Citation:

Gilbert, M., J. Rovet, Z. Chen, AND N. Koibuchi. Developmental Thyroid Hormone Disruption: Prevalence, Environmental Contaminants and Neurodevelopmental Consequences. NEUROTOXICOLOGY. Intox Press, Inc, Little Rock, AR, 33(4):842-52, (2012).

Impact/Purpose:

Thyroid hormones (TH) are critical for growth and development of many organ systems, but particularly for brain development. There are numerous environmental agents that lead to marginal reductions of circulating TH. The EPA must evaluate the risk of exposure of the developing brain to chemicals with the potential to disrupt TH homeostasis, yet the impact of low level TH disruptions induced by environmental contaminants has not been defined. This paper is a synopsis from four invited speakers who presented at the 13th International Neurotoxicology Association meeting held in Xi'an, China in June of2011. Speakers represented expertise in public health, neuropsychology of children with thyroid disorders, and animal research on TH and brain development. Iodine deficiency, a common cause of TH insufficiency and mental retardation in many countries, including China, was addressed. The role of marginal iodine deficiency in the US must be considered in EPA's assessment of risk associated with chemicals that impact the thyroid. Children born with normal thyroid function, but who experienced TH insufficiency in the womb, display subtle cognitive impairments and abnormalities in brain imaging. Despite early detection and treatment, deficiencies also exist in children born with thyroid disorders. Awareness ofthe emerging evidence of persistent deficits in children following mild and brief TH insufficiencies are critical to guide EPA in its regulatory decisions. Recent animal models of low level TH perturbation at the molecular and whole animal level were reviewed and mechanistic studies revealed the shortcomings of current in vitro screening technologies to detect all chemicals with the potential to disrupt the thyroid axis. In summary, epidemiological, preclinical and animal research has clearly identified the critical role of TH in brain development and this synopsis provides an up to date summary of the current state of the science by these key researchers in the field.

Description:

Thyroid hormones (TH) are critical for growth and development and particularly brain development. There are numerous environmental agents that lead to marginal reductions of circulating TH. Although it is clear that severe developmental hypothyroidism is profoundly detrimental to neurodevelopment, there is less information regarding the consequences of modest degrees ofthyroid disruption, especially during critical periods in brain development. The impact of low level TH disruptions induced by environmental contaminants has not been defined. This paper is a synopsis from four invited speakers who presented at the 13th International Neurotoxicology Association meeting held in Xi'an, China during the summer of 2011. An overview of the role of TH in brain development and a review of human and animal data on the neurological sequelae of disruption of the thyroid axis in the pre-and early post-natal periods were presented by Mary Gilbert and Joanne Rovet. Iodine deficiency, a common cause of TH insufficiency and mental retardation in many countries, including China, was addressed by Zupei Chen. In this presentation the current incidence of iodine deficiency and neurological outcome in China and the efficacy of recently implemented iodinization programs to eliminate this cause of mental retardation were reviewed. Joanne Rovet described the impact of TH disruption during pregnancy and under conditions of congenital hypothyroidism. Children born with normal thyroid function, but who experienced TH insufficiency in the womb, display subtle cognitive impairments and abnormalities in brain imaging. Despite early detection and treatment, deficiencies also exist in children born with thyroid disorders. Different patterns ofcognitive effects result from prenatal vs postnatal TH insufficiency. Mary Gilbert reported on the effects of environmental contaminants with thyroid disrupting action on brain development in animals. Results of neurophysiological, behavioural, structural and

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