Associations among thyroid function, white matter microstructure, and emotional disturbances in thyroid eye disease

Abstract Objectives To characterize white matter microstructural abnormalities in thyroid eye disease (TED) using tract-based spatial statistics (TBSS) of diffusion tensor imaging (DTI) and diffusion kurtosis imaging (DKI), and to explore their associations with thyroid function and emotional disturbances. Methods 24 TED patients and 27 age-, sex-, and education-matched healthy controls (HC) were enrolled. DTI- and DKI-derived maps were analyzed using TBSS to obtain voxel-wise measures of fractional anisotropy (FA) and mean kurtosis (MK). Correlation analyses were performed among diffusion metrics, thyroid function indices, and psychological state assessment questionnaire scores. Mediation analysis was conducted to further understand the relationships between these variables. Results Compared with DTI, TBSS analysis of DKI revealed more extensive white matter abnormalities in TED after correction for multiple comparisons. TED patients showed significantly reduced MK values in multiple predominantly left-sided white matter tracts and the corpus callosum, whereas FA showed no significant corrected differences. Lower MK values were associated with lower thyroid function levels and greater emotional disturbances. Exploratory mediation analyses identified significant indirect effects linking thyroid function with emotional disturbances through altered white matter tracts. Conclusions TED is associated with subtle white matter microstructural abnormalities detectable by DKI, particularly in predominantly left-sided tracts. Altered white matter integrity showed exploratory associations with thyroid hormone levels and emotional disturbances and may represent a potential correlate of their relationship in TED.