Reinwein D, Benker G, Lazarus J H, Alexander W D
University of Essen, Department of Clinical Endocrinology, Germany.
J Clin Endocrinol Metab. 1993 Jun;76(6):1516-21. doi: 10.1210/jcem.76.6.8501160.
Some studies have suggested that increasing the daily dose of anti-thyroid drugs might improve long-term remission rates of Graves' disease. Therefore, this question was addressed in a prospective multicenter trial involving 18 thyroid clinics in Europe, mostly in iodine-deficient or moderately iodine-sufficient regions. Five hundred and nine patients with Graves' hyperthyroidism were enrolled in a prospective randomized trial comparing the remission rates after treatment with methimazole (MMI) at two fixed dosages (10 vs. 40 mg) with levothyroxine supplementation. The treatment and follow-up periods lasted 12 months each. Sixty and seven-tenths percent of the recruited patients (total, 309; 153 in the 10 mg, 156 in the 40 mg group) were finally evaluated, and comparison of the two groups showed that they were well matched with respect to a wide range of variables, including parameters of thyroid function. With 10 mg MMI daily, 68.4% of the patients were euthyroid after 3 weeks, and 84.9% after 6 weeks, compared to 83.1% and 91.6%, respectively, with the use of 40 mg MMI daily. TSH receptor antibodies decreased similarly in the two groups, 25% of patients in the 10 mg group, and 30% in the 40 mg group still being TSH receptor antibodies positive after 12 months. One hundred and ninety six (63.4%) of the 309 patients achieved remission of Graves' disease. The two MMI doses were equally effective; 35.9% compared to 37.2% of patients treated with 10 and 40 mg MMI, respectively, had relapses. There was no difference in the length of the time interval between stopping treatment and recurrence between the two groups. However, the rate of adverse drug reactions increased from 39/251 (15.5%) in the 10 mg group to 67/258 (26.0%) in the 40 mg group (P < 0.01). Under conditions of iodine deficiency or borderline sufficient iodine supply, 40 mg MMI daily will render more patients with Graves' disease euthyroid within the first 6 weeks of treatment than 10 mg daily, but at the expense of an increased rate of adverse reactions. However, patients treated with 40 mg MMI daily for 1 yr have no higher chance of remission than patients treated with 10 mg. It does not appear justified at present to recommend MMI doses higher than required for the control of hyperthyroidism (with the goal of immunosuppression).
一些研究表明，增加抗甲状腺药物的每日剂量可能会提高格雷夫斯病的长期缓解率。因此，在一项前瞻性多中心试验中探讨了这个问题，该试验涉及欧洲的18家甲状腺诊所，大部分位于碘缺乏或碘供应适度充足的地区。509例格雷夫斯甲亢患者被纳入一项前瞻性随机试验，比较甲巯咪唑（MMI）两种固定剂量（10毫克与40毫克）加左甲状腺素补充治疗后的缓解率。治疗期和随访期均为12个月。最终对招募患者的67%（共309例；10毫克组153例，40毫克组156例）进行了评估，两组比较显示，在包括甲状腺功能参数在内的广泛变量方面匹配良好。每日服用10毫克MMI时，3周后68.4%的患者甲状腺功能正常，6周后为84.9%，而每日服用40毫克MMI时，相应比例分别为83.1%和91.6%。两组促甲状腺素受体抗体下降情况相似，10毫克组25%的患者和40毫克组30%的患者在12个月后促甲状腺素受体抗体仍为阳性。309例患者中有196例（63.4%）实现了格雷夫斯病的缓解。两种MMI剂量同样有效；分别接受10毫克和40毫克MMI治疗的患者复发率为35.9%和37.2%。两组在停止治疗至复发的时间间隔长度上没有差异。然而，药物不良反应发生率从10毫克组的39/251（15.5%）增加到40毫克组的67/258（26.0%）（P<0.01）。在碘缺乏或碘供应临界充足的情况下，每日40毫克MMI在治疗的前6周内使更多格雷夫斯病患者甲状腺功能正常，但代价是不良反应发生率增加。然而，每日服用40毫克MMI治疗1年的患者缓解机会并不高于服用10毫克的患者。目前，推荐高于控制甲亢所需剂量（以免疫抑制为目标）的MMI似乎没有道理。
