Antithyroid drug — induced agranulocytosis: Clinical experience with ten patients treated at one institution and review of the literature

Abstract

The frequency, predisposing factors and course of agranulocytosis (granulocytes < 250/microliter) secondary to antithyroid drugs were studied in a cohort of 1256 continuously treated outpatients with hyperthyroidism during the 15 year period from 1973 to 1987. Two cases of agranulocytosis were detected; the frequency was 0.18% (95%-confidence intervals, 0.0-0.44%). This prevalence appears to be lower than reported in previous studies (up to 1.8%). For other adverse drug reactions, there was a clear-cut relationship to initial thionamide dose and to the body mass index; most reactions occurred during the first weeks of treatment. In addition, eight patients referred for thionamide drug- induced agranulocytosis were studied, and the following results obtained: Methimazole dose in patients with agranulocytosis was almost twice as in other patients (63.3 +/- 19.7 vs 34.3 +/- 29.7 mg daily) suggesting that this complication was related to dose. The interval between start of antithyroid drug treatment and first symptoms of agranulocytosis was 33 days (median; range, 23-55 days); hence, prolonged treatment beyond this period would appear relatively safe. Withdrawal of the causative agent and treatment of infection led to recovery of leukocyte counts within 15 days (median; range, 5-31 days). Two fatal outcomes were seen in referred patients. In one severely hyperthyroid patient with methimazole-induced agranulocytosis, recombinant human granulocyte/macrophage colony stimulating factor induced clinical and hematologic recovery within a few days of administration. In conclusion, agranulocytosis is the most severe side effect of antithyroid drugs. According to our results and a literature review, it occurs almost exclusively during the first ten weeks of treatment and is probably related to the drug dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Agranulocitose e tonsilite associadas ao uso de metimazol

“…According to the studied literature, agranulocytosis is a very infrequent side effect in patients treated with methimazole 1,6,8,9 . On average, the onset of this complication is present in the first weeks of treatment with the referred drug 6 .…”

“…On average, the onset of this complication is present in the first weeks of treatment with the referred drug 6 . In the present study, the patient had been taking the drug for 2 months.…”

“…The less uncommon side effect of the use of thyourea, even though very important, is agranulocytosis 1 . It may be present regardless of age, dose and treatment duration 8 , even though Meyer-Gebner et al have reported higher incidence with higher doses 6 . It has sudden onset and affects 0.2 to 0.3% of the patients 8,9 .…”

“…The increase in thyroid size, infiltration, ophthalmopathy and dermopathy are mediated by autoimmune processes, differentiating Graves disease from other causes of thyrotoxicosis 1 . There are three main treatment approaches: antithyroid drugs, surgery and radioiodine, but initial therapy normally prefers pharmacological treatment, frequently methimazole 4,6 . It is a drug derived from thyourea or thyonamide that inhibits oxidation of iodine captured by the thyroid and as a consequence, it prevents synthesis of thyroid hormones 7 .…”

“…Monitoring of patients by routine counting of leukocytes has been proposed by same authors as effective in the prevention of agranulocytosis 11 . However, there is no literature consensus and according to MeyerGebner et al it would be important to have appropriate patient guidance for them to identify the symptoms of the disease 6 . Agranulocytic angina ranges from simple erythema to ulceration and necrosis of buccopharyngeal mucosa 12 .…”