不伴有甲状腺相关眼病的甲状腺功能异常与眼表损害的关联性分析

Association of thyroid dysfunction with ocular surface damage in thyroid dysfunction patients without thyroid ophthalmopathy

背景已证实甲状腺相关眼病（TAO）患者常伴有干眼相关症状，并认为与眼球突出造成的泪液蒸发过快有关。但临床工作中发现多数未伴有TAO的甲状腺功能异常患者也可伴有严重的眼表炎症症状，深入研究甲状腺功能异常与眼表损害的关系对其有效的临床诊疗有重要的临床意义。目的观察无TAO的甲状腺功能异常患者的眼表功能变化，探讨甲状腺功能异常与眼表损害的关联性。方法采用前瞻性队列究设计，纳入2015年1月至2016年5月在天津医科大学第二医院初次发现甲状腺腺功能异常但不伴有TAO的患者31例，同期选择16名性别和年龄匹配的健康体检者作为对照。采集受检者周围静脉血行血清游离三碘甲状腺原氨酸（FT3）、游离甲状腺激素（FT4）、促甲状腺激素（TSH）、和促甲状腺激素受体抗体（TRAb）测定，然后根据测定结果将甲状腺功能异常者分为TSH增高组（13例）和TSH降低组（18例）及TRAb阴性组（11例）和TRAb阳性组（20例），对组间患者甲状腺功能学指标、眼球突出度、基础泪液分泌试验（SIt）、泪膜破裂时间（BUT）、角膜荧光染色评分、眼表疾病指数（OSDI）评分和角膜炎症指数评分等检查结果进行比较，并分析甲状腺功能学指标结果与眼表功能相关检查结果的关系。结果甲状腺功能异常组与对照组间患者眼球突出度和sIt结果的差异无统计学意义（t=0．037，P=0．971；t=0．815，P=0．419）。甲状腺功能异常组与对照组患者的BUT值分别为（7．74±1．45）S和（10．56±1．40）s，角膜荧光染色评分分别为5．00（1．50）和2．50（2．38），OSDI评分分别为45．58±9．23和19．47±6．25，角膜炎症指数分别为0．11（0．22）和0．00（0．06），差异均有统计学意义（均P〈0．01）。TSH增高组和TSH降低组患者的眼球突出度、SIt、BUT和角膜炎症指数评分的差异无统计学意义（t=0．473，P=0．640；t=0．650，P=0．521；t=1．634，P=0．113；Z=0．270，P=0．787），TSH增高组和TSH降低组患者角膜荧光染色评分分别为4．00（1．75）和5．75（1．53），OSDI评分分别为（39．85±7．59）和（49．72±8．16），差异有统计学意义（均P〈0．01）。TRAb阴性组与TRAb阳性组间患者眼球突出度、SIt、BUT和角膜炎症指数评分的差异无统计学意义（均P〉0．05），TRAb阴性组和TRAb阳性组患者角膜荧光染色评分分别为4．00（1．50）和5．50（1．50），OSDI评分分别为39．18±6．25和46．78±8．76，差异均有统计学意义（t=2．533，P=0．017；Z=3．572，P=0．000）。角膜炎症指数评分与TSH呈正相关（R^2=0．520，P=0．000），角膜荧光染色评分、OSDI评分、角膜炎症指数评分与TRAb均呈明显正相关（R^2=0．587，P=0．000；R^2=0．329，P=0．024；R^2=0．400，P=0．005）。结论不伴有TAO的甲状腺功能异常患者存在眼表功能异常，血清TSH及TRAb异常可能影响眼表功能。

Background It is determined that the patients with thyroid-associated ophthalmopathy （TAO） often occur dry-eye related symptoms due to increasing tear evaporation caused by exophthalmos. However,more than half of thyroid dysfunction patients without TAO appear ocular surface inflammation. It is very important for us to understand the association of thyroid dysfunction patients without TAO with ocular damage. Objective This study was to observe the ocular surface changes in thyroid dysfunction patients without TAO. Methods A prospective cohort study was performed. Thirty-one patients who were initially diagnosed as thyroid dysfunction without TAO were included in the Second Hospital of Tianjin Medical University from January 2015 to May 2016 as the thyroid dysfunction group, and 16 helthy subjects were simutenniously selected as the control group under the informed consent of all the individuals. The peripheral blood was collected to detect the thyroid function-related indexes. Then the patients with thyroid dysfunction were divided into thyroid stimulating hormone （TSH） reduced group （18 patients） versus TSH elevated group （13 patients） and thyrotrophin receptor antibody （TRAb）＋ group （20 patients） versus TRAb- group （11 patients）. Exophthalmos degree, Schirmer I test （S I t） , tear film break-up time （BUT） , fluorescent integral, ocular surface disease index （OSDI） and corneal inflammation index were examined and intergrouply compared. The correlations of thyroid function indexes with ocular surface examination results were analyzed. Results There were no significant differences in exophthalmos degree and S I t values between thyroid dysfunction group and control group （ t = 0. 037, P = 0. 971 ; t = 0. 815, P = 0. 419 ）. The BUT values were （ 7.74 ± 1.45） seconds and （ 10. 56± 1.40 ） seconds, fluorescent integral scores were 5.00 （ 1.50 ） and 2.50 （2.38）, OSDI scores were 45.58 ± 9.23 and 19.47± 6.25, and corneal inflammation index scores were 0.11 （ 0.22 ） and 0.00 （0.06） in the thyroid dysfunction group and the control group,respectively, showing significant differences between the two groups （ all at P〈0.01 ）. There were not significant differences in exophthalmos degree, S I t, BUT and corneal inflammation index scores between the TSH elevated group and TSH reduced group （ t = 0.473, P = 0.640 ; t = 0.650, P = 0. 521 ;t = 1.634,P = 0. 113 ;Z = 0. 270,P = 0. 787 ）. The fluorescent integral scores were 4. 00 （2. 00 ） and 5.00 （ 1.00）, and OSDI scores were 40.08±9.91 and 47.11 ±9.75 in the TSH elevated group and TSH reduced group,repectively, with statistically significant differences between these two groups （all at P〈0. 01 ）. The exophthalmos degrees, S I t, BUT and corneal inflammation index scores were not considerably different between TRAb^-group and TRAb^＋ group （ all at P〉0. 05 ） ; and significant differences were seen in fluorescent integral scores （4. 00 [ 1.50 ] vs. 5.50 [ 1.50 ] ） and OSDI scores （[ 39. 18±6. 25 ] vs. [ 46. 78 ±8. 76 ] ）. Corneal inflammation index scores were positive correlated with serum TSH （R2 = 0. 520, P = 0. 000 ）, and fluorescent integral scores, OSDI scores and corneal inflammation index scores were positive correlated with serum TRAb （R2 =0.587,P=0.000;R2 =0.329,P=0.024;R2 =0.400, P=0. 005）. Conclusions Thyroid dysfunction patients without TAO have ocular surface dysfunction, which probably is associated with abnormal serum TSH and TRAb.