Cortical thinning in subclinical hypothyroidism: structural and functional brain changes underlying cognitive impairment

Subclinical Hypothyroidism (SHypo), a condition that characteristically presents with normal Thyroid Hormone (TH) levels coexisting with elevated Thyroid-Stimulating Hormone (TSH) levels, has been associated with cognitive impairment. Nonetheless, its neurobiological effects remain somewhat unclear, forming the basis of this study. Herein, using a multimodal neuroimaging approach, we explored cortical thinning and disrupted Functional Connectivity (FC) in SHypo patients—particularly focusing on their relationship with cognitive deficits. Brain areas such as the Prefrontal Cortex (PFC) and Cingulate Gyrus (CG) exhibited substantial cortical thinning. Additionally, a marked decrease in FC was observed between the CG and regions associated with visuospatial processing. Furthermore, serum-free thyroxine (FT4) levels correlated negatively with Cortex Thickness (CT) of the right cuneus. Notably, FC also correlated positively with neuropsychological tests. Besides highlighting the potential for early neural alterations in SHypo, these findings also underscore the significance of early detection and intervention to mitigate cognitive decline.