Thionamide Associated Agranulocytosis: Low Incidence with Low Doses of Methimazole

granulocytosis is an uncommon but a most serious adverse side effect ofthiouracil. it has been reported to affect0.3% - 0.6% of patients treated withthiourea-derivates. both methimazole(mmi) and propylthiuracil (ptu) can causeagranulocytosis. some data indicate that lowdoses of mmi are associated with lower prevalenceof agranulocytosis than either high-dosemmi or conventional doses of ptu. the aim ofthe present study was to determine the frequencyof thionamide-associatied agranulocytosisand to clarify the role of clinical factors suchas gender and age of patient, duration of antithyroidtherapy, dosage and type of thionamideused, in the development of agranulocytosis.materials and methods: the medical records ofall patients with hyperthyroid disease, treatedwith either mmi or ptu in endocrine clinics,were reviewed retrospectively with regard toagranulocytosis, patient age and sex, duration ofantithyroid therapy, diagnosis, dosage, and typeof thionamide used. between april 1985 andseptember 2004, a total of 21,800 patients withhyperthyroidism due to gravesdisease or toxicmultinodular goiter received long term treatment(mean duration of treatment of 15.7±8.4months) with either mmi or ptu at endocrineclinics of tabriz university of medical sciences.of these, 20,840 (95.6%) patients were treatedwith mmi and the remainder 960 (4.4%) receivedptu. results: classic agranulocytosis, defined as severeneutropenia, accompanied by serious symptomsand signs of infection developed in sevencases, 5 in mmi group and 2 in ptu treated patients.thus the overall prevalence of thiomamide-associated agranulocytosis in this study isabout 0.03 percent. there was no significant differencebetween mean ages of patients with andwithout agranulocytosis (42.2±14.8 vs 45.4±13.7years). in the majority of cases, agranulocytosisoccurred during the first 2 months of treatment.there was no case with agranulocytosis among15,412 individuals treated with low doses ofmmi « 20 mg/day).conclusion: in conclusion the majority of casesof agranulocytosis occurred within the first fewweeks of initiation of antithyroid therapy. thisside effect may occur at any times, regardless ofpatient age, gender or duration of treatment. itseems that the likelihood of agranulocytosis isdiminished at low doses of mmi.