Metrnl、S⁃endoglin与初发Graves病患者甲状腺激素水平和ATD治疗后复发的关系

The relationship between Metrnl,S⁃endoglin and thyroid hormones and recurrence after ATD treatment in patients with primary Graves'disease

目的探讨血清镍纹样蛋白(Metrnl)、可溶性内皮糖蛋白(S⁃endoglin)与初发Graves病(GD)患者甲状腺激素和抗甲状腺药物(ATD)治疗后复发的关系。方法选取2018年1-12月期间张家港市中医医院收治的初发GD患者135例作为GD组。另选择同期于本院体检健康的100名志愿者作为对照组。检测两组血清Metrnl、S⁃endoglin水平及甲状腺激素指标[促甲状腺激素(TSH)、游离甲状腺素(FT_(4))、游离三碘甲状腺原氨酸(FT_(3))、促甲状腺素受体抗体(TRAb)]水平。初发GD患者均予以ATD治疗。停药后随访2年,观察患者的复发情况,根据是否复发分为复发组(n=70)与未复发组(n=65),比较复发组与未复发组血清Metrnl、S⁃endoglin水平及甲状腺激素指标水平。使用Pearson法检验血清Metrnl、S⁃endoglin与TSH、FT_(4)、FT_(3)、TRAb水平的相关性。收集GD患者的一般资料,单因素及多因素logistic回归分析影响GD患者ATD治疗后复发的影响因素。结果GD组血清Metrnl、TSH水平低于对照组,血清S⁃endoglin、FT_(4)、FT_(3)、TRAb水平高于对照组,差异均有统计学意义(t=24.511、23.642、16.901、21.902、23.855、17.903,P均<0.05)。Pearson相关性分析显示,血清Metrnl水平与TSH水平成正相关(r=0.679,P<0.05),与FT_(4)、FT_(3)及TRAb均成负相关(r=-0.669、-0.710、-0.626,P均<0.05);血清S⁃endoglin水平与TSH水平成负相关(r=-0.515,P<0.05),与FT_(4)、FT_(3)及TRAb均成正相关(r=0.488、0.523、0.524,P均<0.05)。复发组血清Metrnl、TSH水平低于未复发组,血清S⁃endoglin、FT_(4)、FT_(3)及TRAb水平高于未复发组,差异均有统计学意义(t=8.852、9.044、6.474、3.166、4.347、3.893,P均<0.05);两组性别、年龄、发病季节、甲亢家族史、甲状腺肿疾病史、吸烟史、小剂量药物维持时间、GD严重程度比较,差异均无统计学意义(P均>0.05)。多因素logistic回归分析显示,血清Metrnl、TSH低水平及血清S⁃endoglin、FT_(4)、FT_(3)及TRAb高水平均为影响GD患者停药后复发的危险因素(P均<0.05)。结论初发GD患者血清Metrnl水平下降、S⁃endoglin水平升高,可导致甲状腺激素水平异常表达,同时二者均为影响ATD治疗后复发的危险因素。

Objective To investigate the relationship between serum meteorin⁃like protein(Metrnl),soluble⁃endoglin(S⁃endoglin)and thyroid hormones and the recurrence after antithyroid drugs(ATD)treatment in patients with primary Graves'disease(GD).Methods A total of 135 patients with primary GD who were admitted to the Zhangjiagang Traditional Chinese Medicine Hospital from January to December 2018 were selected as GD group.Another 100 healthy volunteers who were underwent physical examinations in our hospital during the same period were selected as control group.The serum Metrnl,S⁃endoglin levels and thyroid hormones indicators[thyroid stimulating hormone(TSH),free thyroxine(FT_(4)),free triiodothyronine(FT_(3))and thyrotropin receptor antibody(TRAb)]levels were detected.All patients with primary GD were treated with ATD.Followed up for 2 years after discontinuation of medication,the patient's recurrence status was observed;they were then divided into recurrence group(n=70)and non⁃recurrence group(n=65)based on whether there was recurrence,and the serum Metrnl,S⁃endoglin levels and thyroid hormones indicators levels between recurrence group and non⁃recurrence group were compared.The correlation between serum Metrnl,S⁃endoglin and TSH,FT_(4),FT_(3),TRAb levels was tested by Pearson method.The general data in patients with GD were collected,and the influencing factors of recurrence after treatment with ATD in patients with GD were analyzed by univariate and multivariate logistic regression analysis.Results The serum Metrnl and TSH levels in GD group were significantly lower than those in control group;and the serum S⁃endoglin,FT_(4),FT_(3)and TRAb levels were significantly higher than those in control group(t=24.511,23.642,16.901,21.902,23.855,17.903;all P<0.05).Pearson correlation analysis showed that the serum Metrnl level was positively correlated with TSH level(r=0.679,P<0.05),and negatively correlated with FT_(4),FT_(3)and TRAb(r=-0.669,-0.710,-0.626;all P<0.05).The serum S⁃endoglin level was negatively correlated with TSH level(r=-0.515,P<0.05),and positively correlated with FT_(4),FT_(3)and TRAb(r=0.488,0.523,0.524;all P<0.05).The serum Metrnl and TSH levels in recurrence group were lower than those in non⁃recurrence group;and the serum S⁃endoglin,FT_(4),FT_(3)and TRAb levels in recurrence group were significantly higher than those in non⁃recurrence group(t=8.852,9.044,6.474,3.166,4.347,3.893;all P<0.05).The gender,age,onset season,family history of hyperthyroidism,history of goitre disease,history of smoking,maintenance time of low⁃dose drugs and GD severity in two groups were compared,and the difference was not statistically significant(all P>0.05).Multivariate logistic regression analysis showed that low serum Metrnl and TSH levels,as well as high serum S⁃endoglin,FT_(4),FT_(3)and TRAb levels were risk factors for recurrence in patients with GD after discontinuation of medication(all P<0.05).Conclusion The serum Metrnl level decreased and S⁃endoglin level increased in patients with primary GD,which could lead to abnormal expression of thyroid hormones,and both were risk factors for recurrence after treatment with ATD.