High Thyrotropin Is Associated with Reduced Hippocampal Volume in a Population-Based Study from Germany

Previous patient studies suggest that thyroid dysfunction affects volumes of particular regions of the brain. So far, population-based data related to this topic are lacking. The aim of this study was to investigate associations of serum levels of thyrotropin (TSH), free triiodothyronine, and free thyroxine (fT4) with total brain volume, gray matter volume, white matter volume (WMV), and hippocampal volume (HV) in a population-based study.

Data on 2557 individuals were pooled from two independent population-based surveys of the Study of Health in Pomerania conducted in Northeast Germany. Brain volumes were determined from images derived from 1.5 T magnetic resonance imaging. Low and high TSH were defined using the cutoffs 0.40 and 3.29 mIU/L, respectively. Associations between thyroid hormone levels and segmented brain volumes were analyzed by linear regression models. Further, voxel-based morphometry was conducted to search for associations with thyroid hormone levels in a hypothesis-free way throughout the whole brain. All models were adjusted for confounders.

Only 9/70 individuals with high TSH had low free triiodothyronine or fT4 levels. Individuals with high TSH had significantly lower total brain volume (β = -26.9 [confidence interval (CI) -49.0 to -4.8]; p = 0.017), WMV (β = -16.1 [CI -29.4 to -2.7]; p = 0.018), and HV (β = -223 [CI -395 to -50]; p = 0.011) than individuals with TSH within the reference range, while low TSH was not significantly associated with any of the brain volumes. Voxel-based morphometry analyses revealed a significant positive association with serum fT4 levels in the left middle frontal gyrus.

In conclusion, the results of this study indicate that the subclinical hypothyroid state may lead to a reduced brain volume affecting particularly HV in younger subjects and WMV, which might correspond to subtle microstructural changes in white matter fiber tracts or myelination of the axones. Gray matter seems not to be affected by subclinical hypothyroid states.