tion tests has not been advised[ 151, 152]. Liver transplantation has been used with success in several patients [152.1]. As noted above,. Any sign of liver damage must be carefully monitored, and progress of abnormalities in liver function tests demand cessation of the drug[147, 152]. Diffuse interstitial pneumonitis has also been produced by propylthiouracil .
Methimazole is best avoided in early pregnancy. Very rare cases of esophageal atresia, omphalocele, and choanal atresia occurred in Sweden almost only in infants whose mothers took methimazole during early pregnancy.This is thought to be a true, although fortunately very infrequent, complication of methimazole use. Their observations obviously suggest that methimazole should best not be given during early months of pregnancy (153.2).
Potassium Perchlorate, Lithium,and Cholestyramine
Potassium perchlorate was introduced into clinical use after it was demonstrated that several monovalent anions, including nitrates, have an antithyroid action. Perchlorate was the only member of the group that appeared to have sufficient potency to be useful. This drug, in doses of 200 – 400 mg every six hours, competitively blocks iodide transport by the thyroid. Accordingly, therapeutic doses of potassium iodide will overcome its effect. Institution and control of therapy with perchlorate are similar to those discussed for the thiocarbamides. Toxic reactions to this agent occur in about 4% of cases  and usually consist of gastric distress, skin rash, fever, lymphadenopathy, or neutropenia; they usually disappear when the drug is discontinued. The reaction rate is higher when doses of more than 1 g/day are given . Nonfatal cases of neutropenia or agranulocytosis have been reported, and four cases of fatal aplastic anemia have been associated with the use of this drug . Because of toxic reactions, perchlorate is not used at present for routine therapy. It has found a role in therapy of thyrotoxicosis induced by amiodarone . Apparently blocking of iodide uptake is an effective antithyroid therapy in the presence of large body stores of iodide, while in this situation, methimazole and propylthiouracil are not effective alone.
Lithium ion inhibits release of T4 and T3 from the thyroid and has been used in the treatment of thyrotoxicosis, but is most effective when used with a thiocarbamide drug. It does not have a well-established place in the treatment of Graves’ disease[ 157, 158]. It has possible value in augmenting the retention of 131-I  and in preparing patients allergic to the usual antithyroid drugs or iodide for surgery, although propranolol is generally used for the latter problem.
Cholestyramine (4gm, q8h) for a month has been shown to hasten return of T4 to normal [159.1] by binding hormone in the gut. It can be used as an adjunct to help speed return of hormone levels to normal, and may be especially beneficial in thyroid storm.
Iodine – Plummer originally observed that the administration of iodide to thyrotoxic patients resulted in an amelioration of their symptoms. This reaction is associated with a decreased rate of release of thyroid hormone from the gland and with a gradual increase in the quantity of stored hormone. The effect of iodide on thyroid hormone release and concentration in blood is apparent in Figure 11-6. The mechanism of action may be by inhibition of generation of cAMP, and involves inhibition of proteolysis, but is not fully understood. Therapeutic quantities of iodide also have an effect on hormone synthesis through inhibition of organification of iodide. Iodide has similar but less intense effects on the normal thyroid gland, apparently because of adaptive mechanisms. Administration of large amounts of iodide to laboratory animals or humans blocks the synthesis of thyroid hormone and results in an accumulation of trapped inorganic iodide in the thyroid gland (the Wolff-Chaikoff effect, see Ch 2). The thyrotoxic gland is especially sensitive to this action of iodide. Raising the plasma iodide concentration to a level above 5 µg/dl results in a complete