Mazza E, Carlini M, Flecchia D, Blatto A, Zuccarini O, Gamba S, Beninati S, Messina M
Division of Endocrinology, Maria Vittoria Hospital, Turin, Italy.
J Endocrinol Invest. 2008 Oct;31(10):866-72. doi: 10.1007/BF03346433.
Antithyroid drugs may be proposed as the firstline therapy for hyperthyroidism due to Graves' disease since some patients undergo prolonged remission after drug withdrawal. On the other hand, some studies, though controversial, indicated that methimazole (MMI) has some immunomodulating activity. We retrospectively analyzed 384 consecutive patients newly diagnosed with Graves' disease in the years 1990-2002 to ascertain whether long-term therapy with low doses of MMI may prevent relapse of thyrotoxicosis. Two hundred and forty-nine patients were included in our study. The date of reduction of MMI dose to 5 mg/day was considered time 0 for survival analysis. In 121 MMI was discontinued in less than 15 months after time 0 (group D), while in the remaining 128 a daily MMI 2.5-5 mg dose was maintained (group M). One hundred and thirty-five patients were excluded for inadequate response to MMI, relapse of thyrotoxicosis that could be related to an improper withdrawal or reduction of MMI, inadequate or too short followup, iodide contamination, steroid or interferon therapy, pregnancy or post-partum. D and M groups did not differ for clinical and hormonal parameters except age, which was lower in D (p=0.019). Age > vs < 35 yr was relevant in survival analysis; therefore patients were divided in 2 groups according to this age cut-off. In younger patients relapse of thyrotoxicosis occurred in 15 patients of group D 2.4-39.6 months (median 19.0) after time 0, and 8 M after 5.9-40.0 (21.3) months, while 14 D and 5 M maintained euthyroidism until the end of the observation after 31.8-95.3 (56.6) months and 30.4-62.1 (46.5) months, respectively. Survival analysis indicated that the risk of relapse was similar in group D and M. In older patients relapse of thyrotoxicosis occurred in 40 patients of group D after 8.2-65.8 (25.4) months and 29 M after 5.8-62.5 (22.4) months, while 52 D and 86 M maintained euthyroidism until the end of the observation, 20.1-168.0 (46.7) months and 24.1-117.4 (53.4) months respectively. Survival analysis indicated that the risk of relapse was increased in group D. Therefore long-term treatment with low doses of MMI seems to prevent relapse in Graves' disease in patients above 35 yr of age. This should be confirmed in a prospective study.
抗甲状腺药物可作为格雷夫斯病所致甲状腺功能亢进的一线治疗方法，因为一些患者停药后可获得长期缓解。另一方面，一些研究（尽管存在争议）表明甲巯咪唑（MMI）具有一定的免疫调节活性。我们回顾性分析了1990年至2002年期间连续新诊断为格雷夫斯病的384例患者，以确定低剂量MMI长期治疗是否可预防甲状腺毒症复发。我们的研究纳入了249例患者。将MMI剂量减至5mg/天的日期作为生存分析的时间0。在时间0后不到15个月，121例患者停用MMI（D组），而其余128例患者维持每日2.5 - 5mg的MMI剂量（M组）。135例患者因对MMI反应不佳、可能与MMI停药或减量不当相关的甲状腺毒症复发、随访不足或时间过短、碘污染、类固醇或干扰素治疗、妊娠或产后等原因被排除。除年龄外，D组和M组的临床和激素参数无差异，D组年龄较低（p = 0.019）。年龄>35岁与<35岁在生存分析中具有相关性；因此根据该年龄界限将患者分为两组。在年轻患者中，D组15例患者在时间0后2.4 - 39.6个月（中位数19.0）出现甲状腺毒症复发，M组8例患者在5.9 - 40.0个月（21.3）后复发，而14例D组和5例M组患者在31.8 - 95.3个月（56.6）和30.4 - 62.1个月（46.5）后直至观察结束维持甲状腺功能正常。生存分析表明D组和M组复发风险相似。在老年患者中，D组40例患者在8.2 - 65.8个月（25.4）后出现甲状腺毒症复发，M组29例患者在5.8 - 62.5个月（22.4）后复发，而52例D组和86例M组患者在20.1 - 168.0个月（46.7）和24.1 - 117.4个月（53.4）后直至观察结束维持甲状腺功能正常。生存分析表明D组复发风险增加。因此，低剂量MMI长期治疗似乎可预防35岁以上格雷夫斯病患者复发。这一点应在前瞻性研究中得到证实。
