Thyroxine production

Although organs are not shown on the map, it is nonetheless important for the clinician to know which reactions correspond to different organ systems. Certain reaction steps are almost universal dtroughout the body (e.g., glycolysis). Other reactions are more confined to particular organs (e.g. thyroxine production). When a... 

Although the current FDA standards of bioavailability for thyroxine products suggest that several products are bioequivalent, the relationship between T4 serum concentration and TSH response suggests that the products are not truly bioequivalent. New standards of bioequivalency may need to be developed for drug products like thyroxine. 

Similarly the presence of thyroxine inhibits thyrotrophic hormone production and thyrotrophic hormone stimulates thyroxine production. This can be shown diagrammatically as a feedback... 

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. 

The thyroid gland, located in the base of the neck, exerts i key role on growth and metabolism. In contrast with that of some of the other endocrine glands, this control is effected Ihrough a pair of relatively simple molecules, thyroxine, and its close congener, triiodothyronine. Cases of thyroid deficien-cy (hypothyroidism) are common enough to warrant the production... 

Despite the availability of a wide array of thyroid hormone products, it is clear that synthetic levothyroxine (LT4) is the treatment of choice for almost all patients with hypothyroidism. LT4 mimics the normal physiology of the thyroid gland, which secretes mostly T4 as a prohormone. As needed, based on metabolic demands, peripheral tissues convert thyroxine (T4)... 

Levothyroxine (L-thyroxine, T4) is the drug of choice for thyroid hormone replacement and suppressive therapy because it is chemically stable, relatively inexpensive, free of antigenicity, and has uniform potency however, any of the commercially available thyroid preparations can be used. Once a particular product is selected, therapeutic interchange is discouraged. 

Estrogen may increase hepatic production of thyroxine-binding globulin (TBG) and decrease TBG clearance, thus increasing serum total thyroxine (tT4) and, to a lesser extent, total triiodothyronine (tT3). As a result, increased tT4 and tT3 are seen in states of excessive estrogen and/or progestin, such as... 

In addition to neutral loss scans, mass spectrometers can be used to detect other compounds in a different manner. Acylcamitines are fatty acid esters of carnitine. The masses of acylcamitines differ by the size of the fatty acid attached to it. The tandem mass spectrometer can detect these selectively as well because they all produce a similar product, in this case an ion rather than a molecule. Because it is an ion, it can be detected by the second mass separation device. The ion has a mass of 85 Da and is common to all acylcamitines. Performing a precursor ion scan of 85 Da (essentially a scan of only molecules that produce the 85 ion) reveals a selective analysis of acylcar-nitines, as shown in Fig. 14.2. Additional scans have been added to more selectively detect basic amino acids, free carnitine, short chain acylcamitines and a hormone, thyroxin (T4) which has amino acid components. 

Thyroxine (57) was rapidly photodeiodinated by light filtered to give wavelengths above 300 nm. In the first few minutes the main product was 3,3, 5-triiodothyronine, but by 15 min, 3,5-diiodothyronine and 3-iodothyronine were present in major amounts. There were also traces of 3,3, 5-triiodothyronine and 3,3 -diiodothyronine. In some runs traces of 3,3, 5 -triiodothyronine and 3, 5 -diiodothyronine were detected. Over 30 min the main product was 3-iodothyronine. Further deiodination to thyronine was very slow, presumably because the UV spectra had lower-wavelength maxima as iodine was removed. Similar photolysis of 3,3, 5-triiodothyronine for 10 min also gave 3,5-diiodo-... 

The gland is situated in the neck across the front of the trachea. It secretes thyroxine (T4), which is converted to the active form of the hormone, triiodothyronine (T3), in peripheral tissues. It stimulates metabolic activity in tissues so that it increases heat production (for example, by stimulating protein turnover and substrate cycles). 

Flippin JL, Hedge JM, DeVito MJ, LeBlanc GA, Crofton KM (2009) Predictive modeling of a mixture of thyroid hormone dismpting chemicals that affect production and clearance of thyroxine. Int J Toxicol 28 368-381... 

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. 

The substance to be assayed—e.g., the hormone thyroxine in a serum sample—is pipetted into a microtiter plate (1), the walls of which are coated with antibodies that specifically bind the hormone. At the same time, a small amount of thyroxine is added to the incubation to which an enzyme known as the "tracer" (1) has been chemically coupled. The tracer and the hormone being assayed compete for the small number of antibody binding sites available. After binding has taken place (2), all of the unbound molecules are rinsed out. The addition of a substrate solution for the enzyme (a chromogenic solution) then triggers an indicator reaction (3), the products of which can be assessed using photometry (4). 

Oral contraceptives have their most significant effect on endocrine parameters. Blood cortisol, thyroxine, protein-bound iodine, T3 uptake, and urinary free cortisol are elevated. Urinary 17,21-dihydroxy steroids, 17-ketosteroids, and estrogens are decreased. There is no effect on urinary catecholamines or VMA (Table 10) (LIO). The effect of thyroid functions tests is due to the administered hormone stimulating an increase in the production of thyroid-binding globulin which in turn binds 1-thyroxine. The lowering of free thyroxine stimulates the anterior pituitary to produce thyrotropin, which in turn stimulates the thyroid to produce more thyroxine. Since the additional thyroxine is bound to the extra protein, there is an equilibrium and the patient remains clinically euthyroid, but the protein-bound iodine and the thyroxine are elevated. 

The thyroid gland produces thyroxine (T4) and triiodothyronine (T3) and this production is under control of the hypothalamus and the pituitary gland. 

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