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Perfluorinated acids (PFAs) are widespread global and human blood organohalogen contaminants. These monomer decomposition products used in surface treatment products and in fluoropolymer manufacturing and fire fighting may disrupt maternal thyroid hormone homeostasis given that animal studies demonstrate an apparent hypothyroxinemic condition upon PFA exposure. Firstly, we developed a method for properly quantifying perfluorohexane sulfonate (PFHxS), a PFA suspected of overreporting in past literature. We then investigated whether perfluorooctanoate (PFOA), PFHxS and perfluorooctane sulfonate (PFOS) were determinants of maternal hypothyroxinemia in a pregnant women population from Edmonton using a case-control design. Free thyroxine (fT4) and thyroid stimulating hormone (TSH) were screened in 974 women collected during 15-20 weeks of pregnancy. Cases (n=96, hypothyroxinemic: normal TSH and fT4: lowest 10th percentile) and controls (n=175, fT4: 50th and 90th percentile) were matched based on age and physician. Conditional logistic regression indicated that these PFAs are not associated with maternal hypothyroxinemia. / Environmental Health Sciences

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Congenital hypothyroidism (CH), a pediatric endocrine condition that results in early thyroid hormone (TH) insufficiency, is associated with visuospatial dysfunction suggestive of selective dorsal visual stream impairment. However, the ventral visual stream has not been adequately investigated in this population and so the effect of early TH insufficiency on development of the two streams had not been clearly established. This thesis used a comprehensive set of neuropsychological and experimental tests to assess higher-order visual functions in children and adolescents with CH compared with typically developing individuals. The results show that while CH is associated with poorer performance on tasks tapping into dorsal stream functions such as judgment of line orientation, spatial localization, three-dimensional block and two-dimensional mental construction, judgment of object location, and mental rotation, performance on typical ventral stream tasks such as identity discrimination, including abstract shapes, faces, and buildings, is relatively unimpaired. Thus this thesis establishes that the dorsal visual stream is selectively vulnerable to TH insufficiency. In addition to the investigating the nature of the higher-order visual problems in CH, this thesis explores the mechanism underlying these problems and assesses whether they result from organizational effects by early TH or activational effects by current TH levels. The data support the organizational mechanism and suggest that prenatal TH insufficiency results in irreversible changes to the dorsal visual stream due to the timing of dorsal stream development, which occurs earlier than ventral stream development and is thus more vulnerable to insult.

Congenital hypothyroidism (CH), a pediatric endocrine condition that results in early thyroid hormone (TH) insufficiency, is associated with visuospatial dysfunction suggestive of selective dorsal visual stream impairment. However, the ventral visual stream has not been adequately investigated in this population and so the effect of early TH insufficiency on development of the two streams had not been clearly established. This thesis used a comprehensive set of neuropsychological and experimental tests to assess higher-order visual functions in children and adolescents with CH compared with typically developing individuals. The results show that while CH is associated with poorer performance on tasks tapping into dorsal stream functions such as judgment of line orientation, spatial localization, three-dimensional block and two-dimensional mental construction, judgment of object location, and mental rotation, performance on typical ventral stream tasks such as identity discrimination, including abstract shapes, faces, and buildings, is relatively unimpaired. Thus this thesis establishes that the dorsal visual stream is selectively vulnerable to TH insufficiency. In addition to the investigating the nature of the higher-order visual problems in CH, this thesis explores the mechanism underlying these problems and assesses whether they result from organizational effects by early TH or activational effects by current TH levels. The data support the organizational mechanism and suggest that prenatal TH insufficiency results in irreversible changes to the dorsal visual stream due to the timing of dorsal stream development, which occurs earlier than ventral stream development and is thus more vulnerable to insult.

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