COMPARISON BETWEEN INSULIN-LIKE GROWTH FACTOR-I (IGF-I) AND IGF BINDING PROTEIN-3 (IGFBP-3) MEASUREMENT IN THE DIAGNOSIS OF GROWTH-HORMONE DEFICIENCY

To analyze the utility of insulin-like growth factor-I (IGF-1) and ins ulin-like growth factor binding protein-3 (IGFBP-3) radioimmunoassay i n the diagnosis of growth hormone deficiency (GHD) we measured IGF-I a nd IGFBP-3 in sera from normal children (n=309), short children (n=99) and patients with GHD (n=73). In 80% and 93% of classical GHD (cGHD), IGF-I and IGFBP-3 levels, respectively, were below the age-related cu toff levels (lower limit). In 81% and 88% of normal short children (NS ), IGF-I and IGFBP-3 levels, respectively, were above the age-related cutoff levels. Thus, both IGF-I and IGFBP-3 were good parameters for s creening GHD. In contrast, in more than half of partial GHD (pGHD), ei ther IGF-I or IGFBP-3 was above the age-related cutoff levels. The poo r discrimination between patients with pGHD and NS by using these two parameters may be the result of their relatively similar GH levels, as compared to cGHD, or due to the limitations of GH stimulation tests. In about 80-90% of NS, IGF-I and IGFBP-3 were above the age-related cu toff levels at all ages. A hundred percent of cGHD under 10 years old had IGFBP-3 below the age-related cutoff levels, whereas 79% of cGHD u nder 10 years old had IGF-I below the age-related cutoff levels. Thus in the younger age groups, IGFBP-3 may be more sensitive than IGF-1. I t may be because IGFBP-3 levels are relatively higher than those of IG F-I in younger subjects. IGFBP-3 may be less sensitive for diagnosing GHD in older children than in younger children because IGFBP-3 levels may also increase during puberty by mechanisms independent of the GH-I GF-I axis. There was a significant correlation between IGF-I and IGFBP -3 in all the subjects. However, IGF-I and IGFBP-3 classified subjects differently in 25% of patients with GHD and 19% of those with NS. Thi s may reflect differences in daily coefficient of variation in IGF-I a nd IGFBP-3, in assay sensitivity and in non-GH dependent pubertal effe ct. The other explanation for the difference between these two paramet ers in terms of above and below the cutoff levels is that it may be du e to the limitation of GH stimulation tests in the diagnosis of GHD.