Clinical Endocrinology (2004) 60 , 676–681 doi: 10.1111/j.1365-2265.2004.02032.x 676 © 2004 Blackwell Publishing Ltd Blackwell Publishing, Ltd. Comparison of single daily dose of methimazole and propylthiouracil in the treatment of Graves’ hyperthyroidism Chih-Tsueng He*, An-Tsz Hsieh*, Dee Pei*, Yi-Jen Hung*, Ling-Yi Wu*, Tsao-Chin Yang*, Wei-Cheng Lian*, Wen-Sheng Huang† and Shi-Wen Kuo* * Division of Endocrinology and Metabolism, Department of Medicine and †Department of Nuclear Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC (Received 9 September 2003; returned for revision 15 October 2003; finally revised 3 February 2004; accepted 27 February 2004) Summary OBJECTIVE The present study was to compare the efficacy of a single daily dose of methimazole (MMI) and propylthiouracil (PTU) in the treatment of Graves’ hyperthyroidism. BACKGROUND Antithyroid drugs, MMI and PTU, are widely used in the treatment of hyperthyroidism. Previous studies in the treatment of hyperthyroidism with a single daily dose of antithyroid drugs have demonstrated a more favourable result with MMI. However, the efficacy of a single daily dose of PTU was inconsistent. In this study, we examined the therapeutic efficacy of single daily doses of MMI and PTU on the change of thyroid hor- mones and thyrotropin receptor antibodies (TRAb) levels. METHODS Thirty patients with newly diagnosed Graves’ hyperthyroidism were randomly divided into two groups, each receiving a single dose of either 15 mg MMI or 150 mg PTU daily for 12 weeks. The therapeutic efficacy was determined by serum total triiodothyro- nine (TT3), total thyroxine (TT4), thyrotropin (TSH), free thyroxine (FT4), and TRAb levels at baseline and at the end of 4, 8 and 12 weeks during the study period. RESULTS There was no significant difference in base- line thyroid function parameters. Serum TT3, TT4 and FT4 levels in the MMI-treated group were significantly lower than those of the PTU-treated group after 4 weeks and through the end of the study. MMI also has superior effect on reducing serum TRAb levels than PTU after 8 weeks and at the end of the study. CONCLUSION During the 12-week treatment of Graves’ hyperthyroidism, a single daily dose of 15 mg MMI was much more effective in the induction of euthyroidism than a single daily dose of 150 mg PTU. In the doses used in this study, MMI is preferable to PTU when a once-daily regimen of antithyroid drug is considered for the treatment of Graves’ hyperthyroidism. Methimazole (MMI) and propylthiouracil (PTU) are the two most widely used antithyroid drugs for treating Graves’ hyper- thyroidism. The commonly recommended initial daily dosage in patients with hyperthyroidism is 10–40 mg of MMI or 100–600 mg of PTU in clinical practice (Larsen et al ., 1998). Because the serum half-life is 6–8 h for MMI and 1–2 h for PTU, it is suggested that both agents should be administered in divided daily doses (Coope 2000). However, a number of studies have consistently shown tha the single daily dose of MMI is effective in the treatment of hyper- thyroidism (Bouma & Kammer, 1980; Shiroozu et al ., 1986; Roti et al ., 1989; Mashio et al ., 1997). In contrast, previous studies have concluded that PTU can be successfully given to patients with Graves’ disease as a single daily dose (Greer et al ., 1965; Gwinup, 1978). However, the single daily dose regimen of PTU has been sh to be less effective than the divided dose regimen (Gwinup, 1978 Graves’ hyperthyroidism is an autoimmune disease sustained by autoantibodies binding to and activating the thyrotropin (TSH) receptor located on the thyroid follicular cell. Because TSH receptor antibodies (TRAb) have been found to correlate with disease activity, TRAb activities during antithyroid drug therapy reflect the patient’s clinical outcome (Davies et al ., 1977; Zakarija et al ., 1980). TRAb plays an important role in the pathogenesis of Graves’ hyperthyroidism, and that the level of TRAb decreases significantly in patients treated with antithyroid drugs (Teng & Yeung, 1980). However, there have been few reports comparing the difference in the changes of TRAb levels between different antithyroid drug therapies. To our knowledge, there is no randomized study comparing the efficacy of single daily dosage of MMI with a comparable single daily dosage of PTU. The present prospective study was therefore conducted to compare the efficacy of single daily dose Correspondence: Shi-Wen Kuo, MD, Division of Endocrinology and Metabolism, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, No.325, Sec. 2, Cheng-Kung Road., Neihu, 114 Taipei, Taiwan, ROC. Tel: +886-2-87927182; Fax: +886-2-87927183; E-mail: perryguo@seed.net.tw