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

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(100-150mug/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+/-1.5mug/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 0.717mug/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+/-1.2mug/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+/-1.1mug/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+/-0.8mug/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+/-0.6mug/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+/-0.2mug/ml, and their stimulated peak GH level is 2.5+/-1.4ng/ml. Only one CGHD child in Tanner stageIII, IGFBP-3 level is 5.943mug/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%. CONCLUSIONS: 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.