es, either pericytoplasmic or cytoplasmic, during treatment, with or without vasculitis. Most cases appear to be associated with the use of propylthiouracil, and therapy includes cessation of the drug, sometimes treatment with steroids or cyclophosphamide for renal involvement, and rarely plasmapheresis. The commonest cutaneous lesion associated is leukocytoclastic vasculitis associated with purpuric lesions. Symptoms may include fever, myalgia, arthralgia, and lesions in the kidneys and lungs. Prognosis is usually good if the medication is discontinued, although death has occurred. ANCA positivity (pericytoplasmic, cytoplasmic, directed to myeloperoxidase, proteinase3, or human leukocyte elastase) can occur in patients on antithyroid drugs associated with vasculitis. It is also found without clinical evidence of vasculitis, and the significance of this finding is unclear [149.1]. Guma et al recently reported that, in a series of patients with Graves’ disease, 67% were found to be ANCA positive before medical treatment, and that 19% remained positive after one year of antithyroid treatment. This data suggests that ANCA antibodies reflect in some way the autoimmunity associated with Graves’ hyperthyroidism, rather than simply being a manifestation due to the treatment with antithyroid drugs (149.2). In addition to suppression of hematopoiesis and agranulocytosis, methimazole has been associated in one patient with massive plasmocytosis, in which 98% of the cells in the bone marrow were plasma cells. After discontinuation of the drug, and treatment with dexamethasone and G-CSF, the patient’s marrow recovered to normal (149.1).
Liver damage-Thiocarbamides can also cause liver damage ranging from elevation of enzymes, through jaundice, to fatal hepatic necrosis
Toxic hepatitis (primarily with propylthiouracil) and cholestatic jaundice (primarily with methimazole) are fortunately uncommon .Toxic hepatitis can be severe or fatal, but the incidence of serious liver complications is so low that routine monitoring of function 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