Endocrine disrupting chemicals and thyroid hormone action

Thyroid hormones (predominantly thyroxine, T4, and triiodothyronine, T3) are essential for normal development and for adult physiology. There are several challenges, however, that make identifying chemicals that produce adverse effects by interfering with the thyroid system difficult. First, individual variability in serum concentrations of thyroid hormones represent only about 10% of the population reference range that is considered to be "normal." This means that populations studies evaluating the relationship between chemical exposure and serum thyroid hormones must be large enough to overcome this internal variance. In addition, we know that there are chemicals that do not produce changes in thyroid hormone levels, but nevertheless impact thyroid signaling in target tissues. A good example is that of polychlorinated biphenyls (PCBs). PCB exposure during development are clearly associated with cognitive deficits in humans. But PCB exposure isn't uniformly associated with a reduction in serum thyroid hormone in human populations despite mechanistic studies showing that PCBs reduce serum T4 in animals. In contrast, perchlorate is a chemical that inhibits iodide uptake, thereby reducing thyroid hormone synthesis and serum hormone levels. Human studies have been variable in identifying a relationship between thyroid hormone and perchlorate exposure, but studies also show that dietary iodine, cigarette smoking and other factors can modify this relationship. The conclusion is that identifying chemicals that interfere with thyroid hormone could depend on in vitro analysis of chemicals that interact with different proteins important for thyroid hormone to function properly.