Research Lithium in Drinking Water and Thyroid Function Karin Broberg,1 Gabriela Concha,2 Karin Engström,1 Magnus Lindvall,3 Margareta Grandér,4 and Marie Vahter 4 1Division of Occupational and Environmental Medicine, Lund University, Lund, Sweden; 2Division of Toxicology, Swedish National Food Administration, Uppsala, Sweden; 3Department of Child and Youth Psychiatry, Lund University, Lund, Sweden; 4Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden Background : High concentrations of lithium in drinking water were previously discovered in the Argentinean Andes Mountains. Lithium is used worldwide for treatment of bipolar disorder and treatment-resistant depression. One known side effect is altered thyroid function. o Bjectivs : We assessed associations between exposure to lithium from drinking water and other environmental sources and thyroid function. Methods : Women (n = 202) were recruited in four Andean villages in northern Argentina. Lithium exposure was assessed based on concentrations in spot urine samples, measured by inductively cou- pled plasma mass spectrometry. Thyroid function was evaluated by plasma free thyroxine (T4) and pituitary gland thyroid-stimulating hormone (TSH), analyzed by routine immunometric methods. r esult : The median urinary lithium concentration was 3,910 μg/L (5th, 95th percentiles , 270 gμ/L, 10,400 gμ/L). Median plasma concentrations (5th, 95th percentiles) of T 4 and TSH were 17 pmol/L (13 pmol/L, 21 pmol/L) and 1.9 mIU/L, (0.68 mIU/L, 4.9 mIU/L), respectively. Urine lithium was inversely associated with T4 [β for a 1,000-μg/L increase = –0.19; 95% confidence interval (CI), –0.31 to –0.068; p = 0.002] and positively associated with TSH (β = 0.096; 95% CI, 0.033 to 0.16; p = 0.003). Both associations persisted after adjustment (for T4, β = –0.17; 95% CI, –0.32 to –0.015; p = 0.032; for TSH: β = 0.089; 95% CI, 0.024 to 0.15; p = 0.007). Urine selenium was positively associated with T4 (adjusted T4 for a 1 gμ/L increase: β = 0.041; 95% CI, 0.012 to 0.071; p = 0.006). c onclusi : Exposure to lithium via drinking water and other environmental sources may affect thyroid function, consistent with known side effects of medical treatment with lithium. This stresses the need to screen for lithium in all drinking water sources. Key words : bipolar disorder, iodine, lithium, selenium, thyroid-stimulating hormone, thyroxine. Environ Health Perspect 119:827–830 (2011). doi:10.1289/ehp.1002678 [Online 20 January 2011] We recently reported high concentrations of lithium, arsenic, cesium, rubidium, and boron in groundwater in the Puna region in the Argentinean Andes, probably related to influence of thermal water on the drinking water source (Concha et al. 2010). Similar lithium concentrations in drinking water (e.g., 1–3 mg/L) have been reported from northern Chile (Barr et al. 1993), but little is known about the prevalence and geographic distribu- tion of lithium in drinking water in general. A study of trace elements in 132 brands of bottled water from 28 countries reported a median lithium concentration of 4.8 μg/L, with a total range of 0.06–5,460 μg/L (Krachler and Shotyk 2009), suggesting that the findings in Argentina and Chile are not unique. However, there appears to be neither drinking water standards nor risk assessments for lithium in drinking water. The highest levels of lithium in drink- ing water in the Puna region were detected in the village of San Antonio de Los Cobres (1,005 gμ /L; Concha et al. 2010), with little variation over the period measured (years 2004–2008). If we assume a stable exposure, the urinary lithium concentrations in women from San Antonio de los Cobres suggests a total daily lithium intake of 2–30 mg, includ- ing 2–3 mg from drinking water (Concha et al. 2010). For a woman weighing 50 kg, this level of exposure is within an order of magnitude of lithium doses used for maintenance treatment of bipolar disorder, 1–5 mg lithium/kg body weight/day (Grandjean and Aubry 2009a). Major side effects of long-term lithium ther- apy include thyroid abnormalities (presenting mainly as hypothyroidism and goiter), weight gain, edema, gastrointestinal pain, diarrhea, tremor, polyuria, and renal tubular damage (Aral and Vecchio-Sadus 2008; Grandjean and Aubry 2009b). Because of these well-recognized effects of lithium treatment, we wanted to evaluate potential effects of chronic exposure to lithium through drinking water and other environmental sources. We recruited women in a number of Puna villages in the Argentinean Andes with a wide range of lithium concentra- tions in drinking water supplies (8–1,005 gμ/L; Concha et al. 2010) and evaluated the poten- tial impact of urinary lithium on the con- centrations of free thyroxine (T4) and the pituitary gland hormone thyrotropin [thyroid- stimulating hormone (TSH)] in plasma. We also evaluated associations between uri- nary lithium concentration and body mass index (BMI). Materials and Methods Study site and subjects. The Puna is the arid part of the Andean Mountains in northern Argentina, at an altitude around 3,000–4,000 m. Most study participants (n = 161) were from the village of San Environmental Health Perspectives • volume 119 | number 6 | June 2011 Antonio de los Cobres, province of Salta, with about 5,000 inhabitants, mainly of indigenous origin (Concha et al. 2010). Additional participants lived in the small Puna communities Olacapato (n = 14), Salar de Pocitos (n = 5), and Tolar Grande (n = 22), located 60–187 km southwest and west of San Antonio de los Cobres and each with < 200 inhabitants. In each village, all individuals had drinking water from the same source, with small variations in element con- centrations over time (Concha et al. 2010). Element concentrations in drinking water from different sources vary greatly within short geographic distances, mainly because of the presence of volcanic bedrock. Therefore, long-term exposure to lithium is difficult to assess for people not living most of the time in a defined area, where information about levels in drinking water is available. Thus, in the present study we focused on women because they spend more time close to home than do men, who may work outside the monitored region (e.g., in the city of Salta or in Chile) for long periods of time. In San Antonio de los Cobres, women were recruited by physicians and community health workers at the local hospital. In the other villages, women were recruited with the assistance of personnel at local health centers or during visits to homes of village inhabit- ants. Although it was not possible, for practi- cal reasons, to select the women at random, the community health workers at the hospital and health centers tried to recruit women from the whole district, to get as wide a geo- graphic distribution of households as possible. There were no inclusion/exclusion criteria for study participation other than sex. No chil- dren < 12 years of age were recruited. The women were interviewed about what kind of Address correspondence to K. Broberg, Lund University, Division of Occupational and Environmental Medicine, Klinikgatan 21, SE-221 85 Lund, Sweden. Telephone: 46-46-173819. Fax: 46-46-143702. E-mail: karin. broberg@med.lu.se Supplemental Material is available online (doi:10. 1289/ehp.1002678 via http://dx.doi.org/). We thank A. Cardozo, P. Mamaní, E. Casimiro, and E. Assarsson for recruiting the volunteers. This study was supported by the Swedish Council for Working Life and Social Research, the European Union within the Sixth Framework Programme for Research and Technological Development (“PHIME” contract FOOD-CT-2006-016253), and the Kungliga Fysiografiska Sällskapet. The authors declare they have no actual or potential competing financial interests. Received 5 July 2010; accepted 20 January 2010. 827