Environmental chemicals impacting the thyroid: targets and consequences.

Thyroid hormone (TH) is essential for normal brain development, but the specific actions of TH differ across developmental time and brain region. These actions of TH are mediated largely by a combination of thyroid hormone receptor (TR) isoforms that exhibit specific temporal and spatial patterns of expression during animal and human brain development. In addition, TR action is influenced by different cofactors, proteins that directly link the TR protein to functional changes in gene expression. Considering the importance of TH signaling in development, it is important to consider environmental chemicals that may interfere with this signaling. Recent research indicates that environmental chemicals can interfere with thyroid function and with TH signaling. The key issues are to understand the mechanism by which these chemicals act and the dose at which they act, and whether adaptive responses intrinsic to the thyroid system can ameliorate potential adverse consequences (i.e., compensate). In addition, several recent studies show that TRs may be unintended targets of chemicals manufactured for industrial purposes to which humans and wildlife are routinely exposed. Polychlorinated biphenyls, polybrominated diphenyl ethers, bisphenol-A, and specific halogenated derivatives and metabolites of these compounds have been shown to bind to TRs and perhaps have selective effects on TR functions. A number of common chemicals, including polybrominated biphenyls and phthalates, may also exert such effects. When we consider the importance of TH in brain development, it will be important to pursue the possibilities that these chemicals-or interactions among chemical classes-are affecting children's health by influencing TH signaling in the developing brain.     

Environmental perchlorate and thiocyanate exposures and infant serum thyroid function

Background: Breastfed infants rely on maternal iodine for thyroid hormone production required for neurodevelopment. Dietary iodine among women of childbearing age in the United States may be insufficient. Perchlorate (competitive inhibitor of the sodium/iodide symporter [NIS]) exposure is ubiquitous. Thiocyanate, from cigarettes and diet, is a weaker NIS inhibitor. Environmental perchlorate and thiocyanate exposures could decrease breast milk iodine by competitively inhibiting NIS in lactating breasts (thus impairing infants' iodine availability), and/or infants' thyroidal NIS to directly decrease infant thyroid function. The current study assessed the relationships between environmental perchlorate and thiocyanate exposures and infant serum thyroid function. Methods: Iodine, perchlorate, and thiocyanate in breast milk, maternal and infant urine, and infant serum thyroid function tests were cross-sectionally measured in Boston-area women and their 1-3 month-old breastfed infants. Univariate and multivariable analyses assessed relationships between iodine, perchlorate, thiocyanate, thyroid-stimulating hormone (TSH), and free thyroxine (FT4) levels. Results: In 64 mothers and infants, median (range) iodine levels were 45.6?μg/L (4.3-1080) in breast milk, 101.9?μg/L (27-570) in maternal urine, and 197.5?μg/L (40-785) in infant urine. Median perchlorate concentrations were 4.4?μg/L (0.5-29.5) in breast milk, 3.1?μg/L (0.2-22.4) in maternal urine, and 4.7?μg/L (0.3-25.3) in infant urine. There were no correlations between infant TSH or FT4 and iodine, perchlorate, and thiocyanate levels in breast milk, maternal urine, and infant urine. In multivariable analyses, perchlorate and thiocyanate levels in breast milk, maternal urine, and infant urine were not significant predictors of infant TSH or FT4. Conclusions: Boston-area mothers and their breastfed infants are generally iodine sufficient. Although environmental perchlorate and thiocyanate are ubiquitous, these results do not support the concern that maternal and infant environmental perchlorate and thiocyanate exposures affect infant thyroid function.     

Environmental factors and thyroid autoimmunity

Thyroid autoimmune disease, a multifactorial organ-specific autoimmune disorder, is marking a constant increase worldwide. It is thought to be caused by multiple environmental factors triggering autoimmune response in genetically susceptible individuals, though the exact mechanisms linking environmental factors to thyroid autoimmunity are not as yet well understood. Nevertheless, there is increasing evidence that mainly nutritive factors and environmental pollution by metals and chemicals (e.g. organochlorines, pesticides) are the main factors in the present-day spread of this disease. This review presents an overview of the current knowledge regarding environmental factors, their association with genetics and their impact on the immune system.     

肥胖与甲状腺功能

肥胖与甲状腺功能密切相关.肥胖可引起亚临床甲状腺功能减退,甲状腺激素水平在正常范围内的波动可作为体重变化的一个预测指标.肥胖通过升高循环中瘦素水平参与下丘脑-垂体-甲状腺轴的调控;而甲状腺激素通过促进能量代谢、在围产期抑制瘦素的合成与分泌等机制影响体重.甲状腺激素可用于治疗肥胖,但尚需进一步研究.     

Obesity and thyroid function

A moderate elevation of thyrotropin (TSH) concentrations, which is associated with triiodothyronine (T3) values in or slightly above the upper normal range, is frequently found in obese humans. These alterations seem rather a consequence than a cause of obesity since weight loss leads to a normalization of elevated thyroid hormone levels. Elevated thyroid hormone concentrations increase the resting energy expenditure (REE). The underlying pathways are not fully understood. As a consequence of the increased REE, the availability of accumulated energy for conversion into fat is diminished. In conclusion, the alterations of thyroid hormones in obesity suggest an adaptation process. Since rapid weight loss is associated with a decrease of TSH and T3, the resulting decrease in REE may contribute towards the difficulties maintaining weight loss. Leptin seems to be a promising link between obesity and alterations of thyroid hormones since leptin concentrations influence TSH release.     

肥胖与甲状腺功能

肥胖与甲状腺功能密切相关.肥胖可引起亚临床甲状腺功能减退,甲状腺激素水平在正常范围内的波动可作为体重变化的一个预测指标.肥胖通过升高循环中瘦素水平参与下丘脑-垂体-甲状腺轴的调控;而甲状腺激素通过促进能量代谢、在围产期抑制瘦素的合成与分泌等机制影响体重.甲状腺激素可用于治疗肥胖,但尚需进一步研究.     

Amiodarone and thyroid function

Amiodarone blocks the action of thyroid hormone by the inhibition of 5′-deiodinase which reduces production of T₃ in peripheral tissues and possibly by blocking nuclear binding of T₃. Since the drug inhibits peripheral conversion of T₄ to T₃, many patients taking amiodarone have abnormal thyroid function studies (increased T₄ and rT₃; decreased T₃) despite being euthyroid. Treatment of patients with amiodarone generates an iodine excess, which contributes greatly to the significant incidence of altered thyroid status in this population. The diagnosis of hyperthyroidism and hypothyroidism can be difficult. However, using the overall clinical picture and the tolerance limits of hormone levels determined for patients remaining euthyroid on amiodarone therapy, the accurate diagnosis of clinically significant thyroid dysfunction can almost always be made. To screen for thyroid disease, thyroid function should be assessed before initiating therapy, semiannually during therapy or whenever clinical features of thyroid dysfunction occur. Subclinical hypothyroidism as denoted by modest increases in TSH levels do not require treatment or the discontinuation of amiodarone therapy. An appreciation of the mechanism of the interaction between amiodarone and thyroid hormone metabolism allows the clinician to recognize thyroid dysfunction at an early stage and initiate appropriate therapy, thereby minimizing the morbidity associated with forms of amiodarone toxicity.     

Endocrine disrupting chemicals: interference of thyroid hormone binding to transthyretins and to thyroid hormone receptors

We examined the effects of industrial, medical and agricultural chemicals on 3,5,3'-L-[125I]triiodothyronine ([125I]T(3)) binding to transthyretins (TTRs) and thyroid hormone receptors (TRs). Among the chemicals investigated diethylstilbestrol (DES) was the most powerful inhibitor of [125I]T(3) binding to chicken and bullfrog TTR (cTTR and bTTR). Inhibition of [125I]T(3) binding was more apparent in cTTR than bTTR. Scatchard analysis revealed DES, pentachlorophenol and ioxynil as competitive inhibitors of [125I]T(3) binding to cTTR and bTTR. However, cTTR's affinity for the three chemicals was higher than its affinity for T(3). A miticide dicofol (10(-10)-10(-7) M) activated [125I]T(3) binding to bTTR up to 170%. However, at 4x10(-5) M it inhibited [125I]T(3) binding by 83%. Dicofol's biphasic effect upon [125I]T(3) binding was not detected in TTRs from other species. DES and pentachlorophenol, in the presence of plasma, increased cellular uptake of [125I]T(3) in vitro, by displacing [125I]T(3) from its plasma binding sites. These chemicals did not, however, affect the association of cTTR with chicken retinol-binding protein. All chemicals investigated had little or no influence on [125I]T(3) binding to chicken TR (cTR) and bullfrog TR (bTR). Several endocrine disrupting chemicals that were tested interfered with T(3) binding to TTR rather than to TR. Binding of the endocrine disrupting chemicals to TTR may weaken their intrinsic effects on target cells by depressing their free concentrations in plasma. However, this may affect TH homeostasis in vivo by altering the free concentrations of plasma THs.