Association between physical activity and thyroid function in American adults: a survey from the NHANES database.

OBJECTIVE: Physical activity (PA) is closely related to our lives, and the effects of PA on thyroid function have not been elucidated. METHODS: Using data from the National Health and Nutrition Examination Survey (NHANES) 2007-2012, we included 5877 participants and analyzed the associations of thyroid function with weekly physical activity (PAM, expressed in metabolic equivalents of task) and physical activity time (PAT) in American adults. Univariate and multivariate logistic analyses were used to demonstrate the associations of PAM and PAT with the primary outcome. Linear regression analysis was performed to determine the associations between thyroid biochemical indicators/diseases and PAM/PAT. RESULTS: Our study revealed noticeable sex differences in daily PA among the participants. The odds ratio of the fourth versus the first quartile of PAM was 3.07 (confidence interval, CI [1.24, 7.58], p = 0.02) for overt hypothyroidism, 3.25 (CI [1.12, 9.45], p = 0.03) for subclinical hyperthyroidism in adult men. PAT in the range of 633-1520 min/week was found to be associated with the occurrence of subclinical hyperthyroidism [p < 0.001, OR (95% CI) = 5.89 (1.85, 18.80)], PAT of the range of > 1520 min/week was found to be associated with the occurrence of overt hypothyroidism [p < 0.001, OR (95% CI) = 8.70 (2.80, 27.07)] and autoimmune thyroiditis (AIT) [p = 0.03, OR (95% CI) = 1.42 (1.03, 1.97)] in adult men. When PAM < 5000 MET*minutes/week or PAT < 1000 min/week, RCS showed an L-shaped curve for TSH and an inverted U-shaped curve for FT4. The changes in FT3 and TT3 in men were linearly positively correlated with PAM and PAT, while TT4 is linearly negatively correlated. CONCLUSION: The amount of daily physical activity of American adults is strongly associated with changes in thyroid function, including thyroid hormone levels and thyroid diseases. Thyroid hormone levels were varied to a certain extent with changes in PAM and PAT.

Effects of altitude on thyroid disorders according to Chinese three-rung, ladder-like topography: national cross-sectional study.

BACKGROUND: Chinese topography appears a three-rung ladder-like distribution of decreasing elevation from northwest to southeast, which is divided by two sloping edges. Previous studies have reported that prevalence of thyroid diseases differed by altitude, and geographical factors were associated with thyroid disorders. To explore the association between three-rung ladder-like regions and thyroid disorders according to unique Chinese topographic features, we conducted an epidemiological cross-sectional study from 2015-2017 that covered all 31 mainland Chinese provinces. METHODS: A total of 78,470 participants aged ≥ 18 years from a nationally representative cross-sectional study were included. Serum thyroid peroxidase antibody, thyroglobulin antibody, and thyroid-stimulating hormone levels; urine iodine concentration; and thyroid volume were measured. The three-rung ladder-like distribution of decreasing elevation from northwest to southeast in China was categorized into three topographic groups according to elevation: first ladder, > 3000 m above sea level; second ladder, descending from 3000-500 m; and third ladder, descending from 500 m to sea level. The third ladder was further divided into groups A (500-100 m) and B (< 100 m). Associations between geographic factors and thyroid disorders were assessed using linear and binary logistic regression analyses. RESULTS: Participants in the first ladder group were associated with lower thyroid peroxidase (ß = -4.69; P = 0.00), thyroglobulin antibody levels (ß = -11.08; P = 0.01), and the largest thyroid volume (ß = 1.74; P = 0.00), compared with the other groups. The second ladder group was associated with autoimmune thyroiditis (odds ratio = 1.30, 95% confidence interval [1.18-1.43]) and subclinical hypothyroidism (odds ratio = 0.61, 95%confidence interval [0.57-0.66]) (P < 0.05) compared with the first ladder group. Group A (third ladder) (500-100 m) was associated with thyroid nodules and subclinical hypothyroidism (P < 0.05). Furthermore, group B (< 100 m) was positively associated with autoimmune thyroiditis, thyroid peroxidase and thyroglobulin antibody positivity, and negatively associated with overt hypothyroidism, subclinical hypothyroidism, and goiter compared with the first ladder group(P < 0.05). CONCLUSION: We are the first to investigate the association between different ladder regions and thyroid disorders according to unique Chinese topographic features. The prevalence of thyroid disorders varied among the three-rung ladder-like topography groups in China, with the exception of overt hyperthyroidism.

Determination of the Predictive Roles and Potentially Pathogenic Antigen Epitopes of α-Enolase Related to the Development of Miscarriage in Females with Autoimmune Thyroiditis.

Autoimmune thyroiditis (AIT) is a common endocrine disease which causes a significantly increased risk of miscarriage. Our recent study has shown that the increased ENO1 autoantibody (ENO1Ab) expression in an experimental AIT mouse model was induced by thyroglobulin (Tg) immunization only. In this study, we explored the potential roles of ENO1Ab in miscarriage occurrence among AIT women, and the specific epitopes of ENO1 targeted by ENO1Ab. A total of 432 euthyroid pregnant participants were selected from the project of Subclinical Hypothyroid during Early Pregnancy, including 48 women with AIT and miscarriage, 96 with miscarriage but no AIT, 96 with AIT but no miscarriage, and 192 without either AIT or miscarriage. The enzyme-linked immunosorbent assay was used to determine the serum levels of total IgG against ENO1 and 18 predicted antigen epitopes of ENO1. The results showed that women with AIT and miscarriage had the highest serum levels of ENO1Ab compared to the other groups. Logistic regression analysis showed that the serum ENO1Ab was an independent risk factor for miscarriage, especially among AIT females. The serum level of total IgG against the predicted epitope peptide 6 (i.e., P6 and aa168-183) of ENO1 was significantly increased in women with AIT and miscarriage when compared with those of both the AIT non-miscarriage group and non-AIT miscarriage group. This pilot study suggests that serum ENO1Ab may have a fair predictive value for AIT-related miscarriage, and the autoantibody specific to P6 epitope may especially be more specifically related to this disorder.

The effects of maternal anti-alpha-enolase antibody expression on the brain development in offspring.

Anti-alpha-enolase autoantibodies have not only been found to play an important role in autoimmune diseases but also cause neurological damage in adults. In this study, a pregnant mouse model with high serum alpha-enolase (ENO1)-specific antibody (ENO1Ab) was established by immunization with ENO1 protein to explore the effects of maternal circulatory ENO1Ab on the brain development in offspring. The pups showed impaired learning and memory abilities with obviously thinner tight junctions in the brain tissue. IgG deposits colocalized with both ENO1 protein and complement 3 (C3), and the membrane attack complex was obviously detectable in the brain tissues of pups from dams with high serum ENO1Ab expression. Our findings suggest that highly expressed ENO1Ab in the maternal circulation can pass through the blood-placenta-barrier and the compromised blood-brain barrier into the brain tissues of offspring and may cause neurological development impairment mainly through complement-dependent cytotoxicity.

Effects of iodine excess on serum thyrotropin-releasing hormone levels and type 2 deiodinase in the hypothalamus of Wistar rats.

Iodine is an important element in thyroid hormone biosynthesis. Thyroid function is regulated by the hypothalamic-pituitary-thyroid axis. Excessive iodine leads to elevated thyroid-stimulating hormone (TSH) levels, but the mechanism is not yet clear. Type 2 deiodinase (Dio2) is a Se-containing protease that plays a vital role in thyroid function. The purpose of this study was to explore the role of hypothalamus Dio2 in regulating TSH increase caused by excessive iodine and to determine the effects of iodine excess on thyrotropin-releasing hormone (TRH) levels. Male Wistar rats were randomised into five groups and administered different iodine dosages (folds of physiological dose): normal iodine, 3-fold iodine, 6-fold iodine, 10-fold iodine and 50-fold iodine. Rats were euthanised at 4, 8, 12 or 24 weeks after iodine administration. Serum TRH, TSH, total thyroxine (TT4) and total triiodothyronine (TT3) were determined. Hypothalamus tissues were frozen and sectioned to evaluate the expression of Dio2, Dio2 activity and monocarboxylate transporter 8 (MCT8). Prolonged high iodine intake significantly increased TSH expression (P < 0·05) but did not affect TT3 and TT4 levels. Prolonged high iodine intake decreased serum TRH levels in the hypothalamus (P < 0·05). Dio2 expression and activity in the hypothalamus exhibited an increasing trend compared at each time point with increasing iodine intake (P < 0·05). Hypothalamic MCT8 expression was increased in rats with prolonged high iodine intake (P < 0·05). These results indicate that iodine excess affects the levels of Dio2, TRH and MCT8 in the hypothalamus.

Postpartum Levothyroxine Adjustment and Its Impact Factors in Women With Hypothyroidism in Pregnancy.

OBJECTIVE: Women with hypothyroidism need to increase exogenous thyroid hormone levels during pregnancy to reduce adverse outcomes. Few studies have reported the effect of gestational levothyroxine (LT4) variations on postpartum LT4 treatment. METHODS: Women were classified as having subclinical hypothyroidism (SCH) (n = 101), overt hypothyroidism (OH) caused by autoimmune thyroiditis (AIT-OH), OH following thyroidectomy for benign thyroid disease (BA-OH) (n = 66), and OH after surgery for papillary thyroid cancer (PTC-OH) (n = 46). Thyroid function was monitored, and LT4 therapy was adjusted accordingly. RESULTS: After delivery, all women with SCH stopped LT4 treatment, and 57.4% of them restarted LT4 treatment in the following 1 year, independently of the gestational LT4 variations. Among patients with OH, after adjusted by gestational body weight, 49.1% of them had LT4 doses less than the prepregnancy dose (baseline) in late pregnancy, leading to LT4 reduction in postpartum. The LT4 dose was reduced to approximately 50% baseline for women with AIT-OH and BA-OH and reduced by 27% for women with PTC-OH. The reduction reasons for AIT-OH and BA-OH were thyroid-stimulating hormone levels of <2.5 mU/L during pregnancy and postpartum thyrotoxicosis occurrence (39.4%), and for PTC-OH, the reason was thyroid-stimulating hormone overinhibition (<1.0 mU/L) before delivery. CONCLUSION: For patients with SCH, postpartum LT4 treatment could initially be suspended. For women with OH, if the LT4 dose in late pregnancy was less than baseline, a prepregnancy dose reduced by 50%, 50%, and 27% should be applied after delivery for women with AIT-OH, BA-OH, and PTC-OH, respectively.

Age-specific thyrotropin references decrease over-diagnosis of hypothyroidism in elderly patients in iodine-excessive areas.

OBJECTIVE: Acute or chronic exposure to excess iodine has detrimental effects on thyroid physiology; therefore, this study aimed to determine the prevalence of overt hypothyroidism (OH) and subclinical hypothyroidism (SCH) in an elderly population residing in geographical areas with chronic exposure to excess iodine intake and to analyse contributing risk factors. DESIGN: This cross-sectional study was conducted from 2016 to 2017 in areas of Jiangsu Province that have documented chronic exposure to high iodine intake. PATIENTS: We enroled 2559 adult participants using a multistage, stratified sampling method. MEASUREMENTS: Urinary iodine concentration (UIC), serum thyroid-stimulating hormone (TSH) level and other relevant parameters were measured. Demographic information was recorded using a standardized questionnaire. The age-specific TSH references were determined by the National Academy of Clinical Biochemistry guidelines. Univariate and multivariate logistic regression analyses were performed to identify risk factors for hypothyroidism in the study population. RESULTS: The median UIC of participants was 307.3 µg/L (interquartile range: 200.7, 469.8 µg/L). The prevalence of OH in subjects ≥70 years using laboratory reference ranges was 2.37%; however, it decreased to 1.78% with the use of an age-specific reference range. Similarly, the prevalence of SCH also declined drastically from 29.59% to 2.96% with the application of an age-specific reference range. In both univariate and multivariate models, advanced age, female gender and high UIC were identified as risk factors for hypothyroidism. CONCLUSIONS: Usage of age-specific TSH reference ranges led to a significantly lower prevalence of OH and SCH in the study population, thus preventing unnecessary over-diagnosis and over-treatment.

The Iodine Status and Prevalence of Thyroid Disorders Among Women of Childbearing Age in China: National Cross-sectional Study.

OBJECTIVE: Mandatory universal salt iodization in China was implemented 20 years ago. However, the current iodine status and prevalence of thyroid disorders among childbearing-age women are unknown. METHODS: A nationally representative cross-sectional study with 26 166 enrolled participants aged 18 to 49 years from all 31 provincial regions of mainland China was performed. The participants were given a questionnaire and underwent B-mode ultrasonography of the thyroid. The serum concentrations of thyroid hormones and thyroid antibodies and the urinary iodine concentration (UIC) were measured. RESULTS: The median UIC was 178.7 µg/L, indicative of adequate iodine status. pHowever, 19.04% and 19.87% of the participants were classified as having iodine deficiency and excessive iodine, respectively. The weighted prevalence of thyroid disorders was as follows: 1.08% had overt hyperthyroidism, 0.58% had subclinical hyperthyroidism, 0.76% had Graves disease, 1.28% had overt hypothyroidism, 14.28% had subclinical hypothyroidism, 13.53% were positive for thyroid peroxidase antibodies, and 14.55% were positive for thyroglobulin antibodies. Excessive iodine and overweight were associated with higher odds of subclinical hypothyroidism. A family history of thyroid disorders and an age between 40 and 49 years were significantly associated with higher odds of positivity for thyroid peroxidase antibodies and thyroglobulin antibodies. CONCLUSION: Iodine deficiency, excessive iodine, subclinical hypothyroidism, and positivity for thyroid autoantibodies remain prevalent among women of childbearing age in China. Women of childbearing age who are relatively older, are overweight, or have a family history of thyroid disorders are encouraged to undergo active screening of their UIC and thyroid function when planning a pregnancy.

The role of protein disulphide-isomerase A3 as autoantigen in the pathogenesis of autoimmune thyroiditis and related brain damage in adult mice.

Autoimmune thyroiditis (AIT)-related brain damage is one of most severe extrathyroidal manifestations of AIT, but the mechanism remains unclear. In this study, we confirmed that protein disulfide-isomerase A3 (PDIA3) is expressed in both thyroid and brain tissues of mouse, and found the significantly increased serum levels of anti-PDIA3 antibody (PDIA3Ab) in classical mouse models of thyroiditis. In addition, we investigated the PDIA3-specific autoimmune reaction in thyroid and brain tissues in a mouse model with high-serum PDIA3Ab induced by immunization with recombinant PDIA3 protein. PDIA3-immunized mice had elevated serum thyrotropin and impaired learning and memory. PDIA3-expressing cells had IgG deposition, and IgG colocalized with C3 in the thyroid and brain tissues of PDIA3-immunized mice, resulting in membrane attack complex formation. Our results suggest that PDIA3 protein may be a common autoantigen shared by the thyroid and brain tissues and involve in the thyroidal and intracerebral damage through activating complement system.

Functional analysis of thyroid peroxidase gene mutations resulting in congenital hypothyroidism.

OBJECTIVE: Thyroid peroxidase (TPO) is essential for thyroid hormone biosynthesis. TPO mutations might lead to congenital hypothyroidism. In the present study, we analysed the function of a compound heterozygous TPO mutation in a Chinese family. DESIGN: We studied a 23-year-old Chinese girl with a history of growth retardation and severe constipation from the age of 3 months, who was diagnosed as having congenital hypothyroidism. METHODS: Genomic DNA was extracted from peripheral blood samples obtained from the patient's family members. The genomic DNA was sequenced to detect mutations in a panel of genes associated with congenital hypothyroidism. Bioinformatic analysis and structural modelling predicted the potential disease-causing potential mutant genes and the microstructure of the mutant protein, respectively. Western blotting and ELISA were used to measure protein expression, and guaiacol oxidation assay measured the TPO activity of the mutant protein. RESULTS: We identified a compound heterozygous mutation (c.C1993T, c.T2473C) in the TPO gene. Bioinformatic analysis predicted that the TPO mutations were potentially disease causing. Structural modelling predicted damage to the microstructure of the mutant TPO protein. Western blotting and ELISA showed reduced protein levels of the mutant TPO protein compared with that of the wild-type protein. The mutant TPO protein showed weaker activity compared with that of the wild-type protein. CONCLUSIONS: A novel compound heterozygous mutation of TPO gene was identified in a Chinese family. This mutation might alter the extracellular microstructure of TPO, and decrease its expression and the activity, resulting in congenital hypothyroidism.

A negative association between urinary iodine concentration and the prevalence of hyperuricemia and gout: a cross-sectional and population-based study in Mainland China.

BACKGROUND AND AIMS: Iodine is one of the most important trace elements in the human body. It is not only the main component of thyroid hormones but also has extrathyroid biological functions. To date, there have been no large-scale epidemiological studies on the relationship between hyperuricemia and iodine intake, although both are closely related to health. A population-based epidemiological survey in China offers such an opportunity. METHODS: This population-based cross-sectional study recruited 75,653 adults aged ≥ 18 years from 2015 to 2017 with a randomized, multistage, stratified sampling strategy. Serum uric acid levels and urinary iodine concentrations (UICs) were measured. RESULTS: Stratified by UIC, the prevalence of hyperuricemia was 17.8%, 18.8%, 16.0% and 13.7% in the UIC < 100, 100-199, 200-299, and ≥ 300 µg/L groups, respectively; the prevalence of gout was 4.0%, 3.4%, 2.4% and 1.7%, respectively. The prevalence of gout decreased significantly as the UIC increased. The prevalence of hyperuricemia and gout were markedly higher in postmenopausal females than in the premenopausal population (hyperuricemia: 15.9% vs. 8.3%, X2 = 520.072, p < 0.001; gout: 3.6% vs. 1.3%, X2 = 219.889, p < 0.001), and the prevalence decreased as the UIC increased. Subjects in the more than adequate and excessive iodine groups had lower likelihoods of having hyperuricemia [aOR = 0.81 (95% CI 0.77-0.85), aOR = 0.68 (95% CI 0.64-0.72)] and lower odds of having gout than subjects in the adequate iodine (AI) group [aOR = 0.77 (95% CI 0.68-0.86), aOR = 0.59 (95% CI 0.51-0.68)]. CONCLUSIONS: UIC was inversely associated with the occurrence of hyperuricemia and gout. More in-depth research and prospective studies are needed to explore the molecular mechanisms and confirm the observed association.

The Correlation Between Metabolic Disorders And Tpoab/Tgab: A Cross-Sectional Population-Based Study.

OBJECTIVE: Studies have shown that metabolic abnormalities influence the immune system. Because the prevalence of metabolic and autoimmune thyroid diseases has increased synchronously, the correlation between them was worth exploring. The study objective was to investigate the relationship between metabolic disorders and thyroid auto-antibodies in euthyroid subjects. METHODS: Data were obtained from the Thyroid Diseases and Diabetes Mellitus project survey of 55,891 subjects from 31 provinces in China. The body mass index (BMI), waist circumference (WC), blood pressure, thyroid peroxidase antibodies (TPOAbs), thyroglobulin antibodies (TgAbs), thyroid-stimulating hormone (TSH), urinary iodine concentration, blood glucose, lipid profile, and uric acid levels were evaluated. Free thyroxine and free triiodothyronine levels were measured in patients with abnormal serum TSH levels. RESULTS: In males, the BMI, WC, systolic blood pressure (SBP), diastolic blood pressure (DBP), and 2-hour post-glucose oral glucose tolerance test results of the TPOAb-/TgAb-positive group were significantly higher than those of the TPOAb-/TgAb-negative group. In females, the BMI, WC, SBP, DBP, total cholesterol, and low-density-lipoprotein cholesterol (LDL-C) in the TPOAb-/TgAb-positive group were significantly increased compared to the TPOAb-/TgAb-negative group. Multivariate analysis showed that in males, the odds ratio (OR) of positive TgAbs in the abdominal obesity group was 1.175 (95% confidence interval [CI], 1.016 to 1.359; P = .03), and the OR of positive TPOAbs in the hyperuricemia group was 1.195 (95% CI, 1.041 to 1.372; P = .011). In females, the OR of positive TgAbs was 1.19 (95% CI, 1.068 to 1.326; P = .002) in the high LDL-C group. CONCLUSION: Obesity, high LDL-C, and hyperuricemia were positively correlated with the prevalence of positive thyroid autoantibodies in euthyroid subjects in a gender-dependent manner. This cross-sectional survey showed that metabolic disorders are associated with increased positive thyroid autoantibody levels in euthyroid subjects in a gender-dependent manner. ABBREVIATIONS: AIT = autoimmune thyroiditis; BMI = body mass index; CI = confidence interval; DBP = diastolic blood pressure; FPG = fasting plasma glucose; FT3 = free triiodothyronine; FT4 = free thyroxine; HbA1c = glycated hemoglobin; HDL-C = high-density-lipoprotein cholesterol; LDL-C = low-density-lipoprotein cholesterol; OGTT2hPG = oral glucose tolerance test 2-hours post-glucose; OR = odds ratio; SBP = systolic blood pressure; TC = total cholesterol; TG = triglycerides; TgAb = thyroglobulin antibody; TPOAb = thyroid peroxidase antibody; TSH = thyroid-stimulating hormone; UA = uric acid; WC = waist circumference.

Serum polyamine metabolic profile in autoimmune thyroid disease patients.

OBJECTIVE: Polyamines are indispensable polycations and play important physiological roles in living cells. Some polyamine metabolites have been associated with autoimmune disorders. The aims of this study were to profile polyamine metabolites in autoimmune thyroid disease (AITD) and predict whether polyamine metabolites are associated with thyroid hormone, thyroid autoantibodies or disease progression. DESIGN, PATIENTS AND MEASUREMENTS: A total of 136 participants were recruited, including Graves' disease (GD) (n = 36), Hashimoto's thyroiditis (HT) (n = 33) and thyroid autoantibody-positive (pTAb) (n = 29) patients and 38 age- and sex-matched healthy controls (HCs). Fourteen polyamine metabolites, including polyamine precursors, polyamines and polyamine catabolite, were measured by UFLC-MS/MS RESULTS: Both GD and HT patients had higher L-arginine, L-ornithine, lysine and agmatine levels and lower putrescine, 1,3-diaminopropane, spermine, N-acetylputrescine levels than HCs. Some polyamine metabolite levels were different only in GD or HT patients compared to HCs: GD patients had significantly higher spermidine, N-acetylspermidine and γ-aminobutyric acid and lower cadaverine, whereas HT patients had significantly decreased N-acetylspermine. Only spermine and N-acetylspermine were significantly lower in pTAb than HCs. The spermine:spermidine ratio was significantly reduced in all AITD patients. In addition, spermine was negatively correlated with thyroid-specific antibodies grade. N-acetylspermidine might be a risk factor for pTAb progression to overt hypothyroidism. CONCLUSIONS: Compared with the HCs, most metabolites of GD and HT showed similar patterns, suggesting the possibility of a common pathophysiological basis or metabolic pathway. Moreover, pTAb progression to overt hypothyroidism may be related to high N-acetylspermidine. Thyroid autoimmunity was associated with low spermine.

URINARY IODINE CONCENTRATION IS INVERSELY ASSOCIATED WITH THYROGLOBULIN ANTIBODIES.

Objective: Epidemiologic studies on the relationship between iodine and thyroid antibodies are inconsistent. Iodine nutrition, genetic, and environmental factors have been shown to modify the effects of iodine on thyroid autoimmunity. We investigated the relationship between urinary iodine concentration (UIC) and thyroglobulin antibodies (TgAbs) in individuals living in iodine-sufficient areas in this cross-sectional study. Methods: A total of 15,008 participants were recruited according to the age range of the population of China in our study. An oral questionnaire was administered to collect basic demographic information. Serum thyrotropin (TSH), thyroid peroxidase antibodies (TPOAbs), TgAbs, and UIC were measured, and thyroid ultrasonography was performed in all subjects. Participants were further divided according to the level of UIC and the status of TgAb, and logistic regression was applied to determine the relationship between UIC and TgAbs. Results: The median UIC of the study population was 205.23 (95% confidence interval [CI], 65.7 to 537.67) µg/L. A total of 17.6% of participants had UIC <100 µg/L. With the increase in UIC, the prevalence of positive TgAbs decreased gradually. UIC level was lowest in subjects with high TgAb titer (median, 182.36 µg/L; 95% CI, 52.88 µg/L to 506.71 µg/L) and highest in the TgAb-negative group (median, 207.16 µg/L; 95% CI, 66.94 µg/L to 538.72 µg/L). Multilinear correlation analysis showed that gender (ß = 37.632; P<.001), age (ß = 0.467; P = .038), TSH (ß = 13.107; P<.001), TPOAb (ß = 1.150; P<.001), thyroid volume (ß = 2.883; P<.001), and UIC (ß = -0.047; P = .032) were independent predictors of TgAb variations. Low UIC (<100 µg/L) was associated with increased risk of positive TgAbs (adjusted odds ratio = 1.255 [1.004 to 1.568]). Conclusion: Low UIC is an independent risk factor for positive TgAb in individuals living in iodine-sufficient areas. Abbreviations: CI = confidence interval; CV = coefficient of variation; FT3 = free triiodothyronine; FT4 = free thyroxine; OR = odds ratio; TgAb = thyroglobulin antibody; TPOAb = thyroid peroxidase antibody; TSH = thyrotropin; UIC = urinary iodine concentration; USI = universal salt iodization.

Linkage Analysis of the Chromosome 5q31-33 Region Identifies JAKMIP2 as a Risk Factor for Graves' Disease in the Chinese Han Population.

BACKGROUND This study aimed to investigate susceptibility to Graves's disease and the association with the 5q32-33.1 region on chromosome 5 in a Chinese Han population. MATERIAL AND METHODS Eighty Chinese Han multiplex families included first-degree and second-degree relatives with Graves' disease. Eight microsatellite markers on chromosome 5 at the 5q32-33.1 region underwent linkage analysis and the association between the regions D5S1480-D5S2014 were studied. RESULTS The maximal heterogeneity logarithm of the odds (HLOD) score of D5S2090 was 4.29 (α=0.42) and of D5S2014 was 4.01 (α=0.34). A nonparametric linkage (NPL) score of 3.14 (P<0.001) was found for D5S2014. The D5S1480-D5S2014 region on chromosome 5 was associated with Graves' disease, with eight haplotype domains. There were significant differences in the sixth and eighth haplotype domains between patients with Graves' disease compared with normal individuals. Tagging single nucleotide polymorphisms (SNPs) of the sixth and eighth haplotype domains showed that individuals with SNP62 (rs12653715 G/C) who were GG homozygous had a significantly increased risk of Graves' disease compared GC heterozygous or CC homozygous individuals. The transmission disequilibrium test (TDT) indicated that SNP62 (rs12653715) and SNP63 (rs12653081) loci in the Janus kinase and microtubule interacting protein 2 (JAKMIP2) gene showed dominant transmission from heterozygous parents to the affected offspring, and SNPs in the secretoglobin family 3A member 2 (SCGB3A2) gene showed no transmission disequilibrium. The haplotype JAKMIP2-1 was identified as being particularly significant. CONCLUSIONS JAKMIP2 gene polymorphism require further study as potential risk factors for Graves' disease in the Chinese Han population.

Decreased expression of FcγRII in active Graves' disease patients.

BACKGROUND: Graves' disease (GD) is a common autoimmune disease characterized by genetic and environmental factors. Fcγ receptors (FcγRs) are involved in several autoimmune disorders through recognizing immunoglobulin (Ig) G antibodies and mediating immune response. The study on the expression of FcγRs in GD patients is scarce. The purpose of this study was to evaluate the expression of three different types of FcγRs in patients with active and remissive GD. METHODS: Blood samples of patients and healthy subjects were collected to analyze the percentage of FcγRI (CD64), FcγRII (CD32), and FcγRIII (CD16) on peripheral blood mononuclear cells (PBMCs) and monocytes by flow cytometry and Western blotting. CD32 isotypes were also examined in cases and controls by real-time PCR. RESULTS: The cell percentages expressed CD32 and protein expressions of CD32 on PBMCs, and monocytes from patients with active GD were significantly reduced compared to controls and patients with remissive GD. In particular, the expression of CD32B on PBMC was also decreased in active GD patients. However, the cell percentages expressed CD16 and CD64 from PBMCs and monocytes were comparable between three groups. Besides, the percentages of CD14+ CD32+ cells were negatively correlated with TRAb titers in active GD patients (r = -0.5825, P ï¼œ 0.001). CONCLUSION: These results suggested that CD32 may act as a novel marker for active GDs. The expression of monocytic CD32, in particular CD32B, in GD patients might play a crucial role in maintaining FcγRs function and be a therapeutic target in GD patients.

Estrogen receptor ß activation stimulates the development of experimental autoimmune thyroiditis through up-regulation of Th17-type responses.

Estrogens play important roles in autoimmune thyroiditis, but it remains unknown which estrogen receptor (ER) subtype mediates the stimulatory effects. Herein we treated ovariectomized mice with ERα or ERß selective agonist followed by thyroglobulin-immunization to induce experimental autoimmune thyroiditis (EAT), and observed the aggravation of EAT after diarylpropionitrile (DPN, ERß selective agonist) administration. The mRNA levels of interleukin(IL)-17A, IL-21 and RORγt and percentages of T helper (Th) 17 cells were up-regulated in the splenocytes of DPN-treated mice. Activated ERß was found directly binding to IL-17A and IL-21 gene promoters, and also indirectly promoting IL-21 and RORγt gene transcription through interaction with NF-κB. The expressions of co-stimulatory molecules were increased on antigen-presenting cells (APCs) after DPN administration. It suggests that ERß is the predominant ER subtype responsible for EAT development, and its activation may enhance Th17-type responses through genomic pathways and alteration of APCs' activities.

Differential Expression of MicroRNAs and miR-206-Mediated Downregulation of BDNF Expression in the Rat Fetal Brain Following Maternal Hypothyroidism.

To investigate the mechanism responsible for the neurological alterations, miRNA expression profile and brain-derived neurotrophic factor (BDNF) were evaluated in brain tissues of fetal or neonatal rats and from maternal rats with hypothyroidism. Ninety female Wistar rats were divided into a control and a hypothyroid group, which were mated. Brain samples of the offspring were obtained at maternal embryonic day (E) E13 and E17 as well as postnatal day (P) P0 and P7, and the hippocampus and cortex were separated at P7. BDNF mRNA at E13 was tested by real-time PCR and protein expression by Western blot. Luciferase assays were used to confirm that miR-206 targets the 3'-untranslated region (3'-UTR) of BDNF. In the brain tissues of fetal and neonatal rats from maternal rats with hypothyroidism, differentiation miRNAs profile were found at E13, E17, P0, and P7. Compared with the control group, miR-206 levels in the hypothyroidism group were increased by 3.1-fold by micro-array, and were higher as measured by SYBR green real-time qRT-PCR (p<0.01). There was no significant difference in the BDNF mRNA levels at E13 between the hypothyroidism group and the control group (1.767±0.477 vs. 1.798±0.462, respectively; p>0.05), but pro-BDNF and mature BDNF protein levels in the hypothyroid group at E13 were significantly lower than those in the control group (p<0.05). miR-206 targeted 3'-UTR of BDNF. Our data highlight the role of miR-206 as a post-transcriptional inhibitor of BDNF at E13 in pregnant hypothyroid rats.

Association of thyroid nodules with adiposity: a community-based cross-sectional study in China.

BACKGROUND: The association between thyroid nodules and adiposity remains controversial. We performed a cross-sectional, community-based study to examine whether thyroid nodules are associated with overweight and obesity, as defined with body mass index (BMI) and waist circumference. METHODS: The study included 1482 subjects (≥20 years of age; residing in Nanjing, China) receiving questionnaire interview, anthropometric measurements, laboratory tests and thyroid ultrasonography in 2009-2010. Overweight and obesity were defined as BMI ≥24 and ≥28 kg/m2, respectively. Central obesity was defined as waist circumference at ≥90 cm in men and ≥80 cm in women. A sensitivity analysis was conducted using the American Diabetes Association (ADA) criteria for overweight and obesity (BMI ≥ 23 and ≥25 kg/m2). RESULTS: Thyroid nodules were identified in 12.6% of the subjects. A greater proportion of the subjects with thyroid nodules had a BMI at ≥24 kg/m2 (51.9% vs. 40.5% in those without thyroid nodules, P = 0.003) and central obesity (43.3% vs. 24.2%, P < 0.001). After adjustment for other confounders, central obesity was still associated with significantly elevated risk of thyroid nodules (OR 1.62, 95%CI 1.14-2.28), whereas obesity/overweight based on BMI was not in both the main analysis and sensitivity analysis with the alternative criteria. In the subgroup analysis, BMI ≥24 kg/m2 (OR 1.61, 95%CI 1.01-2.54), as well as BMI ≥25 kg/m2 (OR 1.95, 95%CI 1.14-3.34), was significantly associated with higher risk of thyroid nodules among women. Using the ADA criteria, overweight and obesity were associated with thyroid nodules (OR 5.59, 95%CI 1.39-22.51 and 5.15, 95%CI 1.30-20.37) in thyroid-stimulating hormone (TSH) > 4.2 mIU/L subgroup. Central obesity correlated with higher risk of thyroid nodules regardless of age (< 50 years: OR 1.87, 95%CI 1.05-3.32: ≥50 years: OR 1.54, 95%CI 1.00-2.37) and in the following subgroups: men (OR 1.91, 95%CI 1.14-3.20), TSH > 4.2 mIU/L (OR 3.05, 95%CI 1.01-9.22), and urine iodine ≥200 µg/L (OR 1.79, 95%CI 1.14-2.81). CONCLUSION: Waist circumference is superior to BMI for assessing risk of thyroid nodules in Chinese subjects.