Poor reproducibility of IGF-I and IGF binding protein-3 generation test in children with short stature and normal coding region of the GH receptor gene

The IGF-I generation test has been proposed to select patients with GH insensitivity. Studies have shown that children with idiopathic short stature and GH deficiency, who were expected to be sensitive to GH, presented absent IGF-I and IGF binding protein (IGFBP)-3 responses and/or discordant results at IGF-I and IGFBP-3 generation test for unknown reasons. To assess the reproducibility of the generation test, we studied a group of 12 prepubertal children with short stature and normal GH secretion in whom defects in coding region of GH receptor gene were ruled out. All patients underwent the test twice. Discordant responses between the first and second test were found in five and six patients for IGF-I and IGFBP-3, respectively. When the results of the generation tests were compared, one notices that IGF-I generation has more concordant positive results than IGFBP-3. In eight generation tests that showed discordant results between IGF-I and IGFBP-3, seven presented a positive IGF-I with a negative IGFBP-3 response. Taking both tests into account, all children presented a normal IGF-I generation. Our findings showed that IGF-I and IGFBP-3 generation test was not reproducible in children that should have responded to GH stimulation. We suggest that, when IGF-I and IGFBP-3 levels fail to respond in the generation test, another test should be performed to confirm GH insensitivity.