Maternal hypothyroidism and congenital hypothyroidism affected the development of the child’s corpus callosum, resulting in different changes to the size and shape of regions such as the genu and affecting cognitive ability, a presenter said here.

 “The size of specific corpus callosum regions was associated with performance in different cognitive abilities,” said Joanne F. Rovet, MD,of the Hospital for Sick Children and the University of Toronto. “We observed in congenital hypothyroidism, a flat corpus callosum, a smaller and narrower genu and a normal splenium that was unaffected. In the maternal hypothyroidism group, instead, we found a normal shape corpus callosum, a smaller and wider genu and a larger, longer, skinnier splenium.”

In both studies, Rovet and colleagues instituted a quantitative and a qualitative approach, looking at the size and shape of the genu and splenium.

In the maternal hypothyroidism study, Rovet and colleagues looked at 20 children, aged 9 to 12 years (mean age, 10.3 years), born between 1996 and 2001 to women with hypothyroidism. They were age-matched to 22 controls. The researchers conducted a 4-hour neuropsychology exam and performed an MRI on each child.

Children born to mothers who had hypothyroidism during pregnancy showed smaller genus (P=.06) and larger splenium (P=.045) in both an area comparison and proportion comparison. Groups did not differ in overall corpus callosum shape, but they did differ in shape of genu and splenium.

Researchers also found that the children’s corpus callosum size and shape did not correlate with any specific trimester of maternal hypothyroidism, but their size of anterior and posterior segments correlated with duration of hypothyroidism in pregnancy. Anterior segments were smaller for children born to women with two (P=.01) or three (P=.017) trimesters of hypothyroidism vs. the controls. Posterior segments were larger for children born to women with two (P=.032) and three (P=.016) trimesters of hypothyroidism vs. controls. 

Rovet showed that larger anterior corpus callosum was associated with better reading ability, and larger genus was associated with better cognitive flexibility. Smaller isthmus correlated with better nonverbal memory while smaller splenium correlated with better verbal ability, Rovet said.

“Inadequately treated hypothyroidism in pregnancy disturbs corpus callosum development by disrupting the patterning of axonal growth and pruning,” she said.

In the congenital hypothyroidism study, researchers looked at 41 children aged 9 to 16 years (mean age, 12.4 years) whose median onset of congenital hypothyroidism was 13 days, median thyroid-stimulating hormone at diagnosis was 31.1 mU/L and mean thyroxine at diagnosis was 53.9 ± 36.2 nmol/L. They were matched with 42 controls for age (mean age, 12 years), sex and socioeconomic status. They underwent the same testing as in the maternal hypothyroidism group.

Children with congenital hypothyroidism had smaller (P<.01) and narrower (P<.05) genus with an abnormal shape to their overall corpus callosum due to their angle of curvature (P<.001) and less droop of the splenium (P=.017) as well as more “more bulbous” genus than controls.

Researchers found an association of the genu size with matrix reasoning (P=.009), abstract visual memory (P=.005) and visual reasoning (P=.017).

“Youth with [congenital hypothyroidism] show reduced size and width of corpus callosum genu, less curvature, abnormal orientation of splenium and more bulbous genus,” Rovet said. “More severe [congenital hypothyroidism] at diagnosis was associated with reduced size of genu.” – by Katrina Altersitz

PERSPECTIVE

R. Michael Tuttle

·         These findings further verify the critical importance of having normal thyroid functions in the mother and the fetus during pregnancy.  Rather than simply relying on cognitive function testing to prove an effect of hypothyroidism on the fetal brain, the finding of structural differences in specific regions of the corpus callosum clearly document the impact of hypothyroidism on the developing brain.

o    R. Michael Tuttle, MD

o    Professor of medicine 
Attending physician 
Memorial Sloan-Kettering Center

·