ANTITHYROID DRUG-INDUCED AGRANULOCYTOSIS - CLINICAL-EXPERIENCE WITH 10 PATIENTS TREATED AT ONE INSTITUTION AND REVIEW OF THE LITERATURE

Citation
M. Meyergessner et al., ANTITHYROID DRUG-INDUCED AGRANULOCYTOSIS - CLINICAL-EXPERIENCE WITH 10 PATIENTS TREATED AT ONE INSTITUTION AND REVIEW OF THE LITERATURE, Journal of endocrinological investigation, 17(1), 1994, pp. 29-36
Citations number
31
Categorie Soggetti
Endocrynology & Metabolism
ISSN journal
03914097
Volume
17
Issue
1
Year of publication
1994
Pages
29 - 36
Database
ISI
SICI code
0391-4097(1994)17:1<29:ADA-CW>2.0.ZU;2-A
Abstract
The frequency, predisposing factors and course of agranulocytosis (gra nulocytes <250/mu l) secondary to antithyroid drugs were studied in a cohort of 1256 continously treated outpatients with hyperthyroidism du ring the 15 year period from 1973 to 1987. Two cases of agranulocytosi s were detected; the frequency was 0.18% (95%-confidence intervals, 0. 0-0.44%). This prevalence appears to be lower than reported in previou s studies (up to 1.8%). For other adverse drug reactions, there was a clear-cut relationship to initial thiyonamide dose and to the body mas s index; most reactions occurred during the first weeks of treatment. In addition, eight patients referred for thionamide drug- induced agra nulocytosis were studied, and the following results obtained: Methimaz ole dose in patients with agranulocytosis was almost twice as in other patients (63.3+/-9.7 vs 34.3+/-29.7 mg daily) suggesting that this co mplication was related to dose. The interval between start of antithyr oid drug treatment and first symptoms of agranulocytosis was 33 days ( median; range 23-55 days); hence, prolonged treatment beyond this peri od 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 refer red patients. In one severely hyperthyroid patient with methimazole-in duced agranulocytosis, recombinant human granulocyte/macrophage colony stimulating factor induced clinical and hematologic recovery within a few days of administration. In conclusion, agranulocytosis is the mos t severe side effect of antithyroid drugs. According to our results an d a literature review, it occurs almost exclusively during the first t en weeks of treatment and is probably related to the drug dose. Physic ians should be aware of this potentially serious complication particul arly during this period. A reduction of traditionally prescribed thion amide doses seems quite possible and might lead to considerable reduct ion of adverse reactions. In severe cases, a trial of recombinant huma n granulocyte/macrophage colony stimulating factor should be considere d.