Cognitive and White Matter Microstructure Development in Congenital Hypothyroidism and Familial Thyroid Disorders

Context Children with congenital hypothyroidism (CH) are at risk for suboptimal neurodevelopment. Objectives To evaluate neurocognitive function and white matter microstructure in children with permanent or transient CH and to correlate these findings with disease severity. Design, participants and methods A retrospective and prospective observational study was conducted in 39 children with permanent or transient CH, and in 39 healthy children. Cognitive function was assessed by Wechsler Intelligence Scale (WISC-IV) and by other tests; the white matter microstructure was investigated by 3 Tesla magnetic resonance (MRI). Results Children with permanent CH have lower cognitive scores at a median age of 9.5 years than those with transient CH and controls. An IQ score between 71-84 was found in 28.6% of permanent CH and of <70 (p=0.06) in 10.7%. The Processing Speed Index (PSI, p=0.004), sustained visual attention (p=0.02), reading speed (p=0.0001), written calculations (p=0.002) and numerical knowledge (p=0.0001) were significantly lower than controls. Children born to mothers with Hashimoto’s thyroiditis have significantly lower IQ values (p=0.02), Working Memory Index (p=0.03) and PSI (p=0.02). Significantly lower IQ and Verbal Comprehension Index values were found in children with a family history of thyroid disorders (p=0.004; p=0.009), respectively. In children with permanent CH, significant correlations between abnormalities in white matter microstructural, clinical and cognitive measures were documented. Conclusions These findings indicate that children with CH are at risk of neurocognitive impairment and white matter abnormalities despite timely and adequate treatment. The association between offspring cognitive vulnerability and maternal thyroid disorders requires careful consideration.