Age- and sex-specific reference intervals for thyroid hormones in a Chinese pediatrics: a prospective observational study of 1,279 healthy children.

Thyroid hormones are essential for early neurocognitive development and growth and development in childhood and adolescence. However, the reference intervals (RIs) for thyroid hormones in Chinese pediatric individuals remain unclear. This study aimed to establish thyroid hormone RIs for a Chinese pediatric population according to appropriate age- and sex-specific partitioning. In this prospective observational study, a total of 1,279 healthy children (singletons, aged from 1 day to 12 years) were recruited, and serum samples were analyzed on a Mindray automated chemiluminescence immunoassay analyzer CL-6000i for thyroid hormone detection, including thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), total triiodothyronine (T3), and total thyroxine (T4). Age and sex-specific RIs were established, and the corresponding 95% confidence intervals (CIs) were calculated in accordance with the Clinical Laboratory Standards Institute (CLSI) document C28-A3 guidelines. Quantile testing revealed that the median (P50) and RIs [2.5th percentile (P2.5)-97.5th percentile (P97.5)] for TSH, FT3, T3, and T4 of males differed significantly from those of females (P<0.05), except for FT4 (P=0.483). For FT3 and T3, the RIs of males were higher than that of females, and the RI of T4 for males was narrower and higher than that of females [P2.5-P97.5: 72.33-171.60 vs. 72.31-176.27 nmol/L; P50: 116.75 vs. 113.47 nmol/L, P=0.011]. RIs for TSH, FT3, FT4, T3, and T4 showed sex- and age-specific properties and displayed a wide variation during the first month of life but gradually narrowed and concentrated with increasing age. In addition, RIs of TSH, FT3, FT4, and T3 in males differed significantly from females in the first month of life (TSH: 1.46-10.87 vs. 1.08-11.35 mIU/L; FT3: 2.96-7.08 vs. 2.35-7.27 pmol/L, FT4: 13.34-28.65 vs. 13.82-31.83 pmol/L; T3: 0.83-2.33 vs. 0.72-2.46 nmol/L). The RI of T4 also exhibited a difference between males and females in the 9- to 12-year age group (59.31-150.72 vs. 63.29-146.94 pmol/L for males and females, respectively). Pediatric RIs of thyroid hormones display age- and sex-specific trends. The RIs established in this study will improve the accuracy of TSH assay result interpretations and clinical decision-making in clinical laboratories that utilize the Mindray analytical platform.

Yao C ，Wu M ，Liu M ，Chen X ，Zhu H ，Xiong C ，Wang D ，Xiang Y ，Suo G ，Wang J ，Sun H ，Yuan C ，Xia Y ... -  《Translational Pediatrics》

Reference intervals for thyroid-stimulating hormone, free thyroxine, and free triiodothyronine in elderly Chinese persons.

Wang D ，Yu S ，Ma C ，Li H ，Qiu L ，Cheng X ，Guo X ，Yin Y ，Li D ，Wang Z ，Hu Y ，Lu S ，Yang G ，Liu H ... -  《-》

The reference intervals for thyroid hormones: A four year investigation in Chinese population.

The reference intervals (RIs) are of great importance for physicans to determine whether or not an individual is healthy. However, many clinical laboratories in China still adopted the default RI provided by the manufacturers; and these "uncalibrated" RIs might lead to the misdiagnosis of diseases. In the present study, we enroll reference people with the purpose of determining the RIs of serum triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) in Chinese population, and explore the possible roles of age and sex on the levels of biomarkers. Serum samples from 66,609 individuals who met the inclusion criteria were analyzed using an Roche Cobas E 601 hormone analyzer. The dynamic trends of biomarker were visually assessed by their concentrations over age and sex. Specific partitions were determined by the method of Harris and Boyd. RIs, corresponding to the 2.5th and 97.5th percentiles, as well as the 0.5th, 25th, 50th, 75th and 99.5th percentiles were calculated for each reference partition using a non-parametric rank approach. The serum level of T3, T4, FT4 or TSH showed a right-skewed distribution in both males and females while FT3 presented an approximate normal distribution. Females had a higher mode value of serum T3 or T4, but a lower mode value of serum TSH, FT3 or FT4. All five biomarkers did not need age partitioning according to the approach of harris and boyd, while T3 and FT3 need sex partitioning. The present study not only determined the age- and sex-specific trends of the five thyroid hormones, but provided sex-stratified RIs for T3 and FT3, valuably contributing to the current literature and timely evaluation of thyroid health and disease.

Xie T ，Su M ，Feng J ，Pan X ，Wang C ，Tang T ... -  《Frontiers in Endocrinology》

Reference Intervals for Thyroid Hormones and Thyroid Volume in Children Aged 7 ~ 13 Years from Iodine-Sufficient Areas in Tianjin, China.

Reference intervals (RIs) for serum thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) suitable for local children are urgently needed in northern China. The reference interval for thyroid volume (Tvol) in Chinese children also differed greatly from that recommended by the WHO. This study aimed to establish TSH, FT3, FT4, and Tvol RIs suitable for children in northern China. A total of 1070 children aged 7 ~ 13 were recruited from iodine nutrition-sufficient areas in Tianjin, China, from 2016 to 2021. Four hundred fifty-eight children aged 7 ~ 13 years, and 815 children aged 8 ~ 10 years were eventually included to study RIs for the thyroid hormones and Tvol. RIs for thyroid hormones were established in accordance with the Clinical Laboratory Standards Institute (CLSI) document C28-A3 guidelines. Quantile regression was used to analyze the influencing factors of Tvol. RIs for TSH, FT3, and FT4 were 1.23 (1.14 ~ 1.32) to 6.18 (5.92 ~ 7.26) mIU/L, 5.43 (5.29 ~ 5.52) to 7.89 (7.66 ~ 7.98) pmol/L, and 13.09 (12.85 ~ 13.73) to 22.22 (21.61 ~ 22.51) pmol/L. There was no need to establish RIs by age and gender. Our RIs could increase the prevalence of subclinical hyperthyroidism (P < 0.001) and reduce the prevalence of subclinical hypothyroidism (P < 0.001). Body surface area (BSA) and age are correlated with the 97th percentile of Tvol (both P < 0.001). Our reference interval could increase the goiter rate in children from 2.97 to 4.96% (P = 0.007). The thyroid hormones' reference intervals suitable for local children should be established. In addition, BSA and age should be considered when establishing Tvol reference interval.

Cui Y ，Wang Y ，Zhang D ，Duan Y ，Li F ，Li W ，Chen L ，Jia G ... -  《-》

Establishment of Reference Intervals for Thyroid-Associated Hormones Using refineR Algorithm in Chinese Population at High-Altitude Areas.

Diagnosis of thyroid disease among individuals dwelling at high altitude remains a challenge. Reference intervals (RIs) for thyroid-associated hormones among Tibetans living at various high altitudes were established to improve diagnosis. One thousand two hundred eighty-one subjects were randomly recruited from Nyingchi, Shigatse/Lhasa, and Ali of Tibet. Thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were measured by the Cobas e601 electrochemiluminescence analyzer. We used multiple linear regression and variance component analysis to assess the effect of sex, age, and altitude on hormones. RIs were established by refineR algorithm and compared with those provided by the manufacturer. Serum TSH was significantly lower in males than in females, while FT3 and FT4 were higher in males. Both FT3 and FT4 decreased with increasing age. FT3 increased with altitude, while TSH and FT4 were less influenced by altitude. The RI for TSH was 0.764-5.784 μIU/ml, while for FT4, the RIs were 12.36-19.38 pmol/L in females and 14.84-20.18 pmol/L in males. The RIs for FT3 at Nyingchi, Shigatse/Lhasa, and Ali in females were 4.09-4.98, 4.31-5.45, and 4.82-5.58 pmol/L, while in males, the values were 4.82-5.41, 4.88-5.95, and 5.26-6.06 pmol/L, respectively. The obtained RIs for TSH and FT4 were generally higher, while that for FT3 was narrower than the RIs provided by Cobas. Specific RIs were established for thyroid-associated hormones among Tibetans, which were significantly different from those provided by the manufacturer.

Ma C ，Zhong J ，Zou Y ，Liu Z ，Li H ，Pang J ，Liu X ，Zejipuchi ，Tian L ，Hou L ，Wang D ，Cheng X ，Qiu L ... -  《Frontiers in Endocrinology》