Endocrine Abstracts

Background: Thyroid hormone is an important regulator of fetal brain development. Low and high maternal free thyroxine concentrations during pregnancy have been associated with less grey matter and cortex volume. However, it remains unknown whether certain areas of the brain are differently affected. We used state-of-the-art brain MRI analyses in the largest mother-offspring imaging cohort worldwide to further elucidate how maternal thyroid function during early pregnancy affects offspring brain morphology.

Aim: To study the association of maternal thyroid function with local offspring cortical development including gyrification indices using vertex-wise analysis without predefined anatomic boundaries.

Methods: We selected participants from a population-based prospective birth cohort with available measurements of maternal TSH or FT4 during the first half of pregnancy and offspring brain MRI scans at age 10 years (n = 1,980). Multivariable linear regression was used to study the associations of gestational TSH and FT4 concentrations and (sub)clinical thyroid disease entities with surface-based cortical measures including cortical thickness, surface area, volume, gyrification and white/gray matter ratio using a vertex-wise approach.

Results: Lower TSH concentrations across the continuum were associated with smaller surface area in the inferior parietal region (β [se]: -0.015 [0.004] mm2 per 1 mU/l TSH). We found an inverted U-shaped association of FT4 with gyrification in the fusiform gyrus. Subclinical (n = 28) and overt hyperthyroidism (n = 20) were associated with smaller surface area in the rostral middle frontal and lateral occipital regions, respectively. Children born to hyperthyroid mothers also had less gyrification in the insular cortex, the pars opercularis of the inferior frontal gyrus and precentral region. Maternal thyroid function was not associated with cortical thickness or volume, or white/gray matter ratio.

Conclusions: Maternal thyroid function is associated with cortical gray matter morphology in specific brain regions. Our finding of less gyrification after gestational hyperthyroidism is in line with studies in hyperthyroid animals and D3 knockout mice. These findings enhance further understanding of previously identified global brain morphology associations. Further research is needed to replicate our findings and assess potential functional consequences related to developmental differences in specific anatomical areas.