Selenium supplementation in thyroid associated ophthalmopathy: an update

·The therapeutic effect of selenium(Se)has already been proven in thyroid disease and thyroid associated ophthalmopathy(TAO).In spite of clear scientific proof of its benefits in TAO,there appears to be no clear agreement among the clinicians regarding its optimum dose,duration of the treatment,efficacy and safety to date.In this review,the author summarises the findings of 135 English language articles published on this subject over the past four decades from 1973 to 2013.The regulation and metabolism of thyroid hormones require a steady supply of Se and recent studies have revealed several possible mechanisms by which Se improves the severity of thyroid disease and TAO.These mechanisms include 1)inhibitory effect of HLA-DR molecule expression on thyrocytes;2)profound reductions of thyroid stimulating hormone(TSH)receptor antibodies(TSHR-Ab)and TPO antibodies(TPO-Ab);3)prevention of dysregulation of cell-mediated immunity and B cell function;4)neutralising reactive oxygen species(ROS)and inhibition of redox control processes required for the activation,differentiation and action of lymphocytes,macrophages,neutrophils,natural killer cells involved in both acute and chronic orbital inflammation in TAO;5)inhibition of expression of proinflammatory cytokines and 6)inhibition of prostaglandin and leukotriene synthesis.An increased oxidative stress has been observed in both acute and chronic phases of thyroid disease with raised tissue concentrations of ROS.The benefits of Se supplementation in individuals with TAO appear to be proportionate to the degree of systemic activity of the thyroid disease.The maximal benefit of Se supplementation is therefore seen in thesubjects who are hyperthyroid.Restoration of euthyroidism is one of the main goals in the management of TAO and when anti-thyroid drugs are combined with Se,the patients with Graves’disease(GD)and autoimmune thyroiditis(AIT)achieved euthyroidism faster than those treated with anti-thyroid drugs alone.Se status of normal adult humans can vary widely and Se supplementation may confer benefit only if serum Se levels are insufficient.The author recommends that serum Se levels of patients with TAO to be assessed prior to and during Se supplementation at regular intervals to avoid potential iatrogenic chronic Se overdose.

Biomarker identification of thyroid associated ophthalmopathy using microarray data

AIM： To uncover the underlying pathogenesis of thyroid associated ophthalmopathy（TAO） and explore potential biomarkers of this disease.METHODS： The expression profile GSE9340, which was downloaded from Gene Expression Omnibus database, included 18 specimens from 10 TAO patients and 8 hyperthyroidism patients without ophthalmopathy. The platform was HumanRef-8 v2 Expression BeadChip. Raw data were normalized using preprocess. Core package and the differentially expressed genes（DEGs） were identified based on t-test with limma package of R. Functional enrichment analyses were performed recruiting the DAVID tool. Based on STRING database, a protein-protein interaction（PPI） network was constructed, from which a module was extracted. The functional enrichment for genes in the module was performed by the BinGO plugin.RESULTS： In total, 861 DEGs（433 up-regulated and 428 down-regulated） between TAO patients and hyperthyroidism patients without ophthalmopathy were identified. Crucial nodes in the PPI network included TPX2, CDCA5, PRC1, KIF23 and MKI67, which were also remarkable in the module and all enriched in cell cycle process. Additionally, MKI67 was highly correlated with TAO. Besides, the DEGs of GTF2 F1, SMC3, USF1 and ZNF263 were predicted as transcription factors（TFs）. CONCLUSION： Several crucial genes are identified such as TPX2, CDCA5, PRC1 and KIF23, which all might play significant roles in TAO via the regulation of cell cycle process. Regulatory relationships between TPX2 and CDCA5 as well as between PRC1 and KIF23 may exist.Additionally, MKI67 may be a potent biomarker of TAO, and SMC3 and ZNF263 may exert their roles as TFs in TAO progression.

The role of cell mediated immunopathogenesis in thyroid-associated ophthalmopathy

Currently, thyroid-associated ophthalmopathy (TAO) lacks effective treatment due to our lack of clarity in its immunopathogenesis. Orbital fibroblasts play a key role in altering inflammation and immune response in TAO, and are considered as the key target and effector cells in its pathogenesis. The orbit infiltrating CD34+ fibrocytes add on to the process by expressing high levels of autoantigens and inflammatory cytokines, while also differentiating into myofibroblasts or adipocytes. This review focuses on the role of orbital fibroblasts and CD34+ fibrocytes in the pathogenesis of TAO, highlighting the basis of emerging treatments.

The effect of intravenous high-dose glucocorticoids and orbital decompression surgery on sight-threatening thyroid-associated ophthalmopathy

AIM: To report the effects of intravenous high-dose glucocorticoids(iv GC) and orbital decompression(OD) surgery for treatment of sight-threatening thyroid-associated ophthalmopathy(TAO).METHODS: A retrospective review of medical records from patients with sight-threatening TAO [definite or highly suspected dysthyroid optic neuropathy(DON)] treated with iv GC(60 cases) and OD(25 cases) was conducted at the Zhongshan Ophthalmic Center between January 2001 and January 2009. Patients were initially treated with iv GC(iv GC group). If no significant improvement in visual function was obtained, they then received OD surgery(OD group). The pre-versus post-treatment efficacies of either iv GC or OD in these patients were assessed using several indices, including visual acuity, intraocular pressure, ocular alignment, ocular motility, and exophthalmos. RESULTS: Nighty-one eyes had definite DON while 79 were considered to have highly suspected DON. In the iv GC group, 51 individuals(85.0%) eventually demonstrated normal vision, while 10 patients(16.7%) demonstrated a reduction in deviation(P<0.01), and 35 cases(58.3%) showed slight improvements in ocular motility(P<0.01). In OD group, visual acuity improved in 24 cases(96.0%, P<0.01) and all patients showed varying reductions of exophthalmos(mean: 4.35±1.13 mm, P<0.01). Eight cases(32.0%) experienced an 8-15 PD reduction of deviation and ocular motility improved in 12 cases(48.0%), while 3 patients(12.0%) developed new-onset strabismus with diplopia post-surgically(P<0.01). Patients were followed up at an average of 1.55±1.07 y. CONCLUSION: Both iv GC and OD show good therapeutic efficacy in the treatment of sight-threatening TAO. Thepresence of extremely poor eyesight(≥0.5 log MAR) was corrected in some patients with iv GC alone, thus sparing these patients from subsequent OD surgery. In patients who were refractory to steroids, subsequent OD surgery often provided satisfactory outcomes, however, new-onset strabismus with diplopia was observed in 12.0% of these cases.

Presence of thyroid-associated ophthalmopathy in Hashimoto's thyroiditis

·AIM: To determine the prevalence of ophthalmopathy in Hashimoto’s patients and to make a comparison in subgroups of patients·METHODS: The study involved 110 Hashimoto’s thyroiditis patients and 50 control subjects attending to the endocrinology department of the hospital. Subgroup classification of patients was made as euthyroid,subclinic and clinic in Hashimato’s thyroiditis. All patients were evaluated by a single experienced ophthalmologist for the prevalence and characteristics of eye signs.·RESULTS:Theoverallprevalencesofeyechanges were22.7%(25 patients) in patients and 4%(2 persons) in control subjects respectively(P =0.002). In patients the most common symptom was retrobulbar eye pain with or without any eye movement. Thirteen patients had significant upper eyelid retraction(11.8%). Six patients had eye muscle dysfunction as reduced eye movements in up gaze. In control patients one person had proptosis and another had lid retraction. The clinical activity score and classification of the ophthalmopathy did not show any significant differences among subgroups.·CONCLUSION:Theeyesignsweremostlymild(22.7%)and the most common eye sign was the presence of upper eyelid retraction(11.8%). Additionally six patients had eye muscle dysfunction as reduced eye movements in up gaze. Therefore we recommend to make a routine ophthalmic examination in Hashimoto’s thyroiditis patients in order not to omit the associated ophthalmopathy.

CT features of exophthalmos in Chinese subjects with thyroid-associated ophthalmopathy

AIM: To investigate computed tomography (CT) features of exophthalmos in Chinese subjects with thyroid-associated ophthalmopathy (TAO). METHODS: A total of 605 eyes of 325 patients with exophthalmos due to TAO were classified as grade Ⅰ (mild exophthalmos) or Ⅱ (severe exophthalmos) based on orbital CT imaging. The increased orbital volume features, such as changes from extraocular muscles, orbital fat, or both, were analyzed. RESULTS: A total of 605 eyes were analyzed, among them 62.98% presented grade Ⅰ exophthalmos, while 36.02% showed grade Ⅱ exophthalmos. In grade Ⅰ, 56.69% showed orbital fat change, and in grade Ⅱ, 89.29% exhibited extraocular muscle enlargement. CONCLUSION: Orbital fat and extraocular muscle enlargement are likely to be observed on CTs of subjects with mild and severe exophthalmos, respectively. Our results suggest that CT findings may guide TAO clinical therapy recommendations and prognosis.

Orbital decompression surgery and horse chestnut seed extract improved superior orbital vein blood flow in patients with thyroid-associated ophthalmopathy

AIM： To evaluate the efficacy and safety of orbital decomposition （OD） surgery in combination with horse chestnut seed extract （HCSE）, as compared to OD atone, in patients with thyroid-associated ophthalmopathy （TAO）. METHODS： Sixty-two orbits from 62 TAO patients were randomly assigned to OD or OD＋HCSE at 1：1 ratio （31 received OD alone, 31 received OD ＋HCSE）. Forty-two orbits from 21 healthy subjects were used as controls. Complete ophthalmic examination and color Doppler flow imaging （CDFI） were performed before surgery and 3mo post-surgery on all 62 orbits from the TAO patients. CDFI were also performed on the 42 control orbits, The effect of OD ＋HCSE and OD alone on TAO orbits was compared on several endpoints, including superior ophthalmic vein blood flow （SOVBF） parameters, subjective assessment, soft tissue involvement, lid retraction, diplopia, eye movement restriction, degree of exophthalmos, and intraocular pressure. The control orbits were used as reference for the SOVBF parameters. RESULTS： OD surgery with or without HCSE improved SOVBF, symptoms and soft tissue involvement, decreased degree of exophthalmos and intraocular pressure in orbits of TAO patients. The OD ＋HCSE combination led to significantly better improvement of SOVBF than OD alone. The differences between the reductions of SOVBF in the two groups are 1.26 cmls in max-volecity and 0.52 cm/s in min-voiecity （P〈0.0001）. CONCLUSION： SOVBF is significantly reduced in the orbits affected with TAO, indicating that congestion may be an important factor contributing to TAO pathogenesis. OD surgery improves the SOVBF, and combination of HCSE medication and OD surgery further improved venous return than OD surgery alone.

Culture and Differentiation of Human Orbital Preadipocytes in Thyroid-associated Ophthalmopathy

Purpose: To identify whether there are preadipocytes in the orbits of thyroid-associated ophthalmopathy (TAO) patients and whether they possess the capacity to undergo adipocytic differentiation.Methods: Orbital fat tissue from TAO patients was placed in primary culture and proliferating cells were sub-passaged. The preadiocytes were identified with immunohistochemistry. Confluent preadipocytes were subjected to a differentiation protocol. And Peroxisome proliferators-associated receptorγ (PPARγ)transcript levels were determined before and after differentiation.Result: In primary culture, cells were spindly and showed positive immunostaining for preadipocyte factor-1 (pref-1 ) protein. During the process of differentiation, orbital cells showed evidence of adipogenesis and relatively greater PPARγ gene expression with differentiation.Conclusion: There are active preadipocytes in the orbital tissue of TAO patients which might be able to undergo adipocyte differentiation. These observations suggest that the preadipocytes differentiation contributed to excess orbital adipose tissue volume in TAO.

Frequency of IL-10-producing regulatory B cells associated with disease activity in thyroid-associated orbitopathy

AIM： To investigate the association between IL-10-producing regulatory B（B10） cells and the clinical features of thyroid-associated orbitopathy（TAO）. METHODS： A total of 30 patients with TAO were recruited at Zhongshan Ophthalmic Center from May 2015 to December 2015. Peripheral blood mononuclear cells（PBMCs） were separated from blood samples of 30 TAO patients and 16 healthy controls and stimulated with CD40 ligand and CpG for 48h. The frequency of IL-10＋ B cells was examined by flow cytometry and the correlation between the frequency of IL-10＋ B cells and clinical features of TAO was analyzed by SPSS. RESULTS： The frequency of IL-10＋ B cells among CD19＋ B cells in TAO patients was significantly lower than in healthy controls（TAO： 4.66%±1.88% vs healthy control： 6.82%±2.40%, P〈0.01）. The frequency of IL-10＋ B cells showed a positive correlation with disease activity of TAO measured by Clinical Activity Score（CAS）（r=0.50, P〈0.01）, and became higher in TAO patients with family history of Graves＇ disease（GD）（P=0.04）. CONCLUSION： The decrease of the frequency of IL-10＋ B cells in TAO patients indicates the deficiency of B10 cells in TAO, and the positive association with disease activity suggests its important role in TAO inflammation regulation.

Hertel Exophthalmometry and Computed Tomography for the Evaluation of Exophthalmos in Patients with Thyroid-Associated Ophthalmopathy

Objective: To compare the values of exophthalmos measured by computed tomography (CT) and Hertel exophthalmometry (HE) in patients with thyroid-associated ophthalmopathy (TAO). Material and Methods: One hundred and seventy eyes were examined in 85 patients with TAO. Each patient underwent a complete ophthalmic examination, Hertel exophthalmometry, and CT of the orbits through a 16-slice CT scanner (Bright Speed, General Electric), measuring the extraocular muscles, the total muscle thickness sum (MTS), and proptosis. The patients were divided into two groups-with activity and without TAO activity, the activity being assessed by means of the Clinical Activity Score (CAS) and the severity-according to the EUGOGO classification. Results: TAO activity was detected in 45 patients (90 eyes, 53%) with MTS of 23.54 ± 5.73 mm, IOP of 19.78 ± 4.49 mm Hg, Hertel exophthalmos of 23.08 ± 4.19 mm and measured by CT-23.32 ± 4.33 mm. Forty patients (80 eyes, 47%) were without TAO activity, with MTS of 19.28 ± 4.03, IOP of 16.6 ± 4.51 mm Hg, Hertel exophthalmos of 20.03 ± 3.84 mm and measured by CT-19.84 ± 4.47 mm. A correlation was detected between exophthalmos and: MTS, IOP, the activity and severity of TАО. High congruence was established between the two methods of measuring exophthalmos-CT and HE (Pearson correlation, r = 0.690, p = 0.000). Conclusion: Our results showed a high degree of consistency between Hertel exophthalmometry and multidetector CT for the evaluation of exophthalmos in patients with TAO. Exophthalmos is an important clinical feature and its measurement and monitoring over time assess the clinical course and outcome of treatment.

利妥昔单抗联合免疫抑制剂冲击治疗甲状腺相关眼病的疗效及对CAS评分、预后转归的影响

目的 探讨利妥昔单抗联合免疫抑制剂冲击治疗甲状腺相关眼病(TAO)的疗效,并分析其对临床活动性(CAS)评分、预后转归的影响。方法 选取2020年3月至2022年10月黄冈市中心医院收治的136例272眼TAO患者,按照随机数字表法分为观察组(68例)、对照组(68例),其中对照组患者给予免疫抑制剂冲击治疗,观察组患者给予利妥昔单抗+免疫抑制剂冲击治疗,均治疗4个疗程(7 d为1个疗程)。比较两组患者临床疗效、眼征状况、CAS评分、甲状腺状况[甲状腺激素受体抗体(TRAb)、甲状腺过氧化物酶抗体(TPOAb)、甲状腺体积]、T淋巴细胞亚群、不良反应情况。随访6个月,比较两组患者预后转归情况。结果 治疗4个疗程后观察组总有效率[94.12%(64/68)]高于对照组[82.35%(56/68)](P<0.05)。治疗2个疗程、4个疗程后,观察组患者眼球突出度、眼压、平均睑裂宽度、球后软组织体积、球尖距、CAS评分、TPOAb、TRAb、甲状腺体积均小于对照组,均较治疗前减少(均为P<0.05),泪膜脂质层厚度均大于对照组,均较治疗前增加(均为P<0.05)。治疗前两组患者以上指标差异均无统计学意义(均为P>0.05)。治疗前两组患者CD3+、CD4+、CD8+T淋巴细胞表达水平比较差异均无统计学意义(均为P>0.05);治疗2个疗程、4个疗程后两组患者CD3+、CD4+T淋巴细胞表达水平均较治疗前升高,除治疗2个疗程后观察组患者CD4+T淋巴细胞表达小于对照组外,其余时间点患者CD3+、CD4+T淋巴细胞表达水平观察组均高于对照组(均为P<0.05);治疗2个疗程、4个疗程后两组患者CD8+T淋巴细胞表达水平均较治疗前降低,且观察组均低于对照组(均为P<0.05)。两组患者低热、恶心、低血钾等不良反应发生率比较,差异均无统计学意义(均为P<0.05)。随访6个月,观察组好转率[95.59%(65/68)]高于对照组[79.41%(54/68)](P<0.05)。结论 利妥昔单抗联合免疫抑制剂冲击治疗TAO患者疗效显著,可缓解眼征状况、甲状腺状况,降低临床活动性,促进预后转归。

泪腺突出度联合磁共振脂肪定量分析在甲状腺相关性眼病诊断中的价值

目的探讨泪腺突出度和磁共振脂肪定量分析(IDEAL-IQ)在甲状腺相关性眼病(TAO)诊断中的价值。方法回顾性分析38例TAO患者(TAO组)和38例健康志愿者(对照组)的临床资料。通过测量泪腺突出度、脂肪分数(FF)及相对脂肪分数(rFF),比较组间的差异,并采用受试者工作特征(ROC)曲线分析泪腺突出度、FF、rFF单一检测和联合检测对TAO的诊断效能。结果TAO组泪腺突出度、FF和rFF均大于对照组(t分别=8.18、6.10,Z=-5.66,P均<0.05),泪腺突出度联合FF诊断TAO时,AUC最大,为0.88,特异度90.80%,灵敏度73.70%。结论TAO患者的泪腺突出度及脂肪含量大于对照组,泪腺突出度联合FF有助于TAO患者的诊断,具有较高的临床价值。

CD19^(+)CD27^(+)IgD^(+)B细胞与甲状腺相关性眼病患者疾病活动度相关性研究

目的:探讨甲状腺相关性眼病(thyroid-associated ophthalmopathy,TAO)患者外周血CD19^(+)CD27^(+)IgD^(+)B细胞比例变化与病情活动度的关系。方法:采用流式细胞术检测TAO患者和健康对照组CD19^(+)CD27^(+)IgD^(+)B细胞比例,分析TAO患者CD19^(+)CD27^(+)IgD^(+)B细胞比例与健康对照组的差异,并分析CD19^(+)CD27^(+)IgD^(+)B细胞比例与TAO疾病活动度之间的相关性。结果:TAO患者CD19^(+)CD27^(+)IgD^(+)B细胞比例明显低于健康对照(P<0.05);活动性TAO患者CD19^(+)CD27^(+)IgD^(+)B细胞比例细胞显著低于非活动性TAO患者;CD19^(+)CD27^(+)IgD^(+)B细胞比例与TAO患者CAS评分呈显著负相关(r=-0.7128,P<0.001)。结论:TAO患者CD19^(+)CD27^(+)IgD^(+)B细胞比例降低,与疾病活动度呈负相关。

甲状腺相关眼病的危险因素研究进展

甲状腺相关眼病(TAO)是成人较多见的眼眶疾病之一,它与自身免疫性甲状腺疾病有着密不可分的关系。TAO可引起患者容貌损害,严重者可以引起患者视功能受损,甚至致盲,极大地损害了患者身心健康及社会功能。早期预测及诊断TAO的发生和发展,及时进行干预治疗有助于改善患者的临床表现,提高患者的生活质量。TAO危险因素众多,受遗传、免疫、环境及全身状态的共同影响。其中环境因素及全身情况可通过早期干预控制疾病进展,使患者受益。本文将与TAO发生相关的危险因素进行综述,以期为TAO的早期预测及诊断提供参考,对高危人群的疾病预防提供思路。

甲状腺相关眼病临床诊治规范的述评

甲状腺相关眼病(TAO)是一种自身免疫性眼眶炎症性疾病,是成年人最常见的眼眶疾病。在临床诊治过程中,很多医生对该病认识不足,诊断和处理方面存在一些误区。本文总结了TAO与甲状腺疾病的关系、TAO的诊断、影像检查、TAO病情判断、治疗方案选择等方面存在的误区,并对其作一评述,以提高内分泌科和眼科医生对该病的认识水平,避免误诊误治。

CXCR4 MFAP2 KLF4在分化型甲状腺癌中的表达及对预后的预测价值研究

目的:研究趋化因子4受体(CXCR4)、微纤维相关蛋白2(MFAP2)、Krüppel样因子4(KLF4)在分化型甲状腺癌(DTC)中的表达及对预后的预测价值。方法:选择我院2019年7月至2020年7月收治的113例DTC患者,术中留取其肿瘤组织及癌旁正常组织。采用蛋白免疫印迹法检测DTC组织及癌旁正常组织中CXCR4、MFAP2、KLF4表达水平,分析CXCR4、MFAP2、KLF4表达水平与DTC临床病理特征的关系。对DTC患者进行3年随访,统计3年总生存情况,比较死亡组与存活组CXCR4、MFAP2、KLF4表达水平,采用ROC曲线分析CXCR4、MFAP2、KLF4对DTC预后的预测价值,采用Cox回归模型进行DTC预后单因素和多因素分析。结果:与癌旁正常组织比较,DTC组织CXCR4、MFAP2蛋白表达量显著升高(P<0.05),KLF4蛋白表达量显著降低(P<0.05)。TNM分期Ⅲ期、发生淋巴结转移、肿瘤低分化者CXCR4、MFAP2蛋白表达量显著高于TNM分期Ⅰ+Ⅱ期、未发生淋巴结转移、肿瘤中高分化者(P<0.05),TNM分期Ⅲ期、发生淋巴结转移、肿瘤低分化者KLF4蛋白表达量显著低于TNM分期Ⅰ+Ⅱ期、未发生淋巴结转移、肿瘤中高分化者(P<0.05)。113例DTC患者随访3年期间失访8例,最终获得随访者105例。死亡组患者CXCR4、MFAP2蛋白表达量显著高于存活组(P<0.05),KLF4蛋白表达量显著低于存活组(P<0.05)。绘制ROC曲线发现,CXCR4、MFAP2、KLF4单独或联合预测DTC预后的AUC(95%CI)分别为0.692(0.562~0.823)、0.729(0.590~0.869)、0.766(0.622~0.910)、0.832(0.690~0.975),联合预测的效能显著优于单项检测(P<0.05)。Cox回归分析显示,淋巴结转移、TNM分期Ⅲ期、肿瘤低分化、CXCR4表达升高、MFAP2表达升高、KLF4表达降低是DTC预后的危险因素(P<0.05)。结论:分化型甲状腺癌患者肿瘤组织中CXCR4、MFAP2呈高表达,KLF4呈低表达,其表达水平与淋巴结转移、肿瘤分化程度、TNM分期及3年总生存率相关,三者联合检测有助于预测分化型甲状腺癌预后。

血脂联合磁共振参数在甲状腺相关性眼病糖皮质激素治疗疗效预测中的价值

目的:评估血清脂代谢指标联合眼眶磁共振成像(magnetic resonance imaging,MRI)定量参数在预测中重度活动期甲状腺相关性眼病(thyroid-associated ophthalmopathy,TAO)患者糖皮质激素(glucocorticoid,GC)治疗疗效中的价值。方法:回顾性纳入44例接受GC治疗的中重度活动期TAO患者,根据GC疗效将患者分为敏感组(n=28)和抵抗组(n=16)。收集两组患者在GC治疗前的血清脂代谢指标和基于眼眶MRI测得的泪腺突出度/眼眶脂肪厚度(lacrimal gland herniation/orbital fat thickness,LGH/OFT)及其他临床参数,并比较两组间各参数差异。采用Logistic回归和受试者工作特征曲线分析与GC治疗疗效相关的独立预测因子并评估其预测价值。结果:敏感组患者血清总胆固醇和低密度脂蛋白胆固醇水平显著低于抵抗组(P=0.005,P=0.019),且敏感组病程更短(P=0.037)。敏感组患者LGH/OFT显著高于抵抗组(P<0.001)。总胆固醇和LGH/OFT是TAO患者激素是否敏感的独立预测因子(OR值分别为0.230、1.395_(每0.1单位),P均<0.05)。联合血清总胆固醇≤4.8 mmol/L和LGH/OFT≥1.51预测GC治疗敏感性,可以获得最佳预测效能(曲线下面积为0.838,灵敏度为87.5%,特异度为65.6%)。结论:血脂参数和眼眶MRI定量参数均可预测中重度活动期TAO患者GC治疗敏感性,两者联合可进一步提高预测效能。

动态对比增强MRI在甲状腺相关性眼病眼外肌微循环及活动性分期中的评估价值

目的 探讨动态对比增强磁共振成像(dynamiccontrast-enhancedMRI,DCE-MRI)技术在甲状腺相关性眼病(thyroid-associated ophthalmopathy, TAO)临床活动性分期中的价值。材料与方法 前瞻性纳入TAO患者56例,其中活动期组(37例,74只眼),非活动期组(19例,38只眼)。计算并比较两组间眼外肌的半定量参数[达峰时间(time to peak, TTP)、时间-信号强度曲线下面积(area under the time-signal intensity curve, AUC)和时间-信号强度曲线最大斜率值(maximum enhancement slope, Slope_(max))]以及定量参数[容积转运常数(volume transfer constant, K^(trans))、反流速率常数(the rate constant, Kep)和血管外细胞外间隙容积分数(fractional volume of the extravascular-extracellular space, V_(e))]的最小值、平均值和最大值。采用多因素logistic回归筛选TAO活动性分期的独立影响因素。采用受试者工作特征(receiver operating characteristic, ROC)曲线分析显著差异参数及其联合模型在TAO分期中的效能。结果 活动期组眼外肌的TTP均值、AUC最大值、AUC均值、V_(e)最大值和V_(e)均值均高于非活动期组(P<0.05)。AUC最大值和V_(e)均值是TAO活动性分期的独立影响因素(AUC最大值,P=0.030;V_(e)均值,P=0.014)。采用AUC最大值和V_(e)均值预测活动期TAO的ROC曲线下面积分别为0.689和0.673。联合AUC最大值和V_(e)均值可进一步提高对TAO活动性分期的诊断效能(ROC曲线下面积0.731)。结论 眼外肌DCE-MRI半定量和定量参数均可辅助TAO活动性分期。联合AUC最大值和V_(e)均值可以有效评估TAO活动性分期。

甲状腺功能障碍与静脉血栓之间的关系:1项双样本双向孟德尔随机化研究

目的:探究甲状腺功能障碍与静脉血栓栓塞症之间的因果关系,为甲状腺功能障碍与静脉血栓栓塞症发病风险提供遗传学证据支持。方法:采用全基因组关联研究(genome-wide association studies,GWAS)数据进行分析。本研究选择促甲状腺素(thyroid stimulating hormone,TSH)、游离甲状腺素(free thyroxine,FT4)、甲状腺功能亢进(hyperthyroidism)和甲状腺功能减退(hypothyroidism)作为暴露因素。结局变量为静脉血栓栓塞症(venous thromboembolism,VTE),包括深静脉血栓(deep vein thrombosis,DVT)和肺栓塞(pulmonary embolism,PE)。逆方差加权法(inverse-variance weighted,IVW)是评估暴露与结局之间因果关系的主要方法,并辅以MR-Egger、加权中位数法(Weighted median)、简易法(Simple mode)进行分析,同时Cochrane’s Q检验作为敏感性分析方法。结果:IVW显示甲亢与VTE(OR=1.074,95%CI=1.016~1.135,P=0.011)、PE(OR=1.054,95%CI=1.012~1.098,P=0.011)和DVT(OR=1.068,95%CI=1.014~1.126,P=0.013)存在正向的因果关系。结论:研究基于遗传数据认为甲状腺功能障碍与静脉血栓栓塞症存在因果关系,甲状腺功能亢进会增加静脉血栓发生的风险。

生物制剂在甲状腺相关眼病中的研究进展

甲状腺相关眼病(TAO)是一种罕见的器官特异性自身免疫性疾病,发病机制尚未明确。目前治疗仍主要依赖糖皮质激素和传统免疫抑制剂,部分患者对这些药物反应不佳,同时存在治疗相关不良反应,因此迫切需要治疗TAO的新型药物。近年来,随着对TAO发病机制研究的不断深入,针对特定靶点研发的生物制剂层出不穷,其中靶向胰岛素样生长因子-Ⅰ受体(IGF-IR)的替妥木单抗已被美国食品和药物管理局批准用于治疗TAO,还有多种生物制剂处于临床试验阶段。本文通过总结针对IGF-IR、新生儿Fc受体(FcRn)、促甲状腺激素受体(TSHR)、B细胞、细胞因子等的生物制剂在TAO中的临床研究现状,分析其对临床治疗及未来研究趋势的影响,为TAO临床防治和研究提供最新参考。