The ups and downs of thyroid hormone: PCBs may reduce levels in pregnancy.

Maintaining adequate levels of thyroid hormone (TH) during pregnancy is critical for proper placental and fetal development. Environmental contaminants including polychlorinated biphenyls (PCBs), chlorinated pesticides, and mercury have been shown to disrupt the endocrine system in both humans and animals, and experimental studies have shown that these chemicals may decrease circulating TH levels during pregnancy. Now an epidemiologic study by a team of Canadian researchers has revealed that even low-level exposure to some of these chemicals can alter TH status in expectant mothers, with unknown effects [EHP 113:1039-1045].

PCBs and other persistent organohalogens are structurally similar to TH, and are known to have a high affinity for transthyretin, a TH carrier protein. Interference with maternal TH may be one mechanism behind the observed learning and behavioral deficits in children exposed to PCBs in the womb. Most PCB congeners are transferred through the placenta to the fetus such that fetal levels are 30-50% of maternal levels.

The researchers checked the blood of 149 pregnant women for a range of PCB congeners, several organochlorine pesticides, and mercury. The researchers also measured levels of the major forms of TH--[T.sub.4] (the most common circulating form of TH) and [T.sub.3] (the form of TH that regulates cellular metabolism)--as well as thyroid-stimulating hormone (TSH), which is released from the pituitary gland and stimulates production of TH. Cord blood samples were collected at birth and analyzed for the same hormones and contaminants to estimate fetal exposure.

Results showed that total maternal [T.sub.3] decreased with increasing levels of three PCB congeners, the pesticide p,p'-DDE (a persistent metabolite of DDT), the fungicide hexachlorobenzene, and inorganic mercury. No association was found with methylmercury, an organic form of mercury associated with neurologic deficits. In cord blood, the only negative correlation was between free [T.sub.4] and inorganic mercury.

The researchers had expected the women to have high PCB and mercury levels because they lived in the polluted St. Lawrence River basin and were likely to have eaten high levels of potentially contaminated fish. But actual serum levels were 3-45 times lower than those previously reported. The authors say this suggests that pregnant women may be more sensitive than the general population to chemicals that appear to reduce TH levels.

Recent epidemiologic research into PCBs' effects on human TH function has been inconsistent, and some studies have found no effect at exposure levels higher than those in this study. But the current finding of a relationship at such low levels indicates that more investigations are needed in pregnant women, including monitoring of even subtle environmental exposures that can disturb maternal and/or fetal thyroid status. For this purpose, the biomarkers should include not only TSH--which currently is the only element of the thyroid system routinely monitored in pregnant women--but all forms of TH.