Lithium in Drinking Water and Thyroid Function

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. OBJECTIVES: 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 coupled plasma mass spectrometry. Thyroid function was evaluated by plasma free thyroxine (T-4) and pituitary gland thyroid-stimulating hormone (TSH), analyzed by routine immuno metric methods. RESULTS: The median urinary lithium concentration was 3,910 mu g/L (5th, 95th percentiles, 270 mu g/L, 10,400 mu g/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 T-4 [beta for a 1,000-mu g/L increase = -0.19; 95% confidence interval (CI), -0.31 to -0.068; p = 0.002] and positively associated with TSH (beta = 0.096; 95% CI, 0.033 to 0.16; p = 0.003). Both associations persisted after adjustment (for T-4, beta = -0.17; 95% CI, -0.32 to -0.015; p = 0.032; for TSH: beta = 0.089; 95% CI, 0.024 to 0.15; p = 0.007). Urine selenium was positively associated with T-4 (adjusted T-4 for a 1 mu g/L increase: beta = 0.041; 95% CI, 0.012 to 0.071; p = 0.006). CONCLUSIONS: 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

Maternal hormonal milieu influence on fetal brain development

An adverse maternal hormonal environment during pregnancy can be associated with abnormal brain growth. Subtle changes in fetal brain development have been observed even for maternal hormone levels within the currently accepted physiologic ranges. In this review, we provide an update of the research data on maternal hormonal impact on fetal neurodevelopment, giving particular emphasis to thyroid hormones and glucocorticoids. Thyroid hormones are required for normal brain development. Despite serum TSH appearing to be the most accurate indicator of thyroid function in pregnancy, maternal serum free T4 levels in the first trimester of pregnancy are the major determinant of postnatal psychomotor development. Even a transient period of maternal hypothyroxinemia at the beginning of neurogenesis can confer a higher risk of expressive language and nonverbal cognitive delays in offspring. Nevertheless, most recent clinical guidelines advocate for targeted high-risk case finding during first trimester of pregnancy despite universal thyroid function screening. Corticosteroids are determinant in suppressing cell proliferation and stimulating terminal differentiation, a fundamental switch for the maturation of fetal organs. Not surprisingly, intrauterine exposure to stress or high levels of glucocorticoids, endogenous or synthetic, has a molecular and structural impact on brain development and appears to impair cognition and increase anxiety and reactivity to stress. Limbic regions, such as hippocampus and amygdala, are particularly sensitive. Repeated doses of prenatal corticosteroids seem to have short-term benefits of less respiratory distress and fewer serious health problems in offspring. Nevertheless, neurodevelopmental growth in later childhood and adulthood needs further clarification. Future studies should address the relevance of monitoring the level of thyroid hormones and corticosteroids during pregnancy in the risk stratification for impaired postnatal neurodevelopment.This work was supported by the grant "Doutoramento em Medicina Jose de Mello Saude 2014" by Jose de Mello Saude to AM