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      Urinary Perchlorate and Thyroid Hormone Levels in Adolescent and Adult Men and Women Living in the United States

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          Abstract

          Background

          Perchlorate is commonly found in the environment and known to inhibit thyroid function at high doses. Assessing the potential effect of low-level exposure to perchlorate on thyroid function is an area of ongoing research.

          Objectives

          We evaluated the potential relationship between urinary levels of perchlorate and serum levels of thyroid stimulating hormone (TSH) and total thyroxine (T 4) in 2,299 men and women, ≥ 12 years of age, participating in the National Health and Nutrition Examination Survey (NHANES) during 2001–2002.

          Methods

          We used multiple regression models of T 4 and TSH that included perchlorate and covariates known to be or likely to be associated with T 4 or TSH levels: age, race/ethnicity, body mass index, estrogen use, menopausal status, pregnancy status, premenarche status, serum C-reactive protein, serum albumin, serum cotinine, hours of fasting, urinary thiocyanate, urinary nitrate, and selected medication groups.

          Results

          Perchlorate was not a significant predictor of T 4 or TSH levels in men. For women overall, perchlorate was a significant predictor of both T 4 and TSH. For women with urinary iodine < 100 μg/L, perchlorate was a significant negative predictor of T 4 ( p < 0.0001) and a positive predictor of TSH ( p = 0.001). For women with urinary iodine ≥ 100 μg/L, perchlorate was a significant positive predictor of TSH ( p = 0.025) but not T 4 ( p = 0.550).

          Conclusions

          These associations of perchlorate with T 4 and TSH are coherent in direction and independent of other variables known to affect thyroid function, but are present at perchlorate exposure levels that were unanticipated based on previous studies.

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          Most cited references45

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          The Colorado thyroid disease prevalence study.

          The prevalence of abnormal thyroid function in the United States and the significance of thyroid dysfunction remain controversial. Systemic effects of abnormal thyroid function have not been fully delineated, particularly in cases of mild thyroid failure. Also, the relationship between traditional hypothyroid symptoms and biochemical thyroid function is unclear. To determine the prevalence of abnormal thyroid function and the relationship between (1) abnormal thyroid function and lipid levels and (2) abnormal thyroid function and symptoms using modern and sensitive thyroid tests. Cross-sectional study. Participants in a statewide health fair in Colorado, 1995 (N = 25 862). Serum thyrotropin (thyroid-stimulating hormone [TSH]) and total thyroxine (T4) concentrations, serum lipid levels, and responses to a hypothyroid symptoms questionnaire. The prevalence of elevated TSH levels (normal range, 0.3-5.1 mIU/L) in this population was 9.5%, and the prevalence of decreased TSH levels was 2.2%. Forty percent of patients taking thyroid medications had abnormal TSH levels. Lipid levels increased in a graded fashion as thyroid function declined. Also, the mean total cholesterol and low-density lipoprotein cholesterol levels of subjects with TSH values between 5.1 and 10 mIU/L were significantly greater than the corresponding mean lipid levels in euthyroid subjects. Symptoms were reported more often in hypothyroid vs euthyroid individuals, but individual symptom sensitivities were low. The prevalence of abnormal biochemical thyroid function reported here is substantial and confirms previous reports in smaller populations. Among patients taking thyroid medication, only 60% were within the normal range of TSH. Modest elevations of TSH corresponded to changes in lipid levels that may affect cardiovascular health. Individual symptoms were not very sensitive, but patients who report multiple thyroid symptoms warrant serum thyroid testing. These results confirm that thyroid dysfunction is common, may often go undetected, and may be associated with adverse health outcomes that can be avoided by serum TSH measurement.
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            A multi-rule Shewhart chart for quality control in clinical chemistry.

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              Health effects assessment for environmental perchlorate contamination: the dose response for inhibition of thyroidal radioiodine uptake in humans.

              Application of a sensitive new detection method has revealed widespread perchlorate contamination of groundwater in the southwestern United States, typically at 0.005-0.020 mg/L (5-20 ppb). Perchlorate is a competitive inhibitor of the process by which iodide is actively transported from the bloodstream into the thyroid. This inhibitory action of perchlorate is the basis of its pharmaceutical use (in the treatment of hyperthyroidism) as well as its potential toxicity. To establish the dose response in humans for perchlorate inhibition of thyroidal iodide uptake and any short-term effects on thyroid hormones, we gave perchlorate in drinking water at 0.007, 0.02, 0.1, or 0.5 mg/kg-day to 37 male and female volunteers for 14 days. In 24 subjects we performed 8- and 24-hr measurements of thyroidal (123)I uptake (RAIU) before exposure, on exposure days 2 (E2) and 14 (E14), and 15 days postexposure (P15). In another 13 subjects we omitted both E2 studies and the 8-hr P15 study. We observed a strong correlation between the 8- and 24-hr RAIU over all dose groups and measurement days. We found no difference between E2 and E14 in the inhibition of RAIU produced by a given perchlorate dose. We also found no sex difference. On both E2 and E14, the dose response was a negative linear function of the logarithm of dose. Based on the dose response for inhibition of the 8- and 24-hr RAIU on E14 in all subjects, we derived estimates of the true no-effect level: 5.2 and 6.4 micro g/kg-day, respectively. Given default body weight and exposure assumptions, these doses would be ingested by an adult if the drinking-water supply contained perchlorate at concentrations of approximately 180 and 220 micro g/L (ppb), respectively. On P15, RAIU was not significantly different from baseline. In 24 subjects we measured serum levels of thyroxine (total and free), triiodothyronine, and thyrotropin in blood sampled 16 times throughout the study. Only the 0.5 mg/kg-day dose group showed any effect on serum hormones: a slight downward trend in thyrotropin levels in morning blood draws during perchlorate exposure, with recovery by P15.
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                Author and article information

                Journal
                Environ Health Perspect
                Environmental Health Perspectives
                National Institute of Environmental Health Sciences
                0091-6765
                December 2006
                5 October 2006
                : 114
                : 12
                : 1865-1871
                Affiliations
                Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
                Author notes
                Address correspondence to B.C. Blount, Division of Laboratory Sciences, National Center for Environmental Health, CDC, 4770 Buford Highway, NE, Mail Stop F47, Atlanta, GA 30341 USA. Telephone: (770) 488-7894. Fax: (770) 488-0181. E-mail: bkb3@ 123456cdc.gov

                The authors declare they have no competing financial interests.

                Article
                ehp0114-001865
                10.1289/ehp.9466
                1764147
                17185277
                711a635f-653e-4dbe-956c-618f99e07ffe
                This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original DOI
                History
                : 27 June 2006
                : 4 October 2006
                Categories
                Research

                Public health
                exposure,tsh,thyroid,nhanes,perchlorate,iodine,thyroxine
                Public health
                exposure, tsh, thyroid, nhanes, perchlorate, iodine, thyroxine

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