INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-3 GENERATION - AN INDEX OFGROWTH-HORMONE INSENSITIVITY

GH insensitivity may be an inherited condition or may arise as a conse quence of disease or malnutrition. Laron syndrome is the most severe f orm of GH insensitivity, arising from an absent or defective GH recept or. Less severe forms of GH insensitivity, however, may exist, resulti ng in short stature but in few other features of Laron syndrome. We ha ve identified a heterogeneous group of children with short stature and either high basal (>10 mU/L) or high peak GH levels (>40 mU/L) on GH provocation testing, to examine biochemical markers of GH sensitivity. These children received 4 d of GH (0.1 U/kg) and the increment in IGF -I, IGF binding protein (BP)-3, and GHBP was determined. Eight GHD chi ldren, commencing GH therapy, were recruited as positive controls. The two groups could not be differentiated by age, height SDS (SD score), height velocity SDS, or body mass index. IGF-I and IGFBP-3 generation were correlated in all children (Delta SDS IGF-I versus Delta SDS IGF BP-3, r = 0.49, p = 0.03). Neither basal GHBP levels or the increment in GHBP were predictive of the IGF-I or IGFBP-3 response to GH. The GH I group had a significantly reduced IGFBP-3 response to stimulation wi th 4 d of GH (median percent increment in IGFBP-3, 26%, versus 72% in the GHD group, p = 0.03); their IGF-I response to GH was also reduced (median % increment in IGF-I 75% versus 144% in the GH deficient group ), but this did not achieve significance, p = 0.06. In all children, t he percentage rise or Delta SDS in both IGF-I and IGFBP-3 inversely co rrelated with the GH peak obtained on provocation testing, the latter being the most significant determinant of GH peak. We propose that the ''IGF generation test,'' in particular IGFBP-3 generation, can be use d in the investigation of partial GH insensitivity. Further work, howe ver, is required to establish diagnostic criteria for partial GH insen sitivity.