sional bone marrow depression. This drug prevents the concentration of iodide by the thyroid. Beta adrenergic blockers such as propranolol have a place in the treatment of thyrotoxicosis. These drugs alleviate some of the signs and symptoms of the disease but have little or no direct effect on the metabolic abnormality itself. They do not uniformly induce a remission of the disease and can be regarded as adjuncts, not as a substitute for more definitive therapy.
Mechanism of Action– Antithyroid drugs inhibit thyroid peroxidase, and PTU (not methimazole) has the further beneficial action of inhibiting T4 to T3 conversion in peripheral tissues. Antithyroid therapy is associated with a reduction in circulating antithyroid antibody titers , and anti-receptor antibodies [77, 78, 102]. Studies by MacGregor and colleagues  indicate that antibody reduction also occurs during antithyroid therapy in patients with thyroiditis maintained in a euthyroid state, thus indicating that the effect is not due only to lowering of the FTI in Graves’ disease. These authors also found a direct inhibitory effect of PTU and carbimazole on antithyroid antibody synthesis in vitro and postulate that this is the mechanism for diminished antibody levels . Other data argue against this hypothesis [105, 105.1]. Antithyroid drug therapy is also associated with a prompt reduction in the abnormally high levels of activated T lymphocytes in the circulation ., although Totterman and co-workers found that this therapy caused a prompt and transient elevation of activated T suppressor lymphocytes in blood . During antithyroid drug treatment the reduced numbers of T suppressor cells present in most thyrotoxic patients return to normal[106, 108]. Antithyroid drugs do not directly inhibit T cell function . All of these data argue that antithyroid drugs exert a powerful beneficial immunosuppressive effect on patients with Graves’ disease. While much has been learned about this process, the exact mechanism remains uncertain. Evidence that antithyroid drugs exert their immunosuppressive effect by a direct inhibition of thyroid cell production of hormones has been reviewed by Volpe .
Long-Term Antithyroid Drug Therapy with Thiocarbamides
Propylthiouracil warning-Propylthiouracil and methimazole have for years been considered effectively interchangeable, and liver damage was considered a very rare problem. Recently a commission appointed by the FDA reevaluated this problem, and concluded that the rare but severe complications of liver failure needing transplantation, and death, were sufficient to contraindicate the use of PTU as the normal first-line drug (109.1). The Endocrine Society and other advisory groups have suggested that methimazole be used for treatment except in circumstances of inavailability of the drug, patient allergy, or pregnancy. Because of the association of scalp defects and probably a severe choanal syndrome with administration of methimazole during the first 12 weeks of pregnancy, current advice is to give PTU during the first trimester, and then switch to methimazole.
Selection of patients–
Many patients with Graves’ disease under age 40 – 45 are given a trial of therapy with one of the thiocarbamide drugs. Younger patients, and those with recent onset of disease, small goiters , and mild disease, are especially favorable candidates, since they tend to enter remission most frequently. It is generally found that one-fourth to one-third of these patients who satisfactorily complete a one year course have a long term or permanent remission. The remainder need repeated courses of drug therapy, must be maintained on the drug for years or indefinitely [111, 112], or must be given some other treatment. It appears that the percentage of patients responding has progressively fallen over the past years from about 50% to at present 25 – 30%[113, 114]. This change was thought to reflect an alteration in iodide in our diet , which increased from about 150 µg/day in 1955 to 300 – 600 µg/day. However other factors including greater precision in diagnosis and m