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Agranulocytosis Associated with Antithyroid Drugs: Effects of Patient Age and Drug Dose

DAVID S. COOPER, M.D.; DAVID GOLDMINZ, B.S.; ANN A. LEVIN, M.S.; PAUL W. LADENSON, M.D.; GILBERT H. DANIELS, M.D.; MARK E. MOLITCH, M.D.; and E. CHESTER RIDGWAY, M.D.
[+] Article and Author Information

Grant support: Dr. Cooper is the recipient of a New Investigator Research Award 1 R23 AM28465-01.

Presented in part 22-25 September 1982 at the 58th Annual Meeting of the American Thyroid Association, Quebec City, Quebec, Canada.

▸Requests for reprints should be addressed to David S. Cooper, M.D.; Thyroid Unit, Massachusetts General Hospital; Boston, MA 02114.


Boston, Massachusetts


©1983 American College of PhysiciansAmerican College of Physicians


Ann Intern Med. 1983;98(1):26-29. doi:10.7326/0003-4819-98-1-26
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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.

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