Reference intervals for preterm thyroid function during the fifth to seventh day of life.

BACKGROUND: Due to the lack of reference intervals for serum free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) in preterm neonates during the 5th to 7th day of life, we performed a retrospective study using the chemiluminescence immunoassay system. METHODS: A total of 2040 preterm neonates with a gestational age (GA) of 26-35 weeks in the neonatal intensive care unit from 2014 to 2019 were included. Their serum FT3, FT4 and TSH values were calculated and analyzed to establish reference intervals for preterm neonates stratified by GA. The comparisons of FT3, FT4 and TSH were made by sex (males and females) and gestational age (26-28 weeks; 29-32 weeks; 33-35 weeks). RESULTS: The reference intervals for FT3, FT4 and TSH in preterm neonates with a GA of 26-35 weeks were (1.65~5.21) pmol/L, (8.64~25.41) pmol/L, and (0.406~12.468) mlU/L, respectively. There were significant differences between serum FT3 and FT4 values and GA, while TSH levels were not significantly different (P < 0.01). The serum FT3 values of males were lower than those of females, especially in the 29-32 weeks group. No significant differences in serum values between sexes were found in FT4 or TSH (P > 0.05). CONCLUSION: Reference intervals of thyroid function tests were established to determine the early diagnostic criteria of thyroid diseases for neonates with a GA of 26-35 weeks and to avoid unnecessary retesting and interventions. The reference intervals of FT4 can be used as an indicator to regulate the doses of thyroid hormone supplement in the treatments of congenital hypothyroidism.

Reference Intervals for Thyroid-Associated Hormones and the Prevalence of Thyroid Diseases in the Chinese Population.

BACKGROUND: Thyroid diseases are highly prevalent worldwide, but their diagnosis remains a challenge. We established reference intervals (RIs) for thyroid-associated hormones and evaluated the prevalence of thyroid diseases in China. METHODS: After excluding outliers based on the results of ultrasound screening, thyroid antibody tests, and the Tukey method, the medical records of 20,303 euthyroid adults, who visited the Department of Health Care at Peking Union Medical College Hospital from January 2014 to December 2018, were analyzed. Thyroid-associated hormones were measured by the Siemens Advia Centaur XP analyzer. The RIs for thyroid-associated hormones were calculated according to the CLSI C28-A3 guidelines, and were compared with the RIs provided by Siemens. The prevalence of thyroid diseases over the five years was evaluated and compared using the chi-square test. RESULTS: The RIs for thyroid stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), total thyroxine (TT4), and total triiodothyronine (TT3) were 0.71-4.92 mIU/L, 12.2-20.1 pmol/L, 3.9-6.0 pmol/L, 65.6-135.1 nmol/L, and 1.2-2.2 nmol/L, respectively. The RIs of all hormones except TT4 differed significantly between males and females. The RIs of TSH increased with increasing age. The prevalence of overt hypothyroidism, overt hyperthyroidism, subclinical hypothyroidism, and subclinical hyperthyroidism was 0.5% and 0.8%, 0.2% and 0.6%, 3.8% and 6.1%, and 3.3% and 4.7% in males and females, respectively, which differed from those provided by Siemens. CONCLUSIONS: Sex-specific RIs were established for thyroid-associated hormones, and the prevalence of thyroid diseases was determined in the Chinese population.

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

Background Thyroid hormone levels are essential for diagnosing and monitoring thyroid diseases. However, their reference intervals (RIs) in elderly Chinese individuals remain unclear. We aimed to identify factors affecting thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) levels using clinical "big data" to establish hormone level RIs for elderly Chinese individuals. Methods We examined 6781, 6772, and 6524 subjects aged ≥65 years who underwent FT3, FT4, and TSH tests, respectively, at the Peking Union Medical College Hospital between September 1, 2013, and August 31, 2016. Hormones were measured using an automated immunoassay analyzer (ADVIA Centaur XP). RIs were established using the Clinical Laboratory Standards Institute document C28-A3 guidelines. Results The median TSH was significantly higher in women than in men; the opposite was true for median FT3 and FT4 levels. No differences were observed in TSH or FT4 by age in either sex or overall; FT3 levels significantly decreased with age. Seasonal differences were observed in TSH and FT3 levels but not FT4 levels; the median TSH was the highest in winter and lowest in summer, whereas the median FT3 was the lowest in summer (albeit not significantly). RIs for TSH were 0.53-5.24 and 0.335-5.73 mIU/L for men and women, respectively; those for FT3 were 3.76-5.71, 3.60-5.42, and 3.36-5.27 pmol/L in 64- to 74-, 75- to 84-, and 85- to 96-year-old subjects, respectively. The RI for FT4 was 11.70-20.28 pmol/L. Conclusions RIs for TSH in elderly individuals were sex specific, whereas those for FT3 were age specific.

Stability of serum thyroid hormones following 8-11 years of cold storage.

BACKGROUND: Ethnic differences necessitate a need for local reference intervals (RI), but establishing these can be challenging in some cultures that are reluctant to donate blood. Frozen sera are an alternative, but results can be questionable. Between 1998 and 2001, we collected blood samples from 343 healthy pregnant Chinese women (5-41 weeks' gestation), and in 2001 published gestational RI for thyrotropin thyroid stimulating hormone (TSH), free thyroxine (FT4) and free triiodothyronine (FT3) using the ACS180, now obsolete. As a pilot to re-establishing RI, TSH, FT4 and FT3 were re-assayed in archived specimens using contemporary assays. METHODS: Thirty archived specimens (-80 degrees C) with ACS180 TSH concentrations ranging from 0.25 to 3.7 mIU/L were measured using the Roche E170, Advia Centaur and Architect i2000 TSH, FT4 and FT3 assays, along with 10 newer contemporary samples. Results were compared to the original, and examined in context of past and present methodological performances in an external quality assurance (EQA) program. RESULTS: All contemporary assays detected significantly lower TSH and increased FT4 and FT3 concentrations in the stored samples. CONCLUSIONS: With reference to methodological performances in EQA, the results obtained with contemporary assays suggest analyte deterioration in specimens and thus their unsuitability for re-establishing RI.

Towards the certification of the purity of calibrant reference materials for thyroid hormones: a chicken and egg dilemma.

The certification of the purity of CRMs intended for calibration, where no other certified material already exists for comparison, raises principle questions on how to determine the purity of a "first" calibrant in the calibration hierarchy. We developed and certified two calibration CRMs for their purity in thyroid hormones taking into consideration inorganic residues, residual solvents and organic impurities detectable by HPLC-UV and HPLC-MS. IRMM-468 was certified for a thyroxine (T(4)) mass fraction of 98.6+/-0.7% and IRMM-469 was certified for a 3,3',5-triiodothyronine (T(3)) mass fraction of 97.1+/-0.7%. The approach we used aims to determine the purity of these two CRMs to the best of our knowledge and taking all scientific aspects properly into account for the estimation of an uncertainty related to the stated purity.

The medical treatment of non-toxic goiter: several questions remain.

In this review it is concluded that thyroxine (T4), triiodothyronine (T3) and iodine (KI), singly or in combination, are all effective in reducing the goiter size, but there is insufficient evidence to prove which is the best (possibly the combination of T4 + KI?). Higher doses are more effective than smaller, but also lead to more side-effects. Thus, the optimal dose has yet to be found. The suppression of the pituitary thyroid axis plays a major role in the treatment of non-toxic goiter, but it is not definite that this is the only mechanism responsible for the beneficial effect of the agents mentioned. In view of the lack of better evidence, it is simply suggested that non-toxic goiters in young persons should be initially treated aggressively with 200 micrograms of T4/day or more for some months. If the goiter shrinks then the dose should be gradually decreased. If the goiter persists, it is futile to continue with large doses for more than 6-12 months. One may continue with smaller doses, maintaining the serum TSH in the low-normal range. The treatment of benign thyroid nodules with thyroxine is controversial. Probably thyroxine is beneficial in about a third of the cases. For both non-toxic goiters and nodules, autonomy should be excluded before starting thyroxine treatment, and old age, cardiac disease and a poor general condition are contraindications.

Qualitative evaluation of in-house immunoassays of T3, T4 and TSH based on bulk reagents.

Increase in the cost of RIA kit assays has led to our attempts to seek cheaper alternates. Assays based on bulk reagents (supplied free of cost by INMOL in collaboration with IAEA) were started in 1988. Statistical and Quality control data on 50,51 and 52 assay batches of T3, T4 and TSH respectively has been collected from the beginning. Cumulative assay parameters show that T3 and T4 assays are almost equally precise. TSH assay is most imprecise in the group especially at low concentration levels. The working ranges of T3 and T4 assays defined at 10% error limit are quite wide and cover low, medium and high levels of hormones. In TSH the assay working range does not cover levels below 10mu IU/ml. The variability of curve parameters is similar in this group of assays. Quality control results are most reproducible in T4 assays with a between batch variability of 11.9%. T3 and TSH assay results are equally reproducible (20.50% variability). Overall within assay drift is low in all assays. IQC charts of these assays show occasional significant positive or negative shift of results from mean which might be related to methodological variations of quality among various distributions of reagents. The reproducibility and precision of results could be further improved by harmonizing the future distributions of reagents.

Enzyme immunoassay of free triiodothyronine in serum.

In this new solid-phase antibody enzyme immunoassay for free triiodothyronine (FT3) in serum, beta-D-galactosidase conjugated to triiodothyronine is used. Results are uninfluenced by physiological concentrations of thyroxin-binding globulin or albumin. Results correlate well with those determined by equilibrium dialysis (r = 0.95). The mean CVs within and between assays were 6.1 and 9.5%, respectively. The measurable range of FT3 in serum is 0.7 to 26 ng/L; the normal reference interval is 1.9 to 8.9 ng/L. Concentrations of FT3 in serum of patients with hyperthyroidism were high; those of patients with hypothyroidism were within normal limits or low, and those of patients with congenitally decreased or increased TBG were within the normal range. In normal pregnant women, concentrations of FT3 as determined by radioimmunoassay correlated with those of albumin, declining as pregnancy progressed, but FT3 values determined by the proposed method or equilibrium dialysis were within the normal range and did not change during pregnancy.