Agranulocytosis associated with antithyroid drugs. Effects of patient age and drug dose

The records of all patients with antithyroid drug-related agranulocytosis at two Boston hospitals (Group 1, 14 patients), as well as the published case reports of 36 patients with this syndrome (Group 2) were reviewed. The clinical characteristics of these patients were then compared with those of 50 hyperthyroid patients who had taken antithyroid medication without untoward hematologic reactions (Group 3). The mean ages of patients in Group 1 and Group 2 were significantly greater than that of Group 3 (50.6 ± 16 years versus 35.7 ± 13.7 years, p < 0.001; 46.3 ± 18.7 years versus 35.7 ± 13.7 years, p < 0.02). By chi-squared analysis, the relative risk of developing agranulocytosis in patients over age 40 was 6.4 times that among younger patients (p < 0.001). The mean doses of methimazole in Group 1 and Group 2 were significantly higher than that in Group 3 (43.8 ± 9.9 mg/d versus 29.5 ± 10.4 mg/d, p < 0.001; 40.7 ± 15.7 mg/d versus 29.5 ± 10.4 mg/d p < 0.02), with an 8.6-fold increased risk of agranulocytosis with doses greater than 40 mg/d (p < 0.01). In contrast, the mean doses of propylthiouracil did not differ among the three groups. These data suggest that antithyroid drugs should be administered cautiously to patients over age 40. Because no cases of agranulocytosis were seen with methimazole doses less than 30 mg/d, low-dose methimazole therapy may be safer than high-dose therapy or treatment with conventional doses of propylthiouracil.