Serum Free Insulin-Like Growth Factor I (IGF-I), Total IGF-I, and IGF-Binding Protein-3 Concentrations in Normal Children and Children with Growth Hormone Deficiency1

To evaluate the role of serum free or unbound insulin-like growth factor I (IGF-I) on bone growth, we measured serum free IGF-I levels in 354 healthy children and adults (193 males and 161 females, aged 0–40 yr) and in 21 prepubertal GH-deficient (GHD) children (complete GHD, n = 5; partial GHD, n = 16) using a recently developed immunoradiometric assay. We obtained the following results. 1) In the normal children, the serum free IGF-I levels were low in infancy (<1 yr of age; males, 0.71± 0.26 μg/L, mean ± sd; females, 1.05 ± 0.49μ g/L), increased during puberty (males, 5.84 ± 2.18 μg/L; females, 5.80 ± 1.49 μg/L), and declined thereafter. 2) Free IGF-I in the serum occupied about 0.95–2.02% of the total IGF-I values, with the highest ratio occurring in infancy (males, 1.77± 0.60%; females, 2.02 ± 0.87%). 3) The sd scores of serum free IGF-I in the 21 GHD children ranged from −3.30 to 0.30, and the 5 complete GHD children had free IGF-I values more than −2 sd below those of age-matched normal subjects. 4) There was a significant correlation between the sd scores of free IGF-I and those of total IGF-I (r = 0.715; P< 0.0005) in the GHD children. 5) In the 16 partial GHD children receiving GH treatment, the serum free IGF-I levels were elevated to 209% of pretreatment levels after 1 month of GH treatment and remained high during GH therapy. The GH-induced increase in the serum free IGF-I levels was significantly higher than those of the total IGF-I and IGF binding protein-3 levels. 6) The percent increase in the serum free IGF-I level after 1 month of GH treatment showed a significant positive correlation with that of the GH-induced improvement in the percent increase in the height velocity during 1 yr of GH therapy (r = 0.526; P < 0.05). These results show that free IGF-I in the serum has an essential role in bone formation because the higher free IGF-I levels were observed when the growth rate accelerated. The measurement of serum free IGF-I may become a useful tool for both diagnosing GH deficiency and predicting growth responses to long term GH therapy.