Changes in serum IGF-I and IGFBP-3 concentrations during the IGF-I generation test performed prospectively in children with short stature

OBJECTIVE Genotype and phenotype heterogeneity in patients with GH insensitivity syndrome suggests that partial defects exist in the GH receptor. Children with partial GH resistance would be expected to have short stature, elevated GH levels and relatively low levels of IGF-1 and IGFBP-3. Provocation tests of the GH-IGF-I axis may help to identify such children. The IGF-1 generation test in particular may demonstrate impaired secretion of IGF-1 and IGFBP-3. This prospective study assesses the usefulness of the IGF-1 generation test in the identification of short children with possible GH insensitivity. DESIGN Prepubertal children referred for assessment of short stature underwent a standard GH provocation test followed by an IGF-1 generation test. SUBJECTS Thirty-seven prepubertal children (14 girls, 23 boys) with short stature (height < 2nd centile UK standards 1990) aged 4.5-12.6 years were investigated prospectively. METHODS Assessment included history, physical examination, auxological observations (height, weight, bone age). GH provocation tests (glucagon 15 mu g/kg i.m. or insulin 0.15 U/kg/i.v.) was followed by an IGF-1 generation test (hGH 0.1 iu/kg/s.c. daily for 4 days). MEASUREMENTS GH was assayed during the provocation test. IGF-1 and IGFBP-3 were measured at 0900h on day 0 and 4 of the IGF-1 generation test.