measured specific gravity of urine using a digital refractometer (EUROMEX RD 712 clinical refractometer; EUROMEX, Arnhem, the Netherlands), and adjusted measured analyte concentrations to the mean specific gravity of all samples (1.020 g/mL). Free T4 and TSH were measured in 100 μL plasma by an immunometric method with reagents f r o m R o c h e D i a g n o s t i c s ( M a n n h e i m , Germany), performed as a routine analysis at the Department of Clinical Chemistry, Lund University. All plasma samples were stored for approximately 1 year at –20°C before analysis of T4 and TSH. According to the literature (El Ezzi et al. 2010; Männistö et al. 2007), the concentrations of T4 and TSH are very stable over time. Statistical analysis. We calculated the associations between characteristics of study subjects, urinary concentrations of selected elements, and plasma T4 and TSH levels using the Spearman correlation coefficient (rs). Associations between markers of thyroid function and BMI (dependent variables) and the selected elements, age, and parity (inde- pendent variables) were first analyzed with univariate linear regression analysis. Then multivariate models were used to estimate associations between urinary lithium concen- tration and T4, TSH, and BMI adjusted for other influential variables (defined as inde- pendent variables with p-values < 0.25 in the univariate linear regression analysis). Potential influential variables were the elements arse- nic, boron, and cesium, which are elevated in drinking water in the same regions as lithium; and age, parity, and BMI because these factors may influence the markers of thyroid func- tion. All statistical analyses were performed using IBM SPSS Statistics (version 18.0; SPSS Inc., Chicago, IL, USA). Associations were considered statistically significant based on an alpha level of 0.05. Results S t u d y p a r t i c i p a n t s h a d a m e d i a n a g e of 34 years and parity of three children (Table 1). The median BMI was 24.7 kg/ m2 (in the upper range of normal weight, 18.5–24.99 kg/m2), and 17% of the women (n = 35) were considered obese (> 30 kg/m2). T4 values were outside of the normal range (12–22 pmol/L) in 5 (2.6%) of 194 women (1 below and 4 above normal range), and TSH values were outside the normal range (0.4–4.0 mIE/L) in 20 (10%) of 196 women (3 below and 17 above normal range). Ninety- seven percent of the women reported that they had lived > 2 years in the area. Table 1 also shows the concentrations of toxic and essential elements in urine. Lithium, boron, arsenic, and cesium in urine were all negatively correlated to free T4 (Table 1), but we found no significant cor- relations between these elements and TSH. Selenium, but not iodine, in urine was posi- tively correlated to T4 and inversely correlated to TSH. Age, BMI, and parity were all nega- tively associated with T4 but not with TSH. We found a negative correlation between reported number of ingested glasses of water per day and TSH (rs = –0.17; p = 0.015), but water consumption was not correlated with T4 (p = 0.36). Urine lithium concentration was inversely associated with free T4 before and after adjust- ment [Table 2, Figure 1; adjusted β for a 1,000-μg/L increase in urinary lithium con- centration = 0.17; 95% confidence interval (CI), –0.32 to –0.015; p = 0.032] and posi- tively associated with TSH (Table 2, Figure 2; adjusted β = 0.089; 95% CI, 0.024 to 0.15; p = 0.007). The effect of lithium on TSH was still present when we adjusted for arsenic, cesium, selenium, iodine, age, parity, and BMI (β = 0.14; 95% CI, 0.054 to 0.022; p = 0.001). For comparison, the β-coefficient point Lithium in drinking water and thyroid function estimates for the associations between other covariates and markers of thyroid function and BMI are shown in Supplemental Material, Table 1 (doi:10.1289/ehp.1002678). Estimates were similar when we limited multivariate analyses to women who had lived > 2 years in the area (n = 179–180; for T4, β = –0.17; 95% CI, –0.32 to –0.011; p = 0.036; for TSH: β = 0.15; 95% CI, 0.063 to 0.23; p = 0.001). We found no association between lithium and T4 or TSH values outside the normal range (data not shown). We found a nonsignificant positive asso- ciation between urinary lithium and BMI (Table 2, Figure 3). The association between lithum and BMI became less significant after additional adjustment for T4 and TSH (β = 0.068; 95% CI, –0.015 to 0.28; p = 0.53). In contrast with lithium, urinary selenium was positively associated with T4 (unadjusted β for a 1-μg/L increase in selenium = 0.05; 95% CI, 0.022 to 0.078; p = 0.001) and inversely associated with TSH (β = –0.014; 95% CI, –0.029 to 0.001; p = 0.069). However, only the association with T4 was statistically significant after adjustments [see Supplemental Material, Table 1 (doi:10.1289/ehp.1002678)]. Urinary boron was significantly nega- tively associated with T4 (β for a 1,000 gμ/L increase = –0.068; 95% CI, –0.11 to –0.025; p = 0.002) but was not associated with TSH in univariate analyses. However, because of high collinearity (rs = 0.85; p < 0.001) between boron and lithium, we did not include boron in multi- variate analyses of associations between lithium and T4, TSH, or BMI. When boron was mod- eled instead of lithium in a multivariate analy- sis, we found no association between boron and TSH or BMI (p = 0.34 and p = 0.48) but it was inversely associated with T4 (β = –0.075; 95% CI, –0.14 to –0.013; p = 0.018). Cesium and arsenic were not associated with T4 or TSH (see Supplemental Material, Table 1). 0 2,000 4,000 10,000 12,000 14,000 6,000 8,000 Lithium (μg/L) 0 2,000 4,000 6,000 8,000 10,000 12,000 14,000 Lithium (μg/L) Figure 2. Association between urinary lithium concentration and plasma TSH. Figure 3. Association between urinary lithium concentration and BMI. Environmental Health Perspectives • volume 119 | number 6 | June 2011 829 10 8 ) L / U Im 6 ( H S T a sm 4 a l P 2 0 2)m 30 / g k ( I BM 25 40 35 20 15