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The present study aimed to establish new reference intervals (RIs) for serum free triiodothyronine (fT3), free thyroxine (fT4), and thyroid stimulating hormone (TSH) levels in Japanese children and adolescents aged 4 to 19 years. A total of 2,036 (1,611 girls, 425 boys) participants were included over a 17-year period; they all tested negative for antithyroid antibodies (TgAb, TPOAb) and were found to have no abnormalities on ultrasonography. RIs were determined by nonparametric methods. The results showed that serum fT3 was significantly higher in the 4-15-year-olds than in the 19-year-olds. The serum fT4 was significantly higher in the 4-10-year-olds than in the 19-year-olds. The serum TSH was significantly higher in the 4-12-year-olds than in the 19-year-olds. All of them gradually decreased with age to approximate the adult levels. The upper limit of TSH was lower in those aged 13 to 19 years than in adults. The differences were examined by sex. The serum fT3 was significantly higher in boys than in girls between the ages of 11 and 19 years. The serum fT4 was significantly higher in boys than in girls between the ages of 16 and 19 years. There did not seem to be any sex difference in those under 10 years of age. In conclusion, serum fT3, fT4, and TSH levels in children and adolescents differ from those in adults. It is important to evaluate thyroid function using the new RIs that are appropriate for chronological age.

An asymptomatic, 68-year-old Japanese man visited our hospital for further examination of subclinical hypothyroidism. At the first visit, the serum TSH level was markedly elevated (36.6 μIU/mL), but the serum level of free T4 was within the reference interval. Thyroid dysfunction due to dietary iodine excess was initially suspected. However, even after iodine restriction, his thyroid function tests were the same as at the first visit, which suggested false elevation of the TSH level. The TSH levels were compared among three different measurement systems, which showed a similar tendency of TSH elevation above the reference interval, but the different TSH elevation levels among the measurement methods suggested the existence of some interfering substance. Neither serial dilution of the patient's serum nor polyethylene glycol and protein G precipitation tests showed any significant changes in the recovery rate. IgG-bound macro-TSH was ruled out. The TSH peak on gel filtration chromatography was located at a molecular size greater than IgA, which suggested the presence of IgA-bound TSH. After precipitation with Jacalin, which binds specifically to IgA, the TSH level decreased from 30.7 μIU/mL to 2.01 μIU/mL, within the reference interval. Thus, IgA-bound macro-TSH was identified. Macro-TSH is a rare condition in which an immunoglobulin-bound, high-molecular-weight form of TSH results in a false elevation of the serum TSH level. When there is a discrepancy between the results of thyroid function tests and clinical symptoms, and macro-TSH is suspected, it is necessary to know that not only IgG-bound TSH but also IgA-bound TSH could be the cause.

Background: This study analyzed big data for serum thyrotropin (TSH), free triiodothyronine (fT3), and free thyroxine (fT4) concentrations in patients who had attended the outpatient clinic of Ito Hospital (Tokyo, Japan) during a recent six-year period (between January 1, 2010, and December 31, 2015) in order to investigate for seasonal changes., Methods: The serum TSH concentrations were reviewed for all 135,417 patients aged >20 years. Patients with any thyroid diseases were included, irrespective of whether they were receiving drug therapy. In total 1,637,721 serum samples were analyzed for TSH, 1,626,269 for fT3, and 1,669,381 for fT4., Results: It was observed that the TSH concentrations showed annual changes during the six-year period. They decreased during the summer, while they increased during the winter. The TSH concentrations were negatively correlated with the daily temperatures (Spearman rank correlation coefficient -0.4486; p < 0.0001). The same applied for the correlation between fT3 concentrations and daily temperatures., Conclusions: The fact that the TSH concentrations show annual changes in areas where the temperature ranges during the year are rather wide should be borne in mind for interpretation of results.

Background The remote performance of thyroid function blood tests is complicated because it requires blood collection. Objective To compare TSH and free thyroxine (FT4) levels between capillary and venous blood and assess the adequacy of measuring each value in capillary blood. Methods This prospective intervention study was conducted at Ito Hospital and was based on the clinical research method. The participants were 5 healthy female volunteers and 50 patients (41 females and 9 males) between the ages of 23 and 81 years. To measure TSH and FT4 levels in capillary and venous blood, a digital immunoassay (d-IA) method capable of measuring trace samples was used. Chemiluminescence measurements were used as controls. Values obtained for each assay system were compared using Spearman's correlation analysis. Capillary blood was collected using an autologous device (TAP II; not approved in Japan). Results Capillary plasma volume obtained using TAP II was 125 µL or more in 26 cases, 25 µL to 124 µL in 24 cases, and less than 25 µL in 5 cases. Strong correlations were noted in the TSH and FT4 levels between capillary and venous blood, with correlation coefficients of rs = 0.99 and rs = 0.97, respectively. Conclusion Capillary TSH and FT4 levels strongly correlate with venous blood values. Trace samples can be used in high-precision d-IA methods. These results may promote telemedicine in assessing thyroid function. [ABSTRACT FROM AUTHOR]

Background Thyroid stimulating hormone receptor antibody (TRAb) is detected in the serum of patients with Graves' disease (GD). This study aims to investigate the prevalence of euthyroid individuals showing positive results for TRAb and to clarify the clinical course of thyroid function and TRAb levels in these subjects. Objective Subjects were female patients who newly visited our hospital for a screening test prior to fertility treatment and showed normal thyroid function and volume without nodules between 2014 and 2017. After excluding subjects with a history of thyroid disease, 5,622 subjects were analyzed. Results Forty-seven of the 5,622 subjects showed positive results for TRAb (reference range, <2.0 IU/L) at the initial visit. Median initial TRAb was 2.9 IU/L (range, 2.0-14.7 IU/L) and median follow-up was 18.3 months (range, 0-66.5 months). Six of the 47 subjects (12.8%) developed GD and median duration until development was 6.6 months (range, 1.2-13.2 months). Median TRAb values initially and at diagnosis of GD for those 6 patients were 3.7 IU/L (range, 2.7-5.1 IU/L) and 7.2 IU/L (range 3.6-21.4 IU/L), respectively. TRAb results turned negative for 20 of the 47 subjects but remained positive despite normal thyroid function in 13 of the 47 subjects. Conclusion GD developed over time in 12.8% of euthyroid young female patients showing positive TRAb within a median of 6.6 months. A positive result for TRAb itself did not mean development of GD, so other factors must be essential for the pathogenesis of GD. [ABSTRACT FROM AUTHOR]

Background: Euthyroid Graves' disease (EGD) is a rare condition defined as the presence of thyroid-associated ophthalmopathy (TAO) in patients with normal thyroid function. Due to the rarity of this disease, only a limited number of studies and case reports are available for further evaluation of the characteristics of the disease. The aim of this study was to examine the changes in the thyroid function, thyrotropin receptor antibodies (TRAb) and eye symptoms, and then determine whether TRAb is related to TAO in EGD patients. TRAb in this study was defined as including both thyrotropin-binding inhibitory immunoglobulin (TBII) and thyroidstimulating immunoglobulin (TSAb). Patients and methods: Medical records of patients diagnosed with EGD were reviewed. Ophthalmologists specializing in TAO examined the eyes of all subjects. Results: Of the 58 patients diagnosed with EGD, 24.1% developed hyperthyroidism, while 3.4% developed hypothyroidism. A total of 72.4% of the 58 patients remained euthyroid throughout the entire follow-up period. At the initial presentation, TBII and TSAb were positive in 74.5% and 70.5%, respectively. Ophthalmic treatments were administered to 30 (51.7%) out of the 58 patients. A significant spontaneous improvement of the eye symptoms was found in 28 of the EGD patients who did not require eye treatments. EGD patients exhibited positive rates for both TBII and TSAb, with the number of the TRAb-positive patients gradually decreasing while the eye symptoms spontaneously improved over time. There were no correlations found between TRAb at initial presentation and the eye symptoms. Conclusion: TBII and TSAb were positive in about 70% of EGD patients at their initial visit. Thyroid functions of EGD patients who have been euthyroid for more than 6.7 years may continue to remain euthyroid in the future. [ABSTRACT FROM AUTHOR]