White matter microstructural abnormalities in children with severe congenital hypothyroidism

Abstract

This study assessed white matter microstructural integrity and behavioral correlates for children with severe congenital hypothyroidism (CH) who were identified and treated early following newborn screening. Eighteen children with severe CH and 21 healthy controls underwent a battery of behavioral measures of hearing, language and communication, along with diffusion MR imaging. Tract-based spatial statistics were performed on standard diffusion parameters of fractional anisotropy and diffusivity metrics. Microscopic diffusion anisotropy mapping based on the Spherical Mean Technique was also used to evaluate biologically specific metrics. Compared with age-matched controls, children with severe CH had poorer hearing and communication skills, albeit generally within normal limits. Children with severe CH had fractional anisotropy that was significantly lower in the cerebellum, bilateral thalami and right temporal lobe, and radial diffusivity that was significantly higher in the cerebellum and bilateral thalami. Microscopic fractional anisotropy and intra-neurite volume fraction were also significantly decreased, and transverse microscopic diffusivity was significantly increased, in the CH group in areas including the cerebellum, thalamus, occipital lobe, and corpus callosum, and in the white matter adjacent to sensorimotor cortex, particularly in the left hemisphere. Significant and widespread correlations were observed between behavioral measures and measures of white matter microstructural integrity in children with CH. The results indicate that children with severe CH who are identified through newborn screening may have significant brain white matter microstructural abnormalities despite early treatment.

Brain Diffusion Tensor Imaging Findings in Hashimoto's Thyroiditis

“…These findings were associated with impaired myelin sheath and axonal membrane integrity in patients with hypothyroidism 27 . In another study, lower FA and higher RD values were detected in CWM and thalami in patients with congenital hypothyroidism 28 . They considered that these results were related to a decrease in density and an increase in orientation dispersion of white matter microstructure 28 .…”

Monocarboxylate Transporter 8 Deficiency: Delayed or Permanent Hypomyelination?

“…This is corroborated by several other reports mentioning local, more subtle WM abnormalities too, as for instance in the periventricular WM tracts (31,32,42) and indicates regionally hypomyelinated areas may still be present in later life. Similar microstructural WM abnormalities were also observed in children with severe congenital hypothyroidism (72). This indicates that a global brain MRI is insufficient to discern between "normal" vs. "abnormal" myelination, and advocates a high-resolution and regional examination of the myelin status of the entire brain, and by extension the spinal cord.…”

“…Children born to hypothyroxinemic mothers have significantly smaller corpus callosums (97), demonstrating that maternal THs during the first half of pregnancy, when the fetal thyroid gland is not yet functional, already promote cellular events that later drive myelination. Children with severe congenital hypothyroidism displayed poorer hearing and communication skills that could be directly correlated to disrupted WM microstructural integrity (72). WM abnormalities were present despite early postnatal treatment with levothyroxine, again underlining the importance of the developmental period for normal myelination (72).…”

“…Children with severe congenital hypothyroidism displayed poorer hearing and communication skills that could be directly correlated to disrupted WM microstructural integrity (72). WM abnormalities were present despite early postnatal treatment with levothyroxine, again underlining the importance of the developmental period for normal myelination (72). Lastly, maternal T 4 levels during early pregnancy correlate with a higher gray to WM ratio in childhood (98), indicating that reaching optimal WM content requires strictly controlled TH levels.…”

“…The observation that myelination still progresses in most AHDS patients, albeit at a slow rate, implies that intracellular TH levels might however not be completely depleted in the MCT8-deficient brain, in contrast to deeply hypothyroid brains, which probably never reach a normal WM content (72). Since in vitro cellular assays demonstrate that most mutations render the MCT8 protein completely inactive (6), OPCs could be supplied with THs via alternative routes.…”