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Association between Perchlorate and indirect indicators of thyroid dysfunction in NHANES 2001-2002, a Cross-Sectional, Hypothesis-Generating Study
SCHREINEMACHERS, D. M. Association between Perchlorate and indirect indicators of thyroid dysfunction in NHANES 2001-2002, a Cross-Sectional, Hypothesis-Generating Study. Biomarker Insights. Libertas Academica Ltd, North Harbour, New Zealand, 6:135-146, (2011).
Background: A previous study observed associations of urinary perchlorate with thyroid hormones based on the National Health and Nutrition Examination Survey (NHANES) 2001-2002. Increased levels of urinary perchlorate were associated with increased levels of thyroid stimulating hormone among all women, and with decreased levels of thyroxine among women with low urinary iodine. No associations were observed for men. Methods: Using the same NHANES 2001-2002 data, associations of two indirect biomarkers of thyroid hormone disruption with urinary perchlorate were investigated. Perturbation of iron metabolism and decreased HDL have been observed among subjects with subclinical hypothyroidism. To investigate the suitability of these indicators for use in observational studies, subjects were divided into six groups: boys, age 6-19; men, age 20-85; girls, age 6-14; non-pregnant women, age 15-49; women, age 50-85; and pregnant women. Use of perchlorate quintiles and continuous log-transformed perchlorate in the regression models allowed investigation of both non-linear and linear associations. Adjustments were made for age, urinary creatinine, race/ethnicity, BMI, cotinine, poverty index, hours of fasting, thiocyanate, nitrate, daily kcal intake, C-reactive protein. Adjustment for alcohol consumption depended on availability. Adjustment for prescription drugs (beta-blockers, sex hormones, antihyperlipidemic and antidiabetic drugs) was made if it changed the perchlorate estimate by ≥10%. Results: Statistically significant decreases were observed for: serum iron among boys, men, girls, and women age 15-49; percent transferrin saturation among boys (borderline), men, girls, women age 15-49, and women age 50-85; ferritin among women age 15-49; hemoglobin (HGB) and hematocrit (HCT) among boys, men, women age 15-49, and pregnant women; HDL among men. Conclusions: Although the mean response biomarkers were within normal range, their association with urinary perchlorate is of interest. HGB and HCT among pregnant women showed a stronger association with urinary perchlorate than non-pregnant women age 15-49. Statistically significant associations were observed for individual perchlorate quintiles. Assumption of linearity resulted in underestimation of some associations, as shown by the following example. HDL among men, ages 20-85, was statistically significantly decreased at low doses (Q2-Q3) of urinary perchlorate, followed by an increase (Q4-Q5). However, use of continuous log-transformed perchlorate did not show a significant association with HDL.
Perchlorate (CI04) , a widespread environmental contaminant, is present in the environment due to both natural processes and human activities . Exposure of humans, which occurs primarily through ingestion of contaminated water and food, is a current national concern, because perchlorate is known to prevent iodide from entering the thyroid, which may inhibit production of thyroid hormones. Several studies have discussed the potential risks of environmental exposures to perchlorate, which is suspected to be associated with subclinical hypothyroidism [1-4]. This low level of hypothyroidism, which is a risk factor for many biological systems, has also been described as "minimally symptomatic, early hypothyroidism", or "mild thyroid failure" . Urinary perchlorate levels can be used as non-invasive surrogate biological markers of exposure, because perchlorate is not metabolized in the human body . Thyroid stimulating hormone (TSH) and thyroxine (T4) are measured as biological markers of effect on thyroid economy, for example in newborn screening and adult testing for hypo-and hyperthyroidism. A recent study assessed associations of urinary perchlorate with TSH and T4 . Their data source was the National Health and Nutrition Examination Survey (NHANES) 2001-2002. Results of this study showed that increased levels of urinary perchlorate among women were associated with increased levels of TSH for all women and decreased levels of T4 for women with low urinary iodine (<100 ug/L). No association was observed for men. Another study among women in the same NHANES 2001-2002 data observed that smoking and thiocyanate interact with perchlorate in diminishing thyroid function . These studies brought attention to the gender-specific effect of perchlorate on the thyroid .
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Organization:U.S. ENVIRONMENTAL PROTECTION AGENCY
OFFICE OF RESEARCH AND DEVELOPMENT
NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LAB
ENVIRONMENTAL PUBLIC HEALTH DIVISION