Thyroid hormones toxicity

Hypothyroidism describes the clinical state arising from a deficiency in thyroid hormone. Toxicity resulting in hypothyroidism is manifested at several organ systems as... 

Hyperthyroidism (thyrotoxicosis), defined as excessive thyroid activity, causes a state of thyroid hormone excess (thyrotoxicosis) characterized by an increased metabolic rate, increase in body temperature, sweating, tachycardia, tremor, nervousness, increased appetite and loss of weight. Common causes of hyperthyroidism are toxic multinodular goiter, toxic adenoma or diffuse toxic goitre ( Graves disease). Antithyroid diugs (methimazol, carbimazole, propylthiouracil) block thyroid hormone production and are hence suitable for the treatment of hyperthyroidism. 

Thyroid autonomy appears as a solitary toxic nodule or toxic multinodular goitre. In toxic thyroid, the nodule s synthesis and secretion of thyroid hormones is autonomous from the thyroid-stimulating hormone (TSH), which is produced in the pituitary gland. Accordingly TSH is suppressed and the extranodular thyroid tissue is functionally downregulated. Thyroid autonomy occurs frequently in iodine-deficient countries, whereas it is much less common in iodine-sufficient areas. Constitu-tively activating mutations in the TSH receptor and in the Gs a protein are the major molecular aetiology of toxic thyroid nodules. 

The common causes of thyrotoxicosis are shown in Table 41-6.29,30 Thyrotoxicosis can be related to the presence or absence of excess hormone production (hyperthyroidism). Graves disease is the most common cause of hyperthyroidism. Thyrotoxicosis in the elderly is more likely due to toxic thyroid nodules or multinodular goiter than to Graves disease. Excessive intake of thyroid hormone may be due to overtreatment with prescribed therapy. Surreptitious use of thyroid hormones also may occur, especially in health professionals or as a self-remedy for obesity. Thyroid hormones can be obtained easily without a prescription from health food stores or Internet sources. 

Yuan et al. [47] inferred that other e-waste-derived toxic chemicals than PBDEs may have also interfered with the balance of thyroid hormone homeostasis. However, these hypotheses still need further confirmation. 

Atrophy of the thymus is a consistent finding in mammals poisoned by 2,3,7,8-TCDD, and suppression of thymus-dependent cellular immunity, particularly in young animals, may contribute to their death. Although the mechanisms of 2,3,7,8-TCDD toxicity are unclear, research areas include the role of thyroid hormones (Rozman et al. 1984) interference with plasma membrane functions (Matsumura 1983) alterations in ligand receptors (Vickers et al. 1985) the causes of hypophagia (reduced desire for food) and subsequent attempts to alter or reverse the pattern of weight loss (Courtney et al. 1978 Seefeld et al. 1984 Seefeld and Peterson 1984) and excretion kinetics of biotransformed metabolites (Koshakji et al. 1984). 

Thyroid-Releasing Hormone Toxic Substances Control Act Thyroid Stimulating Hormone Treatment Technique Threshold of Toxicological Concern Target-organ Toxicity dose Unscheduled DNA Synthesis Uncertainty Factor United Nations... 

Drugs with thyroid hormone activity, alone or with other therapeutic agents, have been used for the treatment of obesity. In euthyroid patients, doses within the range of daily hormonal requirements are ineffective for weight reduction. Larger doses may produce serious or even life-threatening manifestations of toxicity, particularly when given in association with sympathomimetic amines such as those used for their anorectic effects. 

Treatment-related altered serum th5Toid hormone levels indicate that chlorine dioxide and chlorite may exert toxic effects that are mediated through the neuroendocrine axis. Changes in thyroid hormones have been reported in laboratory animals that were either directly exposed to chlorine dioxide (repeated doses as low as 9 mg/kg/day), or exposed to chlorine dioxide or chlorite via their mothers (maternal doses of chlorine dioxide and chlorite as low as 13 and 9 mg/kg/day, respectively) during pre- and postpartum development (Bercz et al. 1982 Carlton and Smith 1985 Carlton et al. 1987, 1991 Mobley et al. 1990 Orme et al. 1985). 

Children s Susceptibility. Neurodevelopmental delays and postnatal changes in serum thyroid hormone levels have been observed in animals following exposure of their mothers to chlorine dioxide or chlorite during gestation and/or lactation (Carlton and Smith 1985 Carlton et al. 1987 Gill et al. 2000 Mobley et al. 1990 Orme et al. 1985 Taylor and Pfohl 1985 Toth et al. 1990). It is not known whether age-related differences in toxicokinetic parameters exist for chlorine dioxide or chlorite. Additional studies should be designed to further examine neurodevelopmental toxicity and underlying mechanisms. 

Secondary to the societal concerns around chemical-related endocrine disruption, the OECD407 subacute 28-day toxicity study protocol has been updated in 2007 with parameters relating to endocrine homeostasis. Specifically, circulating thyroid hormones and detailed assessment of reproductive organ parameters were added to the protocol. Reproductive hormones were suggested as additional parameters but they were deemed not informative in view of their large variability in untreated animals. 

Possibly relevant to be added to data base in vitro bioassay general toxicity (extract) in vitro bioassay thyroid hormone disruption (extract) (incl. bioactivation) in vitro estrogenicity or androgenicity (extract) Chemicals that only are toxic in high concentration (narcotics, nanoparticles) Chemical analysis of lipophillic POPs in water... 

Subclinical hyperthyroidism is defined as a suppressed TSH level (below the normal range) in conjunction with normal thyroid hormone levels. Cardiac toxicity (eg, atrial fibrillation), especially in older persons, is of greatest concern. The consensus of thyroid experts concluded that hyperthyroidism treatment is appropriate in those with TSH less than 0.1 mlU/L, while close monitoring of the TSH level is appropriate for those with less TSH suppression. 

Available intermediate- and chronic-duration oral studies in animals indicate that the thyroid and liver are the main systemic targets of PBDE toxicity as shown by effects mainly including enlargement and histological alterations in both organs and changes in serum levels of thyroid hormones. Several acute-duration studies of pentaBDE suggest that immunosuppression may also be an important health end point. Very little information is available on potential neurotoxic effects of PBDEs, mainly the results of three... 

Thyroid Effects. Limited information is available on thyroid effects in PBDE-exposed humans. There are suggestive occupational data as shown by effects that included increased serum FSH, low or borderline low serum T4, and increased thyroid antimicrosomal antibody titers in workers exposed to decaBDE and/or unspecified PBBs. There was no clear association between plasma levels of 2,2, 4,4-tetraBDE and thyroid hormone levels (free and total T3 and T4, TSH, free testosterone, follicle-stimulating hormone, lutenizing hormone, and prolactin) in men who consumed varying amounts of fatty fish from the Baltic Sea. Based on consistent evidence in animals, as summarized below, the thyroid is particularly sensitive to PBDEs and is a likely target of toxicity in exposed humans. 

Evidence for thyroid hormone involvement in PBDE toxicity includes observations in rats and mice that were orally exposed to commercial mixtures of deca-, octa-, or pentaBDE (see Section 3.2.2.2, Endocrine Effects). The main findings include (1) histological changes in the thyroid indicative of glandular stimulation (e.g., follicular cell hyperplasia similar to that induced by a hypothyroid state) (IRDC 1976 Norris et al. 1973, 1975b NTP 1986 WIL Research Laboratories 1984), and (2) decreased serum... 

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