Assessment of metabolic changes within normal appearing gray and white matter in children with growth hormone deficiency: Magnetic resonance spectroscopy and hormonal correlation

Objective: The pathogenesis of idiopathic growth hormone deficiency (GHD) in children, including possible cerebral metabolic alterations, remains unclear. The aim of the study was to evaluate metabolic changes within the normal appearing brain in children with GHD using MR spectroscopy (MRS) and to correlate MRS measurements with hormonal concentrations and with pituitary gland size. Methods: Seventy children with GHD (mean age 7.8 yrs) and 11 healthy controls (mean age 8.4 yrs) were enrolled in the study. The MRS examinations were performed on a 1.5T scanner. Voxels were located in the posterior cingulate gyrus (PCG) and the left parietal white matter (PWM). The NAA/Cr, Cho/Cr and mI/Cr ratios were analyzed. The metabolite ratios, pituitary gland size and hormonal concentrations: growth hormone (GH) in two stimulation tests and GH during the night, as well as IGF-1 (insulin-like growth factor) and IGFBP3 (insulin-like growth factor-binding protein) levels were also correlated. Results: There was a significant (p < 0.05) decrease of the NAA/Cr ratios in PCG and PWM in children with GHD compared to the normal subjects. Other metabolite ratios showed no significant differences. We also found significant positive correlations between NAA/Cr ratio in PWM and IGFBP3 level, as well as with GH concentration in a stimulation test with glucagon. Conclusions: The reduction of NAA/Cr ratios may suggest loss of neuronal activity within normal appearing gray and white matters in children with GHD. MRS could be a sensitive marker of cerebral metabolic disturbances associated with GHD and maybe used as an additional indicator for therapy with recombinant GH.