Reference Intervals For Free Thyroxine Research Articles

Routine free thyroxine reference intervals are suboptimal for monitoring children on thyroxine replacement therapy and target intervals need to be assay-specific

Central hypothyroidism is a condition where there is (qualitatively or quantitatively) TSH deficiency, leading to reduced thyroid hormone production. In such patients, serum TSH does not accurately reflect the adequacy of thyroxine replacement, as the log-linear relationship between thyrotropin (TSH) and free thyroxine (FT4) is lost. We aimed to prospectively determine the optimal physiological FT4 treatment range for children treated for primary hypothyroidism, based on their serum TSH concentrations. This information could be used to guide optimal therapy for all children on thyroxine replacement, including those with central hypothyroidism. In total, sixty children (median age: 11 years, range: 11 months to 18 years) were recruited over 21 months. They were prescribed a stable dose of thyroxine for at least 6–8 weeks prior to a thyroid function test that consisted of serum TSH, FT4 and free triiodothyronine (FT3) measurements. The serum sample for the thyroid function tests was collected before ingestion of the daily dose, i.e. the trough concentration, and measured using Beckman Coulter UniCel DxI 800 instrument, Siemens Advia Centaur, Roche Cobas, Abbott Architect, Ortho Clinical Diagnostics Vitros 5600 (Ortho-Clinical Diagnostics, Raritan, NJ) platforms. The FT4 and FT3 reference intervals showed significant inter-method difference. The lower limit of the FT4 reference intervals were generally shifted mildly higher when the TSH concentration of the children were restricted from 0.5–5.0 mIU/L to 0.5–2.5 mIU/L. By contrast, the upper limit of the FT3 and FT4 reference intervals were relatively stable for the different TSH concentrations. Assay-specific target ranges for optimal thyroxine therapy are required until FT4 assay standardisation is realised.

Pediatric Reference Intervals for Free Thyroxine and Free Triiodothyronine by Equilibrium Dialysis-Liquid Chromatography-Tandem Mass Spectrometry.

Objective:Thyroid hormone concentrations fluctuate during growth and development. To accurately diagnose thyroid disease in pediatric patients, reference intervals (RIs) should be established with appropriate age groups from an adequate number of healthy subjects using the most exact methods possible. Obtaining statistically useful numbers of healthy patients is particularly challenging for pediatric populations. The objective of this study was to determine non-parametric RIs for free thyroxine (fT4) and free triiodothyronine (fT3) using equilibrium dialysis-high performance liquid chromatography-tandem mass spectrometry with over 2200 healthy children 6 months-17 years of age.Methods:Subjects were negative for both thyroglobulin and thyroid peroxidase autoantibodies and had normal thyrotropin concentrations. The study included 2213 children (1129 boys and 1084 girls), with at least 120 subjects (average of 125) from each year of life, except for the 6 month to 1 year age group (n=96).Results:Non-parametric RIs (95th percentile) for fT4 were: 18.0-34.7 pmol/L (boys and girls, 6 months-6 years) and 14.2-25.7 pmol/L (boys and girls, 7-17 years). RIs for fT3 were: 5.8-13.1 pmol/L (girls, 6 months-6 years); 5.7-11.8 pmol/L (boys, 6 months-6 years); 5.7-10.0 pmol/L (boys and girls, 7-12 years); 4.5-8.6 pmol/L (girls, 13-17 years); and 5.2-9.4 pmol/L (boys, 13-17 years).Conclusion:Numerous significant differences were observed between pediatric age groups and previously established adult ranges. This emphasizes the need for well-characterized RIs for thyroid hormones in the pediatric population.

Gestation specific reference intervals for thyroid function tests in pregnancy.

Thyroid function tests are frequently assessed during pregnancy to evaluate thyroid dysfunction or to monitor pre-existing thyroid disease. However, using non-pregnant reference intervals can lead to misclassification. International guidelines recommended that institutions should calculate their own pregnancy-specific reference intervals for free thyroxine (FT4), free triiodothyronine (FT3) and thyroid-stimulating hormone (TSH). The objective of this study is to establish gestation-specific reference intervals (GRIs) for thyroid function tests in pregnant Turkish women and to compare these with the age-matched non-pregnant women. Serum samples were collected from 220 non-pregnant women (age: 18-48), and 2460 pregnant women (age: 18-45) with 945 (39%) in the first trimester, 1120 (45%) in the second trimester, and 395 (16%) in the third trimester. TSH, FT4 and FT3 were measured using the Abbott Architect i2000SR analyzer. GRIs of TSH, FT4 and FT3 for first trimester pregnancies were 0.49-2.33 mIU/L, 10.30-18.11 pmol/L and 3.80-5.81 pmol/L, respectively. GRIs for second trimester pregnancies were 0.51-3.44 mIU/L, 10.30-18.15 pmol/L and 3.69-5.90 pmol/L. GRIs for third trimester pregnancies were 0.58-4.31 mIU/L, 10.30-17.89 pmol/L and 3.67-5.81 pmol/L. GRIs for TSH, FT4 and FT3 were different from non-pregnant normal reference intervals. TSH levels showed an increasing trend from the first trimester to the third trimester, whereas both FT4 and FT3 levels were uniform throughout gestation. GRIs may help in the diagnosis and appropriate management of thyroid dysfunction during pregnancy which will prevent both maternal and fetal complications.

Establishment of trimester-specific thyroid stimulating hormone and free thyroxine reference interval in pregnant Chinese women using the Beckman Coulter UniCel™ DxI 600.

Thyroid-stimulating hormone (TSH) and free thyroxine (FT4) reference intervals are essential for screening and diagnosing thyroid dysfunction during pregnancy. The aim of this study was to establish method- and trimester-specific TSH and FT4 reference intervals in pregnant Chinese women using the Beckman Coulter UniCel™ DxI 600. A cross-sectional dataset analysis was performed. A total of 3507 participants were recruited, and 2743 were eligible for analysis to set reference intervals. TSH, FT4, and thyroid peroxidase antibody (TPOAb) levels were analyzed with the Beckman Coulter UniCel™ DxI 600 Access® immunoassay system. Ranges between the 2.5th and 97.5th percentiles were defined as reference intervals for TSH and FT4. The calculated reference intervals for the first, second, and third trimesters were TSH: 0.06-3.13, 0.07-4.13 and 0.15-5.02 mIU/L, respectively, and FT4: 8.72-15.22, 7.10-13.55 and 6.16-12.03 pmol/L, respectively. Our reference intervals for TSH and FT4 are distinct from the ranges reported in the DxI 600 instruction manual and previously reported data, confirming the importance of method-specific reference intervals.

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

Background We 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. Methods This 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. Results FT4 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. Conclusions Whereas 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.

Pediatric Reference Intervals for Free Thyroxine and Free Triiodothyronine

The clinical value of free thyroxine (FT(4)) and free triiodothyronine (FT(3)) analysis depends on the reference intervals with which they are compared. We determined age- and sex-specific reference intervals for neonates, infants, and children 0-18 years of age for FT(4) and FT(3) using tandem mass spectrometry. Reference intervals were calculated for serum FT(4) (n = 1426) and FT(3) (n = 1107) obtained from healthy children between January 1, 2008, and June 30, 2008, from Children's National Medical Center and Georgetown University Medical Center Bioanalytical Core Laboratory, Washington, DC. Serum samples were analyzed using isotope dilution liquid chromatography tandem mass spectrometry (LC/MS/MS) with deuterium-labeled internal standards. FT(4) reference intervals were very similar for males and females of all ages and ranged between 1.3 and 2.4 ng/dL for children 1 to 18 years old. FT(4) reference intervals for 1- to 12-month-old infants were 1.3-2.8 ng/dL. These 2.5 to 97.5 percentile intervals were much tighter than reference intervals obtained using immunoassay platforms 0.48-2.78 ng/dL for males and 0.85-2.09 ng/dL for females. Similarly, FT(3) intervals were consistent and similar for males and females and for all ages, ranging between 1.5 pg/mL and approximately 6.0 pg/mL for children 1 month of age to 18 years old. This is the first study to provide pediatric reference intervals of FT(4) and FT(3) for children from birth to 18 years of age using LC/MS/MS. Analysis using LC/MS/MS provides more specific quantification of thyroid hormones. A comparison of the ultrafiltration tandem mass spectrometric method with equilibrium dialysis showed very good correlation.

Thyrotrophin and free thyroxine trimester-specific reference intervals in a mixed ethnic pregnant population in the United Arab Emirates

Background Physiological alterations in the homeostatic control of thyroid hormones cause changes in thyroid function tests in pregnant women. A lack of method, trimester and population-specific reference intervals for free thyroxine (FT4) and thyrotrophin (TSH) makes interpretation of FT4 and TSH levels in pregnancy difficult. We established trimester-specific reference intervals for TSH and FT4 in a mixed ethnic population of pregnant women attending two antenatal clinics in the United Arab Emirates. Methods TSH and FT4 result from 1140 women with uncomplicated singleton pregnancy were available. The 95% reference intervals were determined for TSH and FT4 for each trimester for Arab women from the United Arab Emirates and other Arab countries and Asian women. Results Suppressed TSH levels in the first trimester recovered to non-pregnant levels in the third trimester. There was a significant difference in TSH levels between trimesters 1 and 2, and 2 and 3 ( p < 0.0005). There was no significant difference in the TSH levels between the various ethnic groups. Mean FT4 levels decreased with each progressive trimester in all groups. There were significant differences in FT4 levels between all three trimesters ( p < 0.005), especially between the first and second trimesters. FT4 differed significantly between UAE nationals and Asians in the first and second trimesters ( p < 0.005). Conclusions In general, the findings were in keeping with earlier reports. Use of trimester-specific reference intervals should help in the appropriate interpretation of thyroid hormone results in the mixed UAE population.