Rittmaster R S, Zwicker H, Abbott E C, Douglas R, Givner M L, Gupta M K, Lehmann L, Reddy S, Salisbury S R, Shlossberg A H, Tan M H, York S E
Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
J Clin Endocrinol Metab. 1996 Sep;81(9):3283-8. doi: 10.1210/jcem.81.9.8784084.
Medical treatment of Graves' disease involves use of antithyroid drugs with or without the addition of exogenous L-T4. There have been conflicting reports as to whether the addition of T4 reduces TSH receptor antibodies and improves remission rates more than antithyroid drugs alone. To further examine the effect of drug therapy on serum concentrations of TSH receptor antibodies. 70 patients with Graves' disease were treated with methimazole (Tapazole) alone until they were euthyroid. Then they were randomized to receive either: 1) methimazole alone in a dose sufficient to normalize TSH (0.3-5.4 mIU/L; Group 1); 2) 30 mg methimazole daily plus sufficient T4 (Synthroid) to maintain TSH in the high-normal range (2.0-5.4 mIU/L; Group 2); or 3) 30 mg methimazole daily plus sufficient T4 to suppress TSH to below 0.6 mIU/L (Group 3). The duration of treatment in all groups was 18 months. At baseline and after 6 and 18 months, TSH receptor antibodies were measured both by the ability of patients' sera to stimulate cAMP production by FRTL-5 cells (thyroid-stimulating Ig) and by the ability of patients' sera to inhibit binding of radiolabeled TSH to solubilized porcine thyroid membranes (TSH-binding, inhibiting Ig). Thyroid-stimulating Ig(TSI) and TSH-binding, inhibiting Ig(TBII) concentrations were similar among the three groups at baseline. Mean baseline TSI (expressed as the percent of normal control) for all patients combined was 306 +/- 21%. Mean baseline TBII (expressed as percent inhibition of TSH binding) was 38 +/- 2%. TSI was elevated in 85% and TBII was elevated in 75% of patients at baseline. After 18 months, TSI was elevated in 64% of patients, and TBII was elevated in 28%. Serum TSI decreased by 36 +/- 5% during the study, and there was no significant difference in the degree of reduction among the three groups (P = 0.99). Serum TBII decreased by 59 +/- 3%, and there also was no significant difference among the groups (P = 0.83). At baseline, serum TBII correlated with free T4 (r = 0.33, P < 0.01), total T3 (r = 0.55, P < 0.01), and thyroid size (r = 0.35, P < 0.01). There was no correlation between TSI and any of the baseline parameters or between TSI and TBII at any timepoint. In conclusion, we found that the addition of T4 to methimazole does not result in a greater decrease in TSH receptor antibody concentrations than treatment with methimazole alone. From these results, we would predict no difference in remission rates among these patients, but confirmation of this prediction will need to await long-term follow-up of these subjects.
格雷夫斯病的医学治疗包括使用抗甲状腺药物，可单独使用，也可加用外源性左甲状腺素（L-T4）。关于加用T4是否比单独使用抗甲状腺药物更能降低促甲状腺激素（TSH）受体抗体并提高缓解率，一直存在相互矛盾的报道。为了进一步研究药物治疗对TSH受体抗体血清浓度的影响，70例格雷夫斯病患者先用甲巯咪唑（他巴唑）单药治疗至甲状腺功能正常。然后将他们随机分为三组：1）继续使用足以使TSH正常化（0.3 - 5.4 mIU/L）的甲巯咪唑单药治疗（第1组）；2）每日服用30 mg甲巯咪唑并加用足够的T4（左旋甲状腺素）以使TSH维持在高正常范围（2.0 - 5.4 mIU/L）（第2组）；3）每日服用30 mg甲巯咪唑并加用足够的T4以使TSH抑制至低于0.6 mIU/L（第3组）。所有组的治疗持续时间均为18个月。在基线以及6个月和18个月后，通过患者血清刺激FRTL-5细胞产生环磷酸腺苷（cAMP）的能力（促甲状腺素刺激免疫球蛋白，TSI）以及患者血清抑制放射性标记的TSH与溶解的猪甲状腺膜结合的能力（TSH结合抑制免疫球蛋白，TBII）来检测TSH受体抗体。三组患者在基线时的TSI和TBII浓度相似。所有患者合并的平均基线TSI（以正常对照的百分比表示）为306±21%。平均基线TBII（以TSH结合抑制百分比表示）为38±2%。基线时85%的患者TSI升高，75%的患者TBII升高。18个月后，64%的患者TSI升高，28%的患者TBII升高。在研究期间血清TSI下降了36±5%，三组之间的下降程度无显著差异（P = 0.99）。血清TBII下降了59±3%，组间也无显著差异（P = 0.83）。基线时，血清TBII与游离T4（r = 0.33，P < 0.01）、总T3（r = 0.55，P < 0.01）以及甲状腺大小（r = 0.35，P < 0.01）相关。TSI与任何基线参数之间以及在任何时间点TSI与TBII之间均无相关性。总之，我们发现甲巯咪唑加用T4并不比单独使用甲巯咪唑更能降低TSH受体抗体浓度。根据这些结果，我们预计这些患者的缓解率无差异，但这一预测的证实还需对这些受试者进行长期随访。
