Alterations in the oxidant‐antioxidant status in prepubertal children with growth hormone deficiency: effect of growth hormone replacement therapy

Abstract

Growth hormone deficiency (GHD) in adults is associated with increased oxidative stress determined by the underlying GH-IGF-1 axis alterations. Despite GHD being a common diagnosis in children with short stature, no data on the oxidant/antioxidant status are available in this age group. This study was designed to detect differences in oxidative stress parameters between prepubertal GH-deficient children and healthy controls. Furthermore, the effect of 12 months of conventional GH replacement (rGH) on oxidant-antioxidant status was evaluated in the GHD group only. Ten (nine males and one female) prepubertal children (mean age 9.1 +/- 1.3 years) with GHD were recruited and matched for sex and age (9.2 +/- 1.9 years) with 20 healthy controls (18 males and two females). At study entry, lag phase, an index of susceptibility of low density lipoprotein (LDL) to in vitro oxidation, malondialdehyde (MDA) and vitamin E were measured in all subjects. These parameters were also evaluated in GH-deficient children after 12 months of rGH treatment. The lag phase was significantly decreased in GH-deficient children compared to healthy controls (15.50 +/- 7.4 vs. 43.00 +/- 9.2 min; P = 0.0007), while MDA was significantly increased (1.33 +/- 0.38 vs. 0.46 +/- 0.10 nmol/mg; P = 0.0006). Vitamin E levels were significantly decreased (22.44 +/- 9.57 vs. 35.38 +/- 16.49 micromol/l; P = 0.001). IGF-1 and IGFBP-3 correlated directly to lag phase (r = 0.48; P = 0.01; r = 0.63, P = 0.002, respectively) and to vitamin E (r = 0.59, P = 0.003; r = 0.58, P = 0.006, respectively). By contrast, IGF-1 and IGFBP-3 correlated indirectly to MDA (r = -0.47, P = 0.01; r =-0.65, P = 0.002, respectively). After 1 year of rGH therapy, lag phase (39.32 +/- 15.24 min; P = 0.005) and vitamin E (34.9 +/- 7.7 micromol/l; P = 0.005) increased significantly, while MDA decreased significantly (0.71 +/- 0.42 nmol/mg; P = 0.005), reaching normal levels. These data show that children with GHD have substantially increased oxidative stress parameters compared to healthy controls and demonstrate a normalization of these parameters after 1 year of rGH therapy.