is 7.5±1.5ng/ml. 3) The mean IGFBP-3 level of six complete GH deficient(CGHD) children in Tanner stage I is 0.7±0.6μg/ml, and their stimulated peak GH level is 1.0±1.2ng/ml. The mean IGFBP-3 level of three complete GH deficient(CGHD) children in Tanner stage II is 2.2±0.2μg/ml, and their stimulated peak GH level is 2.5±1.4ng/ml. Only one CGHD child in Tanner stageIII, IGFBP-3 level is 5.943μg/ml, and his stimulated peak GH level is 3.3ng/ml. 4) There is no significant difference of mean IGFBP-3 levels between NSS and PGHD in Tanner stage I, but the mean IGFBP-3 level is significant difference between NSS and CGHD in Tanner stage I(p<0.05). 5) The sensitivity of IGFBP-3 for CGHD and PGHD less than 9 years old is 83%, 75% and for all age is 80%, 55%, respectively. The sensitivity of IGFBP-3 for GH deficiency in less than and older than 9 years is 80%, 67%, respectively. The specificity of IGFBP-3 for NSS is 64%.
Conclusion
: Because serum IGFBP-3 levels may increased during puberty due to mechanisms independent of the GH-IGF-I axis, it is difficult to distinguish GH deficiency from NSS in older children, but CGHD in Tanner stage I, we may use the basal plasma IGFBP-3 level as a screening test for diagnosing GH deficiency.
Key Words: Insulin-like Growth Factor Binding Protein-3(IGFBP-3), Growth Hormone Deficiency


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