促甲状腺激素受体抗体(TRAb)测定的临床价值

目的:探讨血清TRAb测定对甲状腺疾病的临床价值.方法:采用放射受体分析和放射免疫分析测定210例甲状腺疾病患者血清TRAb和T3、T4、TSH、FT3、FT4含量,以T3、T4、TSH、FT3、FT4含量为标准分为单纯性甲状腺肿组、甲减组、甲亢组、甲亢缓解组;以38例健康人血清中TRAb和T3、T4、TSH、FT3、FT4含量作为对照组.结果:单纯性甲状腺肿组血清TRAb含量与正常对照组无显著差异(P＞0.05);甲亢组、甲减组血清TRAb含量明显高于正常对照组(P＜0.001);甲亢缓解组血清TRAb含量与甲亢组差异显著(P＜0.05),与正常组比较亦有显著性差异(P＜0.05);血清TRAb含量与各组间T3、T4、TSH、FT3、FT4及TSH浓度之间无显著相关性(P＞0.05).结论:监测血清TRAb含量对甲状腺疾病的诊断、鉴别诊断、疗效观察、预后判断有重要的临床价值.     

TRAb检测在GraVes甲亢诊断治疗中的价值

目的:探讨血清TRAb值在Graves’甲亢患者诊断治疗中的价值。方法: 50例正常人和230例Graves’甲亢患者在他巴唑治疗前后分别测定血清TRAb、FT3、FT4、TSH。结果:未经ATD治疗的Graves’甲亢患者,血清TRAb阳性率为93 3%,ATD治疗后6个月时,TRAb阳性率为41 3%,与正常对照组相比有明显差异(P<0 05),治疗6个月、12个月、36个月时TRAb阳性率分别为18 3%、8 9%、4 9%。本组临床缓解停药后有21例复发,其中TRAb持续阳性者复发18例(占80 7% )。结论:血清TRAb是诊断Graves’甲亢的主要依据,有助于判断Graves’甲亢病情进展及复发,有助于指导甲亢治疗。     

Graves’病患者~(131)I治疗后早发性甲减相关因素分析

目的:探讨TRAb、TGA、TMA在G raves’病131I治疗中的价值,了解131I治疗后早发性甲减产生的机理。方法:对167例G raves’病131I治疗患者进行治疗前及治疗后6个月检测TRAb、TGA、TMA和甲状腺功能,依据治疗后甲状腺功能状况分为甲亢未控制组91例、甲亢控制组48例和早发性甲减组28例,并对这三组治疗前后进行比较。结果:早发性甲减组年龄低于甲亢未控制组(P<0.01)。TRAb治疗前甲亢未控制组高于甲亢控制组和早发性甲减组(P<0.05)。各组治疗前后比较:治疗后甲亢未控制组与甲亢控制组的TRAb均高于治疗前(P<0.05),早发性甲减组的TGA、TMA治疗后高于治疗前(P<0.01)。TGA、TMA治疗后早发性甲减组明显高于甲亢未控制组和甲亢控制组(P<0.01)。结论:①G raves’病患者进行131I治疗时,年龄轻的比年龄大的容易发生早发性甲减;②131I治疗前血清中TRAb水平高的不易治愈,反之,要警惕早发性甲减。③Graves’病患者131I治疗后早发性甲减的发生可能与TGA、TMA阳性率增高有关。     

TRAb放射受体分析在甲状腺疾病中的临床应用

目的 :探索TRAb放射受体分析在甲状腺疾病中的临床价值。方法 :采用放射受体法 (RRA)对 2 95例 (5组 )甲状腺疾病患者血清中TRAb进行测定 ,测定结果分别与 4 5例正常对照组进行比较。结果 :Graves’病症状未控制组、Graves’病症状控制组及原发性甲减组TRAb均高于正常对照组 (P <0 0 1～ 0 0 0 1) ;而自主性高功能腺瘤组、单纯性甲状腺肿组与正常对照组比较 ,差别无显著性 (P均 >0 0 5 ) ;Graves’病症状未控制组与Graves’病症状控制组比较 ,差别亦无显著性 (P >0 0 5 )。结论 :Graves’病患者和原发性甲减患者的发病可能与TRAb有关 ,TRAb可作为病因诊断的一种指标 ,但不能用来评价Graves’病的甲亢严重程度。     

甲亢患者血清TGA、TMA与TRAb联检的临床意义

目的 :对 84例甲亢患者的三种抗体进行联合测定 ,探讨在甲亢患者中三种抗体之间的关系及其对诊断自身免疫性甲状腺疾病的价值。方法 :84例甲亢患者按TGA、TMA浓度分为三组即TGA、TMA阴性组 (TGA、TMA <2 0 % )、阳性组 (TGA、TMA≥ 2 0 %～ <4 0 % )、强阳性组 (TGA、TMA≥ 4 0 % )。结果 :阳性率比较TRAb阳性患者占甲亢患者总人数的 71 5 % ,TRAb阳性率在阴性组占 4 2 9% ,阳性组占 75 0 % ,强阳性组占 85 7% ,三组甲亢患者及三组甲亢TRAb阳性患者血清TRAb测定结果的比较 :阳性组与阴性组比较均无显著性差异 ,强阳性组较阴性组与阳性组均明显增高。结论 :本组甲亢患者TRAb阳性率不仅与文献报告相符合 ,且显示TRAb的阳性率随着TGA、TMA阳性率的提高有增加趋势。 84例甲亢患者中TGA、TMA强阳性占 4 1 7% ,其中不能排除有桥本氏甲亢的可能     

血清TRAb测定在Graves'病复发中的临床意义

目的 :探讨血清促甲状腺激素受体抗体 (TRAb)水平在Graves’病复发中的改变及其临床意义。方法 :对 2 5例Graves’病复发患者 (GD复)、18例初诊Graves’病患者 (GDa)、31例经抗甲状腺药物治疗后甲状腺功能基本正常患者 (GDb)、15例单纯性甲状腺肿患者 (单肿 )、10例结节性甲状腺肿大患者 (结肿 )、18例桥本氏甲状腺炎致甲状腺功能减退患者 (桥本 )分别检测血清TRAb、TT4、TT3 、TSH、FT4、FT3 的水平。结果 :GD复 患者血清TRAb阳性率与GDa相似 ,分别为 76 0 0 %、77 78% ,均显著高于GDb组、单肿组、结肿组和桥本组 (P均<0 0 1)。结论 :血清TRAb检测有助于Graves’病复发的诊断。     

血清TRAb检测在Graves甲亢治疗中的意义

目的：探讨血清TRAb值在Graves甲亢患者治疗前后的改变及其临床意义。方法：50例正常人和42例Graves甲亢患者在丙基硫氧嘧啶治疗前、后分别用放射免疫分析作了血清TRAb,TSH,FT3,FT4,rT3检测。结果：未经ATD治疗的Graves甲亢患者,血清TRAb阳性率为88％。Graves甲亢患者接受ATD治疗后3个月时,TRAb阳性率为57．14％,其它检测指标除rT3外均与正常组无明显差异（P＞0．05）;6个月时TRAb阳性率为17．50％;12个月时为7．69％;24个月时为5．71％。本组临床缓解停药后有15例复发,该15例中13例（88．66％）血清TRAb原为阳性,显示确有关联。结论：血清TRAb的检测有助于指导Graves甲亢患者的治疗。     

男性Graves病患者药物治疗后血清免疫指标与性激素测定的临床意义

目的:为了探讨部分男性GD甲亢患者药物治疗后免疫缓解较慢的原因。方法:测定患者血清β2-m、T、E2、P的含量变化及TGA、TMA的阳性率变化,将176例男性GD甲亢患者根据治疗过程分为三组,①初发组(Ⅱ组,62例);②未缓解组(Ⅲ组,58例);③缓解组(Ⅳ组,56例);④60名正常人作为对照组(Ⅰ组)。结果:男性GD甲亢Ⅱ组与Ⅲ组血清β2-m、FT3、FT4、T、E2,P水平明显高于Ⅰ组(P<0.01),而TGA、TMA的阳性率明显下降(P<0.01)。Ⅱ组与Ⅲ组FT3、FT4与β2-m呈明显正相关,而Ⅳ组β2-m、FT3、FT4与Ⅰ组相比,差别无显著性(P>0.05)。而Ⅳ组T、E2、P水平虽明显降低,但与Ⅰ组相比差别仍有显著性(P<0.05),特别是Ⅳ组的T水平仍然较高与Ⅰ组相比差别有极显著性(P<0.01)。Ⅳ组与Ⅲ组相比,TGA、TMA阳性率差别无显著性(P>0.05)。Ⅳ组的TGA、TMA阳性率仍较高,与Ⅰ组相比差别仍有显著性(P<0.01)。最终Ⅳ组仍有21.4%的患者血清β2-m明显增高,26.8%的患者TGA、TMA仍持续阳性。结论:①血清β2-m水平及TGA、TMA阳性率可作为男性GD甲亢免疫缓解指标,男性GD甲亢患者未缓解者常有血清β2-m水平及TGA、TMA阳性率持续升高,提示免疫功能持续紊乱而不能缓解。②男性GD甲亢患者性腺轴功能恢复要慢于甲状腺功能恢复,患者体内血清T水平持续较高也提示免疫功能持续紊乱而缓解缓慢。     

Graves病的遗传学研究

目的探讨G raves病的遗传基础。方法采用SCE观察、G raves病遗传率分析和外周血自发微核率测定等。结果甲亢组与对照组无论是平均自发的SCE频率还是用MMC诱发的SCE频率,两者均有极显著性差异(P<0.01)。另外,两组MMC诱发的SCE频率增加数,也有显著性差异(P<0.01);甲亢组一级亲属的患病率为对照组的22.3倍。经χ2检验甲亢具有明显的家族倾向。此外,本地区甲亢h2为68.6±3.8%;20例甲亢组和对照组平均微核率分别为2.55±0.36和0.95±0.76,经χ2检验,两者有显著性差异(P<0.01)。     

Graves'病患者的TPOAb及TRAb的变化与临床价值

目的：通过检测毒性弥漫性甲状腺肿，即Graves＇病（GD）患者的TPOAb与TRAb，探讨二者的应用与临床价值。方法：对于GD病人27例、GD病人治愈组10例、正常对照35例，采用RIA检测TPOAb与RRA检测TRAb并进行组间显著性比较。结果：GD病人的TPOAb与TRAb的测值和阳性率都显著高于GD病人治愈组和正常对照组，与GD病人治愈组和正常对照组相比较均有十分明显的差异，P值均〈0．01。结论：GD病人TPOAb与TRAb的变化与病情的进展有较为密切的关系，对于GD的诊断与疗效观察具有较重要的参考价值。     

Long-term pathologic changes of alpha1-acid glycoprotein (orosomucoid) glycoforms in autoimmune thyroid disease

OBJECTIVE: We measured alpha1-acid-glycoprotein (AGP) in patients with autoimmune thyroid disease to study a possible relationship between microheterogeneity of the naturally occurring glycoforms of AGP and autoimmune thyroid disease. DESIGN, PATIENTS, MEASUREMENTS: In a group of 12 fasting thyrotoxic patients (11 females, mean age: 43 years) with newly diagnosed Graves' disease (subgroup 1), we measured serum concentrations of total AGP and its 3 glycoforms (micromol/l, crossed affinity immunoelectrophoresis with con A in the first dimension gel) as well as total thyroxine, total triiodothyronine, thyrotropine, thyroid peroxidase antibodies (anti-TPO), antibodies against the TSH receptor (TRAb, TRAK), at baseline and after 12 months of antithyroid drug therapy (ATD). For comparison, 4 subgroups of thyroid patients (patients with Graves' disease and thyroid associated ophthalmopathy (TAO) (subgroup 2, n = 10), radioiodine treated Graves' patients (subgroup 3, n = 7), Graves' patients without TAO (subgroup 4, n = 13), patients with Hashimoto's thyroiditis (subgroup 5, n = 8)) and 25 normal controls (17 females, mean age: 38 years) were studied. RESULTS: In subgroups of TRAb positive Graves patients' serum levels of glycoform 1, 2 or 3 increased significantly (p < 0.005) after 12 months of ATD as compared to both baseline of that person or normal controls. No significant changes were found in the TRAb negative Hashimoto subgroup. CONCLUSION: Patients with autoimmune Graves' disease changed their relationship to AGP, and thus a role of AGP and its 3 glycoforms is suggested in the pathogenesis of Graves' disease.     

Evaluation of immunological tests in thyroid diseases

We evaluated immunological tests for autoimmune thyroid diseases. Although both humoral and cellular immunity are correlated to the onset and pathophysiological progression of these diseases, the major tests employed in daily clinic belong to the former. We measured the anti-TSH receptor antibody (TRAb, TBII), circulating immune complex (CIC), thyroid growth stimulating immunoglobulin (TGSI) and interleukin-2 (IL2) levels in patients with Graves' disease (GD) and chronic thyroiditis (CT). The normal range of TRAb in 190 healthy controls was from -10.9 to +10.3% calculated from the mean +/- 2SD. Sixty eight out of 78 untreated cases of GD (87.2%) showed a higher TRAb than the upper normal level (positive), 92 out of 131 cases of GD under treatment (70.2%) were positive and only 5 out of 57 cases of treated GD (8.8%) were positive. Three neonates out of 12 GD mothers had a positive TRAb and one of them developed neonatal GD. Nine out of the 45 CT (20%) had positive TRAb, but about half were euthyroid and goitrous. In untreated GD, CIC was distributed widely from the normal range to high levels. CIC showed a significantly negative correlation with TRAb. TGSI correlated with goiter size and CIC in GD revealed autologous inhibition on TGSI. Three cases showed markedly decreased levels of TRAb which was found to be due to anti-TSH antibodies. Production of IL2 in GD was impaired, but it was improved by treatment of GD.(ABSTRACT TRUNCATED AT 250 WORDS)     

TGAb、TMAb及TRAb联检在复方甲亢片配合131I治疗Graves病中的价值

通过观察131I治疗前后Graves病(GD)患者TGAb、TMAb及TRAb浓度变化,探讨复方甲亢片配合131I治疗对GD患者的免疫功能的影响.将121例GD患者分为:(1)对照组:单纯131I治疗组58例,采用131I一次性口服治疗;(2)研究组:131I加复方甲亢片治疗组61例.于治疗后2、4、12个月随访患者,比较两组治疗后TGAb、TMAb、TRAb浓度的变化.结果表明治疗前研究组和对照组TGAb、TMAb阳性者分别有9例和8例,治疗后12个月时TGAb、TMAb转阴率分别为44.4%(4/9)和12.5%(1/8),研究组的转阴率高于对照组(P＜0.05);两组治疗后2、4、12个月时TRAb值均逐渐下降,以4、12个月时较治疗前下降明显(P＜0.05),12个月时研究组TRAb值较对照组下降明显(P＜0.05),但2、4个月时两组TRAb值无明显差异(P＞0.05).复方甲亢片配合131I治疗能提高患者TGAb、TMAb的转阴率,较快地降低TRAb值,复方甲亢片具有增强GD患者机体免疫调节功能的作用.     

Marked increase of CD5 + B cells in hyperthyroid Graves' disease

We examined the proportions of B lymphocytes bearing CD5 cell surface antigen (CD5+ B cells), which are capable of making autoantibodies, in peripheral blood from patients with various thyroid diseases. The level of CD5+ B cells was markedly increased (>9.0%) above the normal range (0.5-7.7%) in untreated, hyperthyroid patients with Graves' disease, although about 10% of the patients had no detectable serum thyroid-stimulating hormone (TSH) receptor antibody (TRAb). However, the levels of CD5+ B cells were normal in untreated patients with destructive thyrotoxicosis due to aggravation of Hashimoto's thyroiditis or subacute thyroiditis. In patients with stimulated hyperthyroid Graves' disease the levels of CD5+ B cells were correlated with those of thyroid hormones and TRAb, all significantly increased. However, once hyperthyroidism was controlled by anti-thyroid drugs, CD5+ B cells were decreased, followed in turn by reduction of TRAb. We conclude that the proportion of CD5+ B cells is useful as a therapeutic index and for diagnosis of Graves' disease and its differentiation from destruction-induced thyrotoxicosis.     

Autoantibodies highly increased in patients with thyroid dysfunction

To evaluate the significance of antithyroid antibodie levels, five hundred and twenty-six patients with thyroid diseases and 292 health subjects from Yuci district, Shanxi province, China, were studied. Serum levels were determined for thyroid hormone receptor antibody （TRAb）, microsomal antibody （TMAb） and thyroglobulin antibody （TGAb）. Among patients, the percentages for nodular goiter and thyroid adenoma, Graves＇ disease, and Hashimoto＇s thyroiditis are 44.1%, 19.6% and 17.7%, respectively. The ratios of female to male were 2.0 to 15.6. Antibody-positive patients for TMAb, TGAb and TRAb were detectable as 94.6%, 76.3% and 20.4% for Hashimoto＇s thyroiditis, and 40.0%, 30.0% and 90.3% for Graves＇s disease. In conclusion, the high levels of the TRAb in Graves＇ disease, and those of the TGAbFFMAb in Hashimoto＇s thyroiditis and idiopathic hypothyroidism are meaningful for characterizing the epidemiological basis of the diseases and for using as prognostic indicators for the relapse in individual patients. Cellular ＆ Molecular Immunology.     

Increased serum soluble Fas ligand in hyperthyroid Graves' disease

The interaction of Fas with its ligand (FasL) regulates a number of physiological and pathophysiological process of cell death or apoptosis. Recent studies suggest that Fas and Fas ligand (FasL) interactions among thyrocytes from patients with Hashimoto disease which is caused by thyroid autoimmunity may contribute to clinical hypothyroidism. The role of Fas-FasL interaction in the pathophysiology of Graves' disease has not well been determined. The serum levels of soluble Fas (sFas) and FasL (sFasL) were measured in 48 Japanese patients with Graves' disease (U; untreated hyperthyroidism, T; hyperthyroidism under treatment, E; euthyroidism under treatment and R; remission), destructive thyroiditis (D), subacute thyroiditis (S) and 40 normal controls using commercially available ELISA kits. The levels of sFas (mean +/- SD, ng/ml) were 0.93 +/- 0.30 in normal controls (n = 32), 2.41 +/- 1.28 in U (n = 19), 2.44 +/- 0.79 in T (n = 16), 2.37 +/- 0.55 in E (n = 12), and 2.30 +/- 0.11 in R (n = 6), 2.42 +/- 0.37 in D (n = 3) and 2.68 +/- 0.17 in S (n = 3). There were no significant differences of sFas levels among any groups. While, the mean levels of sFasL (ng/ml) of normal controls were 0.058 +/- 0.02 (n = 40), and those of patients with hyperthyroid Graves' disease (U; 0.34 +/- 0.09 and T; 0.26 +/- 0.05), were significantly higher than those in normal controls (p < 0.005) and with subacute thyroiditis (0.097 +/- 0.001, vs U; p < 0.01, vs T; p < 0.05) but not different from those in E, R and D (E; 0.34 +/- 0.09, R; 0.25 +/- 0.07 and D; 0.31 +/- 0.11, respectively). There was a significant correlation between serum thyrotropin receptor antibody (TRAb) and free thyroxine levels (p < 0.01) while there were no correlation between sFas and sFasL levels and TRAb or free thyroxine levels. The results indicate that the Fas-FasL system contributes to the pathophysiology of hyperthyroid Graves' disease although serum sFas and sFasL levels do not appear to be useful indicators in evaluating disease activity.     

The influence of Epstein-Barr virus reactivation in patients with Graves' disease

In Graves' disease, the IgG class autoantibody against thyrotropin receptor (TRAb) is produced excessively and induces hyperthyroidism. Epstein-Barr virus (EBV) is one of the human herpesviruses that persists for life, mainly in B lymphocytes, and is occasionally reactivated. Therefore, EBV may affect the antibody production of B lymphocytes that would normally produce TRAb. The purpose of the present study was to evaluate the association of EBV reactivation with the etiology of Graves' disease. Serum levels of EBV antibodies and IgE were determined by ELISA. TRAb levels were determined by radioreceptor assay. We performed in-situ hybridization (ISH) of EBV-encoded small RNA (EBER)1 on the thyroid tissue of one of our patients. In Graves' disease patients with TRAb levels ≥ 10%, EA antibody levels, which indicate EBV reactivation, were moderately but significantly correlated with the levels of TRAb, and weakly but significantly correlated with IgE. EBER1-ISH revealed that one of our patients had EBV-infected lymphocytes infiltrating the thyroid gland. EBV reactivation may stimulate antibody-producing B lymphocytes predisposed to make TRAb, and this may contribute to or exacerbate the disease.     

Two-center evaluation of eight kits for antithyroid peroxidase autoantibodies determinations

We compared eight antithyroid peroxidase antibody assay kits in two centres, by use of panel sera from 269 patients: controls (n = 100), patients with autoimmune thyroid diseases (n = 77 Graves' disease, Hashimoto's thyroiditis), with non autoimmune thyroid diseases (n = 69 nodular goiter, differentiated thyroid carcinoma), and with autoimmune disease without thyroid pathology (n = 23 diabetic subjects, rheumatoid polyarthritis). On the controls sera we observed different distributions of values. The cut-off values of each kit was, in most cases, similar to the value noted in the manufacturer's instructions. In the clinical study, we observed few differences. The majority of assays demonstrated high diagnostic performance. Some false positive results and the non assessment of some sera by competitive immunoassay were observed.