Agranulocytosis caused by antithyroid drugs occurs soon after therapy is started and lasts less than two weeks
(July 2007)
The background of the study. Agranulocytosis (defined as a very low white blood cell count) is a well-known side effect of antithyroid drugs, but its timing and duration are not clear. This study was done to determine the onset and duration of agranulocytosis caused by methimazole, carbimazole, and propylthiouracil, and other drugs.
How the study was done. The study subjects were 973 patients who had agranulocytosis (white-cell count, <0.5 x 109 cells/L; normal, >5 x 109) attributed to many drugs, including 87 patients in whom it was attributed to methimazole, carbimazole, or propylthiouracil. The likelihood of a relationship between the drug and agranulocytosis was determined by four findings: (1) onset during therapy or within one month after the drug was stopped, (2) the absence of concurrent illness or therapy with other drugs that might cause agranulocytosis, (3) a rise in cell count to >1.5x 109 cells/L within one month after the drug was stopped, and (4) a positive rechallenge test or strong evidence of the causal effect of the drug. The relationship was deemed definite if all four criteria were met, probable if criteria one to three were met, and possible if criterion 1 was met and criterion 3 was uncertain.
The results of the study. Among the 973 patients, agranulocytosis was considered definite in 6 percent, probable in 45 percent, and possible in 49 percent. The patients in these groups had received 36, 89, and 55 different drugs, respectively.
With respect to antithyroid drugs, agranulocytosis was considered probable in 55 patients treated with methimazole, 21 treated with carbimazole, and 10 treated with propylthiouracil, and definite in 1 treated with propylthiouracil. The time to onset and duration of agranulocytosis were similar for all three drugs (Table).
| Table. Average Duration of Therapy before Onset of Agranulocytosis and Duration of Agranulocytosis in Patients Treated with an Antithyroid Drug. |
| |
Methimazole (n = 55) |
Carbimazole (n = 21) |
Propylthiouracil
(n = 11) |
| Duration of therapy before onset (days) |
42 |
41 |
36 |
| Duration of agranulocytosis (days) |
10 |
8 |
10 |
The conclusions of the study. In patients treated with an antithyroid drug, agranulocytosis usually occurs less than two months after the start of therapy and lasts less than two weeks.
The original article. Andersohn F, Konzen C, Garbe E. Systematic review: agranulocytosis induced by nonchemotherapy drugs. Ann Intern Med 2007;146:657-65.
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