Thyroid compounds

Thyroid compounds Thyroid counter Thyroid gland Thyroid hormone... 

Thyroid compounds are necessary for metabolism, growth, and development. T4 s primary action is related to calorigenesis and protein synthesis. Thyroid hormones potentiate the effects of catecholamines. About half of T4 is converted to T3. T3 is three to five times more potent than T4. 

Fig. 6. L-5-Vinyl-2-thiooxazolidone, the anti-thyroid compound of the cabbage family. ...

After several weeks, regression of the lesions induced by a cholesterol regimen was observed. Kritchevsky et al (1961, 1962) attempted, without success, to produce a regression of pre-established atheromata in animals by adding thyroid compounds and various... 

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). 

Thirty isotopes are recognized. Only one stable isotope, 1271 is found in nature. The artificial radioisotope 1311, with a half-life of 8 days, has been used in treating the thyroid gland. The most common compounds are the iodides of sodium and potassium (KI) and the iodates (KIOs). Lack of iodine is the cause of goiter. 

Selenium is an essential element and is beneficial at low concentrations, serving as an antioxidant. Lack of selenium affects thyroid function, and selenium deficiencies have been linked to Keshan Disease (34). Selenium at high levels, however, is toxic. Hydrogen selenide (which is used in semiconductor manufacturing) is extremely toxic, affecting the mucous membranes and respiratory system. However, the toxicity of most organ oselenium compounds used as donor compounds for organic semiconductors is not weU studied. 

Iodine. Of the 10—20 mg of iodine in the adult body, 70—80 wt % is in the thyroid gland (see Thyroid and antithyroid preparations). The essentiahty of iodine, present in all tissues, depends solely on utilisation by the thyroid gland to produce thyroxine [51-48-9] and related compounds. Well-known consequences of faulty thyroid function are hypothyroidism, hyperthyroidism, and goiter. Dietary iodine is obtained from eating seafoods and kelp and from using iodized salt. 

The only commonly used radioisotope in this class is used in small (- IS.S MBq (500 -lCi) injected dose) quantities as a diagnostic for the evaluation of thyroid function. The compound is adininistered as Nal and these procedures are only possible owing to the favorable biological distribution of iodide. Up to 25% of the entire injected dose of iodide is accumulated in the thyroid with a very slow washout the rest is rapidly excreted in the urine. No other compound exhibits so high a ratio of concentration in a target tissue to that of other tissues. 

USP XXII specifies that sodium iodide contains 99—101.5% Nal, calculated on an anhydrous basis (4). It is used iaterchangeably with potassium iodide as a therapeutic agent, except where sodium ion is contraindicated (see Potassium compounds). Intravenous sodium iodide formulations have been used for a variety of diseases, from thyroid deficiency to neuralgia (see Thyroid and antithyroid preparations). However, these solutions are no longer listed ia the XFXUII (4), iadicatiag that their therapeutic value has not been satisfactorily demonstrated. 

Eig. 3. Stmctures of the thyroidal iodinated amino acids and the halogen-free analogue DlMlT (3). Compound (4) is reverse-T. ... 

Structure—Activity Relationships. In spite of the considerable synthetic and bioassay effort involved in estabhshing the thyromimetic potency of thyroid-hormone analogues, more than 100 compounds have been studied (Table 2). The main stmctural requirements for thyromimetic activity can be summarized as follows (6,12—16). 

Using any of the carrier proteins available in highly purified form, eg, TBG or TBPA, a convenient and accurate quantitative determination of and is possible by displacement of radioiodinated or T. This procedure enables their quick determination at low concentrations even in the presence of coundess other substances that occur in body duids (31). In a similar fashion, intact cell nuclei or solubilized proteins from rat fiver cell nuclei, which display high affinities for thyroid hormones, especially T, have been used to establish relative binding affinities of many thyromimetic compounds (7). 

Aromatic Amines and Phenols. The discovery that sulfaguanidine [57-67-0] was goitrogenic to rats was serendipitous. Many related compounds were then examined, and the aniline moiety was usually present (2,6). Such compounds, as well as resorcinol-like phenols, may act as goitrogens by inhibiting thyroid peroxidases. These are not used clinically. 

Peripheral Antagonists. The relatively long duration of action of the thyroid hormones makes it desirable to have compounds capable of blocking them competitively at their site of action. This is desirable in the treatment of thyroid storm where the reduction of circulating hormone levels brought about by the inhibition of their synthesis is too slow. 

Three hormones regulate turnover of calcium in the body (22). 1,25-Dihydroxycholecalciferol is a steroid derivative made by the combined action of the skin, Hver, and kidneys, or furnished by dietary factors with vitamin D activity. The apparent action of this compound is to promote the transcription of genes for proteins that faciUtate transport of calcium and phosphate ions through the plasma membrane. Parathormone (PTH) is a polypeptide hormone secreted by the parathyroid gland, in response to a fall in extracellular Ca(Il). It acts on bones and kidneys in concert with 1,25-dihydroxycholecalciferol to stimulate resorption of bone and reabsorption of calcium from the glomerular filtrate. Calcitonin, the third hormone, is a polypeptide secreted by the thyroid gland in response to a rise in blood Ca(Il) concentration. Its production leads to an increase in bone deposition, increased loss of calcium and phosphate in the urine, and inhibition of the synthesis of 1,25-dihydroxycholecalciferol. 

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). 

Hyperthyroidism may be treated in several ways. One of these is interference with the synthesis of the thyroid hormones, possibly by removal of iodine. Thiourea and cyclic thioureas have this effect and of such cyclic compounds, thiouracil (1030 R = H), its 6-alkyl derivatives (1030 R = Me or Pr) and thiobarbital (1031) are effective thyroid drugs. Today only propylthiouracil (1030 R = Pr) is widely used, probably because it has fewer side effects than the others (71MI21302). The thiouracils are made by the Principal Synthesis from a /3-oxo ester (1032 R = H, Me, Pr, etc.) and thiourea (45JA2197) their fine structures are experimentally based (64AF1004). 

On a smaller scale, the largest producer of iodine is Japan where it is extracted from. seaweed containing more than 0.05 parts per million. The most important industrial iodine compound is silver iodide used with silver bromide in photography. Iodine is important in medicine for treating thyroid problems by adding it to table salt. It is used directly as a disinfectant, and a component of d vs. Crystalline silver iodide is used for cloud seeding. 

The TAAR receptor system has also been associated with body temperature regulation on the basis of putative thyroid hormone metabolites and their synthetic derivatives (thyronamines) activating TAAR1 in rodents. However, as these effects are only observed with thyronamine concentrations several orders of magnitude above physiological levels, and as the specificity of these compounds has not been determined, the physiological significance of these observations is unclear. 

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