Do residue levels of polychlorinated biphenyls (PCBs) in human blood produce mild hypothyroidism?

PCBs are nearly ubiquitous environmental contaminants, occurring in most human adipose tissue and blood samples. It has recently been recognized that PCBs and related compounds share important structural properties with thyroid hormones and can bind thyroid hormone binding proteins. It is reasonable that such specific binding interactions can modulate the distribution of these compounds in the body and alter hormone-protein interactions that are responsible for the maintenance of normal thyroid status. Most of the available evidence indicates that the levels of free thyroid hormones in plasma are a reflection of the maintenance of normal thyroid status in any individual. A theoretical model for the transport of thyroid hormones in blood has been extended to estimate the modulating effects of PCBs on free thyroid hormones. Using conservative assumptions based on experimental data, our calculations indicate that PCB concentrations normally found in humans can effect significant increases in free thyroxine levels in serum by competing with serum thyroid hormone binding proteins. Experimental data are discussed which support the proposal that antagonist binding of PCBs to thyroid hormone binding proteins in serum could produce varying degrees of hypothyroidism. The biological result is compatible with the "equilibrium hypothesis" in which thyroid hormone redistributes between specific and nonspecific binding proteins rather than emphasizing the importance of free hormone as the active moiety.