Elucidating the genetic and environmental determinants of congenital hypothyroidism

I first identified genetic defects in SLC26A7 as a novel cause of congenital hypothyroidism (CH), however, its function in the thyroid gland remains unknown. I will characterise its role in thyroid hormone biosynthesis using cultured thyroid cells, thereby providing new insights into thyroid hormone production.

Increasing numbers of babies are being diagnosed with CH with a normally-sited but dysfunctional thyroid gland-in-situ (GIS). I will evaluate the contributions of genetic factors, micronutrient deficiencies of iodine and selenium and exposure to endocrine-disrupting chemicals, such as perchlorate, thiocyanate and nitrate, to GIS CH. A causative role for nutritional deficiencies or disruptors would have significant public health implications.

CH due to DUOX2/DUOXA2 mutations often resolves in childhood, however, I will assess whether female mutation-carriers develop hypothyroidism during pregnancy when thyroid hormone biosynthesis increases. Thyroid dysfunction during pregnancy would provide a basis for future studies to evaluate childhood neurodevelopmental outcomes and effects of levothyroxine treatment in such patients.