Thyroid Hyperactivity Caused by Hypolipodaemic Compounds and Polychlorinated Biphenyls: The Effect of Coadministration in the Liver and Thyroid

Abstract

Recent work in this laboratory has emphasised the importance of the thyroid-liver axis in toxicology. It was found that agents which cause peroxisome proliferation in the livers of rats, typified by the hypolipidaemic drug Clofibrate and the plasticiser di-2-ethylhexyl phthalate, have a rapid and sustained effect on thyroid metabolism characterised by changes in the levels of thyroxine in serum and changes in the morphology of the thyroid indicative of hyperactivity (Price et al. 1984, 1986, 1987). These effects are not associated solely with peroxisome proliferation, for similar alterations, which appear associated with liver-thyroid interactions rather than direct thyroid toxicity, have also been reported with phenobarbitone and a range of polyhalogenated hydrocarbons (Cavalieri and Pitt-Rivers 1981) and with the straight chain phthalates (Hinton et al. 1986), which do not cause peroxisome proliferation (Mann et al. 1985). This is important, for while peroxisome proliferation is much more marked in rodents than in other species, other hepatic changes occur more widely. Hence species other than rats may be susceptible to thyroid changes via a liver-thyroid axis. That this is the case is shown by work in Canada demonstrating that herring gulls and fish around the Great Lakes showed marked thyroidal changes indicative of a persistent hyperactivity (Moccia et al. 1986). In addition Bahn et al. (1980) have shown alterations in serum thyroxine and Peters et al. (1982) long-term thyroid damage in people exposed to polyhalogenated hydrocarbons.