Measurement of IGF-1, IGFBP-3 and free IGF-1 levels by ELISA in growth hormone (GH) deficient children before and after GH replacement

Serum insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) levels reflect the growth hormone (GH) status. A few percent of IGF-1 circulate in a free form which is believed to represent the IGF biological activity. We retrospectively studied the changes of serum IGF-1, serum IGFBP-3, and plasma free IGF-1 levels in growth hormone deficient (GHD) children before and after treatment with recombinant human growth hormone (rhGH) for a period of 6 months and 1 year. Twenty-one GHD children (16 boys and 5 girls) who had the mean chronological and bone ages of 7.7 +/- 0.7 and 4.8 +/- 0.6 years, respectively, were treated with a mean rhGH dose of 11.66 +/- 0.42 U/m2 body surface area/week. Serum IGF-1 level increased from 162.5 +/- 42.9 ng/ml before treatment to 252.8 +/- 49.5 ng/ml (p = 0.007) and 282.7 +/- 86.9 ng/ml after treatment for 6 months and 1 year, respectively. Plasma free IGF-1 also increased from 0.38 +/- 0.30 ng/ml before treatment to 1.21 +/- 0.30 (p = 0.001) and 1.17 +/- 0.42 ng/ml after 6 months and 1 year of treatment. However, serum IGFBP-3 did not significantly increase after treatment. In addition, the free/total IGF-1 ratio decreased after treatment with rhGH. The height velocities at 6 months and 1 year after treatment were negatively correlated with plasma free IGF-1 before treatment. In conclusion, therefore, plasma free IGF-1 levels could serve as a good predictor of growth hormone responses. Furthermore, their circulating levels would be modified by serum IGF-1 status, and possibly, IGFBP-3 protease activity.