| Purpose:pediatric growth hormone deficiency (GHD) is a group of endocrine diseases featured by short stature and limited linear growth velocity, resulting from decreased growth hormone (GH) secretion from anterior pituitary gland. Cognitive impairment is suspected in GHD children for the evidence of GH/IGF-1 axis on relating brain regions. We aim to investigate the brain structures and functions by employing multi-modal magnetic resonance imaging techniques, combining evaluation of their endocrine status and intelligent quotient.Methods:school-aged patients with complete pediatric growth hormone deficiency were recruited from endocrine clinics of Peking Union Medical College Hospital since 2013. Children with a bone age smaller than chronological age but a normal growth velocity and GH/IGF-1 levels were recruited as controls. Data from structural imaging, diffusion tensor imaging, resting-state functional MRI and full Wechsler Intelligence Scales for Children were analyzed for brain structure and function investigations.Results:GHD group (n=11) and control group (n=10) were matched for age (10.36±0.61 vs 9.21±0.54), gender (male ratio 81.8% vs 70.0%) and family social economic status. Children with GHD showed decreased scores in IQ, verbal comprehension, perceptual reasoning, working memory and processing speed index. Group difference revealed an increased mean diffusion in both corticospinal tracts. Correlation studies (p<0.05) showed significant positive correlation between serum IGF-1 levels and IQ, working memory and processing speed index. IGF-1 levels are positively correlated with volumes of left thalamus, pallidum and right putamen while negatively correlated with cortical thickness of multiple regions including middle and inferior occipital lobe. Fraction anisotropy of right corticospinal tract and superior longitudinal fasciculus showed negative correlation with serum IGF-1 levels. Regional Homogeneity (ReHo) in left hippocampus and parahippocampal gyrus shows negative correlation with serum IGF-1 levels while amplitude of low frequency fluctuations (ALFF) and ReHo in precentral gyri, postcentral gyri and paracentral lobules were negatively correlated with IGF-1 levels, the latter being a mediate factor between IGF-1 levels and working memory index.Conclusion:patients with GHD displayed mild cognitive impairment in dimensions of verbal comprehension, perceptual reasoning, working memory, processing speed and total IQ, with the latter three scales IGF-1 levels were positively correlated. Abnormalities in volumes of subcortical nuclei such as thalamus, cortical thickness such as middle occipital lobe, diffusion features of corticospinal tracts, resting-state brain activities in regions including hippocampus, parahippocampal gyrus, precentral gyri, postcentral gyri, paracentral gyri may suggest brain features of GHD children. These findings provide novel insights of possible targets of GH/IGF-1 axis and may underline the mechanisms of impaired cognitive functions in GHD children. |
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