Growth hormone stimulation testing in both short and normal statured children: Use of an immunofunctional assay

Accurate interpretation of the results of GH stimulation tests is of pivota l importance not only in the evaluation of the etiology of growth retardati on in children but also in the selection of the best candidates for GH ther apy. We performed this study to test a novel immunofunctional GH (IFGH) ass ay that makes use of the concept that one GH molecule dimerizes two GH rece ptors and compared the results with those obtained using two GH assays, the Diagnostic Systems Laboratories ELISA and a Hybritech immunoradiometric as say in 19 children with short stature undergoing routine GK stimulation tes ting. We also tested 13 normally statured control children to revisit the i ssue of what constitutes normal GH responses to stimuli, using all three as says and arginine and either L-dopa or insulin-induced hypoglycemia as secr etagogues. Concentrations of IGF-I, IGF binding protein-3, and acid labile subunit were measured as well. There was a significant correlation between peak IFGH and Diagnostic Systems Laboratories ELISA GH responses to stimuli (r(2) = 0.93) as well as between the Diagnostic Systems Laboratories ELISA and Hybritech immunoradiometric assay (r(2) = 0.91). There were no signifi cant differences between the short stature and normal group in peak or mean GH concentrations regardless of the assay used; however, the IGF-I, IGF bi nding protein-3, and acid labile subunit concentrations were substantially lower in the shea stature group. There was a wide spectrum of GH concentrat ions in the normal group; similar to 50% of the children had peak GR concen trations <7 ng/mL, <similar to>30% (5 ng/mL, and two pubertal normal subjec ts peaked to only 2 ng/ml, with use of both the ELISA and IFGH assays. We c onclude that 1) sensitive GH assays, ELISA and immunoradiometric assay, acc urately detect a GH capable of generating a biologic signal comparable to a n IFGH and 2) that normal GH stimulation test results can be substantially lower than previously accepted. GH-dependent growth factors may be more sen sitive indicators of GH sufficiency than GH concentrations in response to p harmacologic stimuli.