Benker G, Vitti P, Kahaly G, Raue F, Tegler L, Hirche H, Reinwein D
Department of Clinical Endocrinology, University of Essen, Germany.
Clin Endocrinol (Oxf). 1995 Sep;43(3):257-63. doi: 10.1111/j.1365-2265.1995.tb02030.x.
A variety of regimens continue to be used in the treatment of Graves' disease with antithyroid drugs. We have investigated the factors which determine the initial response to methimazole (time until euthyroidism is achieved) in Graves' disease.
Five hundred and nine patients with Graves' disease in different European countries with normal and subnormal iodine supply. Patients were randomized to treatment with either 10 or 40 mg of methimazole per day for one year, with levothyroxine supplementation as required to maintain euthyroidism. Investigations were carried out before treatment and at 3 and 6 weeks and 3, 6, 9 and 12 months.
Response was assessed by serial measurements of serum thyroid hormones. TSH receptor antibodies, thyroid autoantibodies and urinary iodide excretion were measured centrally. Twenty-minute thyroid uptake was measured by standard techniques. Data were collected and analysed centrally. Standard techniques as well as a stepwise logistic regression model were used to examine the relations between methimazole dose, age, goitre size, presence of endocrine eye signs, thyroid hormone levels, urinary iodide excretion, thyroid uptake, index of disease severity (Crooks), presence of TSH receptor antibodies and duration of the hyperthyroid phase.
Within 3 weeks, 40.2% of patients responded to 10 mg of methimazole and 77.5% responded within 6 weeks. The corresponding figures for 40 mg of methimazole were 64.6 and 92.6%. Significant associations were found between duration of hyperthyroidism and the following variables: goitre size, urinary iodide excretion, methimazole dose, presence of TSH receptor antibodies (TBIAb), index of disease severity (Crooks) and pretreatment thyroid hormone levels. Response to methimazole was delayed in patients with large goitres, iodine excretion of > or = 100 micrograms/g creatinine, high pretreatment thyroid hormone levels, elevated levels of TBIAb and treatment with only 10 mg of methimazole. In the 10-mg group, 46% of patients were euthyroid within 3 weeks when urinary iodide was < 50 microgram/g of creatinine, and only 27% when iodide was above 100 micrograms/g. By stepwise logistic regression, the main factors for the response to methimazole were daily dose, pretreatment T3 levels, and goitre size.
Methimazole dose, pretreatment serum T3 levels, and goitre size are the main determinants of the therapeutic response to methimazole in Graves' disease, at least in areas comprising low, subnormal and normal iodine supply.
在使用抗甲状腺药物治疗格雷夫斯病时，多种治疗方案仍在被采用。我们研究了决定格雷夫斯病患者对甲巯咪唑初始反应（达到甲状腺功能正常状态所需时间）的因素。
来自不同欧洲国家的509例格雷夫斯病患者，碘供应正常及低于正常水平。患者被随机分为每天服用10毫克或40毫克甲巯咪唑治疗一年，并根据需要补充左甲状腺素以维持甲状腺功能正常。在治疗前、3周和6周以及3、6、9和12个月时进行检查。
通过连续检测血清甲状腺激素评估反应。促甲状腺激素受体抗体、甲状腺自身抗体和尿碘排泄在中心实验室检测。采用标准技术测量20分钟甲状腺摄取率。数据在中心实验室收集和分析。使用标准技术以及逐步逻辑回归模型来研究甲巯咪唑剂量、年龄、甲状腺肿大小、内分泌眼病体征的存在、甲状腺激素水平、尿碘排泄、甲状腺摄取率、疾病严重程度指数（克鲁克斯指数）、促甲状腺激素受体抗体的存在以及甲亢期持续时间之间的关系。
3周内，服用10毫克甲巯咪唑的患者中有40.2%有反应；6周内有77.5%有反应。服用40毫克甲巯咪唑的相应数字分别为64.6%和92.6%。发现甲亢期持续时间与以下变量之间存在显著关联：甲状腺肿大小、尿碘排泄、甲巯咪唑剂量、促甲状腺激素受体抗体（TBIAb）的存在、疾病严重程度指数（克鲁克斯指数）和治疗前甲状腺激素水平。甲状腺肿较大、尿碘排泄≥1毫克/克肌酐、治疗前甲状腺激素水平高、TBIAb水平升高以及仅服用10毫克甲巯咪唑治疗的患者对甲巯咪唑的反应延迟。在10毫克组中，当尿碘<0.5毫克/克肌酐时，46%的患者在3周内甲状腺功能正常；当尿碘高于1毫克/克肌酐时，只有27%的患者甲状腺功能正常。通过逐步逻辑回归分析，对甲巯咪唑反应的主要因素是每日剂量、治疗前T3水平和甲状腺肿大小。
甲巯咪唑剂量、治疗前血清T3水平和甲状腺肿大小是格雷夫斯病患者对甲巯咪唑治疗反应的主要决定因素，至少在碘供应低、低于正常水平和正常的地区是这样。
