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PURPOSE: Thyroid peroxidase (TPO) is essential for the synthesis of thyroid hormones. However, specific mutations render TPO antigenic and prone to autoimmune attacks leading to thyroid cancer, TPO deficiency, and congenital hypothyroidism (CH). Despite technological advancement, most experimental procedures cannot quickly identify the genetic causes of CH nor detect thyroid cancer in the early stages. METHODS: We performed saturated computational mutagenesis to calculate the folding energy changes (∆∆G) caused by missense mutations and analyzed the mutations involved in post-translational modifications (PTMs). RESULTS: Our results showed that the functional important missense mutations occurred in the heme peroxidase domain. Through computational saturation mutagenesis, we identified the TPO mutations in G393 and G348 affecting protein stability and PTMs. Our folding energy calculations revealed that seven of nine somatic thyroid cancer mutations destabilized TPO. CONCLUSION: These findings highlight the impact of these specific mutations on TPO stability, linking them to thyroid cancer and other genetic thyroid-related disorders. Our results show that computational mutagenesis of proteins provides a quick insight into rare mutations causing Mendelian disorders and cancers in humans. The effects of TPO mutations linking to thyroid cancer and disorders found via computational mutagenesis. [ABSTRACT FROM AUTHOR]

Hashimoto's thyroiditis (HT) is a prevalent autoimmune disorder marked by chronic inflammation of the thyroid gland, predominantly affecting children and adolescents. In a previous study, we developed a "maximal" mathematical model of thyroid physiology to simulate the complex interactions within the thyroid gland. The present research introduces an enhanced version of the "maximal" model, integrating the pathophysiological impacts of HT. It specifically models the adverse effects of thyroid peroxidase (TPO) and thyroglobulin (Tg) antibodies (TPOAb and TgAb) on TPO, Tg, sodium iodide symporter (NIS), albeit indirectly, and thyroid volume. Additionally, we present a new "minimal" model offering a streamlined interpretation of thyroid physiology and pathophysiology, designed for faster computational analysis while maintaining essential physiological interactions. Both models were fitted against longitudinal clinical data from patients with HT, assessing the concentrations of Thyroid Stimulating Hormone (TSH), Thyroxine (T4), and thyroid volume over 36 months, in both untreated patients and those receiving levothyroxine (LT4) treatment. The adaptation of the models to data shows that both of them accurately reproduce the available observed clinical outcomes, with the "maximal" model providing more detailed physiological insights but requiring extensive data and longer computation times. In contrast, the "minimal" model, despite exhibiting less realistic TSH oscillations, offers rapid parameter estimation and may be more feasible in clinical settings. These models hold significant potential as tools for detailed study and management of HT, enabling simulations of disease progression and therapeutic responses, thus paving the way for personalized treatment strategies. [ABSTRACT FROM AUTHOR]

Background: Excessive saturated fatty acids (SFAs) are known to be detrimental to human health. Although the majority of research and dietary guidelines have focused on the intake of SFAs, there has been limited attention to the relationship between circulating SFA levels and hormonal regulation, such as that of thyroid hormones. Methods: To explore potential associations, we conducted an investigation with 579 participants from the National Health and Nutrition Examination Survey (NHANES) 2011-2012. Subgroup analyses and multivariable linear regression models were used to estimate the relationships between eleven distinct SFA concentrations and various thyroid parameters. Results: For 579 adults, subgroup analysis of thyroid stimulating hormone (TSH) revealed significant differences in nine specific SFAs and the total SFA levels (all p < 0.05). Furthermore, multivariable linear regression analysis identified positive correlations between certain SFAs and various parameters, including TSH, total triiodothyronine (TT3), free triiodothyronine (FT3), thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TgAb), thyroglobulin (Tg), the ratio of FT3 to free thyroxine (FT4) (FT3/FT4), and the thyrotroph T4 resistance index (TT4RI). Conversely, negative correlations were observed between certain SFAs and total thyroxine (TT4), FT4, the ratio of FT3/TT3, and the thyroid feedback quantilebased index (TFQI) (all p < 0.05). Conclusion: These findings collectively suggest associations between SFAs and thyroid parameters, highlighting the need for future studies to elucidate the underlying mechanisms of these interactions. [ABSTRACT FROM AUTHOR]

Objective To explore the association between maternal thyroid peroxidase antibody (TPOAb) exposure and 5- to 6-year-old children's cardiometabolic risk (CMR). Methods A total of 2129 mother–child pairs were recruited from the Ma'anshan Birth Cohort (MABC) study. Serum TPOAb was retrospectively measured in pregnant women using an electrochemiluminescence immunoassay. CMR score was evaluated by the serum glycolipids, blood pressure, and waist circumference for children aged 5-6 years. Growth mixture modelling was used to fit trajectories of TPOAb levels throughout pregnancy. Multiple linear regression models and logistic regression models were used for statistical analyses. Results Two thousand one hundred twenty-nine mother–child pairs (mean [SD] age, 26.6 [3.6] years) were enrolled for the final study. Maternal TPOAb exposure in the first trimester increased children's overall CMR, glucose level, HOMA-IR, triglyceride level, boys' overall CMR, boys' glucose level, and girls' glucose level. TPOAb exposure in the first trimester was also associated with lower boys' high-density lipoprotein cholesterol (HDL-C) level. In the second trimester, maternal TPOAb exposure was positively associated with children's triglyceride level. Compared with low TPOAb trajectory, children with high maternal TPOAb trajectory had an increased risk of developing high CMR (OR = 3.40; 95% CI, 1.30-8.90), hyperglycemia (OR = 5.20; 95% CI, 2.20-12.28), insulin-resistance (adjusted OR = 2.12; 95% CI, 1.10-4.07), and hypertriglyceridemia (OR = 2.55; 95% CI, 1.06-6.14). Conclusions The first trimester of pregnancy is a critical period for maternal TPOAb exposure to affect CMR in children, with some sex specificity, mainly to the detriment of boys. [ABSTRACT FROM AUTHOR]

The mechanisms underlying subclinical hypothyroidism (SCH) remain unclear, making timely and accurate differentiation between hypothyroidism and SCH, as well as severity assessment, challenging. This study aimed to investigate the role of NFE2 like bZIP transcription factor 2 (Nrf2), gp91phox, and interleukin-17 (IL-17) in the pathogenesis of SCH. In this prospective comparative study, 105 SCH patients, 105 hypothyroidism patients, and 105 healthy individuals were enrolled from January 2022 to August 2023. SCH patients were categorized into mild-moderate and severe groups based on thyroid-stimulating hormone (TSH) levels. Levels of TSH, free T4 (FT4), free T3 (FT3), thyroglobulin antibodies (TG-Ab), thyroid peroxidase antibodies (TPO-Ab), cholesterol (TC), triglycerides (TG), high-density lipoprotein-cholesterol (HDL-ch), and low-density lipoprotein-cholesterol (LDL-ch) were measured. Nrf2, IL-1β, IL-6, IL-17, and gp91phox levels were tested using ELISA. Nrf2, IL-17 and gp91phox were significantly higher in SCH and hypothyroidism patients compared to the healthy controls, with hypothyroidism patients showing the highest levels. Nrf2 levels were negatively correlated with TSH, TG-Ab and IL-17, but not gp91phox. Nrf2, IL-17 and gp91phox could be used for diagnosis of SCH and severe SCH. Only TG-Ab, IL-17 and gp91phox were independent risk factors for severe SCH. This study demonstrates a negative correlation between serum Nrf2 levels and SCH severity. TG-Ab, IL-17, and gp91phox are independent risk factors, and their associations with SCH pathology suggest their potential roles in the disease mechanism. These findings provide insights into SCH pathogenesis and highlight the need for further research to elucidate their diagnostic or prognostic significance. [ABSTRACT FROM AUTHOR]

Background: Exposure to particles with an aerodynamic diameter of ≤2.5 μm (PM2.5) is associated with the occurrence of thyroid dysfunction among pregnant women and neonates, but it is not known if this association occurs in the general population. We aimed to determine the association of prolonged exposure to PM2.5 with the prevalence of thyroid disorders among adults in China. Methods: A nationally representative cross-sectional study of thyroid disorders, iodine status, and diabetes status was carried out in all 31 provinces across China from 2015 to 2017. In total, 73,900 adults aged 18 years and older were included. Serum concentrations of thyroid hormones, thyrotropin, and thyroid antibodies and the urine iodine concentration were measured. The environmental concentration of PM2.5 for each participant's residential address at a spatial resolution of 1 × 1 km was estimated. Results: The average long-term exposure to PM2.5 at residential addresses was 66.41 μg/m3, ranging from 17.58 μg/m3 to 120.40 μg/m3. Compared with that of individuals with lower exposure levels, the prevalence of thyroid diseases such as autoimmune thyroiditis and subclinical hypothyroidism was greater in those with PM2.5 concentrations within the third quartile range (60.18 to 73.78 μg/m3). Compared with those in the first quartile (17.58 to 46.38 μg/m3), participants in the highest PM2.5 quartile (73.78 to 120.40 μg/m3) presented an increased risk of overt hypothyroidism (OR 1.23 [CI 0.94–1.61]), subclinical hypothyroidism (1.10 [1.01–1.21]), autoimmune thyroiditis (1.09 [1.00–1.18]), and thyroglobulin antibody positivity (1.17 [1.07–1.29]). However, there was no association between PM2.5 exposure and overt hyperthyroidism, subclinical hyperthyroidism, Graves' disease, or thyroid peroxidase antibody positivity (p > 0.05). Each 10 μg/m³ increase in the PM2.5 concentration was associated with an increased risk of overt hypothyroidism (OR 1.05 [1.00–1.11]), subclinical hypothyroidism (1.02 [1.00–1.03]), and thyroglobulin antibody positivity (1.02 [1.00–1.04]). Furthermore, a nearly linear exposure–response relationship was observed between long-term PM2.5 exposure and thyroglobulin antibody positivity. Conclusions: PM2.5 exposure was associated with thyroid disorders among Chinese adults. A dose–response relationship between PM2.5 exposure and autoimmune thyroiditis, as well as thyroglobulin antibody positivity, was also observed. [ABSTRACT FROM AUTHOR]

Background: To examine the incidence of overt hypothyroidism 1 and 5 years after pregnancies where screening before 21 weeks identified subclinical hypothyroidism (SH) or hypothyroxinemia (HT). Methods: Secondary analysis of two multicenter treatment trials for either SH or HT diagnosed between 8 and 20 weeks gestation. Current analyses focus only on individuals randomized to the placebo groups in the two parallel studies. SH was diagnosed with thyrotropin (TSH) ≥4.0 mU/L and normal free T4 (fT4) (0.86–1.9 ng/dL). HT was diagnosed with normal TSH (0.08–3.99 mU/L) but fT4 <0.86 ng/dL. Serum from initial testing was stored for later thyroid peroxidase (TPO) antibody assay; results were not returned for clinical management. At 1 and 5 years after delivery, participants were asked whether they had either been diagnosed with or were being treated for a thyroid condition. Maternal serum was collected at these visits and thyroid function measured. Subsequent overt hypothyroidism was defined as TSH ≥4.0 mU/L with fT4 <0.86 ng/dL. Results: Data for 1- and 5-year follow-up were available in 307 of the 338 participants with SH and 229 of the 261 with HT. Subsequent hypothyroidism was more common both at year 1 (13.4% vs. 3.1%, p < 0.001) and year 5 (15.6% vs. 2.6%, p < 0.001) for participants with SH compared with those with HT. This progression was more common in individuals with TSH values >10 mIU/mL. Baseline TPO level >50 IU/mL in participants with SH was associated with higher rates of hypothyroidism at year 1 (26.7% vs. 6.5%, odds ratio [OR] = 5.3 [confidence interval (CI) 2.6–10.7]) and year 5 (30.5% vs. 7.5%, OR = 5.4 [CI: 2.8–10.6]) compared with those with TPO levels ≤50 IU/mL. For participants with HT, no differences in overt hypothyroidism were seen at 1 year related to baseline TPO level >50 IU/mL (1/10 (10%) vs. 6/218 (2.8%), OR = 3.9 [CI: 0.43–36.1]), but more participants with TPO levels >50 IU/mL developed hypothyroidism by year 5 (2/10 (20%) vs. 4/218 (1.8%), OR = 13.4 [CI: 2.1–84.1]). Conclusion: SH is associated with higher rates of overt hypothyroidism or thyroid replacement therapy within 5 years of delivery than is HT when these conditions are diagnosed in the first half of pregnancy. [ABSTRACT FROM AUTHOR]

Introduction: Graves' disease (GD) is the most common cause of hyperthyroidism and can affect multiple systems of the body. Currently, commonly-used treatment methods for GD have a series of shortcomings. In contrast, traditional Chinese medicine has been proven to be effective in inhibiting the progression of GD and is expected to become a key direction for the development of new drugs in the future. Therefore, a network metaanalysis was performed to compare the impacts of different traditional Chinese medicines on the curative effect, thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), thyroglobulin antibody (TGAb), thyroid peroxidase antibody (TPOAb) and thyrotropin receptor antibody (TRAb) in patients with GD. Methods: PubMed, Embase, Cochrane Library, Web of Science, WanFang, Weipu, and CNKI were searched for the randomized controlled trials of traditional Chinese medicine on GD patients up to 19 December 2023. The quality of the included studies was evaluated regarding the risk of bias, and the data were analyzed by R software. Results: Thirty-five articles were included in the analysis, involving 2828 GD patients and traditional Chinese medicines including Bailing Capsule, Jinshuibao Capsule, Astragalus injection, Jiakangling Tablet, Jiakangling Capsule, Tripterygium Wilfordii, Sanjie Xiaoying Decoction, Prunella vulgaris (L.) Oral Liquid, P. vulgaris (L.) Granules, Xiehuo Xiaoying Recipe, Xiehuo Yangyin Powder, Yikang Pill and Yinjia Pellet. The results of network meta-analysis suggested that for GD patients, Bailing Capsule, Jiakangling Capsule, Tripterygium wilfordii, P. vulgaris (L.) Oral Liquid and Yinjia Pellet had better curative effect compared with Western medicine. Prunella vulgaris (L.) Granules and Yikang Pill could improve the TSH level. Prunella vulgaris (L.) Granules, P. vulgaris (L.) Oral Liquid and Yikang Pill could reduce FT3 level. Jiakangling Capsule, P. vulgaris (L.) Granules, P. vulgaris (L.) Oral Liquid and Yikang Pill could reduce the FT4 level. Prunella vulgaris (L.) Oral Liquid can reduce the level of TPOAb and TRAb. Besides, Yinjia Pellet was the most helpful in improving the curative effect. Yikang Pill could best improve TSH. Prunella vulgaris (L.) Granules had the best effect on reducing FT3. Prunella vulgaris (L.) Granules performed best in reducing FT4. Prunella vulgaris (L.) Oral Liquid had the most favorable effect on reducing TPOAb and TRAb. Conclusion: Based on the current research, it is safe to conclude that Chinese medicine can improve the curative effect and TSH level of patients with GD, and reduce the levels of FT3, FT4, TPOAb and TRAb. Besides, Yinjia Pellet is the most helpful in improving the curative effect. Yikang Pill can best improve TSH. Prunella vulgaris (L.) Granules have the best effect on reducing FT3. Prunella vulgaris (L.) Granules perform best in reducing FT4. Prunella vulgaris (L.) Oral Liquid has the most favorable effect on reducing TPOAb and TRAb. [ABSTRACT FROM AUTHOR]

Background and Objectives: The available research suggests that dietary patterns with high inflammatory potential, as indicated by a high DII score, may exacerbate inflammation and potentially influence thyroid function. Therefore, the aim of this study was to investigate the associations between the inflammatory potential of a diet and thyroid function in adults with Hashimoto's thyroiditis (HT). Materials and Methods: A total of 149 adults diagnosed with Hashimoto's thyroiditis were enrolled in this observational, cross-sectional, multicenter study. The Dietary Inflammatory Index (DII®) was calculated using a 141-item food frequency questionnaire (FFQ). The serum levels of the thyroid-stimulating hormone (TSH), free thyroxine (fT4), thyroid peroxidase antibodies (TPO-Ab), and high-sensitivity C-reactive protein (hsCRP) were determined. Results: The DII® scores ranged from −3.49 (most anti-inflammatory) to +4.68 (most pro-inflammatory), whereas three DII® tertile ranges were defined as <−1.4, −1.39 to +1.20, and >+1.21, respectively. Participants in tertile 1 (more anti-inflammatory diet) had significantly higher levels of fT4 than those adhering to a more pro-inflammatory diet (p = 0.007). The levels of hsCRP and TSH appeared to increase with increasing the DII® score, but without statistical significance. A significant association was found between the DII® and TSH (β = 0.42, p < 0.001) and between DII® and free thyroxine (β = 0.19, p < 0.001). After adjustment for age, gender, energy intake, and physical activity, a significant positive correlation remained between the DII® and TSH (β = 0.33, p = 0.002) and between the DII® and body mass index (BMI) (β = 0.14, p = 0.04). Conclusions: Adherence to an anti-inflammatory diet appears to be beneficial in patients with Hashimoto's thyroiditis, suggesting that dietary modification aimed at lowering DII® levels may be a valuable strategy to improve clinical outcomes in these patients. [ABSTRACT FROM AUTHOR]

Disruption of the thyroid hormone (TH) system is connected with diverse adverse health outcomes in wildlife and humans. It is crucial to develop and validate suitable in vitro assays capable of measuring the disruption of the thyroid hormone (TH) system. These assays are also essential to comply with the 3R principles, aiming to replace the ex vivo tests often utilised in the chemical assessment. We compared the two commonly used assays applicable for high throughput screening [Luminol and Amplex UltraRed (AUR)] for the assessment of inhibition of thyroid peroxidase (TPO, a crucial enzyme in TH synthesis) using several cell lines and 21 compounds from different use categories. As the investigated cell lines derived from human and rat thyroid showed low or undetectable TPO expression, we developed a series of novel cell lines overexpressing human TPO protein. The HEK-TPOA7 model was prioritised for further research based on the high and stable TPO gene and protein expression. Notably, the Luminol assay detected significant peroxidase activity and signal inhibition even in Nthy-ori 3-1 and HEK293T cell lines without TPO expression, revealing its lack of specificity. Conversely, the AUR assay was specific to TPO activity. Nevertheless, despite the different specificity, both assays identified similar peroxidation inhibitors. Over half of the tested chemicals with diverse structures and from different use groups caused TPO inhibition, including some widespread environmental contaminants suggesting a potential impact of environmental chemicals on TH synthesis. Furthermore, in silico SeqAPASS analysis confirmed the high similarity of human TPO across mammals and other vertebrate classes, suggesting the applicability of HEK-TPOA7 model findings to other vertebrates. [ABSTRACT FROM AUTHOR]

Tetramethyl thiram disulfide (thiram) is a dimethyldithiocarbamate (DTC) pesticide and is widely used in China, but its high residue has caused widespread concern. In this study, we used zebrafish (Danio rerio) embryos as animal models to explore the relationship between notochord curvature and thyroxine caused by thiram in zebrafish embryos. Zebrafish embryos at 3 hours postfertilization (3 hpf) were exposed to low concentrations of thiram (0, 0.0024, 0.024, and 0.24 mg/L) for short-term (10, 30 min) or continuous exposure (1-4 d), and the relevant indicators were observed at 24, 48, 72, and 96 hpf. HPLC analysis results showed that the detectable concentration of thiram in zebrafish was 0.13 mg/kg (exposure from 3 hpf to 72 hpf). Morphological results showed that even short-term (30 min) thiram exposure increased mortality, delayed hatching, and caused notochord curvature in zebrafish embryos. Thiram exposure resulted in a decrease in gene expression of the thyroxine-related gene thyroid peroxidase (TPO). The detection of hormone levels indicated that thiram caused a decrease in the levels of tetraiodothyronine (T4) and triiodothyronine (T3). The results of this study indicate that one-time, short-term exposure to thiram still causes toxic effects on zebrafish embryos, and this effect may be related to thyroid hormones. This study also provides ideas for biological monitoring of dithiocarbamate pesticides. [ABSTRACT FROM AUTHOR]

Background: Maternal hypothyroidism in pregnancy has been proposed to increase the risk of preeclampsia, but uncertainties persist regarding the underlying causal mechanisms. Thus, it remains unclear if an increased risk of preeclampsia in hypothyroid pregnant women is caused by the lack of thyroid hormones or by the autoimmunity per se. Methods: We conducted a retrospective study of two pregnancy cohorts in the Danish population. The nationwide cohort (n = 1,014,775) was register-based and included all singleton pregnancies in Denmark from 1999–2015. The regional cohort (n = 14,573) included the biochemical measurement of thyroid stimulating hormone (TSH), thyroid peroxidase antibodies (TPO-Ab), and thyroglobulin antibodies (Tg-Ab) (ADVIA Centaur XPT, Siemens Healthineers) among pregnant women in The North Denmark Region from 2011–2015 who had a blood sample drawn in early pregnancy as part of routine prenatal screening for chromosomal anomalies. The associations between diagnosed and biochemically assessed hypothyroidism and a diagnosis of preeclampsia were evaluated using logistic regression (adjusted odds ratio (aOR) with 95% confidence interval (CI)) adjusting for potential confounders, such as maternal age, diabetes, and parity. Results: In the nationwide cohort, 2.2% of pregnant women with no history of hypothyroidism (reference group (ref.)) were diagnosed with preeclampsia, whereas the prevalence was 3.0% among pregnant women with hypothyroidism (aOR 1.3 (95% CI: 1.2–1.4)) and 4.2% among women with newly diagnosed hypothyroidism in the pregnancy (aOR 1.6 (95% CI: 1.3–2.0)). In the regional cohort, 2.3% of women with early pregnancy TSH < 2.5 mIU/L (ref.) were diagnosed with preeclampsia. Among women with TSH ≥ 6 mIU/L, the prevalence was 6.2% (aOR 2.4 (95% CI: 1.1–5.3)). Considering thyroid autoimmunity, preeclampsia was diagnosed in 2.2% of women positive for TPO-Ab (> 60 U/mL) or Tg-Ab (> 33 U/mL) in early pregnancy (aOR 0.86 (95% CI: 0.6–1.2)). Conclusions: In two large cohorts of Danish pregnant women, maternal hypothyroidism was consistently associated with a higher risk of preeclampsia. Biochemical assessment of maternal thyroid function revealed that the severity of hypothyroidism was important. Furthermore, results did not support an association between thyroid autoimmunity per se and preeclampsia. [ABSTRACT FROM AUTHOR]

Background: An association between maternal thyroid dysfunction throughout pregnancy and the subsequent risk of neurodevelopmental abnormalities in offspring has been demonstrated. However, the potential effects of maternal thyroid autoimmunity on neurodevelopment in the absence of maternal hypothyroidism remain unclear. Therefore, in this study, we explored the association between maternal thyroid peroxidase antibody (TPOAb) positivity and cognitive development in preschool children. Methods: A total of 1849 mother-child pairs were recruited from the Ma'anshan Birth Cohort (MABC) Study. During the follow-up period, an electrochemiluminescence immunoassay was used to retrospectively measure serum TPOAb levels in pregnant women. The cognitive development of preschool children was evaluated by using the Chinese version of the Wechsler Preschool and Primary Scale of Intelligence-Fourth Edition (WPPSI-IV). A growth mixture model was used to fit the trajectory of TPOAb. Multiple linear regression and logistic regression models were used to explore the associations between the developmental trajectory of TPOAb-positivity at different gestational periods and the cognitive development of preschool children by sex. Results: A total of 1849 mother—child pairs (mean [SD] age: 26.7 [3.6] years) were enrolled in the final study. Maternal TPOAb positivity in the first trimester was associated with a risk of below-average processing speed index in girls (OR: 2.07; 95% CI 1.06 to 4.01) and below-average full-scale intelligence quotient (FSIQ) in boys (OR: 2.36; 95% CI: 1.10 to 5.05). Maternal TPOAb positivity in the third trimester (T3) was associated with below-average working memory index (WMI) (OR: 2.51; 95% CI: 1.02 to 6.20) in girls. In girls, the WMI (β = −3.17, 95% CI: −5.82 to −0.52), fluid reasoning index (FRI) (β = −4.49, 95% CI: −7.18 to −1.80), and FSIQ score (β = −2.43, 95% CI: −4.77 to −0.08) decreased, whereas in mothers, the level of log-transformed thyroid peroxidase antibody (lgTPOAb) increased during pregnancy. Conclusions: Positive maternal TPOAb levels during pregnancy may be associated with poorer cognitive development in preschool children. These findings require independent confirmation in other populations. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) has been considered a T cell-mediated autoimmune demyelinating disorder. Nuclear factor κB (NF-κB) is one of the master transcription factors that regulate the activity of inflammatory cells the present study aimed to investigate the NFKB/P65 mRNA levels in patients with MS and to assess its role in the prediction of Hashimoto' thyroiditis (HT). Methods: 50 patients with clinically definite relapsing-remitting multiple sclerosis (according to the McDonald criteria 2017) compared to 50 healthy age and sex-matched controls. Thyroid serum antibodies, IgG index (IgG), and oligoclonal band (OCB) were assessed. The relative expression of NFKB/P65 mRNA was measured using real-time quantitative PCR. Results: there were significantly higher values of NFKB/P65 mRNA levels in patients with HT (2.4±0.54) compared to other patients without HT (1.3±1.45) and control group (0.8±0.17), p <0 .001. Significant associations were confirmed between NFKB/P65 mRNA correlated to thyroid autoimmunity and MS manifestations, p <0. 001. Linear regression revealed that only FT4 and TSH were independent variables correlated with NFKB/P65 mRNA, p < 0.001. Regarding prediction of MS, ROC curve revealed that the sensitivity of NFKB/P65 mRNA was 96 %, and specificity was 88% at cutoff 0.98 with (95% CI = 0.909-0.999). Concerning HT prediction, the cutoff 1.42 with (95% CI = 0.843-1.000)with a sensitivity of 93.8 % and, a specificity of 87.4%. Conclusions: NFKB/P65 mRNA increased in patients with MS more specifically in HT. Thus, NFKB/P65 mRNA could be used as noninvasive prediction markers of MS and HT. [ABSTRACT FROM AUTHOR]

Background and Objectives: Hashimoto's thyroiditis (HT) is an autoimmune disease, characterized by abnormal elevation in thyroid peroxidase antibody and/or thyroglobulin antibody. In recent decades, HT disease has become more and more widespread. Patients always report multiple symptoms, even though their thyroid hormone levels are kept in normal ranges. However, no treatment exists to effectively reduce the levels of thyroid antibodies. Our study aims to determine whether calorie-restricted diet is helpful in improving health of HT patients. Methods and Study Design: This is a 3-month randomized controlled trial. HT patients will be randomized into a calorie-restricted (CR) group or a calorie-unrestricted control group. All the participants will be instructed to consume a diet that includes a combination of 45-55% calories from carbohydrates, 20-30% from fats, and 15- 25% from proteins, according to current Chinese Dietary Guidelines. Participants in CR group need to limit their calories intake equal to their basal energy expenditure, which means that their daily caloric intake will be limited by about 20-30%. Results: The study population is planned to be 66 HT patients aged 18 to 65 years. The primary outcome is change of thyroid antibody levels from baseline. Secondary outcomes include the changes of nonhypothyroid symptoms scores, thyroid function indexes, morphology of thyroid, T lymphocyte subpopulations, inflammatory biomarkers and lipids from baseline to 12 weeks. Conclusions: This trial will have implications for nutrition treatment policy in regard to thyroid antibodies control, immune dysfunction and related nonhypothyroid symptoms improvement among HT patients. [ABSTRACT FROM AUTHOR]

Background and Objectives: Congenital thyroid dyshormonogenesis is caused by alterations in the synthesis of thyroid hormones in a newborn. Additionally, 10 to 20% of these cases are hereditary, caused by defects in proteins involved in hormonal synthesis. One of the most common causes is mutations in the thyroid peroxidase (TPO) enzyme gene, an autosomal recessive disease. We aimed to detect mutations of the TPO gene in 12 Chilean patients with congenital hypothyroidism due to dyshormonogenesis (CHD) and to characterize these patients clinically and molecularly. Materials and Methods: Twelve patients under 20 years of age with CHD, controlled at San Juan de Dios Hospital in Santiago, Chile, were selected according to the inclusion criteria: elevated neonatal TSH, persistent hypothyroidism, and thyroid normotopic by imaging study. Those with deafness, Down syndrome, and central or transient congenital hypothyroidism were excluded. Blood samples were taken for DNA extraction, and the 17 exons and exon–intron junctions of the TPO gene were amplified by PCR. The PCR products were sequenced by Sanger. Results: Two possibly pathogenic mutations of the TPO gene were detected: c.2242G>A (p.Val748Met) and c.1103C>T (p.Pro368Leu). These mutations were detected in 2 of 12 patients (16.6%): 1 was compound heterozygous c.1103C>T/c.2242G>A, and the other was heterozygous for c.2242G>A. In the diagnostic confirmation test, both patients presented diffuse hyper-uptake goiter on thyroid scintigraphy and high TSH in venous blood (>190 uIU/mL). Conclusions: The frequency of patients with possibly pathogenic mutations in TPO with CHD was 16.6%. Its study would allow for genetic counseling to be offered to the families of affected patients. [ABSTRACT FROM AUTHOR]

Although measurements of blood triiodothyronine (T3), thyroxine (T4), and thyroid‐stimulating hormone (TSH) levels in rodent toxicity studies are useful for detection of antithyroid substances, assays for these measurements are expensive and can show high variability depending on blood sampling conditions. To develop more efficient methods for detecting thyroid disruptors, we compared histopathological and immunohistochemical findings in the thyroid and pituitary glands with blood hormone levels. Six‐week‐old male and female Sprague–Dawley rats (five rats per group) were treated with multiple doses of the thyroid peroxidase inhibitors propylthiouracil (PTU) and methimazole by gavage for 28 days. Significant decreases in serum T3 and T4 and increases in TSH were observed in the ≥1 mg/kg PTU and ≥3 mg/kg methimazole groups. An increase in TSH was also detected in male rats in the 0.3 mg/kg PTU group. Histopathological and immunohistochemical analyses revealed that follicular cell hypertrophy and decreased T4 and T3 expressions in the thyroid gland were induced at doses lower than doses at which significant changes in serum hormone levels were observed, suggesting that these findings may be more sensitive than blood hormone levels. Significant increases in thyroid weights, Ki67‐positive thyroid follicular cell counts, and TSH‐positive areas in the pituitary gland were detected at doses comparable with those at which changes in serum T4 and TSH levels were observed, indicating that these parameters may also be useful for evaluation of antithyroid effects. Combining these parameters may be effective for detecting antithyroid substances without relying on hormone measurements. In rats treated with PTU and MMI for 28 days, histopathological and immunohistochemical findings and serum hormone levels were compared to establish a simplified method for detecting antithyroid chemicals. The results demonstrated that histopathological analysis and T4 immunostaining in the thyroid gland were more sensitive parameters than blood hormone levels and that immunohistochemistry for thyroid Ki67 and pituitary TSH may also be useful for evaluation. [ABSTRACT FROM AUTHOR]

Research on modulation of iodine uptake by thyroid cells could help improve radioiodine treatment of dogs with thyroid tumors. The aim of this study was to characterize the immunohistochemical expression of thyroid transcription factor-1 (TTF-1), thyroglobulin, thyrotropin receptor (TSHR), sodium iodide symporter (NIS), pendrin, thyroid peroxidase (TPO), vimentin, and Ki-67 in follicular cell thyroid carcinomas (FTCs) and medullary thyroid carcinomas (MTCs), and to compare protein expression between FTC causing hyperthyroidism and FTC of euthyroid dogs. Immunohistochemistry was performed in 25 FTCs (9 follicular, 8 follicular-compact, and 8 compact) and 8 MTCs. FTCs and MTCs were positive for TTF-1, and expression was higher in FTCs of euthyroid dogs compared with FTCs of hyperthyroid dogs (P =.041). Immunolabeling for thyroglobulin was higher in follicular and follicular-compact FTCs compared with compact FTCs (P =.001), while vimentin expression was higher in follicular-compact FTCs compared with follicular FTCs (P =.011). The expression of TSHR, NIS, pendrin, and TPO was not significantly different among the different subtypes of FTCs or between FTCs causing hyperthyroidism and FTCs in euthyroid dogs. TSHR, NIS, pendrin, and TPO were also expressed in MTCs. Ki-67 labeling index was comparable between FTCs and MTCs, and between FTCs causing hyperthyroidism and FTCs in euthyroid dogs. Proteins of iodine transport were also expressed in canine MTCs, which could have implications for diagnosis and treatment. The different expression of thyroglobulin and vimentin between FTC histological subtypes could reflect variations in tumor differentiation. [ABSTRACT FROM AUTHOR]

Background: Numerous organs, including the thyroid gland, depend on vitamin D to function normally. Insufficient levels of serum 25-hydroxyvitamin D [25(OH)D] are seen as a potential factor contributing to the emergence of several thyroid disorders, however, the causal relationship remains unclear. Here we use a Mendelian randomization (MR) approach to investigate the causal effect of serum 25(OH)D concentration on the indicators of thyroid function. Methods: We conducted a two-sample MR analysis utilizing summary data from the most extensive genome-wide association studies (GWAS) of serum 25(OH)D concentration (n = 443,734 and 417,580), thyroid-stimulating hormone (TSH, n = 271,040), free thyroxine (fT4, n = 119,120), free triiodothyronine (fT3, n = 59,061), total triiodothyronine (TT3, n = 15,829), as well as thyroid peroxidase antibody levels and positivity (TPOAb, n = 12,353 and n = 18,297), low TSH (n = 153,241), high TSH (n = 141,549), autoimmune hypothyroidism (n = 287,247) and autoimmune hyperthyroidism (n = 257,552). The primary analysis was conducted using the multiplicative random-effects inverse variance weighted (IVW) method. The weighted mode, weighted median, MR-Egger, MR-PRESSO, and Causal Analysis Using Summary Effect estimates (CAUSE) were used in the sensitivity analysis. Results: The IVW, as well as MR Egger and CAUSE analysis, showed a suggestive causal effect of 25(OH)D concentration on high TSH. Each 1 SD increase in serum 25(OH)D concentration was associated with a 12% decrease in the risk of high TSH (p = 0.02). Additionally, in the MR Egger and CAUSE analysis, we found a suggestive causal effect of 25(OH)D concentration on autoimmune hypothyroidism. Specifically, each 1 SD increase in serum 25(OH)D concentration was associated with a 16.34% decrease in the risk of autoimmune hypothyroidism (p = 0.02). Conclusions: Our results support a suggestive causal effect which was negative in direction across all methods used, meaning that higher genetically predicted vitamin D concentration possibly lowers the odds of having high TSH or autoimmune hypothyroidism. Other thyroid parameters were not causally influenced by vitamin D serum concentration. [ABSTRACT FROM AUTHOR]

Vitamin D, an essential nutrient, plays a crucial role in numerous biological functions, acting as a hormone and being important for the proper functioning of the immune system. This review illustrates the interactions between adequate vitamin D levels and an appropriate immune response, highlighting the implications for Hashimoto's thyroiditis (HT), a chronic inflammation of the thyroid characterized by the production of autoantibodies. A comprehensive review of the existing literature shows that vitamin D inhibits the secretion of pro-inflammatory cytokines, leading to an improvement in the clinical picture in HT by switching from a pro-inflammatory to immune balance. Vitamin D supplementation has been shown to reduce elevated serum levels of thyroid peroxidase antibodies, a key marker of HT. Although the results are conflicting, the evidence suggests that an adequate vitamin D intake supports the immune function and counteracts autoimmune conditions such as HT by improving their symptoms. There is evidence of vitamin D's key role in supporting the immune system function and managing autoimmunity, such as in HT. An adequate vitamin D intake is crucial for improving the clinical picture and the symptoms of HT. [ABSTRACT FROM AUTHOR]

The main goal of this research was to determine whether there is a correlation between adherence to the Mediterranean diet (assessed by the Mediterranean Diet Serving Score (MDSS)) and parameters indicating thyroid gland activity, such as concentration of thyroid-stimulating hormone (TSH), thyroid hormones (free triiodothyronine (fT3), free thyroxine (fT4)), thyroglobulin (Tg), antibodies to thyroid proteins (thyroglobulin antibodies (TgAb) and thyroid peroxidase antibodies (TPOAb)), and calcitonin (CT) in plasma and serum samples. An additional objective was to investigate whether there are differences in the values of the MDSS among clinical groups (euthyroid individuals, euthyroid individuals with positive TgAb and/or TPOAb, and hypothyroid and hyperthyroid participants). This cross-sectional study included 4620 participants over 18 years of age from the islands of Korčula and Vis, and the mainland city of Split. The MDSS was assessed from a food frequency questionnaire (FFQ). MDSS values were significantly higher in females compared to males and showed a positive association with the age of the participants. There was no significant difference in the MDSS values among the examined clinical groups. In the group of subjects with euthyroidism, a significant positive association was found between fT3 and the MDSS, while in the group of subjects with subclinical hypothyroidism, a significant positive association was observed between the MDSS and both fT3 and fT4. CT levels were also positively associated with the MDSS. Considering the significant positive association of the MDSS and both fT3 and fT4 levels in patients with subclinical hypothyroidism, the results of this study could be used to create guidelines for selecting an appropriate, potentially protective diet for these patients. [ABSTRACT FROM AUTHOR]

Background and objectives: Hypothyroidism is a clinical condition that needs primary care. It is increased with age and is more prevalent in females. Hypothyroidism is diagnosed biochemically, being overt primary hypothyroidism defined as serum thyroid stimulating hormone (TSH) concentrations above and thyroxin concentrations below the normal reference range. Methods: For this purpose, 180 subjects (40 control groups and 70 patients with hypothyroidism underwent treatment for 3 months) were selected for the study. The study materials were registered from the laboratories in Kirkuk city. Results: The results are summarized in the following points: zinc-α2-glycoprotein was highly significantly increased (p<0.001) in hypothyroid patients compared to the control group, according to before and after treatment. Serum Level of Ischemia Modified Albumin (IMA) was non significantly difference (0.852) in hypothyroid patients compared to the control group, according to before and after treatment. Serum Level of Human TPO (Thyroid Peroxidase) in Women was significantly difference (0.0001 significant) in hypothyroid patients compared to the control group, according to before and after treatment. The parameters of Thyroid hormones TSH, T3 and T4 were highly significantly increased (p<0.001) in the serum of hypothyroid patients compared to the control group, according to before and after treatment. Conclusions: Zinc-α2-glycoprotein levels were significantly higher in patients with hypothyroidism, and no significant differences in IMA levels before and after treatment with levothyroxine in hypothyroid patients, indicating that the differences in IMA levels were due to hypothyroidism itself. [ABSTRACT FROM AUTHOR]

Introduction: Congenital hypothyroidism (CH), the most common neonatal endocrine disorder worldwide, can be caused by variants in the thyroid peroxidase (TPO) gene. This study aimed to identify TPO variants in Chinese patients with CH, analyze their impact on TPO function, and establish relationships between TPO genotypes and clinical characteristics. Methods: A total of 328 patients with CH were screened for TPO variants by performing whole-exome sequencing. The function of the detected TPO variants was investigated via transfection assays in vitro. The pathogenic effect of five novel variants was further assessed in silico. Results: Among 328 patients with CH, 19 TPO variants, including six novel ones, were identified in 43 patients. Eighteen patients (5.5%) carried biallelic TPO variants. In vitro experiments showed that TPO activity was impaired to varying degrees in 17 variants. Furthermore, we determined that a residual TPO enzyme activity threshold of 15% may serve as a criterion for differentiating CH severity. Conclusions: According to our study, the prevalence of TPO variants among Chinese patients with CH was 13.1%. Five novel variants led to impaired TPO function by altering its structure or by affecting its expression or cellular localization, which should result in impaired thyroid hormone synthesis. [ABSTRACT FROM AUTHOR]

Background: Congenital hypothyroidism (CH) is caused by mutations in cysteine residues, including Cys655 and Cys825 that form disulfide bonds in thyroid peroxidase (TPO). It is highly likely that these disulfide bonds could play an important role in TPO activity. However, to date, no study has comprehensively analyzed cysteine mutations that form disulfide bonds in TPO. In this study, we induced mutations in cysteine residues involved in disulfide bonds formation and analyzed their effect on subcellular localization, degradation, and enzyme activities to evaluate the importance of disulfide bonds in TPO activity. Methods: Vector plasmid TPO mutants, C655F and C825R, known to occur in CH, were transfected into HEK293 cells. TPO activity and protein expression levels were measured by the Amplex red assay and Western blotting. The same procedure was performed in the presence of MG132 proteasome inhibitor. Subcellular localization was determined using immunocytochemistry and flow cytometry. The locations of all disulfide bonds within TPO were predicted using in silico analysis. All TPO mutations associated with disulfide bonds were induced. TPO activity and protein expression levels were also measured in all TPO mutants associated with disulfide bonds using the Amplex red assay and Western blotting. Results: C655F and C825R showed significantly decreased activity and protein expression compared with the wild type (WT) (p < 0.05). In the presence of the MG132 proteasome inhibitor, the protein expression level of TPO increased to a level comparable with that of the WT without increases in its activity. The degree of subcellular distribution of TPO to the cell surface in the mutants was lower compared with the WT TPO. Twenty-four cysteine residues were involved in the formation of 12 disulfide bonds in TPO. All TPO mutants harboring an amino acid substitution in each cysteine showed significantly reduced TPO activity and protein expression levels. Furthermore, the differences in TPO activity depended on the position of the disulfide bond. Conclusions: All 12 disulfide bonds play an important role in the activity of TPO. Furthermore, the mutations lead to misfolding, degradation, and membrane insertion. [ABSTRACT FROM AUTHOR]

A 7‐month‐old male French bulldog was referred for abnormal mentation and gait. Physical examination revealed a dome shaped calvarium and persistent bregmatic fontanelle. Neurological examination revealed proprioceptive ataxia, pelvic limb paraparesis and strabismus with moderate ventriculomegaly, thinning of the cerebral parenchyma, and widened cerebral sulci on magnetic resonance imaging. Masses were identified in the region of the thyroid, which appeared heterogeneous and hyperintense in T1‐weighted and T2‐weighted compared with the adjacent muscle signal masses were identified. Radiological diagnosis was hydrocephalus "ex vacuo" and goiter. Blood test revealed abnormally low total thyroxine (TT4), free thyroxine (FT4), and normal thyrotropin concentration. A diagnosis of congenital hypothyroidism was confirmed by positive genetic test for thyroid peroxidase mutation. Thyroxine supplementation treatment rapidly improved clinical signs. [ABSTRACT FROM AUTHOR]

Autoimmune thyroid disease (AITD) is the most common organic specific illness of the thyroid gland. It may manifest as the overproduction or the decline of thyroxine and triiodothyronine. Hyperthyroidism develops due to the overproduction of hormones as an answer to the presence of stimulatory antibodies against the TSH receptor. Hashimoto's thyroiditis (HT) is generally characterized by the presence of thyroid peroxidase and thyroglobulin antibodies, with a concomitant infiltration of lymphocytes in the thyroid. Due to the progressive destruction of cells, AITD can lead to subclinical or overt hypothyroidism. Pathophysiology of AITD is extremely complicated and still not fully understood, with genetic, environmental and epigenetic factors involved in its development. Due to increasing incidence and social awareness of this pathology, there is an urgent need to expand the background concerning AITD. A growing body of evidence suggests possible ways of treatment apart from traditional approaches. Simultaneously, the role of potential new biomarkers in the diagnosis and monitoring of AITD has been highlighted recently, too. Therefore, we decided to review therapeutic trends in the course of AITD based on its pathophysiological mechanisms, mainly focusing on HT. Another aim was to summarize the state of knowledge regarding the role of new biomarkers in this condition. [ABSTRACT FROM AUTHOR]

TPO (Thyroid Peroxidase) is known to be one of the major genes involved in congenital hypothyroid patients with thyroid dyshormonogenesis. The present study aims to validate high-resolution melting (HRM) curve analysis as a substitute method for Sanger sequencing, focusing on the frequently observed non-synonymous mutations c.1117G>T, c.1193G>C, and c.2173A>C in the TPO gene in patients from Bangladesh. We enrolled 36 confirmed cases of congenital hypothyroid patients with dyshormonogenesis to establish the HRM method. Blood specimens were collected, and DNA was extracted followed by PCR and Sanger sequencing. Among the 36 specimens, 20 were pre-sequenced, and variants were characterized through Sanger sequencing. Following pre-sequencing, the 20 pre-sequenced specimens underwent real-time PCR-HRM curve analysis to determine the proper HRM condition for separating the three variations from the wild-type state into heterozygous and homozygous states. Furthermore, 16 unknown specimens were subjected to HRM analysis to validate the method. This method demonstrated a sensitivity and specificity of 100 percent in accurately discerning wild-type alleles from both homozygous and heterozygous states of c.1117G>T (23/36; 63.8%), c.1193G>C (30/36; 83.3%), and c.2173A>C (23/36; 63.8%) variants frequently encountered among 36 Bangladeshi patients. The HRM data was found to be similar to the sequencing result, thus confirming the validity of the HRM approach for TPO gene variant detection. In conclusion, HRM-based molecular technique targeting variants c.1117G>T, c.1193G>C, and c.2173A>C could be used as a high throughput, rapid, reliable, and cost-effective screening approach for the detection of all common mutations in TPO gene in Bangladeshi patients with dyshormonogenesis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Autoimmunity seems to be present in a large proportion of women with spontaneous premature ovarian insufficiency (POI). Whether these women are at increased risk for autoimmune disease has not been determined to date. Therefore, the aim of this study was to investigate a large series of antibodies in order to shed more light into the autoimmune risk of POI women. In a prospective case–control study, blood samples from 66 patients with spontaneous POI and 66 healthy controls were analyzed for a series of autoimmune antibodies. POI women revealed significantly increased thyroglobulin antibodies (TGAb) (p = 0.045) and thyroid peroxidase antibodies (TPOAb) (p = 0.002). At least one abnormal autoimmune parameter was present in 37.9% of POI women, compared to 18.2% in healthy controls (p = 0.045). A strong association between POI and increased TGAb (adjusted odds ratio 3.586, p = 0.028), increased TPOAb (adjusted odds ratio 7.496, p = 0.003) and any increased autoimmune parameter (adjusted odds ratio 3.189, p = 0.008) could be demonstrated in a binary logistic regression model. A high prevalence of autoimmunity in POI women compared to a healthy young collective could be demonstrated. Thyroid antibodies were significantly increased in POI women. Our data highlight the increased risk for autoimmune diseases, especially for thyroid disorders. [ABSTRACT FROM AUTHOR]

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A study published in the journal Thyroid explores the potential link between maternal thyroid peroxidase antibodies (TPOAbs) and neurodevelopmental outcomes in offspring. The study, conducted in a non-iodine-deficiency region in China, found that maternal TPOAb positivity during early gestation was associated with below-average processing speed and full-scale intelligence quotient in girls and below-average working memory index in girls. Another study by the same research team found that persistent TPOAb positivity throughout gestation was associated with autism spectrum problems in boys and depressive problems in girls. However, the exact mechanisms behind these associations remain unclear, and further research is needed to determine whether TPOAbs are a direct cause or simply a marker of underlying immune dysfunction. It is important to approach these findings with caution and not overstate their implications, as causality has not been established and the potential psychological stress on mothers should be considered. [Extracted from the article]

(1) Autoimmune thyroiditis (AIT) is the most common cause of primary hypothyroidism and one of the most frequent organ-specific autoimmune diseases. Its pathogenesis is polygenic and still requires further research. The aim of the study was to assess, for the first time in the Caucasian population, the role of selected TPO gene promoter polymorphisms (rs2071399 G/A, rs2071400C/T, rs2071402 A/G, and rs2071403 A/G) in the development of AIT. A total of 237 patients diagnosed with AIT and 130 healthy controls were genotyped for four TPO gene polymorphisms, and the results were statistically analyzed to check for the role of these polymorphisms. There were no significant differences in the genotype and allele frequencies of the studied TPO gene promoter polymorphisms between patients and controls (p > 0.05). The haplotype distribution (rs2071400–rs2071402–rs2071403) between the two studied groups was similar for the most common variants (CGA, CAG, TGG). Only a rare haplotype (CGG) occurred more frequently among patients compared to controls (p = 0.04). The studied TPO gene promoter polymorphisms did not show an association with susceptibility to AIT in the Caucasian Polish population, contrary to the results in Japanese patients. [ABSTRACT FROM AUTHOR]

Background: Thyroglobulin antibody (TgAb) has been found to be associated with the occurrence and development of differentiated thyroid cancer (DTC) for several years, but there is still controversy over whether thyroid peroxidase antibody (TPOAb) is related to differentiated thyroid cancer. Methods: We scrutinized relevant studies published up to July 2023 across four major databases including PubMed, Embase, Cochrane Library, and Web of Science, to examine the association between TPOAb and DTC. Clinical outcome measures include the incidence of DTC, tumor size, extrathyroidal invasion, lymph node metastasis, multifocality, recurrence and bilaterality. Results: 12 original studies were included, involving a total of 20,330 subjects. Our analysis of the included studies revealed that TPOAb+ individuals exhibited a higher risk of developing DTC (OR=1.57 [95% CI: 1.00-2.45], p=0.049) than TPOAb-individuals. Furthermore, TPOAb+ DTC patients were more prone to present with bilateral (OR=1.40 [95% CI: 1.21-1.62], p<0.00001) and multifocal (OR=1.40 [95% CI: 1.23-1.60], p<0.00001) tumors than TPOAb-patients. Sensitivity analysis indicated a high sensitivity for these three findings. No significant differences in the risk of extrathyroidal extension and lymph node metastasis, recurrence rate, tumor size, were observed between TPOAb+ and TPOAb-DTC patients. Conclusion: The presence of TPOAb is correlated with an increase prevalence of DTC. However, its effectiveness as a prognostic marker for DTC patients warrants further investigation. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the association between mild elevation of thyroid-stimulating hormone (TSH) levels and pregnancy outcomes of in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatments in women with the first fresh embryo transfer. Methods: Large single-center retrospective cohort study of 15,728 patients from January 2018 to December 2022 were enrolled in the analyses. Clinical pregnancy rates, live birth rates, miscarriage rates, and ectopic pregnancy rates were compared between the TSH levels < 2.5 mIU/L group (N = 10,932) and TSH levels ≥ 2.5 mIU/L group (N = 4796). Subgroup analysis was performed for patients with TSH levels ≥ 2.5 mIU/L, dividing them into the thyroid peroxidase antibody (TPO)–negative group (N = 4524) and the TPO-positive group (N = 272). Results: There were no significant differences in the aforementioned pregnancy outcomes between the TSH levels < 2.5 mIU/L group and TSH levels ≥ 2.5 mIU/L group. Similarly, no significant differences were observed in the pregnancy outcomes between the TPO-negative group and the TPO-positive group. Conclusion: Mildly elevated pre-conception TSH levels in thyroid-normal infertile patients did not have an impact on pregnancy outcomes of IVF/ICSI treatments. [ABSTRACT FROM AUTHOR]

Context The presence of thyroid peroxidase antibodies (TPOAbs) may be considered as an indicator of adverse health outcomes. Objective We aimed to investigate the potential determinants of TPOAb levels and to analyze the association between TPOAb titers and the risk of all- and specific-cause mortality. Methods Baseline and longitudinal data of 13 187 participants from the ELSA-Brasil Study were analyzed. We investigated the association of TPOAb, detectability, positivity, and persistent positivity with sociodemographic and lifestyle factors using logistic regressions. Cox proportional hazards and Fine-Gray subdistribution hazard regression analyses were used to verify the association of TPOAbs with mortality. Results The determinants of TPOAb detectability and positivity were younger age, higher body mass index, female sex, and former and current smoking status. Black, mixed, and other self-reported races, intermediate and higher education, and heavy drinking were determinants of detectable and positive TPOAb levels. Female sex, White race, and former smoking were determinants of persistent TPOAb positivity at 2 visits, although only the female sex maintained its association at 3 visits. Moreover, after multivariate adjustment, there were associations between higher levels of TPOAbs and higher risk of cancer-related mortality among men, and TPOAb detectability and mortality by other causes among women. Conclusion Sociodemographic and lifestyle-related factors were determinants of multiple TPOAb categories. TPOAb levels were associated with mortality risk; however, the low mortality rate in this sample might have compromised this finding. We suggest further studies to explore the clinical importance of detectable TPOAb levels, not only its positivity, as a potential marker of inflammation. [ABSTRACT FROM AUTHOR]

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 (β = -4.69; P = 0.00), thyroglobulin antibody levels (β = -11.08; P = 0.01), and the largest thyroid volume (β = 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. [ABSTRACT FROM AUTHOR]

Background: Previous studies have reported gut microbiome alterations in Hashimoto's autoimmune thyroiditis (HT) patients. Yet, it is unknown whether an aberrant microbiome is present before clinical disease onset in participants susceptible to HT or whether it reflects the effects of the disease itself. In this study, we report for the first time a comprehensive characterization of the taxonomic and functional profiles of the gut microbiota in euthyroid seropositive and seronegative participants. Our primary goal was to determine taxonomic and functional signatures of the intestinal microbiota associated with serum thyroid peroxidase antibodies (TPOAb). A secondary aim was to determine whether different ethnicities warrant distinct reference intervals for accurate interpretation of serum thyroid biomarkers. Methods: In this cross-sectional study, euthyroid participants with (N = 159) and without (N = 1309) TPOAb were selected from the multiethnic (European Dutch, Moroccan, and Turkish) HEalthy Life In an Urban Setting (HELIUS) cohort. Fecal microbiota composition was profiled using 16S rRNA sequencing. Differences between the groups were analyzed based on the overall composition (alpha and beta diversity), as well as differential abundance (DA) of microbial taxa and functional pathways using multiple DA tools. Results: Overall composition showed a substantial overlap between the two groups (p > 0.05 for alpha-diversity; p = 0.39 for beta-diversity), indicating that TPOAb-seropositivity does not significantly differentiate gut microbiota composition and diversity. Interestingly, TPOAb status accounted for only a minor fraction (0.07%) of microbiome variance (p = 0.545). Further exploration of taxonomic differences identified 138 taxa nominally associated with TPOAb status. Among these, 13 taxa consistently demonstrated nominal significance across three additional DA methods, alongside notable associations within various functional pathways. Furthermore, we showed that ethnicity-specific reference intervals for serum thyroid biomarkers are not required, as no significant disparities in serum thyroid markers were found among the three ethnic groups residing in an iodine-replete area (p > 0.05 for thyrotropin, free thyroxine, and TPOAb). Conclusion: These findings suggest that there is no robust difference in gut microbiome between individuals with or without TPOAb in terms of alpha and beta-diversity. Nonetheless, several taxa were identified with nominal significance related to TPOAb presence. Further research is required to determine whether these changes indeed imply a higher risk of overt HT. [ABSTRACT FROM AUTHOR]

Objectives. To assess autoimmune thyroiditis prevalence in subclinical and clinical psoriatic arthritis (PsA). Materials and methods. 45 female adult Egyptian patients with psoriatic disease were classified into 3 equal groups: PsA, subclinical PsA, and psoriasis. A full assessment was done including Health Assessment Questionnaire, Psoriasis Area Severity Index (PASI), Leeds Enthesitis Index (LEI), PsA disease activity score (DAPSA), MAdrid Sonographic Enthesitis Index (MASEI), thyroid hormones (TSH, FT4, and FT3), thyroglobulin and thyroid peroxidase antibodies (Tg and TPO Abs), and thyroid ultrasound. Results. Thyroid abnormalities prevalence was: 33.3% with subclinical hypothyroidism, 80% with positive TPO Ab, and 46.7% with positive Tg Ab in PsA group, 26.7% with subclinical hypothyroidism, 60% with positive TPO Ab, and 33.3% with positive Tg Ab in subclinical PsA group and none in psoriasis group. PsA patients had higher TPO Ab levels compared to psoriasis patients with high statistical significant difference and lower FT3 levels compared to psoriasis patients with statistical significant difference. In subclinical PsA group, MASEI was positively correlated with TPO Ab with high statistical significance and with FT3 and Tg Ab with statistical significance, FT4 was negatively correlated with LEI with high statistical significance, and FT4 was correlated with PASI with statistical significance. In PsA group, TPO Ab was correlated with DAPSA with statistical significance. Conclusions. Autoimmune thyroiditis is more common in PsA than subclinical PsA patients. PsA patients are advised to be tested for TPO and Tg Abs. Musculoskeletal ultrasound is a screening tool to detect enthesitis in psoriasis patients. [ABSTRACT FROM AUTHOR]

This article explores the impact of the timing of levothyroxine therapy on the neurological development of babies born to women with gestational subclinical hypothyroidism (SCH) and negative thyroid peroxidase antibodies (TPOAbs). SCH is characterized by elevated thyroid-stimulating hormone (TSH) levels with normal thyroxine (T4) levels. The study found that delayed treatment of SCH in pregnant women with negative TPOAbs and TSH levels between 4.0 and 10.0 mIU/L had more negative effects on the neurobehavioral development of their babies. However, treatment initiated before 8 gestational weeks did not show significant differences in developmental quotient scores compared to the control group. The study suggests that larger multicenter studies and prospective approaches are needed to confirm and expand these findings. The authors express gratitude to the participants and hospital staff and disclose no conflicts of interest. The study was funded by the National Natural Science Foundation of China, the Research Fund for Lin He Academician New Medicine, and the WenZhou Science and Technology Commission project. [Extracted from the article]

Background: Autoimmune thyroid disease is a prevalent condition affecting women of reproductive age, leading to thyroid dysfunction and impacting pregnancy outcomes. While the critical role of thyroid hormone in pregnancy outcomes is well-established, the potential association between positive antithyroid peroxidase antibodies (TPOAb) and adverse pregnancy outcomes in pregnant women with normal thyroid function remains unclear. Objective: This study aims to investigate the relationship between maternal TPOAb positivity and adverse pregnancy outcomes with normal thyroid function. Methods: We collected baseline information from pregnant women who visited our hospital between February 2009 and June 2012. Blood samples were taken to measure thyroid stimulating hormone (TSH), free thyroxine (FT4), TPOAb, and anti-thyroglobulin antibodies (TGAb). The incidence of adverse pregnancy outcomes was compared between TPOAb-positive and TPOAb-negative groups among participants with normal thyroid function. Results: A total of 7,046 pregnant women with normal thyroid function were included, comprising 6,700 with negative TPOAb and 346 with positive TPOAb. The TPOAb-positive group exhibited a higher age (26.0 vs. 27.0 years, p = 0.02) and greater serum TSH levels (1.72 vs. 1.94 mIU/L, p = 0.029), while the gestational week of blood collection was lower (31.9 vs. 26.5 weeks, p = 0.001). Univariate analysis revealed a higher incidence of low birth weight (LBW) in offspring of TPOAb-positive women compared to the TPOAb-negative group (3.5% vs. 1.9%, p = 0.035). After adjusting for confounding factors such as age, gestational week of blood collection, menstrual history, education level, gestational diabetes, gestational hypertension, TGAb, TSH, and FT4, TPOAb positivity emerged as an independent risk factor for LBW infants (OR: 2.317, 95% CI: 1.057-5.076, p = 0.036), while other adverse pregnancy outcomes did not show a significant correlation with TPOAb positivity. Conclusion: Our findings suggest that TPOAb-positive pregnant women with normal thyroid function are more likely to deliver LBW infants. Regular monitoring of TPOAb-positive pregnancies and timely interventions throughout all stages of pregnancy are crucial. [ABSTRACT FROM AUTHOR]

Background: Many studies have reported the link between gut microbiota and thyroid dysfunction. However, the causal effect of gut microbiota on thyroid dysfunction and the changes in gut microbiota after the onset of thyroid dysfunction are not clear. Methods: A two-sample Mendelian randomization (MR) study was used to explore the complex relationship between gut microbiota and thyroid dysfunction. Data on 211 bacterial taxa were obtained from the MiBioGen consortium, and data on thyroid dysfunction, including hypothyroidism, thyroid-stimulating hormone alteration, thyroxine deficiency, and thyroid peroxidase antibodies positivity, were derived from several databases. Inverse variance weighting (IVW), weighted median, MR-Egger, weighted mode, and simple mode were applied to assess the causal effects of gut microbiota on thyroid dysfunction. Comprehensive sensitivity analyses were followed to validate the robustness of the results. Finally, a reverse MR study was conducted to explore the alteration of gut microbiota after hypothyroidism onset. Results: Our bidirectional two-sample MR study revealed that the genera Intestinimonas, Eubacterium brachy group, Ruminiclostridium5, and Ruminococcaceae UCG004 were the risk factors for decreased thyroid function, whereas the genera Bifidobacterium and Lachnospiraceae UCG008 and phyla Actinobacteria and Verrucomicrobia were protective. The abundance of eight bacterial taxa varied after the onset of hypothyroidism. Sensitivity analysis showed that no heterogeneity or pleiotropy existed in the results of this study. Conclusion: This novel MR study systematically demonstrated the complex relationship between gut microbiota and thyroid dysfunction, which supports the selection of more targeted probiotics to maintain thyroid--gut axis homeostasis and thus to prevent, control, and reverse the development of thyroid dysfunction. [ABSTRACT FROM AUTHOR]

To maintain normal level of thyroid hormone, especially for free thyroxine (FT4), individuals with latent thyroid gland damage might have required higher thyroid stimulating hormone (TSH) than those without latent thyroid gland damage. Anti-thyroid peroxidase antibody (TPO-Ab) is a main cause of auto-immune thyroiditis, and therefore euthyroid individuals positive for TPO-Ab might have latent damage to the thyroid gland. Therefore, the association between TSH values and TPO-Ab positivity may be useful to determine the influence of latent thyroid gland damage on requirement of TSH. Furthermore, because latent damage of thyroid might elevate TSH level but not FT4 level, those associations should be observed independent from FT4. This cross-sectional study analyzed 1431 Japanese with normal ranges of free triiodothyronine (FT3) and FT4. Since TPO-Ab is associated with atherosclerosis in euthyroid individuals, cardiovascular risk factors might underlie the association between TPO-Ab and TSH values. After adjusting for FT4 and known cardiovascular risk factors, the adjusted odds ratio (95% confidence interval) of TPO-Ab positivity for logarithmic value of TSH was 1.53 (1.20, 1.95). Essentially the same association was observed when the analysis was restricted to individuals without subclinical hypothyroidism (1.54 [1.15, 2.13]). Euthyroid individuals with latent thyroid gland damage might have increased the requirement of TSH. [ABSTRACT FROM AUTHOR]

Background: Thyroid autoimmunity (TAI) has been associated with the risk of recurrent pregnancy loss (RPL). This systematic review and meta-analysis was conducted to evaluate the influence of TAI on subsequent pregnancy outcome of women with RPL. Methods: A systematic search of Medline, Web of Science, and Embase was conducted to identify studies evaluating the influence of TAI on subsequent risk of pregnancy loss (PL) in women with RPL. Study quality was evaluated via the Newcastle–Ottawa Scale. A random-effects model was utilized to pool the results, accounting for heterogeneity. Results: Ten observational studies were included. Compared to women without thyroid autoantibodies, RPL women with TAI had a higher risk of PL in their subsequent pregnancy (risk ratio [RR]: 1.46. 95% confidence interval [CI]: 1.20 to 1.78, p < 0.001; I2 = 35%). Sensitivity analyses showed consistent results in studies with thyroid peroxidase antibody positivity (RR: 1.50, 95% CI: 1.23 to 1.82) and in studies with TAI assessed before pregnancy (RR: 1.28, 95% CI: 1.07 to 1.53). Subgroup analyses showed that the results were not significantly different in prospective and retrospective studies, in RPL defined as at least two or three PL, in euthyroid women and women with euthyroidism or subclinical hypothyroidism, in women with and without levothyroxine treatment, in studies reporting first-trimester or overall PL, and in studies with different quality scores (p for subgroup difference all > 0.05). Conclusions: In women with RPL, positive for TAI may be related to a higher risk of PL in subsequent pregnancy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of Ophiocordyceps sinensis (OS) preparations for the treatment of Hashimoto's thyroiditis (HT). Methods: We searched eight databases to collect randomized controlled trials (RCTs) of OS combined with a low-iodine diet or levothyroxine for HT. The search period was from inception to June 2023. Meta-analysis was performed using Revman 5.3 software after two evaluators independently screened the literature, extracted data, and evaluated the risk of bias of the included studies. The GRADE system was used to assess the certainty of evidence. Results: A total of 14 RCTs involving 1,014 patients with HT were included. Meta-analysis showed that OS preparations combined with a low-iodine diet were more effective in reducing thyroid peroxidase antibody (TPOAb) [SMD = -3.81, 95% CI (-5.07, -2.54), p < 0.00001] and thyroglobulin antibody (TgAb) [SMD = -4.73, 95% CI (-6.86, -2.61), p < 0.00001] compared to a low-iodine diet. Compared with levothyroxine treatment alone, OS preparations combined with levothyroxine further reduced TPOAb [SMD = -2.04, 95% CI (-2.82, -1.26), p < 0.00001], TgAb [SMD = -2.01, 95% CI (-2.68, -1.33), p < 0.00001], tumor necrosis factor alpha (TNF-a) [SMD = -3.40, 95% CI (-5.66, -1.14), p = 0.003], interleukin-2 (IL-2) [SMD = -2.31, 95% CI (-3.98, -0.65), p = 0.006], and interleukin-6 (IL-6) [MD = -4.16, 95% CI (-6.17, -2.15), p < 0.0001], and elevated free thyroxine (FT4) [SMD = 1.34, 95% CI (0.59, 2.08), p = 0.0004], but no significant effect on free triiodothyronine (FT3) [SMD = 0.83, 95% CI (-0.12, 1.78), p = 0.09] and thyroid stimulating hormone (TSH) [SMD = -0.80, 95% CI (-1.71, 0.11), p = 0.08]. In terms of safety, three studies reported adverse reactions in 10 patients in each of the experimental and control groups. Conclusion: OS preparations in combination with other treatments (low-iodine diet or levothyroxine) may decrease thyroid autoantibodies and inflammatory responses in patients with HT. In HT patients with hypothyroidism, the combination of the OS preparations with levothyroxine also improved FT4. However, the quality of the included studies was generally low. Moreover, the safety of OS preparations remains unclear. Therefore, more high-quality, multicenter, large-sample RCTs are needed in the future to validate the efficacy and safety of OS preparations. [ABSTRACT FROM AUTHOR]

Background: Studies suggest that thyroid peroxidase antibody (TPOAb) positivity exposure during pregnancy may contribute to changes in placental morphology and pathophysiology. However, little is known about the association of maternal TPOAb during pregnancy with placental morphology and cytokines. This study focuses on the effect of repeated measurements of maternal TPOAb during pregnancy on the placental morphology and cytokines. Methods: Based on Ma'anshan Birth Cohort (MABC) in China, maternal TPOAb levels were retrospectively detected in the first, second and third trimesters. Placental tissues were collected 30 minutes after childbirth, placental morphological indicators were obtained by immediate measurement and formula calculation, and cytokine mRNA expression was detected by real-time quantitative polymerase chain reaction (RT-qPCR) afterward. Generalized linear models and linear mixed models were analyzed for the relationships of maternal TPOAb in the first, second and third trimesters with placental indicators. Results: Totally 2274 maternal-fetal pairs were included in the analysis of maternal TPOAb levels and placental morphology, and 2122 pairs were included in that of maternal TPOAb levels and placental cytokines. Maternal TPOAb levels in early pregnancy were negatively associated with placental length, thickness, volume, weight and disc eccentricity, while positively correlated with placental IL-6, TNF-a, CRP, CD68, MCP-1, IL-10, HO-1, HIF-1α and GRP78. In mid-pregnancy, maternal TPOAb levels were negatively correlated with placental length, width and area. In late pregnancy, maternal TPOAb levels were negatively correlated with placental length, area, volume and weight. Repeated measures analysis showed that maternal TPOAb positivity tended to increase placental TNF-a, CD68 and MCP-1 while decreasing placental length, width and area than TPOAb negativity. Repeated measures analysis showed that maternal TPOAb levels were positively correlated with placental IL-6, TNF-α, CD68, MCP-1, IL-10, HO-1, HIF-1α and GRP78, while negatively correlated with placental length, area, volume, weight, and disc eccentricity. Conclusion: There may be trimester-specific associations between maternal TPOAb levels and placental morphology and inflammatory and oxidative stress responses. The effect of maternal TPOAb levels on placental morphology is present throughout pregnancy. Early pregnancy may be the critical period for the association between maternal TPOAb levels and placental inflammatory and oxidative stress responses. [ABSTRACT FROM AUTHOR]

This study explored whether thyroglobulin and thyroid disease prevalence rates were higher in pregnant Chinese women with a median urinary iodine concentration of 100–149 μg/L, compared with those with a median urinary iodine concentration of 150–249 μg/L maintained through sustainable universal salt iodization. This was a cross-sectional study in which 812 healthy pregnant women were enrolled to collect samples of their household edible salt, urine, and blood during their routine antenatal care in the 18 counties in Fujian Province, China. The levels of salt iodine concentration, urinary iodine concentration (UIC), free triiodothyronine (FT3), free thyroid hormone (FT4), thyroid-stimulating hormone (TSH), thyroglobulin (Tg), thyroid peroxidase antibody and thyroglobulin antibody were assessed during the routine antenatal care visits. The median UIC (mUIC) in pregnant women was 130.8 μg/L (interquartile range = 91.5–198.1 μg/L) in the counties with an mUIC of 100–149 μg/L (Group I), and 172.0 μg/L (interquartile range = 123.5–244.4 μg/L) in the counties with an mUIC of 150–249 μg/L (Group II). Goiter prevalence and thyroid nodule detection rates showed no difference between Group I and Group II (P > 0.05). Except for FT4 values, the TSH, FT4, FT3, Tg and Tg values > 40 (μg/L) and the thyroid diseases prevalence rate (TDR) showed no significant differences between Group I and Group II (P > 0.05), whether or not iodine supplementation measures were taken. Compared with an mUIC of 150–249 μg/L, not only there was no difference in thyroid morphology, but also the Tg value, rate of Tg values > 40 μg/L, and TDR were not higher in pregnant women in the counties with an mUIC of 100–149 μg/L achieved through sustainable universal salt iodization in Fujian Province, China. [ABSTRACT FROM AUTHOR]

Objective of this study was to investigate the association between serum thyroid measurements and homocysteine (HCy) in euthyroid participants.Methods: This retrospective study was based on Hospital Information Systems. After excluding participants with thyroid dysfunction and those who had recently taken medications that affected serum HCy, 775 participants were enrolled. We compared the serum thyroid function measurements of patients with or without hyperhomocysteinemia (HHCy) and analyzed the effect of thyroid indicators on HHCy prevalence and HCy levels. Multivariate regression analysis was utilized to analyze the association of thyroid-stimulating hormone (TSH) and thyroid peroxidase (TPOAb) with HCy.Results: The serum TSH level (2.10 ± 1.06 mIU/L) of HHCy patients (n = 98) was significantly higher than controls (n = 677) (1.65 ± 0.90 mIU/L) (p < 0.05), as was the positive rate of TPOAb (19.4% vs 10.0%, p < 0.05). The serum HCy levels in subjects with TSH within the highest quartile were significantly higher than those in the lowest quartile (13.49 ± 7.78 vs 9.81 ± 3.59 μmol/L, p < 0.05). HCy was also significantly higher in TPOAb-positive patients than in negative subjects (14.06 ± 8.89 vs 11.48 ± 5.47 μmol/L, p < 0.05). Among the TSH quartiles, the prevalence of HHCy showed a similar significant upward trend to that described above. The prevalence of HHCy was also significantly higher in TPOAb-positive patients. The results of multivariate regression analysis suggested that both TSH elevation and TPOAb positivity were independent risk factors for HCy elevation and HHCy prevalence. However, we found no definitive association between linear increases in TPOAb titers and HCy concentrations or HHCy prevalence.Conclusion: Patients with HHCy had significantly higher TSH levels and positive rates of TPOAb. Elevated TSH and positive TPOAb levels were independent risk factors for elevated HCy concentrations and HHCy risk. [ABSTRACT FROM AUTHOR]