Epitope mapping of a recombinant human TSH receptor extracellular domain: Identification of a predominant epitope using animal sera

The extracellular domain of the TSH receptor (TSHR-561, amino acids #78-389) was expressed as a hexa-histidine fusion protein in bacteria. The recombinant protein was purified to homogeneity and used to immunize porcine and ovine species. High titre antibodies were obtained from both species that recognized the recombinant protein in Western blot analysis but failed to interfere with the TSH radio receptor assay. An epitope library was constructed and screened with affinity purified ovine and porcine antisera and defected a number of positive clones. Sequence analysis revealed that all of the epitopes contained sequences derived from the carboxyl terminus of the recombinant immunogen. One clone defined an epitope covering 16 amino acids from the carboxyl terminus and was the common epitope found in all of the other clones. Western blot screening of a large panel of Graves' sera with recombinant TSH receptor protein identified one patient sera that also recognized linear epitopes in the TSHR-561 protein. Experimentation demonstrated that the linear epitope recognized by this human sera was identical to the sequence recognised by the animal antisera. This sequence is unique to the TSH receptor and will be useful in further studies to analyze the TSH receptor protein © 1996 Wiley-Liss, Inc.     

Hormones and health outcomes in aging men

Increasing age is a predictor of ill-health and mortality related to cardiovascular disease and to frailty, a syndrome characterized by deterioration of multiple organ systems leading to loss of physiological reserve, diminished capacity to cope with stressors, and increased risk of disability and death. As men grow older, their levels of testosterone decline while the prevalence of ill-health increases. Observational studies have linked lower testosterone levels with cardiovascular disease and mortality in middle-aged and older men. More recently, lower testosterone has been shown to predict reduced sexual activity and frailty in aging men. Additional studies are needed to determine whether lower testosterone is a biomarker or a potentially treatable risk factor for poorer health outcomes in older men. During aging, the response of the pituitary–thyroid axis alters to manifest higher thyrotropin levels. The presences of subclinical hypo- and hyper-thyroidism predict adverse cardiovascular outcomes. Newer results indicate that in euthyroid older men, differences in free thyroxine levels within the normal range predict specific health outcomes including frailty. Clarification of the roles of endogenous testosterone and thyroxine in the genesis of ill-health during male aging offers the prospect of future intervention to preserve health and well-being in this growing population.     

在2型糖尿病患者中探讨慢性肾脏病和亚临床甲减的相关性：一项病例对照研究和剂量-效应分析

目的：最新研究显示亚临床甲减(subclinical hypothyroidism,SCH)与心血管疾病的发生是正相关的。但其与慢性肾脏病(chronic kidney diseases,CKD)之间的关系尚不明确。在本研究中,我们首先进行病例对照研究,然后通过meta分析来探讨SCH和CKD之间的关系,并对TSH与CKD间进行剂量–效应分析。方法：在这项以医院为基础的病例对照研究中,我们纳入了从2011年1月至2015年12月期间在北京同仁医院就诊的3150名甲状腺功能正常的2型糖尿病患者和525名有亚临床甲减的2型糖尿病患者。所有关于SCH与CKD之间关系研究的英文文献均是在2016年1月通过MEDLINE、EMBASE和谷歌学术数据库检索获得的。研究数据采用STATA13.0软件进行meta分析,最终筛选出5项观察性研究。结果：本研究表明,与甲状腺功能正常的2型糖尿病患者相比, SCH患者更容易罹患CKD(OR 1.26;95%CI：1.05~1.52)。累积证据表明SCH和CKD(OR 1.81;95%CI：1.43~2.29)之间有显著的关联性。在TSH正常范围内,与低水平血清TSH相比,高水平血清TSH的CKD合并OR为1.68(95%CI：1.45~1.94);剂量–效应的荟萃分析显示CKD的发病风险与TSH的非线性升高相关(P=0.04);CKD发病风险与血清TSH间呈剂量–效应线性递增关系(合并OR 1.09;95%CI：1.03~1.16;TSH每升高1 mIU/L)。结论：目前证据表明,在2型糖尿病患者中, SCH可能是CKD发生的危险因素;血清TSH升高与CKD发病风险间呈非线性关系。     

甲状腺重量及血清TSH浓度对小剂量131Ⅰ治疗甲亢疗效的影响

目的:评价甲状腺重量及血清TSH浓度对小剂量131Ⅰ治疗甲状腺功能亢进症(甲亢)疗效的影响.方法:患者治疗前均行甲状腺SPECT扫描并检测血清FT3、FT4、TSH浓度;131I治疗的剂量为常规剂量的1/2～2/3.结果:①治疗前一次给药组TSH浓度为0.10±0.34mμ·L-1,重复给药组为0.04±0.10mμ·L-1,两者差异有显著性(P＜0.05);②治疗前甲状腺的重量一次给药组为51.22±26.09g,重复给药组87.34±63.69g,两者差异有显著性(P＜0.0001).结论:小剂量131Ⅰ治疗甲亢的疗效良好,多数患者能一次治愈,但对于大甲状腺患者或血清TSH浓度很低者则需多次治疗.     

50例危重患儿低甲状腺功能和高血糖效应的临床探讨

通过对87例(其中危重患儿50例,对照组37例)患儿甲状腺激素及空腹血糖测定,结果表明:50例危重患儿游离四碘甲状腺原氨酸(FT_1)、游离三碘甲状腺原氨酸(FT_3)均下降,FT_3为1.50±0.52pmol/L,与对照组比较t=4.96,P<0.01;FT_1为10.86±4.66pmol/L,与对照组比较t=6.60,P<0.01;血糖升高至7.78±3.86mmol/L,与对照组比较t=3.41,P<0.01。     

孕周与母儿血甲状腺激素含量的关系

目的：观察不同孕周与母儿血甲状腺激素的关系。方法：应用放射免疫分析法对67例中、晚期妊娠要求引产患者，10例早产及78例孕足月自然分娩患者进行了母血及胎儿脐静脉、脐动脉血中TSH、T3、T4的测定。结果：TSH值在母血及胎儿血中随着孕周的增加而增加．T3值在胎儿血中与母血中比较，显示低T3血症，T4值接近正常母体水平。结论：测定母血中的甲状腺激素，可动态观察不同孕周甲状腺激素变化，可及时发现胎儿低甲血症。     

ROC曲线在新生儿先天性甲低筛查中的应用

[目的]循证试剂盒及教材提供的参考值是否理想。[方法]采用时间分辨镧系荧光免疫（DELFIA）技术进行TSH的检测,应用ROC曲线对我省新生儿先天性甲低（CH）筛查中TSH的不同临界值进行评价。[结果]足跟血纸片TSH≥20 mU/L、TSH≥15 mU/L、TSH≥8.2 mU/L的不同临界值,其诊断新生儿CH的敏感度分别为92.1%、100%、100%;特异度分别为91.9%、86.2%、14.1%;阳性预测值分别为54.0%、42.9%、10.8%;阴性预测值分别为99.1%、100%、100%;假阳性率分别为8.1%、13.8%、85.9%;假阴性率分别为8.0%、0.0%、0.0%;预测准确性分别为91.9%、87.5%、22.2%;复检阳性预测值分别为100%、97%。[结论]应用ROC曲线确立我省新生儿CH筛查的阳性召回参考值为TSH≥15 mU/L;CH阳性（诊断）切值是TSH≥20 mU/L;CH随访观察区为TSH 8.2-14.9 mU/L。     

Screening for congenital hypothyroidism in Hong Kong

A pilot cord blood TSH screening program for congenital hypothyroidism was commenced in Hong Kong in April 1982. By April 1984, 14 411 neonates born in two hospitals were screened for this disorder. Five cases of primary hypothyroidism and two cases of transient hypothyroidism were detected. The detection of cases of congenital hypothyroidism with only moderately elevated cord blood TSH values means that the recall rate will remain high.