 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 whether the reaction subsides spontaneously, as it commonly does. If the reaction is more severe or if neutropenia occurs, another drug should be tried or the medication withdrawn altogether. Usually a switch is made to another thiocarbamide, because cross-reactions do not necessarily occur between members of this drug family. Alternatively, the program of therapy may be changed to the use of RAI, which may be given after the patient has stopped taking the antithyroid drug for 48 – 74 hours, or the patient may be prepared for surgery by the administration of iodides and propranolol.
The incidence of agranulocytosis in a large series of patients was 0.4% . It occurs most frequently in older patients and those given large amounts of the drug (20-30 mg methimazole every eight hours) .
Reactions tend to be most frequent in the first few months of therapy but can occur at any time, with small doses of drug, and in patients of all ages . The most common reactions are fever and a morbilliform or erythematous rash with pruritus. Reactions similar to those of serum sickness, with migratory arthralgias, jaundice, lymphadenopathy, polyserositis, and episodes resembling systemic lupus erythematosus have also been observed . Pyoderma gangrenosum can occur (147.1). Neutropenia and agranulocytosis are the most serious complications. These reactions appear to be due to sensitization to the drugs, as determined by lymphocyte reactivity in vitro to the drugs . Occasionally agranulocytosis can develop even though the total WBC remains within normal ranges- a hazard to be remembered if differential counts are not done. Fortunately, even these problems almost always subside when the drug is withdrawn.
Aplastic anemia with marrow hypoplasia has been reported (perhaps 10 cases), again with spontaneous recovery in 2-5 weeks in 70%, but fatal outcome in 3 patients . Thrombocytopenia and/or anemia may accompany the neutropenia.
Vasculitis is a fortunately rare complication during treatment with antithyroid drugs.
Neutropenia-It is probably wise