Eur J Nucl Med (1987) 13:358-361 European I~11 ir',lL::~,~r" Journal of I ~lllJ~,lE~,C,l./ Medicine © Springer-Verlag 1987 Radioprotective action of carbimazole in radioiodine therapy for thyrotoxicosis- influence of the drug on iodine kinetics J.M.C. Connell 1, T.E. Hilditch 2, J. Robertson 2, G. Coghill 2, and W.D. Alexander 3 1 MRC Blood Pressure Unit and 2 West of Scotland Health Boards Department of Clinical Physics and Bio-Engineering, and 3 Gardiner Institute, Western Infirmary, Glasgow, UK Abstract. Pretreatment with carbimazole of patients given radioiodine (131I) therapy for thyrotoxicosis reduces the incidence of early hypothyroidism. The possibility that this radioprotective effect might be a consequence of drug in- duced alteration in thyroidal iodide turnover, leading to a reduction in thyroid irradiation, was investigated in a prospective study of 24 thyrotoxic patients. Subjects were randomly assigned to receive 131I alone or to be treated with carbimazole for a minimum of three months before ~3~I. Thyroxine supplements were given in the latter group to prevent iatrogenic hypothyroidism. The effective half-life of therapeutic 131I in the thyroid was measured using a gamma camera/computer system after oral administration of the dose, allowing the biological half life of the anion and estimated radiation dose to the thyroid to be derived. Effective half life of 131I, biological half life of 131I and estimated radiation dose to the thyroid were similar in the two groups of subjects. It is concluded that the radioprotec- tive action of carbimazole is not a consequence of altered thyroidal iodide kinetics. Key words: Thyroid - Iodide - Halflife - Antithyroid drugs - Radioprotection Antithyroid drugs of the thiourylene group have been shown to have a radioprotective effect (Crooks et al. 1960; Steinbach et al. 1979; Aro et al. 1981: Bliddal et al. 1982; Connell et al. 1984). Thus, administration of carbimazole or methimazole to patients with thyrotoxicosis before ra- dioiodine (131l) therapy reduces the incidence of early hy- pothyroidism following irradiation. The mechanism of this effect has not been explored, but it is possible that it reflects an action of such drugs on thyroidal kinetics of J31I, leading to altered uptake or retention of the isotope within the gland. As the radiation dose to tissue is a consequence of not only the physical properties of the radionuclide but also its biological turnover, such considerations may influ- ence the radiation dose delivered to the thyroid in subjects given 131I. If antithyroid drugs affect thyroid iodide turn- over then this might explain the effect of these drugs on the response to 131I. Harden et al. (1966) suggested that carbimazole therapy, Offprint requests to . T.E. Hilditch, Department of Clinical Physics and Bio-Engineering, 11, West Graham Street, Glasgow, G4 9LF, UK by blocking incorporation of iodide into organic form, re- duced the thyroid iodine content, a postulate which has gained support from studies of thyroid iodine content (Hoffer and Gottschalk 1971 ; Barandes et al. 1973). A con- tracted intrathyroidal iodine pool could therefore reduce the biological half life of 13~I within the gland and conse- quently reduce the effective half life of the radionuclide. Thus, the effect of carbimazole pretreatment may be to lower the radiation dose delivered to the thyroid from a given amount of 13~I. Detailed studies of dosimetry have therefore been made in a small group of patients given 1311. Patients and methods Twenty four subjects with thyrotoxicosis (Graves' disease) were studied, all were clinically and biochemically thyrotox- ic at the time of entry to the study. Diagnosis was based on elevated total concentrations of triiodothyronine and thyroxine as well as diffuse uptake of tracer iodide (123I) on thyroid imaging. Further details of the subjects studied are given in Table 1. Patients were randomly assigned to receive either 131I directly (Group A) or to have previous therapy with antithyroid drugs (carbimazole 10-15 mg twice daily with thyroxine 0,1 mg per day) for a minimum of 3 months until all were clinically and biochemically euthyroid (Group B). In the latter group, drugs were dis- continued 48 h before a tracer study, which was performed before 131I therapy was given in both groups. Subjects were studied immediately after lunch on the day of the tracer study. 123I-iodide was given intravenously and thyroid uptake at 20 min and 24 h, thyroid size, and the dose of 13~I to be administered calculated as described previously (ConneU et al. 1983, 1984). The dose of 131I was given by mouth 24 h after the tracer study, after a further 24 h, thyroid uptake was measured by a gamma camera/ computer system using an aliquot of ~3~I (37 mBq) as a standard. Thyroid radioactivity was then measured at 5, 15 and 22 days after administration of the therapy dose. At high count rates, camera and computer dead time leads to loss of counting efficiency (Adams et al. 1974). To correct for this, a series of measurements was made using known amounts of 131I in a standard thyroid phantom. The resul- tant curve is shown in Fig. I. The deviation of this curve from the expected linear relationship between quantity of 1311 and measured counts is a consequence of loss of count- ing efficiency. Counts made in patients following 1311 treat-