Evaluation of gray-matter and white-matter microstructural abnormalities in children with growth hormone deficiency: a comprehensive assessment with synthetic magnetic resonance imaging.

Background: Pediatric growth hormone deficiency (GHD) is a disease resulting from the impaired growth hormone-insulin-like growth factor-1 (GH-IGF-1) axis, but the effects of GHD on children's behavior and brain microstructural structure alterations have not yet been fully clarified. We aimed to investigate the quantitative profiles of gray matter and white matter in pediatric GHD using synthetic magnetic resonance imaging (MRI).

Methods: The data of 50 children with GHD and 50 typically developing (TD) children were prospectively collected. Group differences in brain volumetric parameters, individual-level T1 and T2 relaxometry values, and myelin volume fraction (MVF) were assessed. Subsequently, magnetic resonance-based indices with significant differences between groups were correlated with clinical variables via partial correlation.

Results: Compared with TD children, children with GHD showed significantly decreased whole-brain gray-matter volume [P false discovery rate (P_FDR) <0.001] and increased non-gray-matter/white-matter/cerebrospinal fluid (NoN) volume (P_FDR<0.001). For gray-matter microstructural profiles, altered T1 and T2 relaxometry values in children with GHD were mainly distributed in the default mode (P_FDR<0.001) and central executive networks (P_FDR<0.001). For white-matter microstructural profiles, widespread increased regional MVF was mainly distributed in the corpus callosum, corticospinal tract, internal capsule, external capsule, and cingulum (all P_FDR values <0.001). Meanwhile, the T2 relaxation values in the left cuneus (r=0.400; P=0.005) and MVF in the right corticospinal tract (r=0.313; P=0.032) had a positive relationship with IGF-1.

Conclusions: Altered T1 and T2 relaxometry values and MVF in gray and white matter indicate the relevance of the default mode, central executive, somatosensory, visual, and cerebellar networks underlying pediatric GHD, which may imply the involvement of the GH-IGF-1 axis and myelin in the pathophysiological mechanism of GHD. Moreover, the brain microstructure alteration in cortico-striatal-limbic loop might be influenced by the GH-IGF-1 axis and play an important role in the behavioral impairments in children with GHD.