Thyroxine deficiency

Iodine is essential in the mammalian diet to produce the thyroid hormone thyroxine deficiency in humans causes goitre. Collectively, deficiencies of iodine, iron, zinc and vitamin A in humans are thought to be at least as widespread and debilitating as calorie deficiencies (Welch and Graham, 1999). The main source of iodine in soils is oceanic salts rather than parent rock, and so deficiency is most widespread in areas remote from the sea (Fuge, 1996). In principle deficiency is easily corrected with dairy supplements. However in practice this is not always feasible. Addition of iodate to irrigation water has successfully corrected widespread iodine deficiency in parts of China where the usual methods of supplementation had failed (Cao et al., 1994 Jiang et al 1997). However there is not much information on the behaviour of iodine in soil and water systems. 

The resulting thyroxine deficiency subjects the thyroid to continuous stimulation by thyroid-stimulating hormone that eventually induces a malignant change in the organ. However, as with other antithyroids, the hormonal imbalance does not necessarily explain the hepatocarcinogenicity that is also observed. 

Iodine occurs to a minute extent (less than 0.001 %) in sea water, but is found in greater concentration, combined in organic form, in certain seaweeds, in oysters and in cod livers. Crude Chile saltpetre, or caliche contains small amounts of sodium iodate, NalOj. from which iodine can be obtained (see below). Some insoluble iodides, for example liiose of silver and mercury(II), occur in Mexico. Iodine is found in the human body in the compound thyroxin in the thyroid gland deficiency of iodine in diet causes enlargement of this gland (goitre). 

Some hydroxy metabolites of coplanar PCBs, such as 4-OH and 3,3 4,5 -tet-rachlorobiphenyl, act as antagonists of thyroxin (Chapter 6, Section 6.2.4). They have high affinity for the thyroxin-binding site on transthyretin (TTR) in plasma. Toxic effects include vitamin A deficiency. Biomarker assays for this toxic mechanism include percentage of thyroxin-binding sites to which rodenticide is bound, plasma levels of thyroxin, and plasma levels of vitamin A. 

C03-0144. The thyroid gland produces hormones that help regulate body temperature, metabolic rate, reproduction, the synthesis of red blod cells, and more. Iodine must be present in the diet for these thyroid hormones to be produced. Iodine deficiency leads to sluggishness and weight gain, and can cause severe problems in the development of a fetus. One thyroid hormone is thyroxine, whose chemical formula is... 

Iodine is incorporated in thyroid proteins to form thyroxin and 3-I-thyroxine, both hormones essential for life. They are determined by immunochemical methods. Deficiency of I may lead to crop disease. 

Tests to exclude possible causes of dementia include a depression screen, vitamin B12 deficiency, thyroid function tests [thyroid-stimulating hormone (TSH) and free triiodothyronine and thyroxine], complete blood cell count, and chemistry panel.21... 

Prealbumin (trans- thyretin) 2-3 Binds triiodothyronine and to a lesser extent thyroxine carrier for retinolbinding protein Kidney dysfunction Cirrhosis, hepatitis, stress, inflammation, surgery, hyperthyroidism, cystic fibrosis, kidney dysfunction, zinc deficiency... 

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. 

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. 

Carbamoyl phosphate synthetase formation in liver taken from tadpoles treated with thyroxine is enhanced by the addition of orotic acid, uracil or uridine (cytosine and adenosine had no effect). The synthesis of this enzyme is not affected by these pyrimidines in untreated animals. This indicates that there is a relative pyrimidine deficiency during thyroxine-induced metamorphosis [140]. 

Too little thyroxine may lead to cretinism in children, with poor growth and mental deficiency, or myxoedema in adults, resulting in a slowing down of all body processes. 

In older patients with goiter due to iodine deficiency there is a risk of provoking hyperthyroidism by increasing iodine intake (p. 247) During chronic maximal stimulation, thyroid follicles can become independent of TSH stimulation ( autonomic tissue"). If the iodine supply is increased, thyroid hormone production increases while TSH secretion decreases due to feedback inhibition. The activity of autonomic tissue, however, persists at a high level thyroxine is released in excess, resulting in iodine-induced hyperthyroidism. 

TSH, or thyrotropin, is a glycosylated protein of two subunits, a and p. TSH stimulates the thyroid gland to produce thyroid hormones. Deficiencies are treated by giving thyroxine itself rather than TSH, but TSH is available for diagnostic purposes to differentiate between pituitary and thyroid gland failure as causes of hypothyroidism (see Chapter 65). 

Juvenile or adult patients with primary hypothyroidism (as indicated by low serum free T4 and high serum TSH concentrations) are usually treated with thyroxine with the aim of relieving symptoms and reducing the serum TSH concentration into the normal reference range. If the primary hypothyroidism is the result of iodine deficiency, then gradually increasing dietary iodine supplementation may also be instituted in addition to the thyroxine replacement therapy. Iodine supplementation alone may lead to the development of acute hyperthyroidism. 

Iodine is concentrated in humans by the thyroid gland to form the iodo-amino acid thyroxine, which is essential to normal health and development. Iodine is a rather rare element (crustal abundance 0.00003 weight %, cf. Table 1.1), so the thyroid gland has become very efficient at scavenging iodide ion. As iodine is deficient in the diet in some locations, a small amount of iodide ion is routinely added to commercial table salt ( iodized salt ). 

The coupling reaction by which the aromatic group from one residue of mono- or diiodotyrosine is joined in ether linkage with a second residue is also catalyzed readily by peroxidases. One dehydroalanine residue is formed for each molecule of hormone released.108 A possible mechanism involves formation of an electron-deficient radical, which can undergo (3 elimination to produce a dehydroalanine residue and an aromatic radical. The latter could couple with a second radical to form triiodothyronine or thyroxine. However, as depicted in Eq. 25-6, the radical coupling may occur prior to chain cleavage. While P elimination (pathway... 

Thyroxine and triiodothyronine have many effects, a major one in mammals and birds being stimulation of energy metabolism in tissues. It has long been recognized that a deficiency of thyroid hormone is reflected in an overall lower basal metabolic rate (Chapter 6). Maley and Lardy observed that thyroxine uncouples oxidative phosphorylation (Chapter 18) in isolated mitochondria.117 When mitochondria from animals receiving extra thyroxine were compared with those from control animals, an increased rate of electron transport was observed. However, there was little or no change in the P / O ratio. Thus, the hormone apparently increased the rate of electron transport... 

There are relationships between the adrenal cortical hormones and the thyroid and pituitary glands. Depression or the function of the adrenals produces thyroid deficiency, w hereas administration of thyroxine stimulates the ACTH-adrenal conical mechanism. 

There is no such clear cut difTcrcnlialiun as metamorphosis in the mammal, but development is an extremely complex process and has been shown to depend upon the presence of adequate amounts of thyroid hormones. Deficient development, especially of the central nervous system, is marked in ehildren suffering from thyroid deficiency early in life, ansi this inadequacy cannot be overcome completely by medication commenced after the first few weeks. In the adult, thyroxine is important in the maintenance of energy turnover in most of the tissues of the body, such as the heart, skeletal muscle, liver, and kidney, Other physiological functions, most notably brain aclivity and reproduction, are also dependent upon thyroxine, although the metabolic rales of the tissues concerned in these functions do not seem to be altered. 

The complexity of the interaction between iodine intake and autoimmune thyroid disease has been highlighted by reports of evidence that iodide (compared with thyroxine) induces thyroid autoimmunity in patients with endemic (iodine deficient) goiter (43), while in those with pre-existing thyroid autoimmunity, evidenced by the presence of antithyroid (thyroid peroxidase) antibodies, administration of iodine in an area of mild iodine deficiency led to subclinical or overt hypothyroidism (44). 

Thyroid function tests are often altered by somatropin because of increased conversion of T4 to T3, but this is clinically insignificant at low doses (SEDA-21, 453). One child with Prader-Willi syndrome had a fall in serum thyroxine concentration during somatropin therapy and needed thyroxine replacement (33). Hypothyroidism developed in 11 of 46 growth hormone-deficient children treated with somatropin (34). Prior abnormalities in hypothalamic-pituitary function and alterations in thyroid hormone metabolism, probably both, contributed to the high incidence of hypothyroidism, which was similar to that in previous studies. 

Sodium and potassium iodides find limited use as expectorants but a much more important use is as additives, at levels around 5—100 fig/g to table salt in many countries as a prophylactic against goitre. This is a condition arising from iodine deficiency with the result that there is insufficient synthesis of the iodine-containing amino acids, thyroxine and 3,3, 5-triiodothyronine, that are essential components of the... 

Iodine deficiency may result in goiter formation. However, not everyone will experience goiter formation with an iodine-deficient diet. Iodine is needed for synthesis of the thyroid hormones thyroxine (T4) and triodothyronine (T3). 

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