Thyroid-disrupting chemicals: interpreting upstream biomarkers of adverse outcomes.
BACKGROUND
There is increasing evidence in humans and in experimental animals for a relationship between exposure to specific environmental chemicals and perturbations in levels of critically important thyroid hormones (THs). Identification and proper interpretation of these relationships are required for accurate assessment of risk to public health.


OBJECTIVE
We review the role of TH in nervous system development and specific outcomes in adults, the impact of xenobiotics on thyroid signaling, the relationship between adverse outcomes of thyroid disruption and upstream causal biomarkers, and the societal implications of perturbations in thyroid signaling by xenobiotic chemicals.


METHODS
We drew on an extensive body of epidemiologic, toxicologic, and mechanistic studies.


RESULTS
THs are critical for normal nervous system development, and decreased maternal TH levels are associated with adverse neuropsychological development in children. In adult humans, increased thyroid-stimulating hormone is associated with increased blood pressure and poorer blood lipid profiles, both risk factors for cardiovascular disease and death. These effects of thyroid suppression are observed even within the "normal" range for the population. Environmental chemicals may affect thyroid homeostasis by a number of mechanisms, and multiple chemicals have been identified that interfere with thyroid function by each of the identified mechanisms.


CONCLUSIONS
Individuals are potentially vulnerable to adverse effects as a consequence of exposure to thyroid-disrupting chemicals. Any degree of thyroid disruption that affects TH levels on a population basis should be considered a biomarker of adverse outcomes, which may have important societal outcomes.
Miller
Mark D
MD
Office of Environmental Health Hazard Assessment, California Environmental Protection Agency, Oakland, California 94612, USA. mmiller@oehha.ca.gov
Crofton
Kevin M
KM
Rice
Deborah C
DC
Zoeller
R Thomas
RT
D000818:Animals; D052244:Endocrine Disruptors / Q000633:toxicity*; D004785:Environmental Pollutants / Q000633:toxicity*; D006801:Humans; D008962:Models, Theoretical; D015398:Signal Transduction / Q000187:drug effects; D013961:Thyroid Gland / Q000187:drug effects*; D013963:Thyroid Hormones / Q000378:metabolism
D052244:Endocrine Disruptors; D004785:Environmental Pollutants; D013963:Thyroid Hormones