Synthesis of Thyroid Hormone

Because thyroxine contains four iodine residues, this compound is also referred to by the abbreviation T4. Likewise, triiodothyronine contains three iodine residues, hence the abbreviation T3. There has been considerable discussion about which hormone exerts the primary physiologic effects. Plasma levels of T4 are much higher than T3 levels, but T3 may exert most of the physiologic effects on various tissues, which suggests that T4 is a precursor to T3 and that the conversion of T4 to T3 occurs in peripheral tissues.23 Regardless of which hormone ultimately affects cellular metabolism, both T4 and T3 are needed for normal thyroid function. 

FIGURE 31-1 Structure of the thyroid hormones triiodothyronine (T3] and thyroxine (T4X Addition of one iodine atom [I] to tyrosine produces monoiodotyrosine addition of a second iodine atom produces diiodotyrosine. A monoiodotyrosine and diiodotyrosine combine to form triiodothyronine (T3X Coupling of two diiodotyrosines forms thyroxine (T4X 

FIGURE 31-2 Thyroid hormone biosynthesis. Iodide is taken into the follicle cell, where it is converted by thyroid peroxidase to an oxidized form of iodine (Ip). h is transported to the follicle lumen, where it is bonded to tyrosine residues of the thyroglobulin [TGB] molecule. Iodinated TGB is incorporated back into the cell, where it undergoes lysis to yield the thyroid hormones T3 and T4. See text for further discussion. 

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Synthesis of thyroid hormones occurs in several steps. At first, inorganic iodide is actively concentrated by... 

Isoflavones have been implicated in goiter induction. Soybean extracts inhibit reactions catalyzed by thyroid peroxidase (TPO), essential to the synthesis of thyroid hormones (Divi et al., 1997). Genistein and daidzein (at about 1-10 p,M of IC50) may act as alternative substrates for tyrosine iodination (Divi et al., 1997). Furthermore, genistein and daidzein have also been shown to cause the irreversible inactivation of TPO in the presence of hydrogen peroxide. Genistein also inhibits thyroxine synthesis in the presence of iodinated... 

For each inhibitory effect on the synthesis of thyroid hormone listed below, select the agent that causes it. 

The answers are 450-a, 451-b, 452-b. (Katzung, p 652. Hardman, pp 1397—1406.) Agents that can interfere directly or indirectly with the synthesis of thyroid hormone are called thyroid inhibitors. Perchlorate, an ionic inhibitor, interferes with the ability of the thyroid to concentrate F by acting as a competitive inhibitor. It is used in patients with iodide-induced hypothyroidism, such as can occur with the antiarrhythmic agent amio-darone. 

Antithyroid. Counteracting the functioning of the thyroid, especially in its synthesis of thyroid hormone. 

Mechanism of Action A thioimidazole derivative that inhibits synthesis of thyroid hormone by interfering with the incorporation of iodine into tyrosyl residues. Thera-peuticEffect Effectively treats hyperthyroidism by decreasingthyroid hormone levels. Pharmacohinetics Rapid absorption following PO administration. Protein binding Not significant. Widely distributed throughout the body. Metabolized in liver. Excreted in urine. Half-life 5-6 hr. 

Mecfianism of Action A thiourea derivative that blocks oxidation of iodine in the thyroid gland and blocks synthesis of thyroxine and triiodothyronine. Therapeutic Effect Inhibits synthesis of thyroid hormone. 

Steps in the synthesis of thyroid hormone include the following,... 

Iodine 11 mg 150 g Synthesis of thyroid hormones Goiter ( Derbyshire neck in the UK) May lead to thyrotoxicosis... 

Thyroid-stimulating hormone (TSH] t synthesis of thyroid hormones (T3, T4]... 

Small quantities are essential for a healthy person to maintain the synthesis of thyroid hormone, which regulates metabolic rates. Present in soil and any food plants, particularly sea foods, as iodide ions... 

Q8 The drug treatment of thyrotoxicosis involves using antithyroid drugs car-bimazole (which is converted to the active compound methimazole) and propylthiouracil inhibit the synthesis of thyroid hormone. Propylthiouracil also inhibits peripheral conversion of T4 to T3. Many of the symptoms of hyperthyroidism can also be alleviated by fl-adrenoceptor antagonists. Iodine... 

In contrast to arsenic, trace concentrations of selenium are essential for human and animal health. Until the late 1980s, the only known metabolic role for selenium in mammals was as a component of the enzyme glutathione peroxidase (GSH-Px), an anti-oxidant that prevents cell degeneration. There is now growing evidence, however, that a seleno-enzyme is involved in the synthesis of thyroid hormones (Arthur and Beckett, 1989 G. F. Combs and S. B. Combs, 1986). Selenium dehciency has been linked to cancer, AIDS, heart disease, muscular dystrophy, multiple sclerosis, osteoarthropathy, immune system and reproductive disorders in humans, and white muscle disease in animals (Levander,... 

Selenium-requiring proteins indude GSH peroxidase, deiodinase, selenoprotein P, and selenoprotein W, GSH peroxidase is vital for the removal of certain forms of toxic oxygen, i.o, lipid peroxidides and hydrogen peroxide. 5 -Deiodinase is used for the synthesis of thyroid hormone. The functions of selenoproteins P and W are not known,... 

As discussed above, hthium inhibits the synthesis of thyroid hormone and its release from the thyroid, and stimulates the formahon of antithyroid anhbodies in susceptible subjects [122]. Lithium-induced hypothyroidism responds to thyroxine therapy. Lithium... 

MOA Thioamides inhibit the synthesis of thyroid hormones by inhibiting thyroid peroxidase-catalyzed reactions to block iodine organification. Thioamides also block coupling of mono-iodothyronine and diiodothyronine. PTU also inhibits the peripheral conversion of T to Tj. 

In hyperthyroidism, inhibits synthesis of thyroid hormone. Diverts iodine from thyroid hormone synthesis. 

Each step in the synthesis of thyroid hormones is regulated by pituitary TSH. TSH stimulates the iodide pump, Tg synthesis, and colloidal uptalce by foUicular cells. TSH also regulates the rate of proteolysis of Tg for the fib-eration of T4 and T3 is also regulated by TSH. In addition, TSH induces an increase in the size and number of the thyroid foUicular ceUs. Prolonged TSH stimulation leads to increased vascularity and eventual hypertrophic enlargement of the thyroid gland (goiter). 

Synthesis of thyroid hormones that regulate basal metabolic rate Protects against number of cancers... 

PTU and MMI reduce the synthesis of thyroid hormones and are similar in efficacy and adverse effects, but their dosing ranges differ by 10-fold. 

In the adulL hypothyroidism may rarely be caused by iodine deficiency and goitrogens. Rarely, iodine ingestion in the form of expectorants can lead to hypothyroidism. In sensitive persons, the iodide blocks the synthesis of thyroid hormone, leading to an increased secretion of TSH, which causes thyroid enlargement. Thus both iodine excess and iodine deficiency can cause decreased secretion of thyroid hormone. 

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