Reference intervals from birth to adulthood for serum thyroxine (T4), triiodothyronine (T3), free T3, free T4, thyroxine binding globulin (TBG) and thyrotropin (TSH).

Disorders in thyroid function can impair normal development in children. Therefore it was our aim to establish reference intervals for serum triiodothyronine (T3), free T3 (fT3), thyroxine (T4), free T4 (fT4), thyroxine binding globulin (TBG) and thyrotropin (TSH) which are applicable from birth to adulthood by using the non-isotopic automated chemiluminescence immunoassay system, Immulite (DPC Los Angeles, USA). Serum samples from 762 euthyroid newborns, children and adolescents (369 female, 393 male; age 1 day to 19 years) were examined; of these, 381 were classified as pubertal. Due to non-normal distribution, the 2.5th, 50th and 97.5th percentiles (the central 95% interval) were calculated for each group. The median concentrations of T4, fT4 and TSH were up to 3.2-fold higher during the first 2 weeks, while T4 increased during the first month of life. The concentrations in all age groups showed no sex differences. From 1 year onwards, the concentration of all parameters tended to decrease until adult age, with the exception of TBG which increased by >60% (p<0.02) and reached a maximum at approximately 5 years of age. The findings underscore the fact that thyroid hormones are not associated with sexual development, except for TBG, which decreased slightly (p<0.04) between Tanner stages 1 and 5. However, the reference intervals established here demonstrate that marked changes occur in concentrations of thyroid hormones after the neonatal period. Our findings complement these of earlier studies. The developed reference intervals can be used to assess the thyroid status of patients, particularly if the measurements are done on the Immulite/Immulite 2000 system.     

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.     

The effect of thyroid antibody positivity on reference intervals for thyroid stimulating hormone (TSH) and free thyroxine (FT4) in an aged population.

Our aims were: 1) to analyze the effect of the methodology used to derive clinically feasible cut-off values for thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb), which exhibit highly skewed distributions; and 2) to describe the influence of thyroid antibodies on thyroid stimulating hormone (TSH) and free thyroxine (FT4) reference intervals among thyroid disease-free aged subjects. The reference population consisted of 1086 individuals with a mean age of 73 years. The impacts of TPOAb and/or TgAb positivity on the reference intervals of TSH and FT4 were evaluated by both including and excluding subjects with elevated thyroid antibodies. The exclusion of subjects with elevated thyroid antibodies had no effect on the FT4 reference interval in either gender or on the TSH reference interval in men. Among women, the exclusion of 196 (34%) thyroid antibody-positive subjects resulted in lowering of the upper reference limit of TSH from 7.2 to 5.8 mIU/L. When the more stringent "mode-method" by summing mode+(mode-2.5th percentile) was used, 334 women (58%) were excluded and the upper reference limit of TSH remained essentially identical. Regardless of the statistical methodology used to derive cut-off values, the effect of antibody positivity was found to be less than expected.     

Evaluation of a new enzyme immunoassay system for free thyroxine (Enzymun-Test FT4)

Free thyroxine (FT4) represents the metabolically active fraction of the circulating thyroid hormone thyroxine (T4). In this paper the results of the evaluation of a newly developed FT4 assay are reported. This assay system is based on an enzyme-labelled one-step immunoassay. The within-run imprecision, checked using serum pools and several commercial reference materials, showed a coefficient of variation (CV) of between 0.8 and 9.8%, depending on the reference material used. The between-run imprecision showed a CV of between 1.0 and 13.2%. Accuracy experiments yielded values between 80 and 116%. When the new FT4 was compared with the calculation of an index for free thyroxine (FT4I; derived from either the ratio of T4/thyroxine binding coefficient of from T4/thyroxine binding globulin) in a number of samples in the hypo-, eu- and hyperthyroid range, a good correlation was obtained. The same was true when the new FT4 assay was compared with a widely used two-step radioimmunoassay (y = -0.146 + 0.943 x). In euthyroid subjects the measured FT4 concentration was 10.3-25.8 pmol/l. No effect was evident when the influence of EDTA and citrate was investigated, whereas addition of heparin led to an increase in FT4 concentration of about 12 to 15%. Investigation of the possible influence of a large number of drugs showed that probenezid, carbamazepine and furosemide led to an increase in the measured FT4 concentration. Dialysis increased the FT4 concentration, as measured in patients before and after haemodialysis. No effect of alteration in protein concentration and/or protein distribution of FT4 concentration could be detected. In pregnancy, FT4 values were within the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of 3 different methods for determining triiodothyronine (T-3) and thyroxine (T-4)

The authors compare three methodologies based on the immunology (RIA, FPIA, LIA) in the determination of two important parameters of the so-called thyroid outline: triiodothyronine (T-3) and thyroxine (T-4). The correlations between the analytic systems examined are presented and discussed.     

Comparison of FT4 with log TSH on the Abbott Architect ci8200: Pediatric reference intervals for free thyroxine and thyroid-stimulating hormone

BackgroundWe evaluated the clinical validity of serum FT4 measurements by assessing its correlation with log TSH. To provide pediatric reference intervals (representative ranges) for FT4, and TSH on the Architect ci8200 integrated system.MethodsThis population-based study encompassed 6023 children (3369 females and 2654 males). The percentile and Hoffmann approaches for obtaining reference intervals on these analytes were also compared.ResultsFT4 correlation with log TSH was poor ( r = 0.010 for males and 0.050 for females). Reference intervals were established. TSH and FT4 did not show a significant sex difference; moreover, the intervals decreased with age for FT4 and TSH.ConclusionsWhereas in a previous study ultrafiltration tandem mass spectrometry yielded a correlation of r = 0.90 for FT4 vs. log TSH this present study reveals a poor FT4 vs. log TSH correlation in the pediatric population studied and indicates the FT4 immunoassay conducted on the Abbott Architect ci8200 is less useful clinically than might have been expected. Reference intervals using the Hoffmann approach for pediatric in- and out-patients compare well with previously published results utilizing the percentile approach.     

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。     

Predictive values of thyroxine, thyrotropin, and triiodothyronine concentrations in serum.

The predictive values of total thyroxine, thyrotropin, and total triiodothyronine concentrations in serum for clinically apparent and subclinical hypothyroidism and hyperthyroidism were determined by retrospective analysis of clinical cases chosen from the frequency distributions of hormone test results. Very low total thyroxine concentrations, less than 25 microgram/L, were specific for hypothyroidism. Most subclinical hypothyroid cases had intermediate or low total thyroxine concentrations, 35-60 microgram/L, with moderately increased thyrotropin concentrations, greater than 12 milli-int. units/L. Thyrotropin cut-off concentrations were identified that had predictive values greater than 90% for classifying untreated and hormone-treated hypothyroid cases. Above-normal total thyroxine concentrations, regardless of absolute value, were not specific for hyperthyroidism, because binding-protein alterations related to estrogen taking were prevalent and produced occasional marked increases in serum total thyroxine. Nevertheless, cut-off concentrations for serum total thyroxine and total triiodothyronine were identified that had a predictive value greater than 90% for hyperthyroidism, without necessitating measurement of the capacities or concentrations of hormone-binding proteins.     

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。     

Effect of thyroid-suppressive doses of triiodothyronine on thyroxine turnover and on the free thyroxine fraction

The relationship between free thyroxine concentration and thyroxine turnover was studied during thyroid suppression with triiodothyronine. Although there was some increase in the proportion of serum thyroxine bound to thyroxine-binding globulin, the ratio of ultrafilterable to protein-bound hormone was not significantly affected. The fractional disappearance rate of thyroxine increased from an average control value of 11.47%/day to 14.72%/day. Because of contraction of the thyroxine distribution space the clearance of thyroxine was less markedly affected, increasing from 1.37 to 1.56 liters/day. Since the ratio of thyroxine turnover to free thyroxine concentration, i.e., the free thyroxine clearance, increased proportionately (4.79-5.55 liters x 10(3)/day) we conclude that triiodothyronine stimulates thyroxine clearance by a mechanism that is independent of effects on free thyroxine concentration.     

Unforeseen effect of thyroxine binding globulin when using the microencapsulated antibody method to determine free thyroxine (FT4): misleading results due to circulating unsaturated thyroxine binding globulin

The effect of varying concentrations (0-52 mg/l) of purified thyroxine binding globulin (TBG) on the microencapsulated antibody method for free thyroxine was investigated. The results demonstrated that the free thyroxine values were strongly influenced by the concentration of thyroxine binding globulin in the samples. The standard curve could no longer be distinguished at a concentration of purified thyroxine binding globulin of 52 mg/l. In the clinical application, we observed that the values obtained using the microencapsulated antibody method were significantly higher than the expected values in patients receiving triiodothyronine treatment after total thyroidectomy (theoretically nil) and in patients with untreated primary hypothyroidism with negligible thyroxine (less than 12.9 nmol/l). These false positive values are considered to be due to the methodological problem mentioned above, i.e. the microcapsule membrane is not efficient and therefore must be improved. Consequently, any data based on this method should be interpreted with caution.     

A novel method of transport for thyroxine (T4), cortisol, thyroid stimulating hormone (TSH), parathormone (PTH), and insulin

A simple and convenient method of transport of serum in the form of protein disc on water resistant medium is described. The method was used to study the stability of thyroxine (T4), cortisol, thyroid stimulating hormone (TSH), parathormone (PTH) and insulin. The mean recoveries of these hormones were between 98 and 100%. The standard deviations of duplicates of assays for protein disc samples were comparable to that of serum samples except in assays using enzyme immunoassay techniques. The correlation coefficients of the results between the serum and protein disc samples were satisfactory ranging from 0.86-0.99. The proposed method could be used for interlaboratory referral of serum.     

Specificity of sensitive assays of thyrotropin (TSH) used to screen for thyroid disease in hospitalized patients

Thyrotropin (TSH) concentrations were measured in 1580 hospitalized patients and 109 normal persons. Using the mean +/- 3 SD limits of the log values for the controls (0.35-6.7 milli-int. units/L), the proportion of abnormal TSH results in the hospitalized patients was 17.2%. TSH was undetectable (less than 0.1 milli-int. unit/L) in 3.1% of patients, suggesting hyperthyroidism, and high (greater than 20 milli-int. units/L) in 1.6%, suggesting hypothyroidism. On follow-up of 329 patients, 62% with abnormal TSH (less than 0.35 or greater than 6.7 milli-int. units/L) and 38% with normal TSH concentrations, only 24% of those with undetectable TSH had thyroid disease: 36% of them were being treated with glucocorticoids and 40% had nonthyroidal illness (NTI). Although half the patients with TSH greater than 20 milli-int. units/L had thyroid disease, 45% of patients had high TSH values associated with NTI. TSH concentrations usually returned towards normal when patients' therapy with glucocorticoids was discontinued or they recovered from NTI. TSH test sensitivity appeared good when the mean +/- 3 SD limits of the reference population were used, i.e., no cases of hyper- or hypothyroidism, as identified by free thyroxin index (FT4I), were missed. However, TSH test specificity was inferior to that of the FT4I test (90.7% vs 92.3%), although specificity could be improved to 97.0% if the wider TSH reference limits of 0.1 to 20 milli-int. units/L were used--limits considered pathological if applied to outpatients. Evidently, different reference intervals for TSH are needed for hospitalized and nonhospitalized patients. We conclude that a "sensitive TSH assay" is not a cost-effective thyroid screening test for hospitalized patients as compared with the FT4I.