Gray matter volume and structural covariance alterations in young males with childhood-onset growth hormone deficiency.

PURPOSE: This study investigated the differences in gray matter volume (GMV), structural covariance, and structural covariance networks between adults with childhood-onset growth hormone deficiency (GHD) and healthy controls (HCs). MATERIALS AND

METHODS

A total of 70 right-handed male participants (32 GHD patients and 38 HCs) underwent high-resolution T1-weighted magnetic resonance imaging. Atlas-based morphometry was conducted to examine regional GMV differences. Structural covariance matrices were generated using inter-regional partial correlations, and graph-based network analyses were performed to assess global and regional network topological properties.

RESULTS

The GHD group exhibited significantly reduced GMV in the bilateral pallidum and nucleus accumbens compared to HCs, while showing increased GMV in regions such as the frontal, parietal, temporal lobes, and thalamus (family wise error-corrected P < 0.05). Structural covariance analysis indicated increased connectivity in the GHD group between the left precentral gyrus and bilateral temporal poles, as well as between the right subgenual anterior cingulate cortex and right superior parietal gyrus (false discovery rate-corrected P < 0.001). Both groups demonstrated small-world organization in their structural brain networks, with no significant differences in global network metrics across the density range of 0.1 to 0.5. Regional analyses revealed variations in clustering coefficient, nodal degree, and betweenness centrality, predominantly in somatomotor network regions and areas associated with self-reflection and semantic processing. However, these regional findings did not survive false discovery rate correction for multiple comparisons.

CONCLUSION

Despite preserved global brain network organization, childhood-onset GHD demonstrates region-specific GMV abnormalities and altered local structural connectivity, which may impact brain regions involved in motor, cognitive, and emotional regulation.