 taken the antithyroid drugs for a year, the medication is gradually withdrawn over one to two months, and the patient is observed at intervals thereafter. Most of those who will ultimately have an exacerbation of the disease do so within three to six months; others may not develop recurrent hyperthyroidism for several years . Some patients may have a recurrence after discontinuing the drug that lasts for a short time, and then a remission without further therapy . An earlier report that administration of iodide increases the relapse rate after drug therapy is withdrawn has not been confirmed . Hashizume and co-workers reported that administration of T4 to suppress TSH for a year after stopping antithyroid drugs produced a very high remission rate . Similar results were found when T4 treatment was given after a course of antithyroid drugs during pregnancy. . These studies engendered much interest because of the uniquely high remission rate obtained by the continuation of thyroxine treatment to suppress TSH for a year or more after the usual course of antithyroid drug therapy. Possibly such treatment is beneficial since it inhibits the release of thyroid antigens. However subsequent studies have not found a beneficial effect of added T4 therapy [131.1,131.2]. It appears that the results are, for some reason, peculiar to this study group.
The probability of prolonged remission correlates with reduction in gland size, disappearance of thyroid-stimulating antibodies from serum[132, 133], (Fig.11-8) return of T 3suppressibility, decrease in serum TG, and a haplotype other than HLA-DR3 [130, 136]. However, none of these markers predict recovery or continued disease with an accuracy rate above 60-70% [136.1]. Long after apparent clinical remission, many patients show continued abnormal thyroid function, including partial failure of T3 suppression, or absent or excessive TRH responses [127-140]. These findings probably indicate the tenuous balance controlling immune responses in these patients.
Lactating women taking PTU have PTU levels of up to 7.7 µg/ml in blood, but in milk the level is much lower, about 0.7 µg/ml . Only 1-2 mg PTU could be transferred to the baby daily through nursing; this amount is inconsequential except for the possibility of reactions to the drug. Azizi et al. studied intellectual development of children whose mothers took methimazole during lactation, and found that there was no evident effect on physical and intellectual development, at least in children whose mothers took up to 20 mg of MMI daily [141a].
Hypothyroidism– It has long been known that some patients with Graves’ disease eventually develop spontaneous hypothyroidism . Reports have shown that most patients who become euthyroid after antithyroid drug therapy, if followed long enough, also develop evidence of diminished thyroid function . In a prospective study, Lamberg et al found that the annual incidence in these patients of subclinical hypothyroidism was 2.5%, and of overt hypothyroidism 0.6%.
TOXIC REACTIONS TO ANTITHYROID DRUGS
The use of antithyroid drugs may be accompanied by toxic reactions, depending on the drug and dose, in 3 – 12% of patients[ 117, 118, 142- 146]. Most of these reactions probably represent drug allergies[ 147- 148]. Chevalley et al., in a study of 180 patients given methimazole[ 143], found an incidence of toxicity of 4.3%, broken down as follows: Total reactions 4.3%; Pruritus 2.2%; Granulocytopenia 1.6%; Urticaria 0.5%.Methimazole may be the drug least likely to cause a toxic reaction, but there is little difference between it and PTU. When the antithyroid drugs are prescribed, the patient should be apprised of the possibility of reactions, and should be told to report phenomena such as a sore throat, fever, or rash to the physician and to discontinue the drug until the cause of the symptoms has been evaluated. These symptoms may herald a serious reaction.
Allergic rash-If a patient taking a thiocarbamide develops a mild rash, it is permissible to provide an antihistamine and continue using the drug to see whethe