Immunoradiometric assay of thyrotropin as a "first-line" thyroid-function test in the routine laboratory

We compared the utility of a sensitive immunoradiometric assay for serum thyrotropin as a "first-line" thyroid-function test with a strategy based on first measuring total thyroxin in serum. The immunoradiometric assay appears to distinguish primary hypothyroidism and hyperthyroidism from euthyroidism in "new" patients. The role of this test in monitoring antithyroid treatment or thyroxin-replacement therapy is not yet established, there being particular difficulty in interpreting low thyrotropin concentrations in such patients. Nevertheless, because a normal thyrotropin concentration in most, if not all, situations signifies the euthyroid state, thyrotropin determination by immunoradiometric assay merits consideration as an initial test by laboratories performing thyroid-function tests.     

Immunoradiometric assay of serum thyroid stimulating hormone (TSH) as a first-line test in a mixed hospital population

An immunoradiometric assay of thyroid stimulating hormone (TSH-IRMA) was evaluated as a first-line test for the diagnosis of thyroid disease in a prospective study of 318 consecutive patients in a major city hospital. The results of TSH-IRMA were compared with the diagnoses made by means of our usual diagnostic methods. Based on previous studies a serum TSH level of 0.15 mU/l was chosen as cutoff limit for calculation of diagnostic performance. For patients with serum TSH greater than 5.0 mU/l the results of TSH-IRMA were in accordance with the results of our routine radioimmunoassay. Patients with serum TSH levels between 0.15 mU/l and 5.0 mU/l were euthyroid (the diagnostic sensitivity was 100%). Consequently, the final diagnosis could be made with one test and within two days for 88% of patients. Patients with serum TSH less than 0.15 mU/l needed supplementary tests since only 32% of these patients had thyrotoxicosis, 32% had a non-toxic goiter, and 36% had no thyroid disease.     

血清TT3、FT3、TT4、FT4以及TSH检测意义

目的探讨TT3、FT3、TT4、FT4以及TSH在甲状腺疾病患者中检测的价值;总结分析各指标变化情况。方法收集分析本院200例甲状腺疾病患者,并选取健康者50例作为对照组。用化学发光分析法检测各组甲状腺功能,并对各组各指标的检测值进行比较。结果甲亢组T3、T4、FT3、FT4均高于健康对照组,甲减组T3、T4、FT3、FT4均低于健康对照组。TSH含量甲亢组低于健康对照组,甲减组明显高于健康对照组。与健康对照组比较其差异均有统计学意义。甲亢组FT3诊断符合率为96%,TSH为96%,T3为92%,FT4为90%,T4为88%。甲减组TSH诊断符合率为100%,FT4为93%,T4为90%,FT3为77%,T3为70%。结论 FT3、T3、TSH在甲亢诊断中有临床意义;FT4、T4、TSH在甲减诊断中有临床意义。     

非酒精肝硬化肝性脑病患者血清FT3、FT4、TSH的化学发光分析

目的通过检测非酒精肝硬化肝性脑病患者游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)、血清促甲状腺素(TSH)的水平变化,探讨血清甲状腺素在非酒精肝硬化肝性脑病中的临床意义。方法筛选非酒精肝硬化肝性脑病患者60例(实验组)和健康体检者40例(对照组),抽取所有参与者的空腹静脉血,采用化学发光法检测血清FT3、FT4、TSH的水平。结果实验组非酒精性肝硬化肝性脑病患者FT3、FT4和TSH 3者的含量均低于对照组(P<0.01)。B级组在FT3、FT4和TSH 3者的含量明显高于C级组患者(P<0.05)。甲状腺素含量随着肝硬化级别的升高逐渐减少。非酒精性肝硬化肝性脑病患者Child-Pugh分级越高,其死亡率越高,预后越差。结论血清FT3、FT4、TSH水平的变化与肝硬化Child-Pugh分级存在密切相关,检测这些指标对判断病情、估计预后有重要的参考价值。     

电化学发光免疫法检测TSH、T3、T4、FT3、FT4相关性观察

目的观察电化学发光免疫检测血清TSH、T3、T4、FT3、FT4之间相关性。方法对134例临床标本同时进行TSH、T3、T4、FT、3、FT4电化学发光免疫法检测,并对此五项指标间相关性进行统计学分析。结果TSH／T3、TSH／T4、TSH／FT3、TSH／FT4、T3／FT4、FT3／T4之间具有直线相关关系,相关系数分别为:0.362,0.324,0.404,0.335,0.907,0.819,0.808,0.839,0.839,0.955。结论T3／T4、FT3／FT4之间相关系数大,r2>0.8,具有一定的医学意义。     

游离甲状腺素/促甲状腺素比值作为甲状腺功能评价指标的研究

目的　探索甲状腺功能紊乱者最适实验室诊断指标。方法　采用化学发光免疫技术(CLIA)测定不同人群中三碘甲状腺原氨酸 (TT3 )、甲状腺素 (TT4)、促甲状腺素 (TSH)、游离三碘甲状腺原氨酸 (FT3 )、游离甲状腺素 (FT4)浓度 ,比较受试者工作特征曲线 (ROC)下面积及频数分布散点图分离效果。结果　甲减诊断ROC值TSH :0 94± 0 0 2 ,FT3 :0 70± 0 0 7,FT4:0 92± 0 0 4 ,FT4/TSH比值 :0 95± 0 0 2 ;甲亢诊断ROC值分别为 0 86± 0 0 5 ,0 82± 0 0 3,0 83± 0 0 6 ,0 90± 0 0 5。从频数分布散点图显示 ,FT4/TSH的分离效率甲减 93% ,甲亢 85 %。结论　CLIA法测定FT4/TSH比值显示出最佳的性能与分离效果 ,可提高甲状腺功能的诊断效率 ,FT4/TSH比值应被推荐为甲状腺功能评价的首选指标。     

Serum concentration of T3, T4, FT3, FT4, TSH during cycloergometer muscular exercise

The serum concentrations of total and free thyroid hormones and of TSH have been determined in 10 trained subjects before, during and after exercise on a bicycle ergometer. The concentrations of T4 and FT4 increase during the muscular exercise and reduce 30 minutes after the end of work; the decrease is statistically meaningful for the T4. The concentrations of TSH and T3 reduce 30 minutes after the end of work on a bicycle ergometer. The serum concentration of FT3 and of hematocrit doesn't presents any statistically meaningful variation during and after the muscular exercise. The results achieved in our work are in support of the hypothesis that the physic and intense exercise would involve the thyroid gland exalting its activity.     

Reference range of thyroid function (FT3, FT4 and TSH) among Indian adults

ObjectivesTo generate thyroid hormone reference norms using electro-chemiluminescence technique.Design and methodsCross sectional study on apparently normal 4349 Delhi adults (18–86 years). Predetermined exclusion criteria (goiter, hypoechogenicity or nodularity on ultrasound, elevated anti-thyroid peroxidase antibody, hypo or hyperthyroidism and family history of thyroid dysfunction) excluded 2433 subjects leaving 1916 (916 males and 1000 females) as the reference population.ResultsMean age and BMI of the reference population were 41.2 ± 18.1 years and 24.5 ± 4.4 kg/m² respectively. Median urinary iodine excretion was 233.6 μg/L (79–458;3rd–97th centile). The population was categorized into various age groups (18–30, 31–40, 41–50, 51–60, 61–70 and ≥ 70 years). Overall FT3 and FT4 values in the reference population irrespective of age, ranged from 2.4–8.8 (mean 4.6 ± 0.9) pmol/L and 10.1–24.8 (mean 15.40 ± 2.0) pmol/L, respectively. Mean TSH value in the reference population was 2.2 ± 0.9 mIU/L which was significantly lower than that of total population (3.8 ± 6.1; p < 0.001).ConclusionFT3 values were observed to be significantly higher in men than women (p = 0.001). The centiles (3rd, 5th, 10th, 25th, 50th, 75th, 90th, 95th and 97th) of FT3, FT4 and TSH were derived for reference purposes in Indian adults. This community based study in Indian adults has established mean reference intervals for FT3, FT4 and TSH for different age groups for both sexes separately using strict exclusion criteria. These can be used as reference norms for Indian adults.     

滨州高碘区健康人群FT3、FT4、TSH、TPOAb的参考区间探讨

目的：以我院查体中心检测过的健康人群的FT3、FT4、TSH和TPOAb的检验结果为例,探讨建立滨州高碘地区相关检测项目的参考区间。方法：按照CLSI文件C28-P3《医学实验室参考区间的定义、建立和确认》中的推荐方法,参考ISO15189：2003（E）《医学实验室—质量和能力的专用要求》条款要求,先引用权威书刊、厂家试剂说明书或转移其他医院实验室的生物参考区间,然后进行实验验证,验证不通过的项目,收集480例健康参考个体自建适用于本实验室的生物参考区间,定期进行临床评审。结果：FT3、FT4、TSH现用生物参考区间验证通过,可以继续使用：TPOAb验证不通过,不适用,须自建生物参考区间,自建区间为0-36IU／ml。结论：采用本研究方法确立本地区健康人群FT3、FT4、TSH和TPOAb的参考区间,从多途径保证检验指标的生物参考区间可靠、准确、科学、实用。能确保相关参考区间符合临床要求,值得推广应用。     

FT3、FT4、TSH与T3、T4联检评价甲状腺功能及意义

目的探讨甲状腺功能亢进、甲状腺功能减退患者血清中FT3、FT4、TSH与T3、T4水平的变化,以及在评价甲状腺功能中各项指标的诊断符合率及其临床意义。方法应用化学发光免疫分析法测定60例甲状腺功能亢进患者和10例甲状腺功能减退患者血清中的FT3、FT4、TSH与T3、T4的含量,并与50例健康人作对照进行比较。结果疾病组与健康对照组T3、T4、FT3、FT4、TSH血清测定结果比较,差异有统计学意义（P〈0．05）;疾病组与健康对照组T3、T4、FT3、FT4、TSH的诊断符合率比较,差异无统计学意义（P〉0．05）。结论FT3、FT4、TSH与T3、T4联检评价甲状腺功能,对于甲状腺疾病的早期诊断、鉴别诊断及预后判断有着非常重要的临床意义;对临床医生合理用药,提高甲状腺疾病的治愈率和好转率有着科学的指导意义。     

Value of free thyroxine (FT4), free triiodothyronine (FT3), and sensitive thyrotropin (TSH) assay in the assessment of optimal thyroxine therapy

We describe a sensitive thyrotropin (TSH) assay in the evaluation of thyroxine replacement therapy. Patients taking varying amounts of L-thyroxine replacement doses were studied using a thyrotropin-releasing hormone (TRH) test and a sensitive TSH assay as the indices of optimal replacement therapy. There were no differences in the mean thyroxine doses of those patients who had a normal TRH response and those who had a flat response. Similarly there were no significant differences in the serum free thyroxine (FT4), free triiodothyronine (FT3), or total triiodothyronine (TT3) levels between these two groups. The patients in both groups had normal basal serum TSH values as measured by a standard, HTSH RIABEAD (Abbott) method. However, serum TSH values, as measured by a sensitive TSH3 MAIACLONE (Serono) immunoradiometric method, were subnormal in all patients with flat TRH responses. The TSH (Serono) assay provided the best single blood test of optimal thyroxine replacement.     

A new TSH assay. Just another technique or a useful test?

The immunoradiometric assay is a sensitive test for diagnosing thyroid dysfunction. It permits greater accuracy by measuring response of thyrotropin-producing cells of the pituitary to thyroxine (T4) as opposed to comparing circulating T4 to a range of values from healthy controls. The assay allows improved precision in establishing replacement and suppressive doses of hormone for thyroid disease.     

Comprehensive study of a thyroxin-analog-based assay for free thyroxin ("Amerlex FT4")

The basic theory of thyroxin-analog-based radioimmunoassays for free thyroxin has been extended to evaluate definitively the effects arising from residual binding of the tracer analog to serum proteins. Using experimentally determined binding constants and computer simulation techniques, we studied the effects of thyroxin-analog binding to serum proteins on results of Amerlex FT4 radioimmunoassay, using this improved mathematical model. Results from computer-simulation studies were compared both directly with in vitro experimental results and indirectly with clinical studies. Agreement was good among all three approaches. The relatively weak binding of analog to thyroxin-binding globulin and prealbumin does not significantly perturb Amerlex FT4 assay results. Binding of the analog by albumin has a small but quantifiable effect on assay results, amounting to an intrinsic bias of 0.08 pmol of free thyroxin per liter per gram of albumin per liter for euthyroid serum samples. This bias is unlikely to be important for most clinical laboratory samples, but it may be significant when one is interpreting results for those rare patients with genetic albumin abnormalities such as analbuminemia or familial dysalbuminemic hyperthyroxinemia. Massively increased concentrations of nonesterified fatty acids (e.g., after treatment with heparin) will lead to a spurious increase in free thyroxin in this and most other techniques, including equilibrium dialysis.     

血清FT3/FT4比值对伴新月体形成慢性肾脏病患者的预后价值

目的：肾活检中新月体存在和数量是重要的预后指标，甲状腺功能可能与伴新月体形成的CKD患者的危险分层有关。方法：本研究采用回顾性队列研究的方法，调查了单中心119例患者的FT3/FT4比值与发生eGFR下降50%、需要肾脏替代治疗或死亡终点事件的关联。共纳入2012年3月至2014年5月期间经病理确诊为合并新月体形成的慢性肾小球疾病患者119例。根据FT3/FT4比值的中位数（0.271）分为低水平组和高水平组。结果：在单因素分析中，与FT3/FT4高水平组相比，FT3/FT4低水平组的复合终点的风险显著增加。构建不同的多因素Cox回归模型，FT3/FT4低水平组与FT3/FT4高水平组相比，仍与复合终点发生率显著相关（分别为P=0.005，HR=6.086 [95% CI 1.719至21.552]；P=0.006，HR=6.368 [95% CI 1.712至23.684]；P=0.016，HR=4.835 [95% CI 1.349至17.321]）。结论：本研究结果提示FT3/FT4比值是伴新月体形成CKD患者的新型预后因素，可能对治疗方案的制定和调整具有重要意义。     

Evaluation of the usefulness of a sensitive immunoradiometric assay for thyroid stimulating hormone as a first-line thyroid function test in an unselected patient population

A new sensitive immunoradiometric assay for serum thyroid stimulating hormone (TSH) was applied to 1627 consecutive patients from four large clinics at Malm? General Hospital, in whom a thyroid function disorder was suspected. The final diagnoses were taken from the patients' charts at a follow-up 1-2 years after the primary evaluation. If only those patients without thyroid disease were used as a reference population, the 5th percentile was 0.8 mIU/l. When this cutoff limit was applied to the unselected patient population, the TSH assay had a high sensitivity for the diagnosis of hyperthyroidism (96%), a lower specificity (64%) and a very low predictive value (10%). Therefore, in the majority of the patients (72%) the sensitive TSH assay cannot be used alone to define thyroid function.     

Evaluation of a radioreceptor assay for TSH receptor autoantibodies

A commercial radioreceptor assay for TSH receptor autoantibodies (TRAb), based on solubilized porcine receptor and purified radio-iodinated bovine TSH, was tested in 264 subjects with a variety of thyroid disorders. The sensitivity of the assay for the detection of hyperthyroid Graves' disease was 91%. The assay specificity for Graves' disease was 95%. With the exception of one patient with Hashimoto's disease and one patient with de Quervain's subacute thyroiditis no subjects other than Graves' patients had detectable TRAb. Thus purely blocking TSH receptor autoantibodies were not detected with the assay. One female with thyroxine-treated idiopathic primary hypothyroidism who had given birth to two children with transiently elevated TSH, was found to have a circulating TSH-binding substance that resulted in an abnormally negative TRAb value, and highly discrepant results when TSH was measured with a double antibody TSH radioimmunoassay and an immunoradiometric assay. The TSH-binding substance was precipitated like a protein, but was not IgG. Similar findings have not previously been reported.     

Fructosamine Test-Plus, a modified fructosamine assay evaluated

We have evaluated Fructosamine Test-Plus, a commercial fructosamine assay based on the reduction of nitro-blue tetrazolium dye in alkaline buffer (Clin Chem 1985;31:1550-4), modified by including a detergent and uricase in the reagent, by changing the concentrations of buffer and dye, and by changing the approach to primary calibration. Specimens were from 2321 participants in a health screening survey in a local workforce. Compared with the original fructosamine method, the Fructosamine Test-Plus method was less affected by protein concentration in the sample and less subject to interference from hyperlipidemia. The changes have also extended the linearity of the assay in the pathological range. However, as a screening method for diabetes mellitus in a population with a disease prevalence of 2.28%, the performance of Fructosamine Test-Plus was similar to the original assay.