Endocrine Abstracts

Background: The Controlled Antenatal Thyroid Screening II (CATS) study, a large randomised trial of thyroxine supplementation for suboptimal gestational thyroid function (SGTF), reported a higher prevalence of elevated attention deficit hyperactivity disorder (ADHD) scores in 9 year-old children exposed to higher thyroid hormone (TH) in utero. Here we investigated if this was accompanied by altered neurodevelopment.

Methods: 85 children aged 11-16 years (exposed to untreated SGTF (n = 21), normal GTF (n = 24), or treated SGTF (optimally replaced (n = 21), over-treated (n = 19)) recruited from the CATS cohort underwent quantitative characterisation of white matter microstructure and regional brain volumes using 3.0T diffusion MRI. Fractional anisotropy (FA) was measured along white matter tracts known to be influenced by TH and/or implicated in ADHD risk, including the corpus callosum and superior longitudinal fasciculus (SLF).

Results: Maternal TH at 12 weeks’ gestation was not correlated with median FA values for any of the tracts studied, except between TSH and the posterior segment of the corpus callosum (correlation coefficient (τ) -0.2,P = 0.018). The only significant correlation with T4 was found in the right SLF-1 (r -0.57, p 0.028) at 30 weeks’ gestation in the overtreated SGTF group. Weak, but statistically significant positive correlations were found between TSH and brain volume in over 30 regional volumes, notably the nucleus accumbens (r +0.25, P < 0.008) and total cortical volume (r +0.19, p 0.01).

Conclusions: This is the first imaging study to explore tract-specific white matter microstructure in adolescents exposed to both extremes of maternal thyroid function. Weak but consistent correlations suggest maternal TSH levels, but not T4, have an effect on certain cortical volumes. Analysis of free T4 in the treated group suggest that SLF-1, a regulator of motor behaviour, may be a target of TH action in the developing human brain later in pregnancy.