Fact Sheets

Thyroid Hormones

Issue: There is concern that brain development and cognitive function are impaired in the children of women exposed to a variety of persistent man-made pollutants during pregnancy. Therefore it has been suggested that environmental contaminant exposure can alter thyroid physiology and cause adverse health effects particularly in children.

Background: It has long been recognized that impairment of thyroid physiology during critical periods of fetal and neonatal development can cause permanent deficiencies in brain and sensory organ function. The severity and persistence of these deficits depends on the severity of maternal/fetal and/or postnatal hypothyroidism. Hypothyroidism is a condition in which the thyroid gland fails to produce enough thyroid hormone. Severe hypothyroidism may be caused by dietary iodine deficiency (iodine being essential for thyroid hormone production), the inability to synthesize thyroid hormones (genetic) and consumption of large quantities of substances known to impair thyroid hormone synthesis (i.e. goitrogens from canola seed meal, sorghum). There is also evidence to suggest that fetal alcohol syndrome may be a consequence of reduced brain sensitivity to the action of thyroid hormone. Table salt is now iodized to prevent iodine deficiency, and thus, impaired thyroid function. Newborns are now screened regularly for serum thyroid hormone to identify children with metabolic deficiencies. It has recently been demonstrated that even subtle reductions in maternal thyroid status are associated with reduced cognitive, motor and/or sensory ability in offspring.

Experimental evidence: Numerous in vivo studies in lab animals indicate that chemical contaminants, at sufficiently high doses, can reduce blood levels of the major circulating form of thyroid hormone (thyroxine or T4). Reduced circulating T4 levels have been demonstrated in rats exposed to ubiquitous persistent pollutants including but not limited to: dioxins, polychlorinated biphenyls - PCBs, hexachlorobenzene. Other studies have demonstrated that PCB, when administered to pregnant or lactating rats at concentrations comparable to dosages causing thyroid impairment, produced neurodevelopment deficits in the resulting pups. Similarly, developmental neurotoxicity of PCB has also been observed in monkeys exposed to PCB in utero. Neurodevelopmental effects are also induced in rats made severely hypothyroid by treatment with an antithyroid drug, propylthiouracil (PTU). These neurotoxic effects can be reversed in PTU-treated animals using the active form of thyroid hormone (triodothyronine or T3). This study suggests that it is possible that at least some of the effects of PCB on neurodevelopment may be mediated via the disruption of thyroid hormone homeostasis.

Human Evidence: The association between persistent pollutant exposure and neurodevelopment in children has been examined in several large scale studies with estimates of maternal and fetal exposure and with detailed measures of the cognitive, sensory and motor functions of the resulting children. Results from these studies suggest that subtle neurodevelopmental delays were associated with fetal exposure to PCB. However, the effects of a variety of other potential neurotoxic substances (metals, dioxins and furans, etc.) that may have been associated with PCB exposure were not consistently examined. In the majority of these studies, no attempt was made to correlate either neurobehaviour or persistent pollutant exposure with measures of thyroid status, making speculation on the role of hormonal impairment difficult. It should be noted that PCB exposure levels associated with subtle developmental effects in humans are well below the exposure levels that led to neurodevelopmental impairment in either rats or monkeys. The few studies that have examined the association between persistent pollutant exposure during pregnancy and thyroid status have found that a slight reduction in circulating T4 and or an elevation in thyroid stimulating hormone (TSH - the pituitary signal for thyroid hormone synthesis and release) in children is correlated with umbilical cord or maternal serum concentrations of dioxin-like compounds (including some PCBs). All of the T4 and TSH levels seen in these studies were within the normal clinical range suggesting that the effects are subtle at best. It is not currently clear to what extent persistent chemicals may impair neurodevelopment and, what if any, are the effects on thyroid hormone homeostasis.

Biological plausibility: That disruption of thyroid physiology can impair brain and sensory organ development is beyond question. However, whether exposure to persistent contaminants can disrupt thyroid physiology in human children to the extent necessary to cause neurodevelopment effects is not known. Animal studies demonstrating that PCB, dioxin and other persistent pollutants can impair thyroid homeostasis in rodents may not translate to humans because of differences in serum T4 binding proteins. Rodent exposure to PCBs and other substances, leads to an increased metabolic clearance of thyroid hormone from the blood because of impaired binding of T4 to transthyretin, the major T4 carrier protein in rodents, and increased liver catabolic activity. In humans, the major serum T4 carrier protein, thyroid binding globulin, binds T4 more tightly than transthyretin, resulting in a much slower rate of T4 turnover than in rats. The more rapid turnover in rats means that rats are far more vulnerable to hypothyroidism as the thyroid gland has less capacity to keep replacing the T4 cleared. Activators of metabolic clearance are therefore less likely to impair human thyroid function than rats. However, deficiency of iodine or exposure to substances that impair thyroid hormone synthesis may increase vulnerability to the effects of persistent pollutants in causing hypothyroidism. In the absence of direct human evidence for a causal relationship between thyroid hormone levels, exposure to environmental chemicals and relevant alterations in physiological function, it is difficult to ascertain whether exposure to chemical agents has any biologically relevant effects on thyroid function in humans.

Conclusion: Evidence indicates that environmental agents in sufficient concentrations affect thyroid function in animals. However, the extremely low amounts of chemicals present in humans and the minimal evidence of biologically-relevant alterations in thyroid hormone levels in exposed subjects do not support the contention that persistent chemical exposure impairs thyroid homeostasis in humans.