Synthetic triiodothyronine

Thyroid hormone is available as synthetic triiodothyronine (T3, or liothyronine), synthetic tetraiodothyronine (T4, levothyroxine), or natural desiccated animal thyroid (containing both T3 and T4 Table 11-55). Despite concern over the potentially life-threatening manifestations of thyrotoxicosis, serious toxicity rarely occurs after acute thyroid hormone ingestion. 

Mechanism of Action A synthetic form of triiodothyronine (T3), a thyroid hormone involved in normal metabolism, growth, and development. Possesses catabolic and anabolic effects. Therapeutic Effect Increases basal metabolic rate, enhances gluco-neogenesis, and stimulates protein synthesis. 

Cytomel is the synthetic form of T-3/L-triiodothyronine and was a commonly known trade or brand name among athletes. T-3/L-triiodothyronine is used as a form of thyroid hormone therapy mostly in Europe. Most bodybuilders favored this drug over synthetic forms of T-4/L-thyroxine due to its vastly superior activity level. 

The abuse of synthetic T-3/L-triiodothyronine will result in severe suppression of natural (endogenous) thyroid function. This is especially true of this drug because it actually circumvents the normal thyroid hormone manufacturing process the body utilizes to produce endogenous forms as required. Simplified this is because T-3/L-triiodothyronine is the most potent thyroid hormone so the body shuts down each level required for production to try to reduce circulatory T-3/L-triiodothyronine levels. Of course this does not reduce the level if the hormone is being administered exogenously (from outside the body). 

Synthroid is a man-made synthetically manufactured version of T-4/L-thyroxine. The average person produces about 76 MCG/d of T-4/L-thyroxine which is then converted by the liver into the more active T-3/L-triiodothyronine. This is true of the oral T-4/L-thyroxine medications as well. The average conversion rate of T-4 to T-3 is about 30-33%/ MCG. Since the conversion of T-4 to T-3 is dependent upon adequate levels of since and selenium, athletes commonly increase daily intake of these minerals during synthetic T-4/L-thyroxine use. 

Triacana is a trade or brand name for the thyroid drug Tiratricol. The body naturally (endogenously) produces T-4/L-thyroxine, T-3/L-triiodothyronine, and T-2 /L-diiodothyronine. Triacana is simply a synthetic form of these three thyroid hormones natural metabolite product, Triiodothyroacetic acid, or tiratricol for short. This means the body naturally produces Triacana as a metabolic by-product of other thyroid hormones. 

The structural formulas of thyroxine and triiodothyronine as well as reverse triiodothyronine (rT3) are shown in Figure 38-2. All of these naturally occurring molecules are levo (L) isomers. The synthetic dextro (D) isomer of thyroxine, dextrothyroxine, has approximately 4% of the biologic activity of the L isomer as evidenced by its lesser ability to suppress TSH secretion and correct hypothyroidism. 

Chemical/Pharmaceutical/Other Class Synthetic form of triiodothyronine... 

The possibility of using hormone analogs to rescue nuclear receptor mutations was perhaps first explored by DeGroot et al. who demonstrated that some synthetic hormone analogs were more potent than triiodothyronine (T3) in mutant forms of TR, associated with resistance to thyroid hormone [71]. 

Formation of Thyroxine and Triiodothyronine from lodotyrosines. The remaining synthetic step is the coupling of two diiodotyrosyl residues to form or of one monoiodotyrosyl and one diiodotyrosyl residues to form Tj. The same peroxidase catalyzes these oxidative reactions. The conformation of thyroglobulin apparently renders it uniquely efficient for the couphng reaction. T predominantly is formed at the amino terminus of thyroglobulin, while Tj is preferentially localized to the carboxy terminus. 

Clinical use Thyroid hormone therapy can be accomplished with either thyroxine or triiodothyronine. Synthetic levothyroxine (T ) is the form of choice for most cases. Tj (liothy-ronine) is faster-acting but has a shorter half-life and is more expensive. 

Administration of synthetic TRH to humans causes a dose-related release of thyrotropin (TSH) by the pituitary (BIO, HI) between the intravenous doses of 15 and 500 /ig. Oral, subcutaneous, or intramuscular administration requires bigger doses. The TSH response to intravenous TRH is significant within 2-5 minutes, peaking at 20-30 minutes with a return to basal levels by 2-3 hours. An elevation in thyroid hormone levels in response to TRH is seen, with triiodothyronine (Ta) peaking at 3 hours and thyroxine (T ) at 8 hours (LI). TRH stimulates the synthesis as well as the release of TSH (M5). 

It has been shown by Gross and Leblond (1951b) that thyroxine can be partially dehalogenated in the body. Radiothyroxine was injected into thyroidectomized mice and they were killed 13 hours later. Unknown 1 (triiodothyronine) was found, accompanying thyroxine, in the kidneys and feces of these animals. The possibility that triiodothyronine might have been a contaminant of the synthetic radiothyroxine administered was ruled out, since the thyroxine had been chromatographically purified before administration. 

Normal plasma to which synthetic radiothyroxine of high activity had been added was similarly electrophoresed, and the position of the thyroxine on the paper strip compared with the positions of the natural hormone in the patients sera. Both were found to be associated with a protein having a mobility similar to that of ai-globulin. Triiodothyronine does not appear to be specifically associated with this protein in the circulation (Gross unpublished). 

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