The Thyroid Hormones

Amino acid-derived hormones include the catecholamines, epinephrine and norepinephrine (qv), and the thyroid hormones, thyroxine and triiodothyronine (see Thyroid AND ANTITHYROID PREPARATIONS). Catecholamines are synthesized from the amino acid tyrosine by a series of enzymatic reactions that include hydroxylations, decarboxylations, and methylations. Thyroid hormones also are derived from tyrosine iodination of the tyrosine residues on a large protein backbone results in the production of active hormone. 

Metabolic Functions. The functions of the thyroid hormones and thus of iodine are control of energy transductions (121). These hormones increase oxygen consumption and basal metaboHc rate by accelerating reactions in nearly all cells of the body. A part of this effect is attributed to increase in activity of many enzymes. Additionally, protein synthesis is affected by the thyroid hormones (121,122). 

Myxedema and goiter are the main conditions for which thyroid preparations are indicated. The treatment of cretinism is difficult because it is recognized only at or after birth. Even if this disease could be diagnosed m utero, thyroid hormones do not readily cross the placental barrier. In addition, the fetus, as does a premature infant, rapidly deactivates the thyroid hormones. The halogen-free analogue DlMlT [26384-44-7] (3), which is resistant to fetal deiodinases, may prove useful for fetal hypothyroidism (cretinism). 

Chemical Assay. In view of the similarity of their chemical and physical properties (see Table 1) (29), the main problem in the chemical analysis of the thyroid hormones is their separation. A USP procedure gives the details of a paper chromatographic separation in which T is examined for contamination by T and 3,5-diiodothyroiiine (30). Other systems are also employed (29). 

Iodide and Other Inorganic Anions. When large doses of iodide ion are administered, a transient inhibition of synthesis and release of the thyroid hormones is brought about by the so-called Wolff-Chaikoff effect. 

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. 

R. Pitt-Rivers and J. R. Tata, The Thyroid Hormones, Pergamon Press, New York, 1959. 

Amiodarone. Amiodarone, an iodinated benzofuran derivative that has stmctural similarities to the thyroid hormones (qv), was originally... 

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). 

Disruption of thyroid functions in vertebrates has been suggested to constitute a potential threat to many vital functions. For example, there is a possibility that disruption to the thyroid hormone levels during embryogenesis could result in disturbed behaviour patterns in the adult form, possibly interfering with migration in certain species and sonar functions in cetaceans. In anurans, thyroid hormones are essential for initiating metamorphosis. ... 

These drugs are used cautiously in patients with Addison s disease and during lactation. The thyroid hormones are classified as Pregnancy Category A and are considered safe to use during pregnancy. 

When administered with cholestyramine or colestipol there is a decreased absorption of the oral thyroid preparations. These drugs should not be administered within 4 of 6 hours of the thyroid hormones. When administered with the oral anticoagulants there is an increased risk of bleeding. It may be advantageous to decrease the dosage of the anticoagulant when a thyroid preparation is prescribed. There is a decreased effectiveness of the digitalis preparation if taken with a thyroid preparation. 

The nurse carefully observes patients with cardiovascular disease taking the thyroid hormones. The development of chest pain or worsening of cardiovascular disease should be reported to the primary health care provider immediately because the patient may require a reduction in the dosage of the thyroid hormone. 

Strong iodide solutions act by decreasing the vascularity of the thyroid gland by rapidly inhibiting the release of the thyroid hormones. Radioactive iodine is distributed within the cellular fluid and excreted. The radioactive isotope accumulates in the cells of the tiiyroid gland, where destruction of tiiyroid cells occurs without damaging other cells throughout the body. 

Brouwer, A., Morse, D.C., and Lans, M.C. et al. (1998). Interactions of persistent enviromnen-tal organohalogens with the thyroid hormone system Mechanisms and possible conse-qnences for animal and hnman health. Toxicology and Industrial Health 14, 59-84. 

The amino acid tyrosine is the starting point in the synthesis of the catecholamines and of the thyroid hormones tetraiodothyronine (thyroxine T4) and triiodothyronine (T3) (Figure 42-2). T3 and T4 are unique in that they require the addition of iodine (as T) for bioactivity. Because dietary iodine is very scarce in many parts of the world, an intricate mechanism for accumulating and retaining T has evolved. 

The thyroid hormones T3 and T4 are unique in that iodine (as iodide) is an essential component of both. In most parts of the world, iodine is a scarce component of soil, and for that reason there is htde in food. A complex mechanism has evolved to acquire and retain this cmcial element and to convert it into a form suitable for incorporation into organic compounds. At the same time, the thyroid must synthesize thyronine from tyrosine, and this synthesis takes place in thyroglobuhn (Figure 42-11). 

Amine hormones include the thyroid hormones and the catecholamines. The thyroid hormones tend to be biologically similar to the steroid hormones. They are mainly insoluble in the blood and are transported predominantly (>99%) bound to proteins. As such, these hormones have longer half-lives (triiodothyronine, t3, = 24 h thyroxine, T4, = 7 days). Furthermore, thyroid hormones cross cell membranes to bind with intracellular receptors and may be administered orally (e.g., synthryoid). In contrast to steroid hormones, however, thyroid hormones have the unique property of being stored extra-cellularly in the thyroid gland as part of the thyroglobulin molecule. 

The thyroid hormones are lipophilic and relatively insoluble in the plasma. Therefore, they are transported throughout the circulation bound to plasma proteins such as thyroxine-binding globulin (75%) and albumins (25%). Approximately 99.96% of circulating thyroxine is protein bound. Bound hormone is not available to cause any physiological effects however, it is in equilibrium with the remaining 0.04% that is unbound. This free form of the hormone is able to bind to receptors on target tissues and cause its effects. Thyroid hormone has many metabolic effects in the body ... 

PNP-DTP has been used to photoaffinity label the thyroid hormone nuclear receptors in intact cells by preparing a derivative of 3,5,3 -triiodo-L-thyronine with the crosslinker (Pascual et al., 1982 Casanova et al., 1984). Effective photoreactive conjugation was found to occur after irradiation with UV light at 254 or 310 nm. 

Several trace elements are essential for a healthy life. One example is iodine, which is needed to make the thyroid hormone. An iodine deficiency leads to goitre. This disease was once called Derbyshire throat as it was once common in that county. Goitre was common in inland areas where the soil is low in iodine and access to seafood is poor. 

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