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Screening for agranulocytosis in patients treated with antithyroid drugs

Sirs, A recent article in the Drugs and Therapeutics Bulletin (DTB) recommended that patients treated with antithyroid drugs should receive, during the first 3 months of treatment, routine, fortnightly monitoring for the development of agranulocytosis, in keeping with the recommendations from monitoring treatment with sulphasalazine (Anonymous, 1997a). This recommendation was based on a retrospective study from Japan in which an unusually high frequency of agranulocytosis was detected by regular monitoring of the full blood count in patients receiving antithyroid drugs (Tajiri et al., 1990). These recommendations were criticised by several endocrinologists because of weaknesses in this retrospective Japanese study, the lack of evidence that monitoring would benefit patients and the complications and cost of instituting such monitoring (Anonymous, 1997b). In this second article, the Bulletin stood by its conclusions and suggested that the only resolution of the issue would be through studies of the costeffectiveness of monitoring in a UK population. In view of the concern caused by these recommendations, we have conducted a survey of current practice in the UK with regard to monitoring for agranulocytosis. The aims were to determine the current practice of a group of endocrinologists with a particular interest in treating thyroid disease, to determine whether the recommendations of the DTB were being adopted and to determine whether a trial of monitoring would be feasible. A questionnaire was sent to 46 clinically active members of the British Thyroid Association and 35 responses were obtained (response rate 76%). Only one respondent (3%) regularly monitored white blood cell counts in patients taking antithyroid drugs and this was only performed before treatment and once at the first return visit i.e. not in line with the recommendations of the DTB. Another respondent monitored white blood cell counts prior to giving antithyroid drugs but not thereafter. Only one person had altered practice as a result of the DTB article but also performed full blood counts only at the initial and first follow-up visit, therefore not complying with the recommendations of the DTB. A third question asked if respondents were aware of any other published study besides that of Tajiri et al. (1990) supporting the use of monitoring but no other studies were reported. Only 23 (66%) of respondents felt it would be worth conducting a randomized trial to assess the frequency of agranulocytosis picked up by regular monitoring compared to simply telling patients about suggestive symptoms. Respondents were also asked about the number of patients requiring these drugs that they were likely to see in a year and the mean was 86. Thirty respondents would have been willing to participate in a trial giving a total of around 2,500 patients to be entered into any study per year. Assuming such patients are randomly allocated to have regular monitoring or not, we do not believe it would be feasible to detect an effect of monitoring using members of the British Thyroid Association, given the frequency of agranulocytosis induced by antithyroid drugs of around 0.03% per year (International Agranulocytosis and Aplastic Anaemia Study, 1988). The results of this survey show that British thyroidologists do not monitor granulocyte counts routinely in patients receiving antithyroid drugs nor has their practice been altered by the recommendations of the DTB. The survey also demonstrates that mounting a trial to look at monitoring is unlikely to be practical. Based on these results, we believe that patients receiving antithyroid drugs do not need routine monitoring of granulocyte counts. Instead, the recommendations produced by the Committee on Safety of Medicines, published in the British National Formulary, should continue to be used for patients receiving these drugs. A. D. Toft President, British Thyroid Association, Royal Infirmary NHS Trust, Edinburgh, UK and A. P. Weetman Division of Clinical Sciences, University of Sheffield, Northern General Hospital, Sheffield, UK