Thyroid hormone iodide

Iodine radioiodine which destroys the cells making thyroid hormone iodide, an excess of which reduces the production of thyroid hormone temporarily by an unknown mechanism (it is also necessary for the formation of hormone, and both excess and deficiency can cause goitre). 

Discuss the interactions of thyroid hormone, iodide, and antithyroid drugs with radioactive iodine therapy. 

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. 

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

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. 

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). 

Figure 42-11. Model of iodide metabolism in the thyroid follicle. A follicular cell is shown facing the follicular lumen (top) and the extracellular space (at bottom). Iodide enters the thyroid primarily through a transporter (bottom left). Thyroid hormone synthesis occurs in the follicular space through a series of reactions, many of which are peroxidase-mediated. Thyroid hormones, stored in the colloid in the follicular space, are released from thyroglobulin by hydrolysis inside the thyroid cell. (Tgb, thyroglobulin MIT, monoiodotyrosine DIT, diiodotyro-sine Tj, triiodothyronine T4, tetraiodothyronine.) Asterisks indicate steps or processes that are inherited enzyme deficiencies which cause congenital goiter and often result in hypothyroidism.

Excess production of thyroid hormone can be reduced in four ways iodides, antithyroid drugs, radioactive iodine, and... 

Large doses of iodide inhibit the synthesis and release of thyroid hormones. Serum T4 levels may be reduced within 24 hours, and the effects may last for 2 to 3 weeks. Iodides are used most commonly in Graves disease patients prior to surgery and to quickly reduce hormone release in patients with thyroid storm. Potassium iodide is administered either as a saturated solution (SSKI) that contains 38 mg iodide per drop or as Lugol s solution, which contains 6.3 mg iodide per drop. The typical starting dose is 120 to 400 mg/day. Iodide therapy should start 7 to 14 days prior to surgery. Iodide should not be... 

Derived from the amino acid tyrosine, thyroid hormones are unique because they contain iodine. At this time, its incorporation into thyroid hormones is the only known use for iodine in the body. There are two thyroid hormones, named for the number of iodides added to the tyrosine residues of the thyroglobulin triiodothyronine (T3) and tetraiodothyronine (T4, thyroxine). Although significantly more T4 is synthesized by the thyroid gland, T3 is the active hormone. At the target tissue, T4 is deiodoninated to form the more potent T3. 

Another important example of catalytic oxidation of inorganic compounds by peroxidases is the catalysis of iodide oxidation by TPO. TPO is involved in the biosynthesis of thyroid hormone and catalyzes the reactions of iodination and coupling in the thyroid gland. Magnusson et al. [215] considered two possible pathways of iodination the formation of enzyme-bound hypoiodite and the formation of free hypoiodide (Reactions (17) and (18)) ... 

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. 

The concentration of Li+ in the thyroid is three to four times that in serum [179]. It is thought that Li+ may be concentrated in the thyroid gland by a mechanism similar to the incorporation of iodide, I-, resulting in competition between Li+ and I the levels of intracellular 1 decrease when those of Li+ increase, and vice versa [182]. Li+ inhibits both the ability of the gland to accumulate 1 and the release of iodine from the gland. In vitro, Li+ has no effect on thyroid peroxidase, the enzyme that catalyzes the incorporation of I" into tyrosyl residues leading to thyroidal hormone synthesis, but does increase the activity of iodotyrosine-deio-dinase, which catalyzes the reductive deiodination of iodotyrosyls, thus maintaining the levels of intracellular I [182]. The increase in iodoty-rosine-deiodinase activity is probably a response to the Li+-induced decrease in the concentration of thyroidal I". Li+ has no effect on the conversion of thyroxine to triiodothyronine. The overall effect of this competition between Li+ and 1 is, therefore, reduced levels of thyroid hormone in the presence of Li+. 

The thyroid hormones thyroxine (T4) and triiodothyronine (T3) are formed on thyroglobulin, a large glycoprotein synthesized within the thyroid cell. Inorganic iodide enters the thyroid follicular cell and is oxidized by thyroid peroxidase and covalently bound (organified) to tyrosine residues of thyroglobulin. 

Amiodarone may induce thyrotoxicosis (2% to 3% of patients) or hypothyroidism. It interferes with type I 5 -deiodinase, leading to reduced conversion of T4 to T3, and iodide release from the drug may contribute to iodine excess. Amiodarone also causes a destructive thyroiditis with loss of thyroglobulin and thyroid hormones. 

PTU and MMI block thyroid hormone synthesis by inhibiting the peroxidase enzyme system of the thyroid gland, thus preventing oxidation of trapped iodide and subsequent incorporation into iodotyrosines and ultimately iodothyronine ( organification ) and by inhibiting coupling of MIT and DIT to form T4 and T3. PTU (but not MMI) also inhibits the peripheral conversion of T4 to T3. 

Iodide acutely blocks thyroid hormone release, inhibits thyroid hormone biosynthesis by interfering with intrathyroidal iodide use, and decreases the size and vascularity of the gland. 

Iodides are often used as adjunctive therapy to prepare a patient with Graves disease for surgery, to acutely inhibit thyroid hormone release and quickly attain the euthyroid state in severely thyrotoxic patients with cardiac decompensation, or to inhibit thyroid hormone release after RAI therapy. 

Sodium iodide 131 is an oral liquid that concentrates in the thyroid and initially disrupts hormone synthesis by incorporating into thyroid hormones and thyroglobulin. Over a period of weeks, follicles that have taken up RAI and surrounding follicles develop evidence of cellular necrosis and fibrosis of the interstitial tissue. 

Iodides, which rapidly block the release of preformed thyroid hormone, should be administered after PTU is initiated to inhibit iodide use by the overactive gland. 

Fig. 1 Thyroid hormone synthesis in a thyroid follicular cell. NIS and TPO (organification and coupling reaction) have been marked in red dashed line as the two main targets for direct thyroid gland function disrupters. DEHALl iodotyrosine dehalogenase 1, DIT diiodotyrosine, DUOX2 dual oxidase 2, MIT monoiodotyrosine, Na/K-ATPase sodium-potassium ATPase, NIS sodium-iodide symporter, PSD pendrin, TG thyroglobulin, TPO thyroperoxidase. Reprinted from [7] with permission from Elsevier...

Synthesis, storage, and release of thyroid hormones by the thyroid gland are primarily regulated by the thyrotropin hormone, while the iodides necessary for their synthesis are usually present in consumed foods. 

Thioamides are reducing agents. They inhibit thyroid hormone synthesis by inhibiting the peroxidase enzymatic system, which catalyzes oxidation of iodide ions and iodine that are consumed in food, which is necessary for iodination of tyrosine derivatives. Thus they reduce the concentration of free iodine necessary to react with tyrosine derivatives, and they can also block oxidative addition reactions of mono- and diiodtyrosines, which form L-thyroxine and L-triiodothyronin. 

The thyroid hormones T4 and T3 contain 65% and 59% of iodine respectively as an essential component for biological activity of the molecule. Iodine from dietary sources or medication enters the body via gastrointestinal tract. The recommended daily adult intake is 150-300 pg. Iodine is rapidly absorbed and enters the extracellular fluid pool. Iodide is removed from the blood largely by the thyroid and kidneys. The higher the intake the lower the fractional iodine uptake by the thyroid. 

A second dietary trace element, selenium, is also essential for normal thyroid hormone metabohsm. Selenium in the form of selenocysteine is a required component for three enzymes that remove iodide from thyroid hormones. Deiodination is the major metabohc pathway by which T4 and T3 are cleared from the system. After secretion by the thyroid gland, T4 may be deiodinated to yield either T3 or the physiologically inactive reverse Tj (3,3, 5 -triiodothyronine, or rX3). T3 and rTj are further deiodinated to form less active metabolites. Selenium, like iodine, is deficient in many areas of the world. 

Lithium inhibits thyroidal incorporation of L into Tg, as well as the secretion of thyroid hormones, but it does not inhibit the activity of the Na+-I symporter or the accumulation of I within the thyroid. Lithium offers no particular advantage over drugs of the thionamide class but may be employed for temporary control of thyrotoxicosis in patients who are allergic to both thion-amides and iodide. 

A) Thiocyanate inhibits the binding of iodide to thyroid hormone receptors. 

B. Selenium in the form of selenocysteine is required for three enzymes that remove iodide from thyroid hormones. There are no signihcant areas in which dietary intake of sodium or potassium are problems. Fluorine deficiency is not associated with thyroid hormone metabolism. 

Levothyroxine is taken orally or intravenously and is normally prescribed to treat hypothyroidism or to suppress the release of thyroid hormone so as to manage cancerous thyroid nodules (i.e., thyroid cancer) and growth of goiters. Other less frequently prescribed thyroid and parathyroid drugs include methimazole (Tapazole), various iodides, lithioronine (Triostat), and liotrix (Thyrolar). 

---