ESPE Abstracts

Thyroid hormone is the only hormone for which all babies are screened at birth. This is because it has been known for decades that the consequences of thyroid hormone insufficiency during postnatal development, cretinism, are severe and irreversible. However, the last 15 years have witnessed major, and unexpected, insights how thyroid hormone acts during prenatal brain development across vertebrates. For instance, even mild maternal hypothyroidism or hyperthyroidism during early pregnancy are associated with IQ loss and modified brain structure in their children. Other recent insights include the tight control of tissue thyroid hormone levels by deiodinases and the existence of membrane thyroid hormone transporters (THTs). Mutations in THTs are associated with Allen Dudley Hernon syndrome, a severe form of intellectual and physical disability. In parallel to this increased understanding, we are witnessing an unprecedented increase in autism spectrum disorders (ASD) incidence, often correlated with IQ loss. Although, changes in diagnosis and awareness contribute to the ASD increase, many authors consider that environmental factors are implicated. Four arguments support this hypothesis. First, numerous chemicals are found routinely in human amniotic fluid including, pesticides, plasticizers (such as phthalates, BPA), nitrates, perchlorate, antimicrobials (such as Triclosan), flame-retardants, surfactants and mercury. Second, many chemical categories are demonstrated thyroid hormone disruptors. Third, prenatal exposure to many chemicals is significantly associated with IQ loss and/or increased ASD risk. Fourth, chemical production has risen exponentially in the last few decades, continually increasing exposure. I shall present data on how we exploit the evolutionary conservation of thyroid signalling to use transgenic Xenopus as a screening tool for environmental chemicals affecting thyroid hormone signalling and brain development. I shall also consider the evidence that interference with thyroid hormone orchestration of human brain development could be implicated in the observed increase in neurodevelopmental disease as well as in significant IQ loss at a population level, engendering enormous socio-economic costs.