Affect the Thyroid Gland

While the sulfone was inactive as an inhibitor of gastric acid secretion, the sulfoxide, H 83/69, was found to be a very potent inhibitor of acid secretion. Pharmacokinetic studies of H 124/26 conducted at Abbott Laboratories indicated a rapid formation of two main metabolites, the sulfoxide H 83/69 and the corresponding sulfone [9]. However, there followed further setbacks, initially when H 124/26 turned out to be known from a Hungarian patent aimed at tuberculosis treatment. Moreover, both compounds (H 124/26 and H 83/69) were found to be toxic, particularly affecting the thyroid gland. Despite this, H 83/69 - which became known as timoprazole - proved to be a breakthrough, mainly because of a number of key observations that were made about the compound. 

Diffuse and toxic goiters are among the main thyroid disorders caused by iodine deficiency (Figure 81.1). Lack of iodine, when present over a longer period of time, results in both morphological alterations and functional perturbations that affect the thyroid gland. 

Subacute thyroiditis exhibits easily recognizable clinical features. It is not a common cause of hypothyroidism in the elderly. Painless thyroiditis is also infrequent in aged people. These conditions may cause transient hyperthyroidism followed by a transient permanent thyroid hypofunction phase. Infiltrative diseases affecting the thyroid gland (Riedel s thyroiditis, hemochromatosis, scleroderma, leukemia, amyloidosis) and infections are rare causes of hypothyroidism at all ages. Toxic injury to the thyroid gland has been reported after exposure to polybrominated biphenyls and polychlorinated biphenyls (Roberts and Ladenson, 2004). 

Peritoneal sarcoidosis is rare and can present with ascites (240). The CA-125 serum level may be elevated and therefore, this entity may be confused with ovarian carcinoma (241). Very rarely sarcoidosis may involve the gastrointestinal tract (242). Any portion of the gastrointestinal tract may be involved (242), and care must be taken to distinguish it from the granulomatous inflammation from Crohn s disease (242,243). Rarely sarcoidosis can affect the thyroid gland, presenting as thyroiditis, a nodule, or mass (244,245). 

Several nonoccupational health problems have been traced to cobalt compounds. Cobalt compounds were used as foam stabilizers in many breweries throughout the world in the mid to late 1960s, and over 100 cases of cardiomyopathy, several followed by death, occurred in heavy beer drinkers (38,39). Those affected consumed as much as 6 L/d of beer (qv) and chronic alcoholism and poor diet may well have contributed to this disease. Some patients treated with cobalt(II) chloride for anemia have developed goiters and polycythemia (40). The impact of cobalt on the thyroid gland and blood has been observed (41). 

Demonstration that the effects of thyrotoxicosis or goiter are due to an excess or deficiency in (thyroxine + T3) secretion does not explain how the diseases originate nor why development and metabolic rate are affected. It is thought that some cases of thyrotoxicosis (Graves disease) may be caused by abnormal immune responses mimicking the effects of thyroid-stimulating hormone on the thyroid gland. 

Thyroid hormone an iodine-containing amino acid that affects the action of the thyroid gland. 

A deficiency of iodine results iu insufficient synthesis of thyroxine and a low plasma level, so that secretion of TSH is increased in an attempt to stimulate synthesis but this results in enlargement of the thyroid gland (goitre). Iodine deficiency in pregnancy impairs brain development in the foetus, causing mental retardation (known as cretinism). Indeed iodine deficiency is one of the major public health issues worldwide an estimated 200 million people are affected. 

Three hormones, thyroxine (3,5,3, 5 -tetraiodothy-ronine, or T4), triiodothyronine (3,5,3 -triiodothyronine, or T3), and calcitonin (see Chapter 66) are secreted by the thyroid gland. The hormones T4 and Tj are iodine-containing amino acid derivatives and are unique in that they have no discrete target tissue. Every tissue in the body is affected in some way by thyroid hormones, and almost all cells appear to require constant optimal amounts for normal operation. 

Like iodine, astatine tends to accumulate in the thyroid gland of the living animal (31). The radioactivity of the element thus concentrated seems to cause severe damage to thyroid tissue without affecting the adjacent parathyroid glands. It may therefore be useful in cases of hyperthyroidism (32). Therefore it is important to determine the amount... 

Perchlorates, which inhibit iodine uptake by the thyroid gland, reducing T4 and T3 synthesis, constitute another class of environmental chemicals that affect thyroid function. In the past, high doses of these compounds were used to treat hyperthyroidism. In recent years, there has been concern that contamination of drinking-water... 

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