Graves病患者甲状腺激素水平正常后sTSH长期抑制机制的探讨

Mechanism of persistent thyrotropin suppression in euthyroid patients with Graves＇ disease after treatment

目的探讨临床上部分Graves病（GD）患者经抗甲状腺药物（ATD）治疗后甲状腺激素水平达到正常，但促甲状腺素（TSH）仍长期处于被抑制状态的机制。方法入选初发122例GD甲亢患者，予以初始等效剂量的ATD治疗，每月随访时根据甲状腺功能测定的结果酌情减量，并适时添加左旋甲状腺素（L-T4）。当甲状腺激素（FT3、FT4）水平持续正常3个月即达随访标准，复查FT3、FT4、sTSH、TSH受体抗体（TRAb），并根据TRAb是否阳性分组比较。结果122例GD甲亢患者经（7．1±1．1）个月的ATD治疗后，甲状腺激素水平均已经达到正常3个月。随访时，58例TRAb转为阴性，64例TRAb持续阳性。两组甲状腺激素水平无差异，TRAb阳性组的sTSH水平明显低于阴性组[0．044mIU／L（0．001～4．163mIU／L）vs1．749mIU／L（0．079～4．646mIU／L），P〈0．01]；血清sTSH水平与TRAb呈明显负相关（r=-0．539，P〈0．01），与FT3、FT4、年龄、病程、治疗时间、L-T4剂量、L-T4添加时间等均无相关性。结论药物治疗过程中，甲状腺激素水平正常的GD患者，其TSH水平长期受抑制的原因与高水平TRAb相关，可能由于TRAb盲接与垂体内TSH受体结合，通过超短环反馈抑制TSH的分泌所致。

Objective To explore the mechanism of persistent thyrotropin suppression in euthyroid patients with Graves＇ disease after antithyroid drugs （ATD） treatment. Methods A prospective clinical study was performed in 122 patients with newly diagnosed Graves＇ disease. All the patients were treated with 30 mg methimazole or 300 mg propylthiouracil daily, to whom L-T4 was added, aiming at normalizing FT3 and FT4 but avoiding elevated TSH level. When the patients were clinically and biochemically euthyroid for at least 3 months, their blood levels of thyroid hormones, TSH, TSH receptor antibody （TRAb） and thyroid peroxidase antibody （TPOAb） were detected again and the cases were divided into two groups according to negative or positive TRAb. Results After treatment as long as （7.1 ± 1.1 ） months, stable euthyroid status was restored for 3 months. When the patients reached the euthyroid state, 64 of them still had detectable TRAb levels, and 58 became negative TRAb. The two groups had similar levels of FT3 and FT4, but patients with positive TRAb had lower TSH level than patients with negative TRAb[ 0. 044 mIU/L（0. 001-4. 163 mIU/L） vs 1. 749 mIU/L（ 0. 079-4. 646 mIU/L）, P 〈 0.01 ]. In addition, the TSH level was negatively correlated with TRAb level （r = -0. 539, P 〈0.01 ）, and not with FT3, FT4 levels or other factors. Conclusion The present study showed that elevated TRAb level is associated with persistent suppression of TSH in patients with Graves＇ disease after being rendered euthyroid. This finding may be due to the binding of TRAb to pituitary TSH receptor.