Higher prevalence of thyroid-specific autoantibodies (TPOAb and TgAb) is related to a higher prevalence of fractures in females: results from NHANES 2007-2010.

A retrospective analysis was conducted using data from the NHANES. Bone mineral density (BMD) was compared in different thyroid-specific autoantibodies groups. Strengths of associations were calculated by using binary logistic regression models. Higher titers of thyroid-specific autoantibodies (TgAb and/or TPOAb) may lead to decreased BMD. Higher prevalence of TgAb and TPOAb significantly associated with fractures in females but not in males. PURPOSE: Hashimoto's thyroiditis is characterized by elevated thyroid-specific autoantibodies. It is currently believed that osteoporosis is not only a disease with abnormal mineral metabolism but also with immune abnormalities. This study investigated the relationship between thyroid-specific autoantibodies and osteoporosis, including the bone mineral density (BMD) values and fractures. METHODS: A retrospective analysis was conducted using data from the National Health and Nutrition Examination Survey (2007-2010). BMD was compared in different thyroid-specific autoantibodies groups. The associations between thyroid-specific autoantibodies and fractures were explored. Strengths of associations were calculated by binary logistic regression models. Candidate variables for binary logistic regression model were selected after screened in univariate analysis (variables with P < 0.05). RESULTS: A total of 3865 study participants were included in this analysis; 224 participants were TgAb positive and 356 were TPOAb positive. A total of 392 participants reported hip, spine or wrist fractures. Participants with higher prevalence of TgAb or TPOAb had lower BMD. In females, significant cigarettes use, higher prevalence of TgAb and TPOAb, and the BMD of the total femur and femoral neck were significantly associated with fractures. Higher prevalence of TPOAb was particularly associated with a higher possibility of hip or spine fractures. In males, significant cigarettes use, 25OHD3, the BMD values of the total femur, femoral neck and total spine were significantly associated with fractures. CONCLUSION: Higher prevalence of thyroid-specific autoantibodies may lead to decreased BMD. In females, higher prevalence of TgAb and TPOAb significantly associated with fractures and TPOAb especially relating to the fractures of hip and spine. Males patients with vitamin D deficiency or insufficiency associated a higher possibility of fractures.

Evaluation of the therapeutic efficacy of different doses of LT4 in pregnant women with high-normal TSH levels and TPOAb positivity in the first half of pregnancy.

BACKGROUND: The objective was to investigate the efficacy of different doses of levothyroxine therapy among pregnant women exhibiting high-normal thyroid stimulating hormone levels and positive thyroid peroxidase antibodies throughout the first half of pregnancy. METHODS: Pregnant women exhibiting high-normal thyroid stimulating hormone levels and thyroid peroxidase antibodies positivity throughout the initial half of pregnancy were selected from January 2021 to September 2023. Based on the different doses of levothyroxine, the pregnant women were categorized into the nonintervention group (G0, 122 women), 25 µg levothyroxine intervention group (G25, 69 women), and 50 µg levothyroxine intervention group (G50, 58 women). Serum parameters, gastrointestinal symptoms, small intestinal bacterial overgrowth (SIBO), maternal and neonatal outcomes were compared after the intervention among the three groups. RESULTS: After the intervention, in the G25 and G50 groups, the thyroid stimulating hormone, triglyceride and low-density lipoprotein levels were notably less in contrast to those in the G0 group (P < 0.05). The rates of abdominal distension and SIBO in the G25 and G50 groups were notably lower in contrast to the G0 group (P = 0.043 and 0.040, respectively). The G50 group had a lower rate of spontaneous abortion and premature membrane rupture than the G0 group (P = 0.01 and 0.015, respectively). Before 11+ 2 weeks of gestation and at thyroid peroxidase antibodies levels ≥ 117 IU/mL, in contrast to the G0 group, the G50 group experienced a decreased rate of spontaneous abortion (P = 0.008). The G50 group had significantly higher newborn weight than the G0 group (P = 0.014), as well as a notably longer newborn length than the G0 and G25 groups (P = 0.005). CONCLUSIONS: For pregnant women with high-normal thyroid stimulating hormone levels and thyroid peroxidase antibodies positive during the first half of pregnancy, supplementation with 50 µg levothyroxine was more effective in improving their blood lipid status and gastrointestinal symptoms, reducing the incidence of SIBO and premature rupture of membranes, and before 11+2 weeks, TPOAb ≥ 117 IU/mL proved more beneficial in mitigating the risk of spontaneous abortion.

Preconceptual thyroid peroxidase antibody positivity in women with recurrent pregnancy losses may contribute to an increased risk for another miscarriage.

OBJECTIVE: To investigate preconceptual thyroid peroxidase antibody (TPO-ab) positivity and/or thyroid stimulating hormone (TSH) levels in the upper range of normal as risk factors for recurrent unexplained first-trimester miscarriage. DESIGN: A post-hoc study of a randomized trial, in which acetylsalicylic acid did not affect the risk of a new miscarriage. PATIENTS: Women (n = 483) with at least three unexplained recurrent first-trimester miscarriages investigated at a Swedish secondary referral center. MEASUREMENTS: The levels of TPO-ab and TSH were determined before pregnancy. The occurrence of a new first-trimester miscarriage was analyzed by logistic regression with adjustments when applicable, for age, number of previous miscarriages, obesity and the investigated covariates levels of TPO-ab and TSH. RESULTS: Including all first trimester miscarriages, odds ratio (OR) according to presence of TPO-ab was 1.60 (95% confidence interval [CI]; 0.99-2.57), after adjustment 1.54 (95% CI; 0.94-2.53). Very early (biochemical) pregnancy losses occurred more often in women with than without preconceptual TPO-ab (6.8% vs. 2.0%), OR 3.51 (95% CI; 1.15-10.71), after adjustment 2.91 (95% CI; 0.91-9.29). There was no association between TSH in the upper range of normal and a new miscarriage, adjusted OR 0.76 (95% CI; 0.32-1.83). A prediction model for a new miscarriage included number of previous miscarriages, woman's age and presence of TPO-ab. CONCLUSION: In women with at least three recurrent unexplained pregnancy losses, the presence of TPO-ab may contribute to an increased risk of a first-trimester miscarriage, possibly more pronounced in very early pregnancy. TSH levels 2.5-4.0 mU/L do not seem to increase the miscarriage risk.

Exposure of Akwesasne Mohawk women to polychlorinated biphenyls and hexachlorobenzene is associated with increased serum levels of thyroid peroxidase autoantibodies.

Persistent organic pollutants (POPs) including polychlorinated biphenyls (PCBs), hexachlorobenzene (HCB), and dichlorodiphenyltrichloroethane (p,p'-DDT) were reported to influence immunological activity. As endocrine-disrupting chemicals (EDC), these pollutants may disrupt normal thyroid function and act as catalysts for development of autoimmune thyroid disease by directly and indirectly affecting levels of thyroid peroxidase antibodies (TPOAbs). Native American communities are disproportionately exposed to harmful toxicants and are at an increased risk of developing an autoimmune disease. The aim of this study was to determine the association between POPs and TPOAbs in serum obtained from Native American women. This assessment was used to measure whether increased risk of autoimmune thyroid disease occurred as a result of exposure to POPs. Data were collected from 183 Akwesasne Mohawk women, 21-38 years of age, between 2009 and 2013. Multivariate analyses were conducted to determine the association between toxicant exposure and levels of TPOAbs. In multiple logistic regression analyses, exposure to PCB congener 33 was related to elevated risk of individuals possessing above normal levels of TPOAbs. Further, HCB was associated with more than 2-fold higher risk of possessing above normal levels of TPOAbs compared to women with normal levels of TPOAbs. p,p'-DDE was not associated with TPOAb levels within this study. Exposure to PCB congener 33 and HCB was correlated with above normal levels of TPOAbs, a marker of autoimmune thyroid disease. Additional investigations are needed to establish the causes and factors surrounding autoimmune thyroid disease which are multiple and complex.

Thyroid Disease and Systemic Lupus Erythematosus.

Background and Objectives: Thyroid disease has been associated with autoimmune disorders. As systemic lupus erythematosus (SLE) is a systemic autoimmune disease with diverse manifestations spanning across all organ systems, the relationship of SLE with thyroid disorders needs investigation. In particular, the relationship of SLE with autoimmune thyroid disease has attracted the interest of the research community. The aim was to evaluate the relationship of SLE with autoimmune thyroid disease. Materials and Methods: A cohort of 45 consecutive patients with a mean age of 47.97 years (range 21-79 years) and 45 age- and sex-matched controls were prospectively studied over a period of 12 months for the presence of thyroid disease and the prevalence of antithyroid antibodies. Results: Four patients (8.9%) were found to suffer from primary hypothyroidism, five (11.11%) from subclinical hypothyroidism and one (2.22%) from hyperthyroidism, whereas one (2.22%) of the controls had primary hypothyroidism and one (2.22%) had hyperthyroidism. Five patients (11.11%) had a thyroid hormone profile that was compatible with the presence of euthyroid sick syndrome. Thyroid peroxidase (TPOab) and thyroglobulin (Tgab) antibodies were detected in 20/45 and 15/45 of the SLE population and in 7/45 and 5/45 of the controls, respectively (p < 0.05, chi-square test). Conclusions: In conclusion, the incidence of clinical thyroid disease is greater amongst SLE patients than in a control population, and in a significant number of these patients, antithyroid antibodies are detectable. Thus, a subset of lupus patients appears to be predisposed to the development of thyroid disease, and this should be considered when evaluating patients with SLE.

Cord blood metabolomics reveals gestational metabolic disorder associated with anti-thyroid peroxidase antibodies positivity.

BACKGROUND: Thyroid disease is one of the common endocrine disorders affecting the pregnant women, in which thyroid autoimmunity can alter the progress and the outcome of pregnancy. Women with euthyroid status but anti-thyroid peroxidase (anti-TPO) antibodies positivity before pregnancy are prone to subclinical gestational hypothyroidism. However, the connections between anti-TPO antibodies positivity and gestational hypothyroidism remain largely unknown. The aim of the present study is to investigate the differences of fetal metabolic profile at birth according to maternal anti-TPO status. METHODS: We performed 1H-NMR metabolomics on cord blood of a nested case control cohort of 22 pregnant women with matched thyroid hormone levels and demographic data, including 11 women with euthyroid status but anti-thyroid antibodies positivity (into the anti-TPO antibodies positivity group) and 11 matched women as controls with euthyroid status and negative anti-thyroid antibodies (into the control group). RESULTS: Distinct metabolic profiles were observed between the anti-TPO antibody positivity group and the nested control group, from which a total of 10 metabolites with between-group altered abundances were structurally identified. Five out of the 10 metabolites were up-regulated in the anti-TPO antibodies positivity group, including D-Glucose, L-Glutamine, 3-Hydroxybutyric acid, Myo-Inositol, Creatinine. The other 5 metabolites were down-regulated in the anti-TPO antibodies positivity group, including L-Leucine, L-Lysine, L-Glutamic acid, L-Tyrosine, and L-Phenylalanine. All the 10 metabolites have been previously reported to be correlated with hypothyroidism. Metabolite set enrichment analysis and pathway analysis suggested that amino acid metabolism pathways (especially the phenylalanine metabolism) were associated with anti-TPO antibodies positivity. CONCLUSION: The results of this study suggested that fetal metabolic disorder is correlated with anti-TPO antibodies positivity, representing by abundance alteration of hypothyroidism associated metabolites and the related disturbance of amino acid metabolism pathways.

Decreased Immunoglobulin G Core Fucosylation, A Player in Antibody-dependent Cell-mediated Cytotoxicity, is Associated with Autoimmune Thyroid Diseases.

Autoimmune thyroid diseases (AITD) are the most common group of autoimmune diseases, associated with lymphocyte infiltration and the production of thyroid autoantibodies, like thyroid peroxidase antibodies (TPOAb), in the thyroid gland. Immunoglobulins and cell-surface receptors are glycoproteins with distinctive glycosylation patterns that play a structural role in maintaining and modulating their functions. We investigated associations of total circulating IgG and peripheral blood mononuclear cells glycosylation with AITD and the influence of genetic background in a case-control study with several independent cohorts and over 3,000 individuals in total. The study revealed an inverse association of IgG core fucosylation with TPOAb and AITD, as well as decreased peripheral blood mononuclear cells antennary α1,2 fucosylation in AITD, but no shared genetic variance between AITD and glycosylation. These data suggest that the decreased level of IgG core fucosylation is a risk factor for AITD that promotes antibody-dependent cell-mediated cytotoxicity previously associated with TPOAb levels.

Effects of animal protein intake during pregnancy on autoimmune thyroiditis in pregnant women with mild iodine deficiency.

BACKGROUND: Iodine and animal protein may affect thyroid function. In the present study, we explored the association between animal protein intake and thyroid antibody status in pregnant women following universal salt iodisation. METHODS: Pregnant women were enrolled using a multistage, stratified random sampling method in Shanghai. In total, 4646 eligible women were interviewed in person. We used a validated food frequency questionnaire and food composition tables to calculate the daily intakes of protein and iodine. We collected urine samples and performed thyroid antibody tests. RESULTS: Positive thyrotropin receptor antibody (TR-Ab) rates were different among animal protein intake groups (p < 0.05). Median urinary iodine concentration (UIC) was higher in the thyroid peroxidase antibody (TPO-Ab) positive group than in the negative group (p < 0.05). The median of total protein intake, animal protein intake and UIC was higher in the TR-Ab positive group than in the negative group (p < 0.05). The median of total protein intake and UIC was higher in the TPO-Ab/TG-Ab/TR-Ab positive group than in the negative group (p < 0.05). Multivariable logistic regression results showed that insufficient iodine had a negative correlation with positive TPO-Ab and positive TR-Ab (p < 0.05). The middle third and top third animal protein intakes served as protective factors for TR-Ab (coefficient = 0.559, 95% confidence interval [CI] = 0.415-0.752, p < 0.001; coefficient = 0.0.406, 95% CI = 0.266-0.621, p < 0.001) and positive TPO-Ab/TR-Ab/TG-Ab (coefficient = 0.817, 95% CI = 0.687-0.971, p = 0.022; coefficient = 0.805, 95% CI = 0.672-0.964, p = 0.018). CONCLUSIONS: Adequate animal protein intake protects against elevated anti-thyroid antibody levels in pregnant women with mild iodine deficiency.

The importance of iodine nutrition during pregnancy - clinical aspect.

Iodine is an essential constituent of thyroid hormones. Thyroid hormones regulate brain development, growth and metabolism of the human body. Inadequately low iodine intake and decreased thyroid hormone synthesis can lead to iodine deficiency disorders. The severity of disorders depends not only on the degree of iodine deficiency, but also on the stage of the human development. Many areas of the world, including the Czech Republic, have been affected by natural iodine deficiency and the incidence of iodine deficiency disorders has been historically high. Fortification of food-grade salt was an effective step towards reduction of iodine deficiency impact. Although the Czech Republic has been considered to be an iodine sufficient area since 2004, iodine deficiency is still a threat to subgroups of population with an increased demand for iodine, such as pregnant women and newborns. Moreover, these groups are particularly sensitive to even mild iodine deficiency, because it could permanently affect the cognitive development of the fetus and have a negative effect on the course of pregnancy. Conversely, in other groups of the population steps taken to prevent iodine deficiency diseases may lead to excessive iodine intake with potential risks. It is necessary to control the iodine fortification and regularly monitor the iodine status of the population considering the individual risk groups.

Prevalence of thyroid autoimmunity and effect of levothyroxine treatment in a cohort of 1064 patients with recurrent pregnancy loss.

RESEARCH QUESTION: Does initiating levothyroxine treatment based on thyroid-stimulating hormone (TSH) >2.5 mIU/l or thyroid autoimmunity improve pregnancy continuation rates in recurrent pregnancy loss (RPL) patients? DESIGN: A retrospective cohort study of 1064 RPL patients, in which subjects were classified as either euthyroid (TSH 0.1 to ≤2.5 mIU/l), borderline-subclinical hypothyroid (borderline-SCH, TSH 2.5 to ≤4 mIU/l) or subclinical hypothyroid (SCH, TSH 4 to ≤10 mIU/l). For subjects with ≥2 pregnancy losses and a subsequent pregnancy with known outcome, a comparison was done of the pregnancy continuation rate past 10 weeks of treated and untreated borderline-SCH (n = 98) and untreated euthyroid (n = 279) subjects, and between subjects with positive (n = 18) and negative (n = 206) thyroid peroxidase (TPOAb tests) within the borderline-SCH and euthyroid groups. RESULTS: 72.7% were euthyroid (721/992), 19.4% (192/992) were borderline-SCH, and 5.4% (54/992) were subclinically hypothyroid (SCH). Of 401 women with a subsequent pregnancy of known outcome at 10 gestational weeks, 21% received treatment with levothyroxine. 57.7% of subjects had a TPOAb test, which was positive in 9.25% (37/400) in euthyroid, 16.5% (22/133) in borderline-SCH subjects and 35.3% (12/34) in SCH subjects. Treatment did not improve pregnancy continuation rates in borderline-SCH subjects (P = 0.392). There was no difference in pregnancy outcomes based on TPOAb status and treatment for borderline-SCH subjects (P = 0.4214), or based on TPOAb status for euthyroid subjects (P = 0.2668). CONCLUSIONS: Treatment of hypothyroidism in pregnancy should be initiated based on a TSH >4 mIU/l. Treatment initiation based on thyroid autoimmunity or a TSH >2.5 mIU/l may result in overtreatment.

Relationship between anti-thyroid peroxidase antibody positivity and pregnancy-related and fetal outcomes in Euthyroid women: a single-center cohort study.

BACKGROUND: Thyroid autoimmunity (TAI) and subclinical hypothyroidism (SCH) have been associated with poor pregnancy and fetal outcomes. However, whether euthyroid women with anti-thyroid peroxidase antibody (TPOAb) positivity have a higher risk of poor pregnancy and fetal outcomes is debatable. Therefore, this study aimed to investigate the association between TPOAb positivity and pregnancy-related and fetal outcomes in euthyroid women. METHODS: In total, 938 pregnant women participated in this prospective cohort study. The euthyroid group included 837 pregnant women and the TPOAb-positive group included 101 euthyroid pregnant women. Serum TPOAb, thyroglobulin antibody (TGAb), thyroid-stimulating hormone (TSH), and free thyroxine (FT4) levels were assessed. Pregnancy and fetal outcomes included gestational diabetes mellitus, spontaneous abortion, premature rupture of membranes, hypertensive disorders of pregnancy, preterm birth, fetal distress, low birth weight, fetal macrosomia, and small for gestational age infant. RESULTS: Logistic regression analysis showed TPOAb positivity was not associated with an increased risk of poor pregnancy or fetal outcomes in euthyroid women. However, TPOAb-positive euthyroid women pregnant with a female fetus were independently associated with preterm births (OR: 4.511, 95% CI: 1.075-18.926) after adjustment for potential confounding factors. CONCLUSIONS: TPOAb positivity was not found to be associated with poor pregnancy-related or fetal outcomes in euthyroid women. However, in euthyroid women with a female fetus, TPOAb positivity was strongly associated with preterm births. The risk of preterm birth in the euthyroid women with TPOAb positivity should be emphasized in clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02966405 . Registered on October 24th 2016 - Retrospectively registered.

Assessment of thyroid functions and thyroid volume in normal pregnant Egyptian females.

The normal range of thyroid functions during pregnancy differs between ethnic groups. This study assessed the thyroid functions in normal pregnant Egyptian females. Thyroid peroxidase antibodies (TPO Abs) and thyroid volume were also assessed. The study included 150 normal pregnant Egyptian females, recruited from Cairo University Hospital Antenatal Care Clinic (50 in each trimester), with 40 age-matched non-pregnant females, as a control group. Serum thyroid stimulating hormone (TSH) and TPO Abs were measured. Thyroid volume was assessed by ultrasonography. TSH ranges were 0.21-1.7, 0.52-3.2 and 0.72-2.6 mIU/L during first, second and third trimesters, respectively. The mean TSH level in pregnant females was significantly lower than that of non-pregnant women (1.2 ± 0.7 vs 2.7 ± 0.9 mIU/L, p < .001). TPO Abs were significantly higher in the first trimester compared to both second and third trimesters (p < .001 for both). Thyroid volume of pregnant females was non-significantly higher than that of non-pregnant control subjects (p = .126). A significant positive correlation was found between thyroid volume and body mass index in pregnant females (p < 0.001). Our study established trimester-specific reference ranges for thyroid functions in normal pregnant Egyptian females. A larger population-based study would help to confirm those ranges. Thyroid volume was non-significantly higher than that of non-pregnant control subjects.

Vitamin B12 and Vitamin D Levels in Patients with Autoimmune Hypothyroidism and Their Correlation with Anti-Thyroid Peroxidase Antibodies.

BACKGROUND: This study was designed to investigate the vitamin D (vit-D) and vitamin B12 (vit-B12) levels and their correlation with anti-thyroid peroxidase (anti-TPO) antibodies in patients with autoimmune hypothyroidism. METHODS: A total of 130 patients diagnosed with autoimmune hypothyroidism were included in the study retrospectively. The patients were divided into two groups as those having vit-B12 levels below 200 pg/mL (n = 60) and vit-B12 levels equal to or above 200 pg/mL (n = 70). These two groups were compared in terms of age, sex, thyroid-stimulating hormone (TSH), free-T4 (FT4), vit-D, and anti-TPO. The correlation between vit-B12 and anti-TPO levels was also investigated in these groups. Patients were then divided into four groups according to their vit-D levels. Patients with normal vit-D levels (25[OH]D >30 ng/mL; n = 5), those with vit-D insufficiency (20-30 mg/mL; n = 9), those with vit-D deficiency (10-20 ng/mL; n = 43), and those with severe vit-D deficiency (<10 ng/mL; n = 73). These four groups were compared in terms of age, gender, TSH, FT4, vit-B12, and anti-TPO levels. In addition, the correlation between levels of vit-D and anti-TPO was also investigated. RESULTS: We found that vit-B12 deficiency and vit-D deficiency were associated with autoimmune hypothyroidism, and that there was a negative correlation between vit-B12 and vit-D levels and anti-TPO antibodies in these patients. CONCLUSION: In patients with autoimmune hypothyroidism, vit-D and vit-B12 deficiency should be investigated at the time of diagnosis and periodically on follow-ups.

Thyroid-associated genetic polymorphisms in relation to breast cancer risk in the Malmö Diet and Cancer Study.

Previous studies have suggested that thyroid function is associated with breast cancer risk, which could have an important clinical impact, as one in eight women will develop a thyroid disorder during her lifetime. However, the underlying pathomechanism behind the association is still unknown. We used the Malmö Diet and Cancer Study (a population-based prospective study consisting of 17,035 women) to examine 17 single nucleotide polymorphisms (SNPs) previously related to levels of free thyroxine (free T4) and thyroid peroxidase antibodies (TPO-Ab) as potential genetic risk factors for breast cancer. A baseline examination including free T4 and TPO-Ab levels was conducted at the time of inclusion. Genotyping was performed on 901 breast cancer patients and 3335 controls. Odds ratios (95% confidence intervals) for high free T4, TPO-Ab positivity, and breast cancer were calculated by logistic regression and adjusted for confounders. We identified one free T4-related SNP (rs2235544, D101 gene) that was significantly associated with both free T4 level and breast cancer risk. There was a suggested association between rs11675434 (TPO gene) and TPO-Ab level, and TPO-Ab-related rs11675434 (TPO), rs3094228 (HCP5), rs1033662 (no registered gene), and rs301806 (RERE) were associated with breast cancer risk. There was an indicated interaction between rs6485050 (no registered gene) and free T4 level in regards to breast cancer risk. This is the first study to suggest an association between thyroid-related SNPs and breast cancer risk. All SNPs have a biological plausibility of being associated with breast cancer risk, and may contribute to the genetic predisposition to breast cancer.

A quarter of patients with type 1 diabetes have co-existing non-islet autoimmunity: the findings of a UK population-based family study.

Individuals with type 1 diabetes (T1D) are at increased risk of coeliac disease (CD), autoimmune thyroiditis and autoimmune gastritis, but the absolute risks are unclear. The aim of this study was to investigate the prevalence of autoantibodies to tissue transglutaminase (TGA), thyroid peroxidase (TPOA) and gastric H+ /K+ -ATPase (ATPA) and their genetic associations in a well-characterized population-based cohort of individuals with T1D from the Bart's-Oxford family study for whom islet autoantibody prevalence data were already available. Autoantibodies in sera from 1072 patients (males/females 604/468; median age 11·8 years, median T1D duration 2·7 months) were measured by radioimmunoassays; HLA class II risk genotype was analysed in 973 (91%) using polymerase chain reaction with sequence specific primers (PCR-SSP). The prevalence of TGA (and/or history of CD), TPOA and ATPA in patients was 9·0, 9·6 and 8·2%, respectively; 3·1% had two or more autoantibodies. Females were at higher risk of multiple autoimmunity; TGA/CD were associated with younger age and TPOA with older age. ATPA were uncommon in patients under 5 years, and more common in older patients. Anti-glutamate decarboxylase autoantibodies were predictive of co-existing TPOA/ATPA. TGA/CD were associated with human leucocyte antigen (HLA) DR3-DQ2, with the DR3-DQ2/DR3-DQ2 genotype conferring the highest risk, followed by DR4-DQ8/DR4-DQ8. ATPA were associated with DR3-DQ2, DRB1*0404 (in males) and the DR3-DQ2/DR4-DQ8 genotype. TPOA were associated with the DR3-DQ2/DR3-DQ2 genotype. Almost one-quarter of patients diagnosed with T1D aged under 21 years have at least one other organ-specific autoantibody. HLA class II genetic profiling may be useful in identifying those at risk of multiple autoimmunity.

Serum thyroid-stimulating hormone levels and smoking status: Data from the Korean National Health and Nutrition Examination Survey VI.

OBJECTIVE: We aimed to evaluate differences in serum thyroid-stimulating hormone (TSH) levels according to smoking status and urine iodine concentration (UIC) in a healthy Korean population using data from the Sixth Korean National Health and Nutrition Examination Survey (KNHANES VI). STUDY DESIGN: Sixth Korean National Health and Nutrition Examination Survey (2013-2015) is a nationwide, cross-sectional survey of the Korean population. PATIENTS: Research subjects were selected by two-stage stratified cluster sampling of the population and housing census data. A total of 5639 subjects aged >18 years, who were not pregnant, and had undergone thyroid function testing during the survey period, were included. MEASUREMENT: The level of serum TSH according to smoking status, iodine intake and presence of TPOAb were evaluated. RESULTS: In the reference population, mean serum TSH level in current smokers (1.87 mIU/L, 95% CI, 0.52-5.37 mIU/L) was significantly lower than that in nonsmokers (2.33 mIU/L, 95% CI, 0.79-6.69 mIU/L, P < .001). The rate of thyroperoxidase antibody (TPOAb) positivity was higher in never smoker (7.7%) than past smokers (5.1%) and current smokers (4.7%), but sex-specific rate of TPOAb was not different according to smoking status. The lower serum TSH levels in current smokers were more apparent in iodine-deficient subjects (UIC < 100 µg/L), and this change was diminished in subjects with UICs between 100 and 299 µg/L. The difference in serum TSH levels in current smokers disappeared in subjects with UICs ≥ 300 µg/L. CONCLUSIONS: Smoking is associated with a left-shift in serum TSH level that is more apparent in iodine-deficient subjects. Smoking status is not associated with the presence of TPOAb or iodine intake. The results suggest that smoking has a direct effect on thyroid function that is not mediated by autoimmune processes in the thyroid gland.

Comparison of thyroglobulin and thyroid peroxidase antibodies measured by five different kits in autoimmune thyroid diseases.

It is generally believed that the detection of thyroid peroxidase antibodies (TPOAb) is superior to that of thyroglobulin antibodies (TgAb) for the diagnosis of Hashimoto's thyroiditis. However, limited data are available on the comparison of TgAb and TPOAb prevalence as a diagnostic measurement for Hashimoto's thyroiditis using sensitive immunoassays. We herein used five different current immunoassay kits (A-E) to compare the prevalence of TgAb and TPOAb in Hashimoto's thyroiditis (n = 70), Graves' disease (n = 70), painless thyroiditis (n = 50), and healthy control subjects (n = 100). In patients with Hashimoto's thyroiditis, positive TgAb was significantly more frequent than positive TPOAb in kits A-D (mean ± SD of the four kits: 98.6 ± 1.7 vs 81.4 ± 2.0%). In patients with Graves' disease, TgAb prevalence was almost equivalent to that of TPOAb in five kits. Patients with painless thyroiditis exhibited positive TgAb significantly more frequently than positive TPOAb in kits A-D (73.5 ± 4.1 vs 33.0 ± 3.4%). The prevalence of TgAb alone was significantly higher than that of TPOAb alone in both Hashimoto's thyroiditis and painless thyroiditis in kits A-D. In kit E, TgAb and TPOAb prevalence did not differ significantly for any disease, and TgAb distribution was different from other kits. In conclusion, the prevalence of TgAb was higher than that of TPOAb in patients with Hashimoto's thyroiditis and painless thyroiditis using commercially available kits. We suggest that TgAb immunoassay is the first choice of screening test for thyroid autoimmune abnormalities in Japan.

Thyroid autoimmunity: is really associated with papillary thyroid carcinoma?

The incidence of thyroid cancer has been greatly increasing. Several studies aimed to investigate biomarkers for prediction of thyroid cancer. Some of these studies have suggested that thyroid autoantibodies (TAb) could be used as predictors of thyroid cancer risk, but the correlation between TAb and PTC is still a matter of debate. The aim of this study is to evaluate thyroid autoimmunity and TAbs in patients with PTC and benign multinodular goiter (MNG) to investigate if TAbs and autoimmune thyroid disease (ATD) could predict thyroid malignancy. A total of 577 patients with thyroid papillary carcinoma (PTC) and 293 patients with benign MNG disease were enrolled postoperatively. Demographic features, thyroglobulin (TgAb) and thyroid peroxidase antibodies (TPOAb) and histologic outcome of the patients were evaluated. The prevalence of ATD and TgAb or TPOAb measurements was not statistically different in PTC and MNG groups. However, tumors were significantly smaller and tumor capsule invasion was seen less frequently in patients with PTC and ATD than without ATD. Patients without ATD had more advanced stage (TNM stage III/IV) tumors than with ATD. Only one of the 11 patients with distant organ metastasis had ATD. The present study demonstrated that the prevalence of ATD diagnosed even with histology or TAb positivity was not different in patients with PTC and MNG. However, having ATD might be associated with a better prognosis in PTC patients.

Initial serum thyroid peroxidase antibodies and long-term outcomes in SREAT.

OBJECTIVE: To quantify clinical outcome in patients with steroid-responsive encephalopathy and associated autoimmune thyroiditis (SREAT) after the acute phase and explore potential associations of initial serum thyroid peroxidase antibody titers (TPO-Abs) with outcome. MATERIALS AND METHODS: Retrospective chart review of patients diagnosed with SREAT between 01/2005 and 05/2014 in a tertiary care center and followed in an affiliated autoimmune outpatient clinic. Outcome was quantified using the extended Glasgow Outcome Scale (GOS-E). We calculated Pearson's correlation coefficients to quantify associations with clinical outcome at follow-up. RESULTS: Among 134 patients with encephalopathy of unknown etiology, we identified 13 patients diagnosed with SREAT. In two patients, the diagnosis was revised at subsequent hospitalization (NMDA-R encephalitis and adult-onset Still's disease). The median follow-up time was 11 months, and the median GOS-E was 6 (range 3-8). Higher serum TPO-Ab-titers correlated with more favorable outcomes (Pearson coefficient 0.65, P = 0.03). CONCLUSION: A correlation between TPO-Ab-titers and outcome has not been reported previously and challenges the notion of a mere bystander role of TPO-Abs in SREAT.

Effect of low-dose selenium on thyroid autoimmunity and thyroid function in UK pregnant women with mild-to-moderate iodine deficiency.

PURPOSE: Selenium is an essential trace mineral and a component of selenoproteins that are involved in the production of thyroid hormones and in regulating the immune response. We aimed to explore the effect of low-dose selenium supplementation on thyroid peroxidase antibody (TPO-Ab) concentration and thyroid function in pregnant women from a mild-to-moderate iodine-deficient population. METHODS: Samples and data were from a secondary analysis of Selenium in PRegnancy INTervention (SPRINT), a double-blind, randomized, placebo-controlled study that recruited 230 women with singleton pregnancies from a UK antenatal clinic at 12 weeks of gestation. Women were randomized to receive 60 µg/day selenium or placebo until delivery. Serum thyroid peroxidase antibodies (TPO-Ab), thyrotropin (TSH) and free thyroxine (FT4) were measured at 12, 20 and 35 weeks and thyroglobulin antibodies (Tg-Ab) at 12 weeks. RESULTS: 93.5% of participants completed the study. Se supplementation had no more effect than placebo in decreasing TPO-Ab concentration or the prevalence of TPO-Ab positivity during the course of pregnancy. In women who were either TPO-Ab or Tg-Ab negative at baseline (Thy-Ab(-ve)), TSH increased and FT4 decreased significantly throughout gestation (P < 0.001), with no difference between treatment groups. In women who were Thy-Ab(+ve) at baseline, TSH tended to decrease and was lower than placebo at 35 weeks (P = 0.050). FT4 fell more on Se than placebo supplementation and was significantly lower at 35 weeks (P = 0.029). CONCLUSIONS: Low-dose selenium supplementation in pregnant women with mild-to-moderate deficiency had no effect on TPO-Ab concentration, but tended to change thyroid function in Thy-Ab(+ve) women.