Measurements of elemental iodine in soy sauces in Taiwan using a modified microplate method.

Background: Soy sauce is widely used in a variety of Asian dishes to enhance flavor. Soybean and most soybean products, including soy sauces, are listed as prohibited foods in a low iodine diet. However, the iodine content in soy sauces is largely unknown. The aim of this study was to determine the iodine content in domestic soy sauces in Taiwan. Methods: Twenty-five different kinds of soy sauces were diluted with distilled water and with a dilution factor of fifty or above. Iodine concentrations of the diluted samples were measured colourimetrically based on the Sandell-Kolthoff reaction by a modified microplate method. All the measurements were repeated twelve times on three different days for determination of mean and standard deviation (SD), and coefficients of variance (CV). Serial dilution and recovery tests were also performed for validation. The results were confirmed by an inductively coupled plasma mass spectrometry (ICP-MS) method. Results: Among the twenty-five surveyed soy sauces, most of them (n=22) were iodine-free (<16 ug/L, and thus un-detectable). The iodine concentrations (mean ± SD) of the three iodine-containing soy sauces were 2.7 ± 0.1, 5.1 ± 0.2, and 10.8 ± 0.6 mg/L, respectively. The inter-assay, intra-assay and total CVs were all <5.3% for the modified microplate method. The results obtained by ICP-MS were consistent with those of the modified microplate method. The recovery rates in the serial dilution test and recovery test ranged from 94.7% to 118.6%. Two of the three iodine-containing soy sauces were supplemented with kelp extract, while the other one without kelp extract had the highest amount of salt among the three iodine-containing soy sauces. Therefore, we postulate that iodized salt instead of kelp extract is the source of higher iodine content in that sauce. Conclusion: The results suggest that most soy sauces are iodine-free and may be allowed during low iodine diets.

Analytical validation of an inductively coupled plasma mass spectrometry method for urinary iodine concentration measurements in Taiwan.

BACKGROUND: Urinary iodine concentration (UIC) measured by Sandell-Kolthoff spectrophotometric method has been used in the Nutrition and Health Surveys in Taiwan but this method is time consuming and produces toxic waste from arsenic trioxide. The aim of this study was to develop and validate an inductively coupled plasma mass spectrometry (ICP-MS) system to determine UIC in Taiwan. METHODS: Samples and iodine calibrators were diluted 100-fold into an aqueous solution containing Triton X-100, 0.5% ammonia solution, and tellurium (128Te) as an internal standard. Digestion prior to analysis was not necessary. Precision, accuracy, serial dilution, and recovery tests were performed. A total of 1243 urine samples covering a wide range of iodine concentrations were measured by both Sandell-Kolthoff method and ICP-MS. Passing-Bablok regression and Bland-Altman plots were used to compare values across methods. RESULTS: The limit for detection and quantification by ICP-MS was 0.95 µg/L and 2.85 µg/L, respectively. The intra-assay and inter-assay coefficients were <10%, with a recovery range of 95%-105%. The results obtained by ICP-MS and the Sandell-Kolthoff method were highly correlated (Pearson's correlation: r = 0.996, 95% confidence interval [CI]: 0.9950-0.9961, p < 0.001). For UIC between 20 and 1000 µg/L, the y-intercept for the Passing-Bablok regression was -1.9 (95% CI: -2.5599 to -1.3500) and the slope was 1.01 (95% CI: 1.0000-1.0206). CONCLUSION: This validated ICP-MS system can be used for measuring UIC.

Differential serum interferon-ß levels in autoimmune thyroid diseases.

Introduction: Interferon (IFN)-ß is known as an environmental trigger for the occurrence of autoimmune thyroid disease (AITD). However, the association of another type-1 IFN, IFN-ß, with AITD is unknown. Material and methods: In the study, we explored the association of serum IFN-ß levels with AITD in an ethnic Chinese (i.e., Taiwanese) population. We enrolled 160 patients with Graves' disease (GD), 47 patients with Hashimoto's thyroiditis (HT), and 119 healthy controls. Serum IFN-ß and B-cell activating factor (BAFF) levels were quantified in healthy controls at the baseline and in patients with AITD either prior to receiving medication or while under medication. Thyroid function and thyroid-stimulating hormone receptor antibody (TSHRAb) levels were measured at the time of serum collection. Results: Serum IFN-ß levels were lower in the HT group than in the control group (p = 0.031). A significant inverse correlation was observed between IFN-ß and TSHRAb levels in men with GD (r = -0.433, p = 0.044). Serum IFN-ß levels were also negatively associated with BAFF levels in men with GD, HT, and AITD (r = -0.320, p = 0.032; r = -0.817, p = 0.047; and r = -0.354, p = 0.011, respectively), but not in women with GD, HT, or AITD. Conclusions: Serum IFN-ß levels were lower in HT patients. Correlations of serum IFN-ß with TSHRAb and BAFF levels were found to be gender-specific. Further well-designed studies with larger sample sizes are required to confirm our findings.

The pathogenic role of IFN-α in thyroiditis mouse models.

AIM: Patients with chronic hepatitis C are frequently treated with interferon (IFN)-α. Autoimmune thyroid disease occurs in 20% ~ 40% of IFN-α-treated patients. In this study, the effects of IFN-α administration on triggering and regulating autoimmune thyroiditis in various animal models were evaluated. MAIN METHODS: Exogenous IFN-α was given to naive CBA mice, and both thyroglobulin (TG) immunization-induced (CBA) and spontaneous autoimmune thyroiditis (NOD·H-2 h4) models. Thyroid function, and anti-thyroglobulin antibody (ATA) and B-cell-activating factor (BAFF) levels were measured. Alterations in transcriptome profiles were analyzed. KEY FINDINGS: In the TG-induced thyroiditis model, IFN-α administration reduced plasma free thyroxine levels but did not alter ATA titers, BAFF levels, or the severity of histological changes. Interestingly, even without changes in thyroid functions, four of eight mice in the IFN-α alone group exhibited thyroiditis compared to the control group. Immunologically, mice in the IFN-α group exhibited profound CD3+ cell infiltration in the thyroid and higher plasma BAFF levels compared to the control group. Meanwhile, pathological and serological alterations after IFN-α administration were not observed in the NOD·H-2 h4 model. An RNA sequencing analysis revealed that immunoregulatory signatures were not excited by IFN-α treatment in naive CBA mice. Meanwhile, innate and adaptive immunity, inflammatory cytokine, chemokine, and cell-killing signaling pathways were all stimulated by IFN-α administration after TG immunization of CBA mice. SIGNIFICANCE: We confirmed the remarkable effects of IFN-α in both initiating thyroid immunity and modulating thyroid function and immunoregulatory signatures in established autoimmune thyroiditis. We suggest that IFN-α should be administered with caution in clinical settings.

Possible interplay between estrogen and the BAFF may modify thyroid activity in Graves' disease.

A link between sex hormones and B-cell activating factor (BAFF), a crucial immunoregulator of autoimmune thyroid disease (AITD), may exist. The study aimed to elucidate the role of estrogen (E2) in regulating BAFF in Graves' disease (GD). In clinical samples, serum BAFF levels were higher in women than in men in both the GD and control groups. serum BAFF levels were associated with thyroid-stimulating hormone receptor antibody levels and thyroid function only in women and not in men. BAFF transcripts in peripheral blood mononuclear cells were higher in women with GD than those in the control group. Among GD patients with the AA genotype of rs2893321, women had higher BAFF transcripts and protein levels than men. In the progression of a spontaneous autoimmune thyroiditis (SAT) murine model, NOD.H-2h4, serum free thyroxine and BAFF levels were higher in female than in male mice. Moreover, exogenous E2 treatment increased serum BAFF levels in male SAT mice. Meanwhile, female SAT mice exhibited higher thyroid BAFF transcripts levels than either the E2-treated or untreated male SAT mouse groups. Our results showed that E2 might be implicated in modulating BAFF expression, and support a possible mechanism for the higher incidence of AITD in women.

Iodine nutritional status of lactating women in northern Taiwan in 2019.

BACKGROUND: Pregnant and lactating women are vulnerable to iodine deficiency. This study was conducted to evaluate the iodine nutritional status of lactating women in northern Taiwan. METHODS: Women recruited from Taipei Veterans General Hospital (TVGH) in 2019 provided a spot urine sample and completed a Food Frequency Questionnaire. The urinary iodine concentration (UIC) was measured by inductively coupled plasma mass spectrometry. RESULTS: The overall median UIC in 198 women was 120.4 µg/L, indicating a sufficient iodine status. Univariate analysis revealed a lower median UIC in women of younger age (p = 0.004), who were not taking multivitamins (p = 0.004), not on a postpartum nourishment diet (p = 0.04), and whose infant received more breast milk (p = 0.004). The median UIC was <100 µg/L in the group aged 20 to 29 years (UIC: 74.4 µg/L) and in women whose infants' diet was composed of >50% breast milk (UIC: 86.1 µg/L). A postpartum nourishment diet was followed by 73.7% (n = 146) of the women. Nevertheless, a significant decrease in the intake frequency of iodine-containing foods, including seaweeds (p < 0.001), seafood (p < 0.001), dairy products (p = 0.009), and multivitamins (p < 0.001) was observed compared with the intake noted in a previous survey of pregnant women in TVGH. Following multivariate analysis, only younger age (20-29 vs ≥30 years; odds ratio [OR]: 3.38; 95% confidence interval [CI]: 1.49-7.65), no use of multivitamin (OR: 1.89; 95% CI: 1.03-3.48), and infant diet composition (>50% breast milk vs <50% breast milk; OR: 2.93; 95% CI: 1.37-6.25) were independently associated with UIC < 100 µg/L. CONCLUSION: The results suggest that the iodine status in lactating women in northern Taiwan is adequate. However, iodine deficiency may continue to be present in certain subgroups, such as women of younger age and those who do not take multivitamins.

Serum interferon levels associated with the disease activity in women with overt Graves' disease.

BACKGROUND: Inflammatory cytokines participate in immune reactions and the pathogenesis of autoimmunity. Herein, we quantified four groups of inflammatory cytokines, including interferons (IFNs), the tumor necrosis factor (TNF) superfamily (TNFSF), interleukin (IL)-related cytokines, and bone and extracellular matrix remodeling-related cytokines to determine their contributions in women with overt Graves' disease (GD). METHODS: Forty-three women with GD were enrolled in this cross-sectional study. Thirty-seven cytokines, thyroid-stimulating hormone (TSH), free thyroxine, and TSH receptor antibody (TSHRAb) were quantified. GD patients with a low TSH level at the time of sample collection were defined as having active GD. RESULTS: Patients with active GD had higher IFN-α2, IFN-γ, IFN-λ1, and IFN-λ2 levels than those with inactive GD. In addition, certain TNFSF cytokines, including soluble cluster of differentiation 30 (sCD30), TNFSF member 14 (TNFSF14), pentraxin (PTX)-3, soluble TNF receptor 2 (sTNF-R2), and thymic stromal lymphopoietin (TSLP) were higher in active GD than in inactive GD. Moreover, active GD patients had higher IL-2, IL-12(p40), osteocalcin (OCN), and matrix metalloproteinase (MMP)-3 than inactive GD patients. All IFNs except IFN-λ1 were correlated with TSHRAb titers. Moreover, TNFSF cytokines, consisting of B-cell-activating factor, sCD30, TNFSF14, PTX-3, sTNF-R2, and TSLP, were associated with TSHRAb levels. CONCLUSIONS: Serum IFNs could be the most remarkable cytokines in modulating the disease severity and TSHRAb titers in women with full-blown GD. Further molecular-based research to clarify the actual role of IFNs in the disease progression of GD is needed.

Iodine nutritional status of pregnant women in an urban area of northern Taiwan in 2018.

Pregnant women are considered as one of the most vulnerable groups for iodine deficiency. The Nutrition and Health Survey in Taiwan 2013 revealed that the median urinary iodine concentration (UIC) of non-pregnant women of child-bearing age of 15-44 years was 124 µg/L, which was adequate in general, but insufficient according to pregnancy criteria. The aim of this study was to determine the iodine nutritional status of pregnant women in an urban area of Northern Taiwan. A hospital-based cross-sectional survey was conducted in Taipei Veterans General Hospital. Random spot urine samples were collected from January to October, 2018 and UIC was determined by inductively coupled plasma mass-spectrometry. A food frequency questionnaire was also delivered to the participants. The overall median UIC was 225.3 µg/L (IQR: 109.1-514.2 µg/L) for 257 pregnant women ranging from 21-47 years-old. The distribution of UIC was as follows: 35.4% with UIC <150 µg/L, 17.1% with UIC within 150-249 µg/L, 21.8% with UIC within 250-499 µg/L, and 25.7% with UIC ≥500 µg/L. The use of prenatal multivitamin was very common among the participants: 79.4% (n = 204) took multivitamin either every day or less frequently, with 52.5% (n = 135) taking one pill every day, and only 20.6% (n = 53) never took multivitamin during their pregnancy. Other commonly consumed iodine-containing foods were dairy products and fish. Our results indicate that the iodine status in the studied women is adequate. However, efforts are still needed to avoid iodine deficiency as well as iodine excess.

Simultaneous measurement of twenty-nine circulating cytokines and growth factors in female patients with overt autoimmune thyroid diseases.

Cytokines and growth factors participate in immune responses, and the pathogenesis of autoimmune diseases. Herein, we simultaneously examined differential levels of 29 circulating factors to determine their associations in female patients with overt autoimmune thyroid disease (AITD). We enrolled 40 patients with Graves' disease (GD), 20 patients with Hashimoto's thyroiditis (HT), and 14 healthy controls. Twenty-nine circulating factors were simultaneously measured. GD patients with low thyroid-stimulating hormone at the time of sample collection were defined as having active GD. B-cell activating factor (BAFF) levels were associated with GD and HT (p = .001 and .001, respectively) and interferon (IFN)-α levels were higher in the HT group than in the control group (p = .021). Significant associations of serum BAFF and tumour necrosis factor (TNF)-α levels with free thyroxin (FT4) were present in HT (r = -0.498, p = .026, and r = 0.544, p = .013, respectively). Meanwhile, there were significant associations of FT4 with interleukin (IL)-4 and eotaxin levels in GD (r = 0.354, p = .025 and r = 0.384, p = .014, respectively). In active GD, serum BAFF and eotaxin level were correlated with FT4 levels (r = 0.465, p = .034, and r = 0.463, p = .035, respectively). In conclusion, BAFF is the best circulating indicator to identify GD and HT among all chosen 29 biomarkers, and it could be used to predict the disease severity in HT and active GD. Meanwhile, IFN-α could be another reliable parameter for recognising HT.

Associations of gene polymorphisms in interferon-alpha signature-related genes with autoimmune thyroid diseases.

Interferon (IFN)-α treatment predisposes patients to the occurrence of autoimmune thyroid disease (AITD). METHODS: We investigated associations of single nucleotide polymorphisms (SNPs) of molecules participating in the IFN-α signature, including rs2304204 and rs2304206 of IFN regulatory factor 3 (IRF3), rs1061501 of IRF7, and rs7708392 of TNFA1P3-interacting protein 1 with serum IFN-α levels and AITD in an ethnic Chinese (ie Taiwanese) population. Totally, 319 patients with Graves' disease (GD), 83 patients with Hashimoto's thyroiditis (HT) and 351 healthy controls were recruited. RESULTS: There were increased percentages of the C allele, and CC and TC + CC genotypes of rs1061501 in GD patients compared to the controls. HT patients had higher serum IFN-α levels compared to the controls, while there was no difference in serum IFN-α levels between patients with GD and controls. However, patients with GD in a remission status had lower serum IFN-α levels than those without remission. On the other hand, the C allele of rs1061501 was only associated with serum IFN-α levels in patients with HT. CONCLUSIONS: The SNP rs1061501 of IRF7 was associated with the development of GD. Serum IFN-α levels were associated with HT, while they might modify the disease status of GD. Moreover, a genetic effect of rs1061501 on regulating serum IFN-α production was observed in HT.

Author Correction: Effects of exogenous melatonin on clinical and pathological features of a human thyroglobulin-induced experimental autoimmune thyroiditis mouse model.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

Effects of exogenous melatonin on clinical and pathological features of a human thyroglobulin-induced experimental autoimmune thyroiditis mouse model.

Melatonin (MLT) plays a significant role in both innate and adaptive immunity, and dysregulation of the MLT signature can modify autoimmune disease phenotypes. In this study, the influence of exogenous MLT administration on regulating autoimmune thyroiditis animal models was evaluated. An experimental autoimmune thyroiditis model was established in MLT-synthesizing (CBA) and MLT-deficient (C57BL/6) mice by immunization with human thyroidglobulin (TG), which features thyrotoxicosis, thyrocyte damage, and CD3+ T cell infiltration. In TG-immunized CBA mice, exogenous MLT administration in drinking water (6 µg/ml) enhanced thyroiditis and increased TG-specific splenocyte proliferation but not the anti-thyroglobulin antibody (ATA) titer, while MLT alone caused no significant alteration in thyroid function or histopathology. Meanwhile, MLT administration did not modify thyroid function, the ATA titer, or the thyroid histopathology, but results showed an increase in the splenocyte proliferative capacity in TG-immunized C57BL/6 mice. Collectively, our data showed that early exogenous MLT modified the progression of autoimmune thyroiditis through T cell-driven immunity, and excess MLT worsened the clinical and pathological features.

Synchronized expressions of serum osteopontin and B cell-activating factor in autoimmune thyroid disease.

BACKGROUND: Osteopontin (OPN) is recognized as a potent immunoregulator of autoimmune disease. In the study, we tried to explore the association of serum OPN levels with autoimmune thyroid disease, including Graves' disease (GD) and Hashimoto's thyroiditis (HT), in an ethnic Chinese population. MATERIALS AND METHODS: We enrolled 131 patients with GD, 33 patients with HT and 123 healthy controls. Serum OPN, B cell-activating factor (BAFF) and interferon (IFN)-α levels were quantified. Graves' disease patients with high thyroid function at the time of sample collection were defined as having active GD, while the other patients were defined as having inactive GD. RESULTS: Serum OPN levels were higher in active GD than in inactive GD and the control groups (P = 0.001 and P = 0.018, respectively). In GD, significant associations of OPN levels with thyroid-stimulating hormone receptor antibody (TSHRAb) levels were observed in women (r = -0.344, P = 0.002, and r = 0.440, P = 0.004, respectively) but not in men. Osteopontin levels were associated with BAFF levels only in women with GD or HT (r = 0.506, P < 0.001 and r = 0.430, P = 0.025, respectively), but not in men with GD or HT. CONCLUSIONS: Serum OPN levels were upregulated in active GD, and serum OPN levels were associated with thyroid function and TSHRAb levels in GD. Additionally, OPN levels were correlated with BAFF levels in GD and HT. The associations of OPN levels with clinical phenotypes of GD and BAFF levels showed a dimorphic pattern.

Associations of secreted phosphoprotein 1 and B lymphocyte kinase gene polymorphisms with autoimmune thyroid disease.

BACKGROUND: Dysregulation of the type 1 interferon (IFN)-related signalling pathway predisposes one to autoimmune diseases. Possible associations of single-nucleotide polymorphisms (SNPs) of secreted phosphoprotein 1 (SPP1) and B lymphocyte kinase (BLK) of the type 1 IFN-related signalling pathway with autoimmune thyroid disease (AITD) in an ethnic Chinese (ie Taiwanese) population were tested. METHODS: Totally, 83 Hashimoto's thyroiditis (HT) patients, 319 Graves' disease (GD) patients and 369 controls were enrolled. Genotypes of the two SNPs (rs1126772 and rs1126616) of SPP1 and two SNPs (rs13277113 and rs2736340) of BLK were determined. RESULTS: Our results showed reduced percentages of the G allele of rs13277113 of BLK in GD (P = 0.037, odds ratio [OR] = 0.78, 95% confidence interval [CI] = 0.62-0.99) and HT (P = 0.002, OR = 0.54, 95% CI = 0.36-0.81), compared to the controls. At the same time, lower frequencies of the C allele of rs2736340 of BLK in GD (P = 0.025, OR = 0.76, 95% CI = 0.60-0.97) and HT (P = 0.003, OR = 0.53, 95% CI = 0.35-0.81) than the controls were also observed. There were significantly higher AT haplotype frequencies of rs1327713 and rs2736340 in GD and HT patients than in the controls (P = 0.025, OR = 1.31, 95% CI = 1.03-1.67, and P = 0.003, OR = 1.89, 95% CI = 1.24-2.87, respectively). Moreover, the anti-microsomal antibody titre was associated with rs2736340. CONCLUSIONS: Genetic variants of rs13277113 and rs2736340 of BLK were associated with susceptibility to GD, HT and AITD in an ethnic Chinese population. Our results suggest the BLK may participate in the pathogenesis of GD, HT and AITD.

Iodine Status of Taiwanese Population in 2013: 10 Years After Changing From Mandatory to Voluntary Salt Iodization.

BACKGROUND: In 2003, Taiwan's iodine policy changed from mandatory to voluntary. The Nutrition and Health Survey in Taiwan (NAHSIT) 2001-2002 for schoolchildren showed adequate iodine nutrition, while NAHSIT 2005-2008 for adults showed the iodine status was at borderline adequacy. OBJECTIVE: To investigate the iodine status of the Taiwanese population from schoolchildren to adulthood 10 years after the change of the salt iodization policy. METHOD: Urinary iodine was measured in samples from subjects in NAHSIT 2013. RESULTS: The median urinary iodine concentration (UIC) of the Taiwanese population aged 6 years and above in 2013 was 96 µg/L, indicating mild iodine deficiency. The median UIC of 6- to 12-year-old schoolchildren was 124 µg/L (interquartile range [IQR]: 92-213 µg/L), and 115 µg/L (IQR: 80-166 µg/L), 125 µg/L (IQR: 74-161 µg/L), 73 µg/L (IQR: 52-131 µg/L), and 78 µg/L (IQR: 52-132 µg/L) in populations aged 13 to 18 years, 19 to 44 years, 45 to 64 years, and ≥65 years, respectively. Declining iodine nutrition in age groups ≥45 years old was noted that the median UIC of populations aged 45 to 64 years and ≥65 years was 99 and 88 µg/L, respectively, in NAHSIT 2005-2008. The median UIC of schoolchildren was not lower than that during the mandatory salt fortification period, but the distribution of urinary iodine levels signified a dietary pattern change. CONCLUSION: Wide-ranging variation in iodine nutrition levels was observed in different age groups. Universal salt iodization, as suggested by the World Health Organization, should be the best strategy to achieve adequate iodine nutrition.

Associations of melatonin receptor gene polymorphisms with Graves' disease.

BACKGROUND: Melatonin plays an important role in immunity and has been linked to autoimmune diseases. Possible associations of single-nucleotide polymorphisms (SNPs) of melatonin receptor type 1A (MTNR1A) and 1B (MTNR1B), with autoimmune thyroid disease in an ethnic Chinese (i.e., Taiwanese) population were examined. MATERIALS AND METHODS: Totally, 83 Hashimoto's thyroiditis patients, 319 Graves' disease (GD), and 369 controls were recruited. Three SNPs (rs6553010, rs13140012, and rs2119882) of MTNR1A and three SNPs (rs1387153, rs10830963, and rs1562444) of MTNR1B were genotyped. RESULTS: There were a reduced frequency of the C allele of rs2119882 and a reduced percentage of the CC+CT genotype in the GD group compared to the control group (p = 0.039, odds ratio (OR) = 0.79, 95% confidence interval (CI) = 0.63~0.99, and p = 0.032, OR = 0.72, 95% CI = 0.53~0.97, respectively). There was a significant difference in the percentage of the AT haplotype of the combination of rs13140012 and rs2119882 between the GD and control groups (p = 0.010, OR = 1.34, 95% CI = 1.07~1.67). In addition, there were significant associations of anti-thyroid peroxidase antibody titers with rs13140012 and rs2119882, and the AATT genotype of the combination of rs13140012 and rs2119882 (p = 0.003, 0.003, and 0.004, respectively). There were no significant associations of SNPs and possible haplotypes of MTNR1B with susceptibility to GD. CONCLUSIONS: Genetic variants of rs2119882 of MTNR1A and the AT haplotype of the combination of rs2119882 and rs13140012 were associated with GD susceptibility in an ethnic Chinese population. The results support the involvement of the melatonin pathway in the pathogenesis of GD.

Serum BAFF and thyroid autoantibodies in autoimmune thyroid disease.

BACKGROUND: This study investigated the association of serum B-lymphocyte activating factor (BAFF) levels with autoimmune thyroid disease (AITD) in a Chinese population. MATERIALS AND METHODS: We enrolled 221 patients with AITD [170 patients with Graves' disease (GD), 51 patients with Hashimoto's thyroiditis (HT)], and 124 healthy controls. Serum BAFF levels, thyroid function and thyroid autoantibody (TAb) levels, including of thyroid-stimulating hormone receptor antibody (TSHRAb), anti-thyroid peroxidase antibody (Anti-TPO Ab), and antithyroglobulin antibody (ATA), were measured at baseline. RESULTS: Serum BAFF levels were higher in the GD, HT, and AITD groups than in the control group. Significant correlations were observed between BAFF and TSHRAb levels (r=0.238, p=0.018), between BAFF and Anti-TPO Ab levels (p=0.038), and between BAFF and ATA titers (p=0.025) in women but not in men. In addition, serum BAFF levels were significantly associated with free thyroxine (r=0.430, p=0.004) and TSHRAb (r=0.495, p=0.001) levels in women with active GD but not in those with inactive GD. CONCLUSIONS: Serum BAFF levels are increased in GD, HT, and AITD. The correlation between serum BAFF and TAb levels exhibits a dimorphic pattern, particularly in active GD.

Iodine Nutritional Status of School Children in Nauru 2015.

Little is known about iodine nutritional status in island countries in the Pacific Ocean. The primary objective of this study was to report for the first time the iodine nutritional status of people in Nauru. In addition, sources of iodine nutrition (i.e., water and salt) were investigated. A school-based cross-sectional survey of children aged 6-12 years was conducted in three primary schools of Nauru. Urinary iodine concentration (UIC) was determined by spot urine samples. Available water and salt samples in Nauru were collected for the measurement of iodine content. A food frequency questionnaire was conducted. The median UIC was 142 µg/L, and 25.2% and 7.4% of the population had median UIC below 100 µg/L and 50 µg/L, respectively. Natural iodine-containing foods such as seaweeds and agar were rare. Iodine was undetectable in Nauruan tank water, filtered tap water, and raindrops. Of the analyzed salt products, five kinds were non-iodized, and three were iodized (iodine content: 15 ppm, 65 ppm, and 68 ppm, respectively). The results indicate that the iodine status in Nauruan school children is adequate. Iodized salt may serve as an important source of iodine nutrition in Nauru.

Analysis of Associations of Human BAFF Gene Polymorphisms with Autoimmune Thyroid Diseases.

BACKGROUND: The B-lymphocyte-activating factor (BAFF) is associated with B-cell functions, and gene polymorphisms of the BAFF have been linked to autoimmune diseases (AIDs). In this study, we explored possible associations of two BAFF single-nucleotide polymorphisms (SNPs), rs1041569 and rs2893321, with autoimmune thyroid diseases (AITDs) in an ethnic Chinese population. MATERIAL AND METHODS: In total, 319 Graves' disease (GD), 83 Hashimoto's thyroiditis (HT) patients, and 369 healthy controls were enrolled. Polymerase chain reaction-restriction fragment length polymorphism and direct sequencing were used to genotype rs2893321 and rs1041569. RESULTS: There was a significant difference in frequencies of the G allele and AG+GG genotype of rs2893321 between the GD and control groups (p = 0.013, odds ratio (OR) = 0.76, and p = 0.017, OR = 0.68, respectively) and between the AITD and control groups (p = 0.009, OR = 0.76, and, p = 0.014, OR = 0.69, respectively). The AA genotype of rs2893321 was associated with low titers of the thyroid-stimulating hormone receptor antibody (TSHRAb) (p = 0.015) in males but not in females. The AA genotype of rs2893321 was associated with the presence of two different types of thyroid autoantibody (TAb) (TSHRAb and Hashimoto's autoantibody (anti-thyroglobulin or anti-microsomal antibody)) in females and with that of one type in males. CONCLUSIONS: rs2893321 may be a susceptible genetic variant for the development of GD and AITDs. Associations of rs2893321 with susceptibility to GD and AITDs and the correlation between rs2893321 and TAb exhibit a dimorphic pattern. Additional studies with larger sample sizes are required to confirm our findings.

Clinical Manifestations and Gene Expression in Patients with Conventional Papillary Thyroid Carcinoma Carrying the BRAF(V600E) Mutation and BRAF Pseudogene.

BACKGROUND: The association of BRAF(V600E) with the clinical manifestations of papillary thyroid carcinoma (PTC) remains controversial. Recent studies have shown that the BRAF pseudogene can activate the MAPK pathway and induce tumorigenesis. This study investigated the association of BRAF(V600E), the BRAF pseudogene, and their mRNA levels with clinical features and thyroid-specific gene expression in conventional PTCs. MATERIALS AND METHODS: A total of 78 specimens were collected from patients with conventional PTCs. RNA was isolated, and quantitative polymerase chain reaction was used to measure the mRNA levels of BRAF, the BRAF pseudogene, and thyroid-specific and tumor-related genes. Immunohistochemical (IHC) staining of BRAF, ERK, sodium-iodide symporter (NIS), thyrotropin receptor, glucose transporter 1, and Ki67 was also performed. RESULTS: BRAF(V600E) and the BRAF pseudogene were detected in 73.0% (57/78) and 91.7% (44/48), respectively, of the conventional PTCs. The presence of BRAF(V600E) was not associated with the multiple clinical features assessed or the recurrence rate during 76.9 ± 47.2 months of follow-up. Neither was it associated with IHC staining or tumor-related/thyroid-specific gene expression, except for decreased NIS gene expression. The BRAF pseudogene was not associated with clinical characteristics or thyroid-specific gene expression, except for decreased decoy receptor 3 (DCR3) expression. High BRAF mRNA levels were associated with bilateral and multifocal lesions, and BRAF-pseudogene mRNA levels were positively correlated with BRAF mRNA levels (r = 0.415, p = 0.009). CONCLUSION: These results do not support the use of the BRAF(V600E) mutation as a prognostic marker of conventional PTC. However, the association of high BRAF mRNA levels with more advanced clinical features suggests that BRAF mRNA levels might be a more useful clinical marker of PTCs, independent of the BRAF(V600E) mutation status. The correlation between BRAF-pseudogene mRNA levels and BRAF mRNA levels in PTCs is in agreement with the hypothesis that the BRAF pseudogene regulates BRAF expression during tumorigenesis by acting as competitive noncoding RNA. However, additional studies with larger sample sizes are required to confirm these findings.