Thyroid Toxicity

The thyroid gland, one of the largest endocrine glands in the body, synthesizes thyroid hormones (THs), which present a wide variety of functions affecting metabolism, growth and maturation, and other organ-specific effects. From a metabolic perspective, thyroid hormones increase oxygen consumption and heat generation. Moreover, they increase protein catabolism, promote gluconeogenesis, increase utilization of glucose and promote lipid metabolism. With regard to other organ-specific effects, thyroid hormones influence cardiac function by increasing heart rate, myocardial contractility, blood volume, and cardiac output while decreasing peripheral vascular volume. They stimulate the production of cytokines, growth factors and other factors to stimulate bone development and growth. In addition, thyroid hormones also promote increased motility in the gastrointestinal system and increase adrenergic activity and sensitivity in the central nervous system. Because they also promote cell differentiation, growth and maturation, thyroid hormones are essential in early fetal life to promote normal growth and brain development. Deficiencies and elevations in thyroid hormone levels may cause many clinical signs and symptoms. This chapter discusses the anatomy and physiology of the thyroid gland and the thyroid disorders that could be induced, especially, by toxic substances.

The thyroid system controls several developmental processes and participates in many physiological functions such as metabolic regulation, energy homeostasis, bone remodeling, reproduction, cardiac function and mental status in both children and adults. Thyroid function is regulated through the interaction between the hypothalamus, the pituitary and the thyroid. A large number of compounds such as pesticides, drugs, heavy metals, cosmetics, industrial chemicals and natural compounds have been shown to disrupt thyroid system homeostasis by acting on diverse regulation points of thyroid hormones metabolism, binding to thyroid receptors or altering gene transcription regulated through thyroid hormones among other mechanisms involved. There is special concern about thyroid disruptors because even slight variations in thyroid homeostasis may negatively affect human health, particularly during critical periods of vulnerability such as development and senescence or in sensitive population groups. This chapter focusses on known disrupting mechanisms and key factors influencing them.

Autoimmune thyroid diseases are the most common autoimmune endocrine disorders. Expression of thyroid dysfunction is dependent upon the interaction of genetic factors and environmental exposures. The genes identified so far account for only a small portion of genetic susceptibility for autoimmune thyroid disease. A number of environmental exposures are associated with exposing thyroid dysfunction in subjects with autoimmune thyroid disease and some are clearly identified as inducing thyroid autoimmunity although this is actually less common. Understanding the relationship between environment and the genetic background should help in identifying patients at risk and may provide therapeutic options for the future.

Biological Select Agents and Toxins (BSATs) are a specific group of pathogens, toxins and substances of biological origin that pose not only a severe threat to human, plant, and animal health, but also have the potential to be used deliberately to cause disease, prompt fear, or destroy agricultural or animal products as biological warfare or bioterrorism agents. BSATs may cause a disruption of the thyroid system either directly or indirectly through the systemic effects they induce. Bioregulator agents, toxins and microbiological infections, which could induce acute, subacute or chronic thyroiditis, among others, could cause thyroid functional alteration. The thyroiditis induced through colonization of thyroid gland by these pathogen agents (induced mainly by virus or bacteria) or as a particular manifestation of a systemic disease, results in inflammation of the thyroid gland that can sometimes degenerate into destructive thyrotoxicosis. Otherwise, the possibility of their use as terrorist or criminal agents makes it necessary to know and recognize the implications arising from the intended use of these agents on the thyroid system. This chapter will refer to the main agents that induce thyroid disruption and the known mechanisms through which these effects are induced.

Thyroxine is one of the most widely used drugs all over the world. Normally thyroid hormones are used in the treatment of hypothyroidism or goiter, but cases of drug overdose have been frequently reported (thyrotoxicosis factitia). This chapter will focus on the prevalence, consequences and the treatment of the thyrotoxicosis factitia, as a complication of inappropriate L- thyroxine treatment for obesity, following the ingestion of beef contaminated with thyroid gland and after accidental thyroid hormone ingestion.

The thyroid is a highly specialized endocrine organ devoted to the production of thyroid hormone, via organification of inorganic iodine. To accomplish this task, the thyroid follicular cell employs a rather complex of unique enzymes, transporters and regulatory factors. Both a classical endocrine feedback mechanism and less understood intracellular mechanisms maintain a constant output of thyroid hormone in normal physiology. Such a complex system can be altered by a number of pharmacological interferences. These interferences can be grouped under two broad categories: direct toxic effects on the thyroid gland, and immune mediated effects precipitated by immune modulators. Drug effects on the thyroid have been studied for several decades thanks to the availability of accurate methods for assessing thyroid physiology. The effects of some of these drugs, such as amiodarone and lithium have been known for many years, but novel antineoplastic agents introduced more recently have been the focus of intense attention over the past few years. This chapter concisely summarizes our current knowledge on drugs capable of altering thyroid function or structure, with attention to underlying mechanisms.

The thyroid system, due to its complex histological structure and functions, is often the target of many endocrine toxins, including metals. In this regard, metals such as Cd, Pb, Cr, Mn, Hg and Cu are known to induce thyroid toxicity in man and animals. On the other hand, other metals are essential for the proper functioning of thyroid system such as Se, Zn, Fe among others, and their deficiency has been related to thyroid disruption. Metals could alter the thyroid system at many levels. In this regard, metals could reduce iodide uptake, alter production of thyroid stimulation hormone (TSH) at the pituitary level, alter thyroid hormones (THs) synthesis and release via many different mechanisms at the thyroid gland level and/or could induce histopathological alterations of the thyroid. In addition, metals could alter the metabolism of THs or action on their receptors. This chapter is focused on the main metals reported to induce thyroid toxicity, and the mechanisms through which their effects occur.

Experimental evidence has shown the ability of multiple pesticides to affect thyroid homeostasis. The thyroid-disrupting effects of organochlorine (OC) pesticides are the most studied. OC pesticides can affect the deiodination of thyroid hormones (TH) leading to increased T3 degradation; can bind to TH-binding proteins altering circulating TH levels; may mimic TH action; and interfere with their binding to hormonal receptors, altering TH-mediated gene expression. Epidemiological studies have shown inverse relationships between exposure to OC pesticides and levels of T3 and T4, and positive associations with TSH among pregnant women, newborns and adults. Non-persistent contemporary pesticides such as organophosphates (OP), carbamate and pyrethroids may also interfere with thyroid function, as suggested by various animal studies. Evidence from human studies linking non-persistent pesticides to thyroid function is still limited and controversial. However, alterations compatible with hypothyroidism were observed in some studies, particularly in relation to OP pesticides. Overall, experimental and epidemiological studies indicate that hypothyroid effect are the general effects from pesticide exposure, supporting that pesticide exposure causes a decrease in TH, but also an increase in TSH. The varying methodological approaches used in epidemiological research particularly hamper drawing conclusions about the evidence on the topic. In addition, exposure levels, modes of action of individual substances, and genetic variability might be important sources of variation between studies. Given the important role of TH on metabolism and brain development, exposure to even low doses of thyroid-disrupting pesticides may contribute to increase the risk of thyroid disease and neurodevelopmental disorders.

The thyroid gland is virtually unique since it can be affected by both external radiation (and thus, it shares with other organs histopathologic changes due to irradiation effects) and by the so-called "internal" radiation, wherein administration of radioactive iodide preferentially affects the thyroid gland (almost to the exclusion of all other organs). This review will focus on both types of radiation and the changes that can be seen acutely and chronically in the thyroid after it has been subjected to irradiation. In addition, the neoplastic potential of radiation exposure on thyroid follicular epithelium will be presented and illustrated.

Foods are composed of a variety of natural compounds with nutritional effects. However, some of them may also possess anti-nutritional and thyroid toxic effects, such as glucosinolate compounds, which are present in foods derived from higher plants. Currently, functional foods have been incorporated as sources of nutrients to our diet in order to meet certain nutritional requirements not present in conventional food; their effects on the thyroid gland are unknown and should be determined in order to perform a complete risk assessments of these foods. Food supplements, which are used widely by the population in many countries, are another source of nutrients, especially minerals and trace elements such as iodine and zinc that are necessary for the proper functioning of the thyroid gland, but if their use is not controlled they may induce alterations of the thyroid system. Furthermore, many of these dietary supplements also contain plants, algae and soybean in their composition that can exert harmful effects on normal thyroid function. Finally, during food processing different chemical compounds such as nitrate and erythrosine could be used, which could also induce harmful effects on the thyroid system. This chapter will discuss all of the foods and supplements mentioned above and their possible effects on normal thyroid function.

Thyroid hormones (THs) play a key role during development, especially of the Central Nervous System and in adulthood in homeostasis control. They are regulated by the dynamic interrelationships between the hypothalamus, pituitary and thyroid gland. It has been shown that a large number of industrial chemicals could affect the hypothalamic-pituitary-thyroid axis and disrupt the thyroid system, which is a cause of concern, because these alterations could induce severe neurological effects during development as well as alterations in homeostasis. Classically, these chemicals have been identified and classified as toxic agents due to their ability to alter TH levels. However, other mechanisms have been shown to contribute to thyroid system disruption, such as interference with thyroid hormone receptors or enzymes or transporters that play an important role in mediating the action of these hormones. The aim of this chapter is to provide a review of the effects of industrial chemicals on the thyroid system and the mechanisms through which they induce these effects.