Serum thyroglobulin in the monitoring of differentiated thyroid cancer

Abstract

Patients with differentiated thyroid cancer (DTC) usually have an excellent prognosis. Following surgical and radioiodine treatment to remove the cancer cells and suppressive doses of levothyroxine, long-term follow-up, including measurement of serum thyroglobulin (Tg) using a sensitive assay is required to detect recurrence. To interpret Tg results clinicians need to know the corresponding serum TSH concentration, have an appreciation of the clearance of Tg from patient serum following various interventions and the limitations of its measurement. The limitations of Tg immunoassay are well described and include potential interference from TgAb. For the majority of patients with DTC who are TgAb-negative, Tg measurement remains the most useful method of follow-up. For the TgAb-positive minority, interference and the possibility of producing erroneous results is a concern. Some assays are less badly affected than others and laboratories are advised to choose their assays carefully. Laboratories have sought to identify interferences using measurement of TgAb, lack of concordance between RIAs and immunometric assays and recovery of added Tg. More recently LC-MSMS assays to quantify Tg have been developed. They are not currently as sensitive as Tg immunoassays and it is likely these assays will, like immunoassays, be limited by Tg heterogeneity and standardization issues, although initial evaluations indicate that they may have value in the clinical setting as a second line test in antibody-positive DTC patients in whom Tg is unmeasurable by immunoassay.     

Management of differentiated thyroid cancer of the follicular epithelium

Abstract The incidence of thyroid cancer has been increasing in many countries over the last 30 years (from 3.6/100,000 people in 1973 to 8.7/100,000 people in 2002) while mortality has been slowly decreasing ( 1 , 2 ). The increase is mainly represented by papillary thyroid cancer, while follicular and anaplastic histotypes remained stable. It is a general opinion that the increase is attributable to better detection of small papillary carcinomas as a result of improved diagnostic accuracy (neck ultrasound and fine-needle aspiration cytology). Consequently, it is common experience in thyroid cancer referral centers that nearly 60%-80% of thyroid carcinomas detected nowadays are micropapillary thyroid carcinomas (less than 1 cm in size) carrying an excellent long-term prognosis. In view of this change in the presentation of the disease, the objective of thyroid cancer management should be aimed at achieving complete cure using the less aggressive diagnostic and therapeutic procedures.     

中高风险分化型甲状腺癌患者术后血清甲状腺球蛋白水平与临床结局的相关性研究

目的 探究中高风险分化型甲状腺癌(DTC)患者术后血清甲状腺球蛋白(Tg)水平对远期临床结局的预测价值.方法 回顾性分析2011年1月至2019年6月就诊于四川大学华西医院的DTC患者共296例,依据最后一次随访结果 分为3组:A组为存在结构性复发患者、B组为生化反应不全患者、C组为无病生存患者.3组患者均接受甲状腺全...     

分化型甲状腺癌患者促甲状腺激素抑制治疗期间骨质疏松风险筛查及影响因素分析

目的了解分化型甲状腺癌患者术后长期行促甲状腺激素(TSH)抑制治疗期间骨质疏松风险,并探索其相关影响因素。方法选取接受分化型甲状腺癌术后行TSH抑制治疗的300例患者为研究对象,利用国际骨质疏松基金会骨质疏松一分钟测试法和亚洲人骨质疏松自我筛查工具(OSTA)进行骨质疏松风险筛查,并根据结果进行影响因素分析。结果300例接受分化型甲状腺癌术后行TSH抑制治疗的患者中,66.00%的患者存在骨质疏松风险;OSTA显示该组患者骨质疏松低度风险为96.00%,中度风险为1.00%,高度风险为3.00%。患者的服药剂量、性别、绝经、婚姻状况、医保支付类型以及是否知晓甲状腺癌术后激素治疗会增加骨质疏松的发病率是骨质疏松的影响因素。结论大部分分化型甲状腺癌TSH抑制治疗患者都存在患有骨质疏松的风险,但多为低度风险。患者对骨质疏松的防范意识普遍不高。     

Diagnosis of follicular carcinoma of the thyroid: role of sonography in preoperative diagnosis of follicular nodules

The purpose of this study was to evaluate sonographic examination, as well as other clinical tests, for clarifying the parameters for predicting follicular carcinoma in follicular nodules of the thyroid. Nine hundred and ten consecutive patients with follicular nodules were pathologically classified as having follicular carcinoma (109 patients) or benign tumor (811 patients). Benign tumors included follicular adenoma (237 patients) and adenomatous thyroid nodules (574 patients). A case-control study was performed for follicular carcinomas and benign tumors. “Thyroglobulin 1000 ng/ml≦”, “cytology class 3≦”, and a “solid pattern”, “low-echoic level of internal echo”, and “jagged borders” of follicular carcinomas were found to be significantly higher than those of benign tumors. The sensitivities of a solid pattern (79.8%) and a low-echoic level (75.2%) were found to be relatively higher than those of other features and findings. The specificities of thyroglobulin 1000 ng/ml≦(84.0%), cytology class 3≦, and jagged borders (86.2%) were found to be relatively higher than those of other features and findings. We concluded that thyroglobulin 1000 ng/ml≦ and cytology class 3≦ in clinical features, and a solid pattern, low-echoic level, and jagged borders on sonography, indicated an increased risk of follicular carcinoma of the thyroid in follicular nodules.     

促甲状腺激素抑制疗法在分化型甲状腺癌治疗中的作用

目的探讨促甲状腺激素(TSH)抑制疗法在分化型甲状腺癌患者术后治疗中的作用。方法 130例分化型甲状腺癌患者于甲状腺切除术后分别行TSH抑制治疗(观察组)和甲状腺素替代治疗(对照组),比较2组患者术后无复发和/或无转移率。结果观察组术后3、5、10年的无复发和/或无转移率分别为98.76%、93.21%及79.54%,对照组分别为92.17%、82.36%及51.25%,2组差异有统计学意义(P<0.05)。结论 TSH抑制疗法是分化型甲状腺癌患者行全或近全甲状腺切除术后的有效治疗手段。     

分化型甲状腺癌再次手术46例临床分析

目的 探讨分化型甲状腺癌再次手术的原因和选择合理的手术方式.方法 对甲状腺癌再次手术46例的资料进行回顾性分析并结合文献进行讨论.结果 本组病例首次手术前均诊断为良性甲状腺疾病;首次手术方式肿物切除或甲状腺部分切除术28例,甲状腺次全切除术12例,甲状腺叶全切除术3例,甲状腺腺叶全切除＋峡部切除＋颈淋巴结切除3例.再次手术原因主要为甲状腺癌术前诊断率低、首次手术方式不当及肿瘤复发或颈淋巴结转移.结论 由于甲状腺癌的术前误诊或首次手术方式不当,致术后的残癌率高,再次手术是必要的;术中冰冻病理切片检查是避免再次手术的关键;对于甲状腺癌切除术后复发或淋巴结转移者,应积极作合理的再次手术.     

Imaging,genetic testing,and biomarker assessment of follicular cell-derived thyroid cancer

Abstract

Thyroid carcinoma is the most common endocrine malignancy worldwide, and its incidence continues to increase. As such the approach to a recently identified thyroid nodule is important to understand. The relevant imaging, examination, and need for fine-needle aspiration biopsy (FNA) are discussed. In approximately 25% of nodules, the diagnosis cannot be established with FNA-based cytology, and surgical excision is necessary for definitive diagnosis. Recent advances in genetic and molecular testing may increase the diagnostic accuracy of FNA in managing thyroid nodules.     

儿童分化型甲状腺癌术后辅助治疗效果观察

目的探讨儿童分化型甲状腺癌术后辅助治疗效果。方法回顾性分析≤14岁122例分化型甲状腺癌患儿的临床资料。结果 122例手术均顺利完成。24例行单侧甲状腺腺叶切除术,98例行双侧甲状腺全切术,其中72例行选择性颈淋巴结清扫术,26例行根治性颈淋巴结清扫术;所有患者术后均给予左旋甲状腺素钠片治疗,剂量1.5-2.5μg/（kg·d）,使术后促甲状腺激素〈0.1mIU,其中79例辅以131I治疗;所有患儿均获随访,随访时间6个月-10a;患儿身高、体质量均不低于WHO推荐的儿童生长发育标准;随访期间,无死亡病例;11例（9%）出现颈淋巴结转移,5例（4%）出现远处脏器转移;5例肺转移患儿在131I及内分泌辅助治疗后,肺部CT提示有4例转移灶完全消失,1例病灶明显缩小。结论儿童分化型甲状腺癌术后辅以131I内照射和内分泌抑制疗法,可降低肿瘤复发,对转移病灶有较好疗效,明显改善患者预后。     

TSH对分化型甲状腺癌病人血Tg的影响

目的对分化型甲状腺癌行双侧甲状腺全切术后停用内分泌治疗前后所测得的Tg进行对比分析。方法采用化学发光法对2003～2006年我院收治的83例分化型甲状腺癌的血TSH和Tg水平进行检测，在停用左旋T4前1天以及”。I内照射治疗前1天各测1次。结果在内分泌治疗期间Tg水平≤30μg／L时，停用内分泌治疗后Tg水平没有明显升高（P〉0．05）；但内分泌治疗期间Tg水平〉30μg／L时，停用内分泌治疗后Tg水平出现明显升高（P〈0．05）。结论风是分化型甲状腺癌较好的随诊指标．监测血Tg不必停用内分泌治疗．     

Thyroid cancer review 2: management of differentiated thyroid cancers

This is the second review article on thyroid cancer dealing with the common differentiated types that comprise 90% of thyroid cancers. Despite clinical management guidelines offered by a number of organisations including the British Association of Otolaryngologists and Head and Neck Surgeon, The British Thyroid Association, The American Association Of Endocrinologists, The American Thyroid Association and the National Cancer Centre Network, debate regarding the management of differentiated thyroid cancer continues. This is because of the absence of good quality research evidence as a consequence of the natural history of this disease.     

Comparison of the influence of thyroglobulin antibodies on serum thyroglobulin values from two different immunoassays in post surgical differentiated thyroid carcinoma patients

Measurement of serum thyroglobulin (Tg) is a highly specific test in the management of patients with differentiated thyroid cancer (DTC) after surgical treatment. The aim of our study was to evaluate and compare Tg levels in these patients found by radioimmunoassay (RIA) and immunoradiometric assay (IRMA) and to assess the influence of Tg antibodies (TgAbs) on the values obtained for Tg concentration. Both Tg and TgAb were determined postoperatively in the serum of 71 DTC patients using RIA Tg‐PEG (INEP) and Tg IRMA (CIS) for Tg, together with TgAb (CIS) for circulating endogenous anti‐TgAbs. The obtained concentrations were evaluated statistically. We found a significant difference of Tg concentrations between paired samples from the IRMA and RIA, although the intermethod comparison yielded satisfactory concordance of the twoassays (Spearman correlation coefficient ?0.792). Positive TgAb was found in 28.2% of the serum samples analyzed. Spearman rank correlation analysis revealed a significant negative relationship between serum TgAb and Tg level measured by IRMA (P=0.02), but not by RIA (P=0.417). On the other hand, our clinical data revealed that 1/18 and 3/18 patients with proven lymph node metastasis had Tg values below the detection limit by RIA and IRMA assay, respectively. Their sera were TgAb positive. We concluded that RIA was less prone to influence of TgAb than IRMA. As the presence of TgAbs may interfere in Tg measurement irrespective of the method selected for determination, this should be considered during the clinical management of these patients. J. Clin. Lab. Anal. 23:341–346, 2009. © 2009 Wiley‐Liss, Inc.     

甲状腺癌靶向治疗进展

甲状腺癌是头颈部常见的恶性肿瘤,也是内分泌系统中最常见的恶性肿瘤,其病理类型较多,不同类型的肿瘤在临床表现及治疗方法等方面差异较大.甲状腺癌的治疗主要采取以手术为主的综合治疗,但仍存在局限性.近年来,在晚期甲状腺癌的治疗中,靶向治疗逐渐发展,在延长患者的生存时间,改善患者的生存质量等方面发挥着重要作用.本文回顾目前靶向...     

益气养阴方配合左甲状腺素钠片对分化型甲状腺癌手术患者甲状腺功能的改善效果

目的分析益气养阴方配合左甲状腺素钠片对分化型甲状腺癌手术患者甲状腺功能的改善效果。方法纳入2016年10月至2021年1月于我院诊治的120例分化型甲状腺癌手术患者为研究对象,按照红绿双色球法将其分为对照组(n=60,左甲状腺素钠片)与试验组(n=60,益气养阴方⁺左甲状腺素钠片)。连续治疗8周后,比较两组患者治疗前、后的甲状腺功能指标、白细胞介素-6(IL-6)、β₂-微球蛋白(β₂-MG)、骨代谢指标、免疫功能指标水平及中医证候积分,统计并比较两组患者的不良反应发生情况。结果治疗后,两组的促甲状腺激素(TSH)、甲状腺球蛋白(TG)以及甲状旁腺激素(PTH)水平均降低,且试验组明显低于对照组,差异具有统计学意义(P<0.05)。治疗后,两组的中医证候积分及IL-6、β₂-MG水平均降低,且试验组低于对照组,差异具有统计学意义(P<0.05)。治疗后,两组的碱性磷酸酶(ALP)、骨钙素(BGP)、β-胶原特殊序列(β-CTX)、Ⅰ型前胶原氨基端前肽(PⅠNP)水平均升高,但试验组低于对照组,差异具有统计学意义(P<0.05)。试验组的不良反应总发生率为6.67%,明显低于对照组的26.67%,差异具有统计学意义(P<0.05)。治疗后,两组的CD3⁺、CD4⁺以及CD4⁺/CD8⁺均升高,CD8⁺均降低,且试验组优于对照组,差异具有统计学意义(P<0.05)。结论益气养阴方⁺左甲状腺素钠片用于分化型甲状腺癌术后患者中的治疗效果理想,对于甲状腺功能以及临床症状具有改善效果,有利于减轻患者的炎症反应,优化骨代谢指标水平与免疫功能,且不良反应少,临床可进一步推广应用。     

KDM2B调控FAK信号通路在卵巢癌细胞骨架排列中的作用

目的 分析组蛋白去甲基化酶(KDM2B)对卵巢癌细胞骨架排列中的调控作用,并探讨KDM2B作用的可能分子机制.方法 以人卵巢癌细胞系HO8910为研究模型,采用慢病毒pLKO.1-puro-shRNA表达系统建立KDM2B稳定敲减细胞系(KDM2B敲减组);采用KDM2B慢病毒质粒包装慢病毒,并感染上述人卵巢癌细胞,建...     

Molecular advances in medullary thyroid cancer diagnostics

Germline activating mutations in the RET proto-oncogene cause inherited medullary thyroid cancer (MTC) and the multiple endocrine neoplasia type 2 (MEN2) syndrome. Identification of a RET mutation in an individual with MEN2 allows pre-symptomatic genetic testing of other at-risk family members, and guides early intervention to prevent death and serious morbidity from MTC. Developments in the understanding of downstream RET receptor signalling pathways and how activating mutations disturb receptor function has led to insights into the possible molecular mechanisms underlying the different MEN2 phenotypes. Mutation analysis of RET in individuals with MEN2 has identified a number of different mutations, and correlation with cancer biology and clinical outcome has led to tailoring of management according to the mutation detected.     

Targeting EGFR and HER-2 receptor tyrosine kinases for cancer drug discovery and development

Conventional anticancer therapy using cytotoxic drugs lacks selectivity and is prone to toxicity and drug resistance. Anticancer therapies targeting aberrant growth factor receptor signaling are gaining interest. The erbB receptor family belongs to the type I, the receptor tyrosine kinases class, and comprises EGFR, HER-2, HER-3, and HER-4. It has been targeted for solid tumor therapy, including breast, ovarian, colon, head-and-neck, and non-small-cell lung cancers. This review summarizes structural aspects of this class of growth factor receptors, their oncogenic expression, and various pharmacological interventions including biological products and small molecules that inhibit these enzymes. We have also discussed various mutations that occur in EGFR and their consequences on anticancer therapy.     

Use of recombinant human thyroid-stimulating hormone in the management of well-differentiated thyroid cancer

Recombinant human (rh) thyroid-stimulating hormone (TSH) has changed the care of patients with well-differentiated thyroid cancer (DTC). Traditionally, thyroid hormone withdrawal has been used to increase TSH concentrations for optimising trapping and retention of radioiodine for thyroid remnant ablation and for diagnostic procedures (measurement of thyroglobulin and whole body scan) used in the follow-up of patients with DTC. The resulting hypothyroidism is, however, accompanied by substantial morbidity. rhTSH is an effective and safe alternative to thyroid hormone withdrawal for follow-up of DTC. Its ability to detect persistent or recurrent disease is similar to that of thyroid hormone withdrawal. At the present time, rhTSH is approved for diagnostic monitoring of patients with DTC as well as for pretherapeutic stimulation in low-risk patients for remnant ablation with 100 mCi ¹³¹I (in the EU). In addition, rhTSH has potential for use in facilitating the treatment of metastasis in patients with DTC and in patients with non-toxic nodular goiter; however, more clinical trials are needed to confirm its use in these situations.     

分化型甲状腺癌术后131I治疗1周后辐射相对安全距离的分析

目的探讨分化型甲状腺癌术后131I治疗1周后辐射相对安全距离。方法 149例分化型甲状腺癌（DTC）术后接受131I治疗的患者,服药1周后测定颈前甲状腺部位辐射相对安全距离,探讨1周后辐射相对安全距离与服药剂量、治疗次数的关系。分层分析第1次接受131I治疗后辐射相对安全距离与摄131I率24小时/2小时比值的关系。结果服药1周后辐射相对安全距离与服药剂量无关（P=0.12〉0.05）;而与治疗次数有关（P=0.01〈0.05）。第1次接受131I治疗的患者,1周后辐射相对安全距离与摄131I率24小时/2小时比值有关（P=0.04〈0.05）。结论分化型甲状腺癌术后131I治疗1周后辐射相对安全距离与131I治疗的次数有关,第1次治疗的患者,1周后辐射相对安全距离与甲状腺摄131I率24小时/2小时比值有关。     

Sonography in the diagnosis of cervical recurrence in patients with differentiated thyroid carcinoma.

OBJECTIVE: To determine the sensitivity of thyroglobulin (Tg), iodine scanning, and sonography in the diagnosis of cervical recurrence of thyroid cancer. METHODS: This prospective study assessed 81 patients with cervical metastases or extrathyroid invasion at first appearance who underwent clinical examination, scanning, measurement of Tg after thyroxine withdrawal, and sonography about 8 months after thyroidectomy followed by radioiodine treatment. Only patients without distant metastases and without anti-Tg antibodies were included. RESULTS: Fifty patients showed persistence of the disease in the cervical region, with only 16% of them having had a suspicion on clinical examination, 33 with Tg levels of 2 ng/mL or greater (66% sensitivity), and 29 with positive scan findings (58% sensitivity). A combination of the 2 methods detected disease in 40 (80%) of 50 patients but failed to show 20% of cases that were identified by sonography and confirmed by fine-needle aspiration. Sonography had sensitivity of 96%. Specificity values for Tg, iodine scanning, and sonography were 80.6%, 90.3%, and 87%, respectively. CONCLUSIONS: Classic follow-up methods may not detect cervical disease in some patients with differentiated thyroid carcinoma, and sonography is necessary even in patients apparently free of the disease.