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GH replacement improves numerous metabolic abnormalities in GH-deficient patients; increased lipid peroxidation (LPO) has been observed in GH-deficient patients; however, it is unknown if LPO is influenced by GH replacement.To evaluate the extent to which GH replacement might reverse the increased LPO in GH-deficient adults and to analyse if this phenomenon might be involved in the improvement of metabolic disturbances due to GH treatment. Serum concentrations of malondialdehyde + 4-hydroxyalkenals (MDA + 4-HDA), as an index of LPO, were measured at baseline, and after 12 and 24 months of GH replacement in 40 adult patients with severe GH deficiency (both in adult- and childhood-onset) and in 40 healthy volunteers, matched for sex, age and body mass index (BMI). Correlations were evaluated between LPO and lipids, IGF-I, metalloproteinase-2 and -9 (MMP-2, -9), vascular endothelial growth factor (VEGF), BMI and GH dose.LPO values in GH-deficient patients were several-fold higher than in controls [55·36 ± 2·27 vs. 4·19 ± 0·42 nmol/mg protein (mean ± SEM), P < 0·0001] and decreased significantly over time with GH replacement to 38·61 ± 2·15 nmol/mg protein (i.e. by approximately 30%), though still remaining markedly elevated compared with controls (P < 0·0001). The proatherogenic lipid profile parameters correlated positively with LPO in the childhood-onset subgroup before GH replacement. GH replacement restored the positive correlation between LPO and age in male patients (r = 0·57, P = 0·013; r = 0·8, P < 0·001, at 12 and 24 months of GH replacement, respectively).GH replacement partially reverses the grossly abnormal LPO in GH-deficient adults. It is highly probable, therefore, that oxidative mechanisms are involved in the overall improvement of metabolic changes due to GH replacement.