血清甲状腺球蛋白测定与甲状腺疾病

甲状腺球蛋白(Tg)是自身免疫性甲状腺疾病(AITD)的主要自身抗原.各种甲状腺疾病均可出现Tg浓度异常.血清Tg测定对分化型甲状腺癌(DTC)复发或转移的诊断和疗效的监测有重要意义.但是Tg的测定受多种因素影响,其中甲状腺球蛋白抗体(TgAb)的干扰在临床上最常见.另外,不同甲状腺疾病Tg抗原表位不同,Tg基因多态性与甲状腺疾病也有一定关系.     

血清甲状腺球蛋白测定与甲状腺疾病

甲状腺球蛋白(Tg)是自身免疫性甲状腺疾病(AITD)的主要自身抗原.各种甲状腺疾病均可出现Tg浓度异常.血清Tg测定对分化型甲状腺癌(DTC)复发或转移的诊断和疗效的监测有重要意义.但是Tg的测定受多种因素影响,其中甲状腺球蛋白抗体(TgAb)的干扰在临床上最常见.另外,不同甲状腺疾病Tg抗原表位不同,Tg基因多态性与甲状腺疾病也有一定关系.     

甲状腺疾病血清甲状腺球蛋白检测的临床意义

目的 探讨血清甲状腺球蛋白（Tg）对不同甲状腺疾病的临床诊断意义.方法 916例甲状腺疾病患者,按其临床特征分为Graves病组、原发性甲状腺机能减退组、亚急性甲状腺炎组、良性甲状腺结节组、分化型甲状腺癌组,检测各类甲状腺疾病的血清Tg,比较各组间及分化型甲状腺癌术前、术后血清Tg的水平差异.结果 分化型甲状腺癌组Tg明显高于其他各组（P均＜0.05）,术后6个月分化型甲状腺癌患者Tg水平显著下降（P＜0.05）.结论 血清Tg水平结合临床表现检测有助于甲状腺疾病的诊断及鉴别.     

甲状腺球蛋白的测定和临床

甲状腺球蛋白 (Tg)是甲状腺分化癌治疗后随访的一个很好的监测标志 ,单纯测定Tg对诊断甲状腺分化癌没有意义。甲状腺分化癌经甲状腺全切手术和大剂量1 31 I治疗后 ,如果血中Tg阳性或者明显升高 ,应考虑肿瘤转移或者未切除干净 ;如果Tg<5 μg L ,肿瘤转移的可能性很小。血清Tg是尿碘不足的指标 ,比促甲状腺素更为敏感。Graves甲状腺功能亢进 (甲亢 )、Plummer甲亢、亚急性甲状腺炎、无痛性甲状腺病人的血清Tg都升高 ,药物性甲亢的Tg低下。Tg抗体会干扰Tg测定     

自身免疫性甲状腺炎自身抗原的实验研究进展

目前认为甲状腺球蛋白 (Tg) ,甲状腺过氧化物酶 (TPO)和促甲状腺激素受体 (TSHR)可能是参与自身免疫性甲状腺炎发生的主要自身抗原 ,就近年来对Tg、TPO和TSHR等甲状腺自身抗原表位及其抗原性等研究进展做一介绍。     

碘摄入量对血清甲状腺球蛋白的影响——5年流行病学随访研究

目的 观察碘摄入量对血清甲状腺球蛋白(Tg)水平的影响.方法 对1999年盘山(轻度碘缺乏地区)、彰武(碘超足量地区)和黄骅(碘过量地区)血清Tg水平正常的3 099人进行随访,将2004年随访到的2 448人作为研究人群.测定Tg、甲状腺球蛋白抗体(TgAb)、甲状腺过氧化物酶抗体(TPOAb)、促甲状腺素(TSH)、甲状腺容积,并询问甲状腺疾病的家族史和个人史.分析Tg的影响因素.结果 1999年初访时,不同碘摄入地区Tg水平差异显著[盘山7.5(4.4～13.1)μg/L、黄骅6.8(3.6～11.2)μg/L彰武5.9(3.2～10.7)μg/L,P<0.01];年龄、性别、TgAb阳性、甲状腺肿大、TSH异< 凹鬃聪偌膊「鋈耸范訲g水平的影响亦显著.为排除混杂因素的影响,对TgAb、甲状腺容积、TSH、甲状腺疾病个人史均无异常的1 856人的随访数据进行分析,其初访及随访的Tg水平均有显著地区差异,轻度碘缺乏以及碘过量地区都显著高于碘超足量地区.三地区随访时Tg水平均显著升高,且增加值(△Tg)存在显著地区差异[盘山3.1(-0.2～8.0)μg/L、黄骅3.5(0.5～9.0)μg/L/35彰武2.5(0.3～6.1)μg/L,P<0.01];碘摄入量、初访时的Tg水平、TSH水平及年龄为ATg的独立影响因素.结论 碘摄入量显著影响血清Tg水平,当用血清Tg水平来估计地区碘摄入水平及其变化时,应该同时考虑年龄及TSH等因素.     

甲状腺球蛋白基因与自身免疫性甲状腺疾病

甲状腺球蛋白在自身免疫性甲状腺疾病(AITD)的发生中起重要作用。近几年的连锁及相关分析发现,位于人类染色体8q24.2-q24.3区域的甲状腺球蛋白基因及其内部的微卫星标记不仅与AITD相连锁,还与其相关;同时,在动物及人体均发现甲状腺球蛋白基因的单核苷酸多态性与AITD具有相关性。因此认为,甲状腺球蛋白基因是AITD疾病相关抗原中第一个AITD易感基因。     

外周血甲状腺肿瘤标记物的研究进展

甲状腺肿瘤是常见内分泌疾病,为鉴别甲状腺良、恶性病变,避免不必要的手术治疗,近年来一些学者研究外周血甲状腺肿瘤标记物.一些为甲状腺组织特异性物质,如甲状腺球蛋白(Tg)、Tg mRNA、促甲状腺激素受体(TSHR)mRNA、甲状腺过氧化物酶(TPO)mRNA、DNA甲基化物及降钙素(CT)等,其中TPO mRNA及DNA甲基化物特异性及敏感性高,而Tg敏感性易受Tg抗体影响,Tg mRNA、TSHR mRNA缺乏组织特异性.一些非甲状腺组织特异性肿瘤标记物如血管内皮生长因子、细胞角蛋白片段等在鉴别甲状腺良、恶性病变中亦有一定作用.     

甲状腺球蛋白基因多态性与甲状腺球蛋白抗体的相关性

分析陕西地区汉族自身免疫性甲状腺疾病(AITD)患者体内甲状腺球蛋白(Tg)外显子10、12及33的单核苷酸多态性与甲状腺球蛋白抗体(TgAb)产生的相关性.对222例AITD患者依据TgAb滴度进行分组,采用PCR-RFLP方法 检测甲状腺球蛋白基因外显子10、12和33的单核苷酸多态性,并对其进行单体型分析.4个位点的等位基因及基因型在TgAb阳性组和TgAb阴性组两组分布频率差异无统计学意义;但单体型分析结果提示:在TgAb阳性组中,单体型G-C-A-C所占频率明显增高(P=0.028,OR=3.34),而单体型G-C-G-C的频率明显降低(P=0.048,OR=0.62),提示单体型G-C-A-C增多与单体型 G-C-G-C 的减少可能与AITD患者体内TgAb的产生有关.甲状腺球蛋白的基因多态性可能是导致TgAb产生的重要机制之一.

Abstract：

To identify association between the presence of previously reported four single nucleotide polymorphisms(SNPs) at exon 10, 12 and 33 of thyroglobulin(Tg) gene with autoimmune thyroid disease(AITD) patients whose TgAb is positive. In this case-control association study, the Tg gene polymorphisms at exon 10, 12, and 33 were determined by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)method in 222 patients with AITD. According to the titers of the Tg autoantibodies(TgAb) in serum, they were divided into two subgroups: TgAb positive group and TgAb negtive group. And a haplotype case-control analysis was also done in two groups.The difference of their frequencies was analyzed by Chi-square test. No differences in alleles and genotypes frequencies were observed in all patients whose TgAb iseither positive or negative(P＞0.05). But there was a significant association of G-C-A-C haplotype with the patients whose TgAb was positive(P=0.028,OR=3.34). There is association of thyroglobulin gene polymorphisms with TgAb in patients with AITD.     

人甲状腺原代细胞的长期培养

目的　探索人甲状腺细胞长期原代培养的方法及细胞在不同时期的功能变化。方法　常规分离甲状腺细胞,并用含有10%胎牛血清(FBS)、谷氨酰胺、牛胰岛素、10mU/LTSH和氢化可的松的MEM培养,细胞铺成单层后换用4% FBC的培养基培养,分别在不同时间观察甲状腺细胞吸碘率、细胞生长情况,免疫组化观察甲状腺特异抗原甲状腺球蛋白(Tg)表达水平,RT PCR测定钠碘转运子(NIS)基因表达水平。结果　甲状腺细胞在培养40d左右仍生长良好,培养14d细胞具有80%的吸碘率,培养7dTg表达可达95%,培养14dTg表达仍达60%,NISmRNA表达在培养7d达98%,而培养14d表达率只有40%。结论　应用该研究所建立的培养条件可以使甲状腺细胞生存40d以上,该实验条件下培养3, 7, 14,28d的原代甲状腺滤泡上皮细胞以培养7d的细胞NISmRNA,Tg表达、摄碘功能最接近基线水平。     

Circulating thyroid cancer biomarkers: Current limitations and future prospects

Differentiated thyroid cancer (DTC) is the most common malignancy of the endocrine system. There has been a significant increase in its incidence over the past two decades attributable mainly to the use of more sensitive diagnostic modalities. Ultrasound‐guided fine needle aspiration cytology is the mainstay of diagnosis of benign disorders and malignancy. However, approximately 20% of lesions cannot be adequately categorized as benign or malignant. In the postoperative setting, monitoring of thyroglobulin (Tg) levels has been employed for the detection of disease recurrence. Unfortunately, Tg antibodies are common and interfere with Tg measurement in this subset of patients. Despite this limitation, Tg remains the sole widely used thyroid cancer biomarker in the clinical setting. In an attempt to bypass antibody interference, research has focused mainly on mRNA targets thought to be exclusively expressed in thyroid cells. Tg and thyroid stimulating hormone receptor (TSHR) mRNA have been extensively studied both for discerning between benign disease and malignancy and in postoperative disease surveillance. However, results among reports have been inconsistent probably reflecting considerable differences in methodology. Recently, microRNA (miRNA) targets are being investigated as potential biomarkers in DTC. MiRNAs are more stable molecules and theoretically are not as vulnerable as mRNA during manipulation. Initial results have been encouraging but large‐scale studies are warranted to verify and elucidate their potential application in diagnosis and postoperative surveillance of thyroid cancer. Several other novel targets, primarily mutations and circulating cells, are currently emerging as promising thyroid cancer circulating biomarkers. Although interesting and intriguing, data are limited and derive from small‐scale studies in specific patient cohorts. Further research findings demonstrating their value are awaited with anticipation.     

Recombinant human thyroid-stimulating hormone (Thyrogen) in thyroid cancer follow up: experience at a single institution

Background: Recombinant human thyroid‐stimulating hormone (Thyrogen^®; Genzyme Corporation, Cambridge, MA, USA) (rhTSH)‐stimulated serum thyroglobulin (Tg) (stim‐Tg) and ¹³¹I whole‐body scanning (WBS) have been reported to allow follow up of patients with thyroid cancer without the symptoms of thyroxine withdrawal and with equivalent diagnostic information to that obtained after thyroxine withdrawal. The aim of the study was to report results of rhTSH use at the Alfred Hospital, Melbourne, from 1999 to 2006 and in particular to examine the significance of detectable serum Tg after rhTSH in relation to thyroid cancer staging and to compare the sensitivity of rhTSH‐stimulated serum Tg to whole‐body ¹³¹I scanning (WBS) in the detection of residual and recurrent thyroid cancer. Methods: The study was a retrospective chart review. Results: In 90 patients, rhTSH was used for 96 diagnostic episodes and 18 doses of rhTSH were used to facilitate treatment with ¹³¹I. In stages I and II cancer (n = 42), of three patients with stim‐Tg 1–2 μg/L, none had identifiable disease, and the three patients who had stim‐Tg >2 μg/L did not experience recurrent disease during follow up. In contrast, in stages III and IV cancer (n = 43) 2 of 5 with stim‐Tg 1?2 μg/L had identifiable disease and 7 of 10 with stim‐Tg >2 μg/L had identifiable disease. In Tg‐positive, WBS‐negative disease, further imaging identified persistent/recurrent disease. Conclusion: rhTSH was effective and safe in the management of thyroid cancer follow up for diagnosis of persistent/recurrent cancer and to enable ¹³¹I treatment. In no case did rhTSH‐stimulated WBS identify the presence of disease not also identified by raised basal Tg or stim‐Tg. Therefore, in low risk cancer WBS may be omitted.     

Serum thyroglobulin in patients with toxic and non-toxic goitres compared to sex- and age-matched control subjects

To study serum thyroglobulin (Tg) levels in patients with thyroid disorders compared to sex- and age-matched control subjects and to correlate the Tg levels to the thyroid function, 71 patients were investigated before treatment was started. Serum Tg, measured by a double antibody radioimmunoassay, was elevated in all groups with thyroid disorders, as compared to their controls, but the values showed large overlaps between groups. The highest median values were seen in the two groups of patients with toxic goitres (toxic adenoma and Graves' disease). The Tg values in patients with non-toxic goitres (diffuse and nodular) and in controls showed a log normal distribution, whereas the distribution of values from patients with toxic goitres was different. No correlation was found between serum Tg and serum thyroxine, serum triiodothyronine and serum TSH, respectively. It is concluded that determination of serum Tg is of little diagnostic value in thyroid diseases.     

Lessons from a review of thyroglobulin assays in the management of thyroid cancer

Thyroglobulin (Tg) measurement has become increasingly an important and integral part of the follow up and management of patients with differentiated thyroid cancer. Clinicians predominantly rely on Tg for decision-making for surveillance of patients with differentiated thyroid cancer, but despite this new reliance, issues regarding Tg measurement have not been appropriately addressed especially within a local context. In the process of developing an institutional protocol we have identified that there are significant clinical and technical issues regarding Tg measurement, and surprisingly Tg assessment is currently not part of an external quality control programme. We conducted a small pilot study to specifically emphasize some of the assay issues. We aim to inform endocrinologists, pathologists and nuclear medicine physicians, the need and urgency for these issues to be addressed to improve the ongoing surveillance of differentiated thyroid cancer.     

Correlations of thyroid autoantibodies with allergic diseases: A case-control study of 434 Chinese patients

There is growing interest in the relationship between allergies and autoimmune diseases, although previous studies have yielded inconsistent results.The thyroglobulin (Tg)/thyroid peroxidase antibody (TPOAb) group consisted of 217 patients with positive thyroglobulin antibody (TgAb) and/or TPOAb test results. Another set of 217 age- and sex-matched individuals with both TgAb- and TPOAb-negative results were selected as control group. History of allergic rhinitis (AR), chronic spontaneous urticaria (CSU), and/or atopic dermatitis (AD) was elicited before autoantibody detection. The association of thyroid autoantibodies with allergic diseases was assessed using univariate and multivariate logistic regression analysis, and the results were reported as odds ratios (ORs).TgAb positivity (OR, 2.333) was identified as a risk factor for AR, AD, or CSU in Chinese patients, suggesting the involvement of thyroid autoantibodies in the pathogenesis of atopic reactions. Multivariate regression analysis also confirmed that the presence of TgAb (P = .004), rather than TPOAb (P = .468), had a significant impact on the occurrence of allergic disease.Physicians should carefully monitor atopic symptoms in individuals with elevated TgAb or TPOAb levels to reduce the risk of allergic diseases, such as AR, AD, and CSU.     

Megalin in thyroid physiology and pathology.

Megalin, a member of the low density lipoprotein endocytic receptor family, is expressed on the apical surface of thyroid epithelial cells, directly facing the follicle lumen, where colloid is stored in high concentrations. Studies in vivo and with cultured thyroid cells have provided evidence that megalin expression on thyroid cells is TSH-dependent. Thyroglobulin (Tg), the major protein component of the colloid and the precursor of thyroid hormones, binds to megalin with high affinity and megalin mediates in part its uptake by thyrocytes. Tg internalized by megalin avoids the lysosomal pathway and is delivered by transepithelial transport (transcytosis) to the basolateral membrane of thyrocytes, from which it is released into the bloodstream. This process competes with pathways leading to thyroid hormone release from Tg molecules, which occurs following internalization of Tg molecules from the colloid by other means of uptake (fluid phase endocytosis or endocytosis mediated by low affinity receptors) that result in proteolytic cleavage in the lyosomes. During transcytosis of Tg, a portion of megalin (secretory component) remains complexed with Tg and enters the circulation, where its detection may serve as a tool to identify the origin of serum Tg in patients with thyroid diseases. Tg endocytosis via megalin is facilitated by the interaction of Tg with cell surface heparan sulfate proteoglycans, which occurs via a carboxyl terminal heparin binding site of Tg functionally related with a major megalin binding site. Although autoantibodies against megalin can be found in the serum of approximately 50% of patients with autoimmune thyroiditis, a role of megalin in this and other thyroid diseases remains to be established.     

Thyroid ultrasonography as a tool for detecting thyroid autoimmune diseases and predicting thyroid dsfunction in apparently healthy subjects.

In order to establish its usefulness for the diagnosis and follow-up of thyroid autoimmune diseases, thyroid ultrasonography together with free T4 (FT4), free T3 (FT3), TSH, antibodies (Tg Ab) and thyroperoxidase antibodies (TPO Ab) were performed and re-evaluated during a 3-yr follow-up in 482 apparently healthy subjects, living in a borderline iodine-sufficient urban area. Thyroid dysfunction was found in 7 out of 12 (58.3%) subjects with circulating thyroid autoantibodies, who also had thyroid hypoechogenicity (2 had overt and 3 subclinical hypothyroidism at booking; 2 developed subclinical hypothyroidism during the follow-up), and in none of the 12 subjects with normal thyroid echostructure (chi2=7.26, p=0.007). Thyroid dysfunction was found in 4 out of 29 (13.7%) subjects with negative Tg and/or TPO Ab who also had thyroid hypoechogenicity (1 had Graves' disease at booking, 1 developed Graves' disease and 2 subclinical hypothyroidism during the follow-up), and in none of the 429 with normal thyroid echostructure (chi2=82.03, p<0.0001). Although positive TPO and/or Tg Ab were more frequent (24/482, 5%) in subjects with thyroid dysfunction (7/11) than in those who remained euthyroid during the study (17/471, chi2=69.66, p<0.0001), thyroid hypoechogenicity had a higher sensitivity than the positivity of thyroid autoantibody tests (100 vs 63.3%) for diagnosing or predicting thyroid dysfunction. In conclusion: 1) thyroid ultrasonography is a useful tool to detect thyroid autoimmune disease in apparently healthy subjects; 2) present and future thyroid dysfunction is more readily predicted by a hypoechogenic pattern at thyroid ultrasound than by the occurrence of serum thyroid autoantibodies.