Iodine hormonal effects

Prior to any evaluation of the functional integrity of labeled molecules, they must be separated from unlabeled molecules that may still be present. This is especially important for hormones which can elicit physiological effects at minute concentrations. Separation is usually based on a physicochemical change in the molecule as a result of iodination. Figure 8-36 depicts one such separation using ion exchange chromatography and Table 8-8 lists a number of other methods that have also been used to successfully isolate various iodinated hormones. 

Metabolic Functions. The functions of the thyroid hormones and thus of iodine are control of energy transductions (121). These hormones increase oxygen consumption and basal metaboHc rate by accelerating reactions in nearly all cells of the body. A part of this effect is attributed to increase in activity of many enzymes. Additionally, protein synthesis is affected by the thyroid hormones (121,122). 

Thiocyanate ion, SCN , inhibits formation of thyroid hormones by inhibiting the iodination of tyrosine residues in thyroglobufin by thyroid peroxidase. This ion is also responsible for the goitrogenic effect of cassava (manioc, tapioca). Cyanide, CN , is liberated by hydrolysis from the cyanogenic glucoside finamarin it contains, which in turn is biodetoxified to SCN. 

Hyperthyroidism may be treated in several ways. One of these is interference with the synthesis of the thyroid hormones, possibly by removal of iodine. Thiourea and cyclic thioureas have this effect and of such cyclic compounds, thiouracil (1030 R = H), its 6-alkyl derivatives (1030 R = Me or Pr) and thiobarbital (1031) are effective thyroid drugs. Today only propylthiouracil (1030 R = Pr) is widely used, probably because it has fewer side effects than the others (71MI21302). The thiouracils are made by the Principal Synthesis from a /3-oxo ester (1032 R = H, Me, Pr, etc.) and thiourea (45JA2197) their fine structures are experimentally based (64AF1004). 

Iodine, most ancient of the therapeutic agents for thyroid disorders, inhibits the secretion of thyroid hormone by retarding both the pinocyto-sis of colloid and proteolysis. This effect is observed in euthyroid as well as hyper thyroid persons. 

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+. 

Studies of low-dose perchlorate exposure in healthy human subjects A small number of studies have been published investigating the effects of low doses of perchlorate in thyroid function in healthy adults (without thyroid disease). One study was conducted in healthy male volunteers, involving the administration of 10 mg of perchlorate in drinking water for 14 days. A significant decrease in the uptake of iodine by the thyroid was observed at this dose, but there was no evidence of adverse effects on thyroid hormones or TSH concentrations [262]. Another recent study was conducted in healthy adults to determine the highest dose of perchlorate at which there is no effect on the uptake of iodine by the thyroid gland [263]. 

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. 

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. 

---