The Relation of Initial Methimazole Dose to the Incidence of Methimazole-induced Agranulocytosis in Patients with Graves' Disease

Abstract

Abstract. The relation between the incidence of methimazole (methylmercaptoimidazole; MMI)-induced agranulocytosis and initial MMI dose was evaluated in a group of 514 patients with Graves' disease who were treated between 1995 and 2005. One hundred and forty-six (28.40%) patients had received an initial dose of 30 mg MMI and 277 (53.89%) patients had been treated with 15 mg MMI. Nine patients (1.75%) developed agranulocytosis due to MMI treatment. Six (4.11%) of 146 patients who received an initial dose of 30 mg MMI, two (4.54%) of 44 patients given an initial dose of 20 mg MMI, and one (0.36%) of 277 patients given an initial dose of 15 mg MMI developed agranulocytosis. There was a statistically significant difference in agranulocytosis incidence between patients receiving an initial dose of 30 mg MMI and those who received an initial dose of 15 mg. Although 8 (4.10%) of 195 patients in the high-dose group (20 mg or higher) developed agranulocytosis, only 1 (0.31%) of 319 patients in the low-dose group (15 mg or lower) did. In conclusion, the incidence of agranulocytosis with low-dose MMI therapy was ten times lower than that of the high-dose regimen.

Sudden Onset Agranulocytosis and Hepatotoxicity after Taking Methimazole

“…It is dose and concentration dependent (10). There have been several studies suggesting that MMI-induced agranulocytosis is dose related (8,11,12), but in the present patient, this theory seems unreasonable, because this patient developed agranulocytosis only six days after commencement of MMI (total dosage 120 mg), which is a much shorter time than other patients reported (8,13,14). Also the concentration of MMI in the present case should be in a low level.…”

Antithyroid Drug-Induced Aplastic Anemia

“…1A), but as illustrated by Patient 2 (see below), AA can occur six months after the start of antithyroid drugs or even longer. Agranulocytosis due to antithyroid drugs is more common, with more than 400 cases published up-todate (6)(7)(8)(9)(25)(26)(27)(28)(29)(30)(31). It usually occurs within the first 2-3 months of therapy, but can also develop even after years of continuous or intermittent treatment with antithyroid drugs (3).…”

“…As all patients with antithyroid induced AA have concomitant agranulocytosis, it is probable that these two side effects have common pathogenic mechanisms. The risk of agranulocytosis is greater in female patients, especially those who receive high doses of MMI (29), and in elderly patients, who may also exhibit a higher mortality rate (6). Although, antithyroid drug-induced AA occurs more often in females and those who receive medium or high doses of these drugs, it is not age-related (Table 1).…”

Therapeutic Plasmapheresis in Patients with Thyrotoxicosis. Report of Two Cases

“…Adverse reactions to drug therapy may, however, be frequent and serious to the point of threatening the life of patients, as in the cases described here. The use of antithyroids is associated with agranulocytosis in 0.2 to 1.75% of patients and is more frequent in patients who also use methimazole in the first 100 days of treatment [5][6][7][8]. Other treatment options, such as radioactive iodine (I-131) and surgery should therefore be considered in such cases.…”