Iodine organification

The answer is c. (Katzung, pp 651-652.) Propylthiouracil is a thioamide that interferes with the production of thyroid hormone. Its primary action is prevention of thyroid hormone synthesis by blocking thyroid peroxidase catalysis leading to interference with iodine organification. 

The available agents with antithyroid activity are the thioamides propylthiouracil, carbimazole and methimazole also known as thiamazole. Their thio-carbamide group is indispensable for antithyroid activity. The mechanism of action is complex. The most important action is the prevention of hormone synthesis by an inhibition of the thyroid peroxidase-catalyzed reactions involved in iodine organification. These agents also block the coupling of the iodoty-rosines. 

Propylthiouracil (PTU) Inhibit thyroid peroxidase reactions block iodine organification inhibit peripheral deiodination of T4 and T Hyperthyroidism Oral duration of action 6-8 h delayed onset of action Toxicity Nausea, gastrointestinal distress, rash, agranulocytosis, hepatitis,hypothyroidism... 

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. 

The iodinated tyrosine residues monoiodotyrosine (MIT) and diiodotyrosine (DIT) combine to form iodothyronines (Fig. 73-3). Thus, two molecules of DIT combine to form T4, whereas MIT and DIT constitute T3. In addition to its role in iodine organification. 

Which antithyroid medication inhibits both iodine organification, and the conversion of T, (thyroxine) to T3 (triiodothyronine) ... 

TPO mutations are among the most frequent cause of inborn abnormahties of thyroid hormone synthesis, as confirmed in a large survey indicating that TPO gene defects are the most common cause of severe defects in iodine organification (Bakker et at, 2000). 

Acute excess iodine ingestion has long been known to result in a transient decrease in iodine organification, termed the Wolff—Chaikoff effect (Wolff and Chaikoff, 1948). With sustained excess iodine exposure, however, most individuals thyroid glands escape from acute Wolff— Chaikoff effect, despite continued excess iodine exposure, and resume synthesis of normal amounts of T4 and T3. The mechanism responsible for this escape or adaptation to the iodine load probably involves a decrease in the Na /H symporter protein, resulting in a decrease in thyroid iodide content (Eng et ai, 1999). In some individuals... 

Markou et aL, 2001), and this was the case in about 1% of our patients. Iodine excess inhibits iodine organification and T4andT3 synthesis (WoUf-Chaikoff effect). Normal subjects escape from this effect however, patients with abnormal thyroid gland do not and may develop thyroid hypofunction. Iodine also inhibits thyroid hormone release and decreases serum T4 and T3 levels (Woeber, 1991). Furthermore, iodine seems to be an important factor in thyroid autoimmunity in genetically predisposed individuals (Laurberg... 

Organification Binding of iodine to tyrosine residues of thyroglobulin. 

Iodine inhibits hormone release. They inhibit organification and hormone release and also decrease the size and vascularity of hyperplastic gland on regular administration. Peak antithyroid affect is seen in two weeks after which thyrotoxicosis may reoccur. It is well absorbed orally and crosses the placental barrier. 

The thyroid gland also regulates its uptake of iodide and thyroid hormone synthesis by intrathyroidal mechanisms that are independent of TSH. These mechanisms are primarily related to the level of iodine in the blood. Large doses of iodine inhibit iodide organification (Wolff-Chaikoff block, see Figure 38-1). In certain disease states (eg, Hashimoto s thyroiditis), this can inhibit thyroid hormone synthesis and result in hypothyroidism. Hyperthyroidism can result from the loss of the Wolff-Chaikoff block in susceptible individuals (eg, multinodular goiter). 

Possible mechanisms need to be clarified. Since thyroid autoantibodies are detected in most patients who develop thyroid disorders, the induction or exacerbation of preexisting latent thyroid autoimmunity is the most attractive hypothesis. This is in accordance with the relatively frequent occurrence of other autoantibodies or clinical autoimmune disorders in patients who develop thyroid disorders (168). However, 20-30% of patients who develop thyroid diseases have no thyroid antibodies, and it is thus not yet proven that autoimmunity is the universal or primary mechanism. In fact, there were subtle and reversible defects in the intrathjroidal organification of iodine in 22% of antithyroid antibody-negative patients treated with interferon alfa (169). In addition, the acute systemic administration of interferon alfa in volunteers or chronic hepatitis patients reduces TSH concentrations (SED-13,1093) (170), and in vitro studies have suggested that interferon alfa directly inhibits thyrocyte function (SED-13, 1093) (171). Finally, the thyroid autoantibody... 

FIGURE 73-3. Scheme of coupling reactions. After tyrosine is iodinated to form MiT or DiT (organification of the iodine), MiT and DiT combine to form triiodothyronine (T3), or two molecules of DIT form T4. 

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