Thyroid Peroxidase Antibody Levels Research Articles

Potential Determinants of Thyroid Peroxidase Antibodies and Mortality Risk: Results From the ELSA-Brasil Study.

The presence of thyroid peroxidase antibodies (TPOAbs) may be considered as an indicator of adverse health outcomes. 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. 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. 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. 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.

Gender differences in the association between anxiety symptoms and thyroid hormones in young patients with first-episode and drug naïve major depressive disorder.

Gender differences are prevalent in major depressive disorder (MDD), but the gender differences in the relationship between comorbid anxiety and thyroid hormones in young first-episode and drug-naive (FEND) MDD patients are unknown. A total of 1,289 young outpatients with FEDN MDD were recruited. Demographic and clinical data were collected for each patient. The patient's blood glucose, blood pressure, thyroid hormone, and thyroid antibody levels were measured. The Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA), and Positive and Negative Syndrome Scale (PANSS) were used to assess patients' depression, anxiety, and positive symptoms, respectively. The prevalence of comorbid anxiety disorders was 80.4 and 79.4% in male and female MDD patients, respectively. Patients with anxiety had higher HAMD and PANSS scores, higher serum thyroid stimulating hormone (TSH), anti-thyroglobulin antibody (A-TG), and thyroid peroxidase antibody (A-TPO) levels, higher blood glucose and blood pressure levels, and more patients with psychotic symptoms and suicide attempts. Male patients were younger and had a younger age of onset. Logistic regression analysis showed that HAMD score and comorbid suicide attempts were significant predictors of anxiety symptoms in both males and females, whereas A-TG predicted anxiety symptoms in female patients only. Limitations: No causal relationship could be drawn due to the cross-sectional design. This study showed gender differences in factors associated with anxiety symptoms in patients with MDD. Some factors were associated with anxiety symptoms in both male and female patients, while A-TG was only associated with anxiety symptoms in female patients.

Circadian clock disruption in autoimmune thyroiditis.

A vicious cycle between circadian disruption and escalating immune responses has been described in diverse inflammatory disease. The current study aimed to explore the role of circadian clock disruption in autoimmune thyroiditis (AIT). Thirty AIT patients and 30 controls were enrolled and biopsied for thyroid tissues. Alterations of core clock genes expression in AIT thyroid tissues, and its association with serum and tissue inflammatory biomarkers were assessed. For animal studies, C57BL/6J mice administered with porcine thyroglobulin or PBS (as control) combined with adjuvants were sacrificed at four time points to investigate the circadian characteristic of experimental autoimmune thyroiditis (EAT). Light shift (LS) conditions were used to explore the influence of external circadian disturbance on EAT. The expression of clock genes BMAL1 and PER2 was significantly reduced in thyroid tissues from AIT patients and was negatively correlated to levels of thyroid peroxidase antibodies. In mouse models, diurnal fluctuations of proinflammatory cytokines were demonstrated, and further exposing mice to LS led to overproduction of TNF-α, IFN-γ, and anti-thyroglobulin antibodies. Circadian analysis revealed significant oscillations of Bmal1, Clock, Per2, Cry1, Ror, and Rev-erb, which was broadly disturbed in EAT, LS, and EAT + LS groups. This study demonstrates that expression pattern of clock genes was disrupted in AIT thyroid, and chronic circadian disruption may aggravate the inflammatory responses in AIT. Whether maintaining a regular circadian rhythm can alleviate autoimmune thyroid diseases warrants further research.

Dioscin Ameliorates Experimental Autoimmune Thyroiditis via the mTOR and TLR4/NF-κB Signaling.

Autoimmune thyroiditis (AIT) is a common autoimmune disease that causes thyroid dysfunction. Clinical symptoms in Hashimoto thyroiditis patients were improved after oral administration of dioscin. However, the mechanisms involved in the therapeutic effect remain unclear. The protective effects and potential mechanisms of dioscin for autoimmune thyroiditis were explored in a rat model of thyroglobulin-induced autoimmune thyroiditis. Firstly, the rat model of AIT was obtained by subcutaneous injection of thyroglobulin and drinking the sodium iodide solution, followed by gavage administration for 8 weeks. Rats were sacrificed after anaesthesia, serum and thyroid samples were preserved. Serum triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH), thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb), and thyrotropin receptor antibody (TRAb) expressions were measured by enzyme-linked immunosorbent assay (ELISA). Morphological changes were observed by H&E staining. Next, we used transcriptomics techniques to find the potential therapeutic target of dioscin. Finally, we validated the transcriptomic results by reversetranscription-polymerasechainreaction (RT-PCR) and immunohistochemistry (IHC-P), respectively. Animal experiments showed that dioscin regulated T3, T4, FT3, TSH, TgAb, TPOAb, and TRAb and alleviated the pathological process in a dose-dependent manner, with the high-dose group showing optimal efficacy. In the transcriptome, the nuclear factor kappa B (NF-κB) pathway was identified by KEGG enrichment analysis and validated by RT-PCR and IHC-P. The relative expression of NF-κB, mechanistic target of rapamycin (mTOR), and toll-like receptor 4 (TLR4) mRNA and protein were decreased in the dioscin-treated group compared to the AIT model group. Our results suggest that dioscin treatment improved thyroid function and downregulated TGAb, TPOAb and TRAb levels in rat models of AIT, which may alleviate the pathological process and suppress the inflammatory response by inhibiting mTOR and TLR4/NF-κB pathways.

Retrospective analysis of low-dose interleukin-2 therapy on chronic autoimmune thyroid disease with concurrent systemic lupus erythematosus

Introduction Low-dose interleukin-2 (IL-2) regulates the homeostasis of CD4+ T cells by modulating the proportions of effector and regulatory T cells, thus reducing disease activity in patients with systemic lupus erythematosus (SLE). However, to date, no research has been carried out on the efficacy of low-dose IL-2 for treating autoimmune thyroid disease (AITD). The aim of this study was to observe the effects of IL-2 on AITD patients with concurrent SLE, and explore potential mechanism of action. Methods A retrospective analysis was conducted on 29 SLE patients with concurrent AITD. Among them, 11 patients were in IL-2 therapy group and 18 patients without IL-2 treatment were considered as control group. Two groups had similar disease activities and were treated with comparable regular strategy. Free triiodothyronine (FT3), free thyroxine (FT4), thyroxine(T4), triiodothyronine(T3), thyroid stimulating hormone (TSH), thyroglobulin antibody (TG-Ab), thyroid peroxidase antibody (TPO-Ab) levels and immune cell subgroups were measured. Results After receiving low-dose IL-2 therapy, the TG-Ab and TPO-Ab levels decreased drastically (TG-Ab p = 0.008, TPO-Ab p = 0.007), and the majority of the AITD patients became seronegative, while there was no discernible change in control group. In IL-2 group, percentage of CD4+ T cells showed a significant increase after treatment (p = 0.029), with an upward trend in the ratio of regulatory T (Treg) cells to follicular helper T (Tfh) cells (Treg/Tfh). The percentage as well as absolute count of B cells demonstrated a decreasing trend. Conclusion Low-dose IL-2 may downregulate the levels of TG-Ab and TPO-Ab by modulating the immune balance of Treg/Tfh and B-cells, providing new avenue for clinical treatment of AITD.

The Effects of Selenium Supplementation in the Treatment of Autoimmune Thyroiditis: An Overview of Systematic Reviews.

The available evidence on selenium supplementation in the treatment of autoimmune thyroiditis (AIT) was inconclusive. This research serves to assess the effects of selenium supplementation in the treatment of AIT. Online databases including PubMed, Web of Science, Embase, and the Cochrane Library were searched from inception to 10 June 2022. The AMSTAR-2 tool was used to assess the methodological quality of included studies. The information on the randomized controlled trials of the included studies was extracted and synthesized. The GRADE system was used to assess the certainty of evidence. A total of 6 systematic reviews with 75 RCTs were included. Only one study was rated as high quality. The meta-analysis showed that in the levothyroxine (LT4)-treated population, thyroid peroxidase antibody (TPO-Ab) levels decreased significantly in the selenium group at 3 months (SMD = -0.53, 95% CI: [-0.89, -0.17], p < 0.05, very low certainty) and 6 months (SMD = -1.95, 95% CI: [-3.17, -0.74], p < 0.05, very low certainty) and that thyroglobulin antibody (Tg-Ab) levels were not decreased. In the non-LT4-treated population, TPO-Ab levels decreased significantly in the selenium group at 3 and 6 months and did not decrease at 12 months. Tg-Ab levels decreased significantly in the selenium group at 3 and 6 months and did not decrease at 12 months. The adverse effects reported in the selenium group were not significantly different from those in the control group, and the certainty of evidence was low. Although selenium supplementation might reduce TPO-Ab levels at 3 and 6 months and Tg-Ab levels at 3 and 6 months in the non-LT4-treated population, this was based on a low certainty of evidence.

Antithyroid antibody (TPO-Ab) Status in Type 2 Diabetic Patients

Background: Presence of thyroid peroxidase antibody (TPO-Ab) in type 2 diabetic patients is a risk factor for future development of thyroid dysfunction.Objective: To observe thyroid antibody status in type 2 diabetic patients.Materials &amp; Methods: This cross sectional study was carried out in the Department of Physiology, Sir Salimullah Medical College, Dhaka from July 2016 to June 2017. Total 60 subjects including male and female, age ranged from 40 to 60 years were included in this study, among them 30 were non-diabetic subjects and 30 were type 2 diabetic patients.Results: In this study, mean serum TPO-Ab level was significantly (&lt;0.01) higher in diabetic subjects in comparison to that of apparently healthy non-diabetic subjects and mean serum TPO-Ab level was higher in uncontrolled diabetic subjects in comparison to that of controlled diabetic subjects but the difference is not statistically significant. However, On the other hand, among the diabetic patients 6.67% had positive TPO-Ab whereas, among the uncontrolled diabetic patients 11.76% had positive TPO-Ab. There was no correlation between TPO-Ab and HbA1c.Conclusion: The present study reveals that TPO-Ab may present in type 2 diabetic patients. KYAMC Journal Vol. 14, No. 01, April 2023: 35-38

Urinary iodine concentration and its associations with thyroid function in pregnant women of Shanghai.

To assess the iodine status and its associations with thyroid function in pregnant women of Shanghai. In this cross-sectional study, a total of 562 pregnant women were enrolled from January to December 2021. Both serum thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), thyroid peroxidase antibody (TPOAB), thyroglobulin antibody (TGAB), and urinary iodine concentration (UIC) were detected. Participants were divided into four groups based on their UIC values. Correlation analysis was used to investigate the association between UIC and thyroid function-associated parameters. The median UIC of the pregnant women studied was 158.25µg/L (interquartile range [IQR] 90.15, 245.65µg/L). Among all the subjects, 45.55% had iodine deficiency according to the World Health Organization (WHO) criteria, and 15.65% had thyroid autoimmunity. FT3, FT4, TSH, TPOAB and TGAB levels were not different among different UIC groups (P > 0.05). UIC and TSH were negatively correlated (r=-0.127, p=0.043) in UIC<150 µg/L group. In the group with UIC 250- 499 µg/L, UIC was positively correlated with total T4 (TT4), total T3 (TT3) and TPOAB (r= 0.228, p=0.022, r=0.208, p= 0.039, r=0.190, p=0.042, respectively). A negative correlation between UIC and TPOAB values was observed in TPOAB-positive (+) pregnant women (r=-0.384, p=0.012). The prevalence of isolated hypothyroxinemia in UIC<150 µg/L group was significantly higher than that of other groups(p=0.033). The relationship between the prevalence of thyroid diseases and UIC embodied a U-shaped curve. Pregnant women on Chongming Island of Shanghai were iodine sufficient during the second trimester, but iodine deficiency was still prevalent. Both low and high gestational iodine status was related to thyroid function and autoimmunity. Optimal iodine nutrition status during gestation was important.

Normalized TSH strategy can improve the initial assessment of thyroid nodules

Background Serum thyrotropin (TSH) has been recommended for the initial assessment of patients with thyroid nodules to exclude functional thyroid nodules (FTN). However, the sensitivity of TSH is very low. The increased level of thyroid peroxidase antibody (TPOAb) is considered to be one of the reasons. Objective To investigate whether normalized TSH (nTSH) can improve diagnostic efficiency by removing TPOAb interference in the first evaluation of thyroid nodules compared with traditional TSH strategy. Methods Thyroid nodules were retrospectively analysed in 90 patients with FTN and 1038 patients with non-functioning thyroid nodules (non-FTN). The regression coefficient (β) of TPOAb affecting the TSH levels was assessed in patients with thyroid nodules, and then, the nTSH level was calculated based on the following formula: nTSH = TSH-β*TPOAb. We used nTSH levels to initially evaluate the thyroid nodules instead of the traditional TSH values and finally compared the results of the two strategies. Results The sensitivity, specificity, accuracy, positive prediction rate (PPV) and negative prediction rate (NPV) of nTSH for accessing FTN were 50.00%, 87.70%, 84.67%, 26.01% and 95.29%, respectively, which were better than the values of 48.90%, 78.70%, 76.33%, 16.60% and 94.67% associated with TSH, respectively (p < 0.001). Conclusion Serum TPOAb testing is recommended for the first assessment of thyroid nodules. Normalized TSH levels can improve assessment efficiency compared to traditional TSH assessment, increase the specificity and reduce an unnecessary 99mTc-TS test.

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

ABSTRACT 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.

Influence of Thyroid Peroxidase Antibodies Serum Levels in Graves' Disease: A Retrospective Cohort Study.

Purpose Graves' disease (GD) is an autoimmune disorder caused by the presence of antibodies to the thyroid stimulating hormone (TSH) receptor (TRAbs), usually presenting with clinical signs of hyperthyroidism. Previous evidence suggests that higher serum levels of thyroid peroxidase antibodies (TPOAbs) may lead to more sustained remission of hyperthyroidism after treatment with antithyroid drugs (AT). However, doubts about the influence of TPOAbs in Graves' disease outcomes still remain. Methods A retrospective, unicenter cohort study was performed. All patients with GD (TRAbs > 1.58U/L), biochemical primary hyperthyroidism (TSH < 0.4µUI/mL), and TPOAbs measurement at diagnosis, treated with AT between January 2008 and January 2021, were included for analysis. Results One hundred and forty-two patients (113 women) with a mean age of 52 ± 15 years old were included. They were followed up for 65.4 ± 43.8months. TPOAbs positivity was present in 71.10% (n=101) of those patients. Patients were treated with AT for a median of 18 (IQR (12; 24)) months. Remission occurred in 47.2% of patients. Patients with remission presented with lower TRAbs and free thyroxine (FT4) levels at the diagnosis. (p-value <0.001, p-value 0.003, respectively). No association was found in the median TPOAbs serum levels of patients who remitted and those who maintained biochemical hyperthyroidism after the first course of AT. Relapse of hyperthyroidism occurred in 54 patients (57.4%). No difference was found in TPOAbs serum levelsregarding the patient's relapse. Moreover, a time-based analysis revealed no differences in the relapse rate after 18 months of AT therapy between patients with and without TPOAbs positivity at the diagnosis(p-value0.176). It was found a weak positive correlation (r=0.295; p-value <0.05) between TRAbs and TPOAbs titters at the moment of Graves' diagnosis. Conclusion In this study, a correlation between TRAbs measurements and TPOAbs titter was described, although no significant association was found between the presence of TPOAbs and the outcomes of patients with GD treated with AT. These results do not support the use of TPOAbs as a useful biomarker to predict remission or relapse of hyperthyroidism in GDpatients.

Effects of Antioxidant Supplementation on Graves’ Disease: A Meta-Analysis

Objective. The main objective of this study is to evaluate the clinical efficacy of antithyroid drugs combined with antioxidant supplementation represented by selenium in the treatment of Graves’ disease. Methods. Relevant randomized controlled trials (RCTs) were searched in PubMed, MEDLINE, Embase, the Cochrane Library databases, and the Chinese Medical Association. The search was conducted from the time of library construction to December 20, 2022. Three writers gradually examined, evaluated, and graded the literature and then used RevMan 5.3 to analyze the data and develop conclusions. Results. A total of seven papers were screened according to the search requirements. The results showed that free triiodothyronine (FT3) (WMD = −2.29, 95% CI: −3.55 to −1.02, P = 0.0004 ), free thyroxine (FT4) (WMD = −0.62, 95% CI: −1.05 to −0.18, P = 0.0005 ), thyrotropin receptor antibody (TRAb) (WMD = −1.31, 95% CI: −1.63 to −0.99, P &lt; 0.00001 ), and thyroid peroxidase antibody (TPOAb) (WMD = −9.8, 95% CI: −16.57 to −3.03, P = 0.005 ) in the observation group (selenium supplementation combined with antithyroid drugs) were significantly lower than those in the control group (antithyroid drugs combined with or without placebo). In addition, selenium supplementation can increase serum selenium (WMD = 33.29, 95% CI: 30.7 to 35.87, P &lt; 0.00001 ), selenoprotein levels (WMD = 1.3, 95% CI: 0.8 to 1.8, P &lt; 0.00001 ), and blood lipid levels (WMD = 32.3, 95% CI: 17.87 to 46.74, P &lt; 0.0001 ). It cannot be excluded that the process of selenium supplementation treatment will affect the patient’s lipid levels. Conclusion. Selenium is a trace mineral that is crucial for human health. In patients with Graves’ disease, the use of antithyroid medications along with selenium supplementation can considerably enhance thyroid function. It has the potential to drastically lower TPOAb and TRAb levels as well as FT3 and FT4 levels, which is crucial for the treatment, recovery, and prognosis of hyperthyroid patients. Further research is required to determine whether the impact of antioxidant supplementation on blood lipids will restrict the use of this medication.

Clinical efficacy of selenium supplementation in patients with Hashimoto thyroiditis: A systematic review and meta-analysis.

Evidence suggests that selenium supplementation could be useful in the treatment of Hashimoto thyroiditis (HT), but the available trials are heterogeneous. This study investigates clinically relevant effects of selenium supplementation in patients with HT. A systematic search was performed in PubMed, Web of Science, EMBASE, Scopus, and the Cochrane Library. The latest update was performed on December 3, 2022. We investigated the changes in thyroid peroxidase antibodies (TPOAb) and thyroglobulin antibodies (TgAb) after selenium supplementation. The effect sizes were expressed as weighted mean difference (WMD) with 95% confidence intervals (CIs). After screening and full-text assessment, 7 controlled trials comprising 342 patients were included in the systematic review. The results showed that there was no significant change in TPOAb levels (WMD = -124.28 [95% CI: -631.08 to 382.52], P = .631, I2 = 94.5%) after 3 months of treatment. But there was a significant decrease in TPOAb levels (WMD = -284.00 [95% CI: -553.41 to -14.60], P < .05, I2 = 93.9%) and TgAb levels (WMD = -159.86 [95% CI: -293.48 to -26.24], P < .05, I2 = 85.3%) after 6 months of treatment. Selenium supplementation reduces serum TPOAb and TgAb levels after 6 months of treatment in patients with HT, but future studies are warranted to evaluate health-related quality or disease progression.

Relationship between thyroid antibody levels and ovarian reserve function in infertile chinese women with normal thyroid-stimulating hormone

BackgroundTo analyze the relationship of thyroid peroxidase antibody and thyroid globulin antibody levels with ovarian reserve function in infertile women.MethodsThe data of 721 infertile patients who visited the hospital from January 2019 to September 2022 and whose thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) levels were in the normal range, were retrospectively analyzed. These patients were divided into two sets of three groups—the negative group, the 2.6 IU/ml ~ 100 IU/ml group and the TPOAb > 100 IU/ml group according to the TPOAb (thyroid peroxidase antibody) level, or the TgAb (anti-thyroglobulin antibody) negative group, the 14.58 IU/ml ~ 100 IU/ml group and the TgAb > 100 IU/ml group according to the TgAb level. They were compared for differences in ovarian reserve function index and thyroid hormone levels and analyzed for the relationship among thyroid antibody levels, ovarian reserve function, and thyroid hormone levels.ResultsWhen TSH > 2.5 mIU/L, the bFSH (basal follicle stimulating hormone) level in the TPOAb > 100 IU/ml group (9.10 ± 1.16 IU/L) was significantly higher than that in the TPOAb negative group (8.12 ± 1.97 IU/L) and the 2.6 IU/ml ~ 100 IU/ml group (7.90 ± 1.48 IU/L) (P < 0.05); when TSH ≤ 2.5 mIU/L, there were no statistically significant differences in the bFSH and AFC (antral follicle count) number at different TPOAb levels. Whether TSH ≤ 2.5 mIU/L or TSH > 2.5 mIU/L, there were no statistically significant differences in the bFSH and AFC number at different TgAb levels (P > 0.05). FT3/FT4 ratio in the TPOAb 2.6 IU/ml ~ 100 IU/ml group and the > 100 IU/ml group was significantly lower than in the negative group. FT3/FT4 ratio in the TgAb 14.58 ~ 100 IU/ml group and the > 100 IU/ml group was also significantly lower than in the TgAb negative group (P < 0.05). TSH level in the TPOAb > 100 IU/ml group was significantly higher than in the 2.6 ~ 100 IU/ml group and the TPOAb negative group, but there were no statistically significant differences among different TgAb groups.ConclusionsWhen TPOAb > 100 IU/ml and TSH > 2.5 mIU/L, it may affect the ovarian reserve function in infertile patients, and the mechanism may be associated with increased TSH and the imbalance of FT3/FT4 ratio caused by the increase of TPOAb.

Relationship Between Serum 25-Hydroxyvitamin D Deficiency and Thyroid Disease in Postmenopausal Women with Type 2 Diabetes Mellitus.

It is unknown whether there is an association between 25-hydroxyvitamin D (25(OH)D) level and thyroid disease in postmenopausal women with type 2 diabetes. This study aimed to evaluate the relationship between blood 25(OH)D levels and thyroid function in postmenopausal women with type 2 diabetes mellitus (T2DM). This cross-sectional study involved Chinese postmenopausal women who presented to our diabetes clinic from March 2021 to May 2022 and were diagnosed with T2DM collected via a convenience sampling method. Blood samples were obtained from each patient to detect serum thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), free T3 (FT3), free T4 (FT4), thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb) and 25(OH)D levels. Deficiency was defined as a 25(OH)D < 20 ng/mL. Comparative analysis was via t-test or chi-square test. Pearson correlation was then used to estimate the relationship between different thyroid function parameters and 25(OH)D. Multivariate logistic regression analysis was used to explore potential risk factors for 25(OH)D deficiency. In total, 157 out of 230 participants (68.26%) had 25(OH)D deficiency. Compared with patients with normal 25(OH)D levels, patients with 25(OH)D deficiency had shorter medical histories of diabetes mellitus (DM, p = 0.001) and higher rates of hyperthyroidism (p = 0.007), hypothyroidism (p < 0.001), TPOAb positive (p < 0.001) and TgAb positive (p < 0.001). Correlation analysis revealed that TSH (r = -0.144, p = 0.030), FT4 (r = -0.145, p = 0.029), TPOAb (r = -0.216, p = 0.001) and TgAb (r = -0.150, p = 0.024) levels were correlated with serum 25(OH)D levels. Further multivariable logistic regression analyses suggested that the length of DM history, presence of hyperthyroidism, presence of hypothyroidism and positive TPOAb were significantly associated with the presence of 25(OH)D deficiency in postmenopausal women with T2DM. Hyperthyroidism, hypothyroidism and TPOAb positivity were significantly associated with the presence of 25(OH)D deficiency in postmenopausal women with T2DM.

Correlation between the intestinal microflora and peripheral blood Th1/Th2 balance in hypothyroidism during the first half of pregnancy.

This study aimed to investigate the relationship between intestinal microflora characteristics and the peripheral blood T helper cell (Th)1/Th2 balance in patients with hypothyroidism during the first half of pregnancy. The Th1/Th2 ratios in the peripheral blood of pregnant women in the hypothyroidism and control groups were determined using flow cytometry. The cytometric bead array assay was used to determine the serum levels of interleukin-2 (IL-2), IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ. Moreover, 16S rRNA amplicon sequencing was used to determine the intestinal microbial composition in the two groups. Finally, the relationships between intestinal microflora, Th1/Th2 cells, cytokines, and clinical indicators were analyzed. C-reactive protein levels were higher in the hypothyroidism group than in the control group. In contrast to the control group, the hypothyroidism group showed an increase in Th1 cells and the Th1/Th2 ratio, and a decrease in Th2 cells. The hypothyroidism group had higher serum IL-2, TNF-α, and IFN-γ levels, and lower IL-10 levels, than the control group. The richness of the intestinal microflora in the hypothyroidism group increased whereas the diversity decreased. The linear discriminant analysis effect size revealed that the hypothyroidism group had a higher abundance of Prevotella and Faecalibacterium, but a lower abundance of Bacteroides, compared to the control group. Prevotella was positively correlated with Th1 cells, the Th1/2 ratio, and TNF-α. Bacteroides was positively correlated with Th2 cells and IL-10, but negatively correlated with Th1 cells, the Th1/2 ratio, TNF-α, and IFN-γ. The thyroid peroxidase antibody level was directly proportional to TNF-α. A Th1/Th2 imbalance occurs in patients with hypothyroidism during the first half of pregnancy. Disorders of the intestinal microflora may lead to hypothyroidism during pregnancy by affecting the Th1/Th2 balance.

Prediction of preterm delivery based on thyroid peroxidase antibody levels and other identified risk factors

ObjectiveThyroid dysfunction and TPOAb positivity during pregnancy are associated with adverse pregnancy outcomes such as preterm delivery. The aim of this study was to predict preterm delivery based on identified risk factors, especially TPOAb levels. Study designA secondary analysis was run on data collected in the Tehran Thyroid and Pregnancy study (TTPs). We used the data of 1515 pregnant women with singletons. The association between risk factors and preterm birth (delivery before 37 completed weeks of gestation) was investigated in univariate analysis. Multivariate logistic regression analysis was performed to identify independent risk factors, and a stepwise backward elimination method was used to determine the helpful combination of risk factors. The nomogram was developed based on a multivariate logistic regression model. The performance of the nomogram was evaluated using a concordance index and calibration plots with bootstrap samples. Statistical analysis was performed using STATA software package; the significance level was set at P < 0.05. ResultsBased on multivariate logistic regression analysis, a combination of previous preterm delivery [OR: 5.25; 95 %CI: (2.13–12.90), p < 0.01], TPOAb [OR: 1.01; 95 %CI: (1.01–1.02), and T4 [OR: 0.90; 95 %CI: (0.83–0.97); p = 0.04] as independent risk factors that most precisely predicted preterm birth. The area under the curve (AUC) was 0.66 (95% CI: 0.61–0.72). The calibration plot suggests that the fit of the nomogram is reasonable. ConclusionA combination of T4, TPOAb, and previous preterm delivery was identified as independent risk factors that accurately predicted preterm delivery. The total score obtained based on the nomogram designed based on risk factors can predict the risk of preterm delivery.

High level of thyroid peroxidase antibodies as a detrimental risk of pregnancy outcomes in euthyroid women undergoing ART: A meta-analysis.

Thyroid autoimmunity (TAI) triggered by genetic and epigenetic variation occurs mostly in women of reproductive age. TAI is described mainly by positivity of anti-thyroid peroxidase antibody (TPO-Ab) and/or thyroglobulin antibody (TG-Ab). TPO-Ab, but not TG-Ab, was suggested to be associated with pregnancy outcome in euthyroid women undergoing assisted reproductive technology (ART), but their results are conflicting. This meta-analysis was performed to decide whether the presence of TPO-Ab-in a concentration dependent manner-correlates with the success of ART. A systematic literature search was performed in the PubMed, Web of Science, and EMBASE databases for relevant articles published from January 1999 to April 2022, and these studies focused on the effect of TAI on pregnancy outcomes of women who underwent in vitro fertilization, intracytoplasmic sperm injection and intrauterine insemination and met the inclusion criteria: (i) the studies were prospective or retrospective study; (ii) all patients undergoing ART were tested for thyroid-related antibodies; (iii) the assessed ART outcomes included miscarriage rate (MR) or delivery rate (DR). The exclusion criteria were: (i) female congenital uterine malformation, chromosomal diseases and other infectious diseases; (ii) overt hypothyroidism or pre-existing thyroid disease; (iii) thrombus tendency. We divided the included patients into three groups according to the TPO-Ab threshold they defined: (i) TPO-Ab (-), threshold <34 IU/mL; (ii) TPO-Ab-34, threshold >34 IU/mL; (iii) TPO-Ab-100, threshold >100 IU/mL. We then extracted necessary relevant data, including MR and DR. Egger's test was used to evaluate the risk of publication bias. This meta-analysis included a total of 7 literatures involving 7466 patients with TAI (-) and 965 patients with TAI (+) and revealed that there was no significant difference between group TPO-Ab-34 and group TPO-Ab (-) in MR [risk ratio (RR): 0.61 (0.35, 1.08), p = 0.09] and DR [RR: 0.97 (0.83, 1.13), p = 0.69]. By contrast, compared to TPO-Ab (-) group, TPO-Ab-100 patients showed markedly higher MR [RR: 2.12 (1.52, 2.96), p = 0.0046], and lower DR [RR: 0.66 (0.49, 0.88), p < 0.0001] with high degree of statistical significance. This meta-analysis suggests that, for euthyroid patients, high level of TPO-Ab (>100 IU/mL) could adversely influence the pregnancy outcome of ART.

Abstract P104: Association of Thyroid Peroxidase Antibodies and Mortality Risk in Participants of the ELSA-Brasil Cohort Study

Introduction: Thyroid peroxidase antibodies (TPOAb) has been considered a new indicator of low-grade inflammation. The presence of TPOAb was associated with a higher risk of cardiovascular diseases and mortality in previous studies. Hypothesis: We assessed the hypothesis that there is an association of TPOAb and risk of mortality in middle-aged participants from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Methods: Baseline data of 6,115 men and 7,265 women (median age of 50 years-old) were analyzed. Fasting serum TPOAb levels were determined and categorized as detectable (&gt; 5.00 IU/mL) and positive (≥ 34.00 IU/mL). All-cause, cardiovascular, and cancer-related mortality data up to December 2018 were confirmed by death certificate. The association of TPOAb levels, detectability and positivity with mortality was determined by Cox regression, using hazard ratios (HR) and 95% confidence intervals (CI). The final model was adjusted for age, sex, research center, TSH, smoking status, natural log transformed (ln) BMI, alcohol intake, diabetes mellitus, (ln) serum CRP, (ln) serum LDL cholesterol, and hypertension. Results: After a median follow-up of 9 years, the number of events was 296, 86 and 112 for men, and 182, 50, and 85 for women, for all-cause, cardiovascular and cancer-related mortality, respectively. For men, higher levels of TPOAb were significantly associated with cancer-related mortality (HR: 1.25; CI: 1.00-1.57; p=0.049). There was no association of TPOAb levels with all-cause (HR: 1.07; CI: 0.92-1.25) and cardiovascular (HR: 0.73; CI: 0.50-1.08) mortality risk; neither of TPOAb positivity and detectability with any overall or specific mortality risk (p&gt;0.05). For women, the results showed no significant association of TPOAb levels with all-cause (HR: 1.10; CI: 0.97-1.25), cardiovascular (HR: 1.05; CI: 0.81-1.35), and cancer-related (HR: 1.08; CI: 0.89-1.31) mortality. No significant associations were seen between TPOAb detectability and positivity and mortality risk (p&gt;0.05). Conclusions: In conclusion, higher levels of TPOAb were associated with a trend for increased risk of cancer-related mortality among men. Despite this interesting association, a longer period of follow-up is necessary to confirm those results. ELSA-Brasil is a cohort with relatively younger participants and low rates of mortality.

Assessment of the association between genetic factors regulating thyroid function and microvascular complications in diabetes: A two-sample Mendelian randomization study in the European population.

Observational studies have identified a possible link between thyroid function and diabetic microangiopathy, specifically in diabetic kidney disease (DKD) and diabetic retinopathy (DR). However, it is unclear whether this association reflects a causal relationship. To assess the potential direct effect of thyroid characteristics on DKD and DR based on Mendelian randomization (MR). We conducted an MR study using genetic variants as an instrument associated with thyroid function to examine the causal effects on DKD and DR. The study included the analysis of 4 exposure factors associated with thyroid hormone regulation and 5 outcomes. Genomewide significant variants were used as instruments for standardized freethyroxine (FT4) and thyroid-stimulating hormone (TSH) levels within the reference range, standardized free triiodothyronine (FT3):FT4 ratio, and standardized thyroid peroxidase antibody (TPOAB) levels. The primary outcomes were DKD and DR events, and secondary outcomes were estimated glomerular filtration rate (eGFR), urinary albumin-to-creatinine ratio (ACR) in diabetes, and proliferative diabetic retinopathy (PDR). Satisfying the 3 MR core assumptions, the inverse-variance weighted technique was used as the primary analysis, and sensitivity analysis was performed using MR-Egger, weighted median, and MR pleiotropy residual sum and outlier techniques. All outcome and exposure instruments were selected from publicly available GWAS data conducted in European populations. In inverse-variance weighted random-effects MR, gene-based TSH with in the reference range was associated with DKD (OR 1.44; 95%CI 1.04, 2.41; P = 0.033) and eGFR (β: -0.031; 95%CI: -0.063, -0.001; P = 0.047). Gene-based increased FT3:FT4 ratio, decreased FT4 with in the reference range were associated with increased ACR with inverse-variance weighted random-effects β of 0.178 (95%CI: 0.004, 0.353; P = 0.046) and -0.078 (95%CI: -0.142, -0.014; P = 0.017), respectively, and robust to tests of horizontal pleiotropy. However, all thyroid hormone instruments were not associated with DR and PDR at the genetic level. In diabetic patients, an elevated TSH within the reference range was linked to a greater risk of DKD and decreased eGFR. Similarly, decreased FT4 and an increased FT3:FT4 ratio within the reference range were associated with increased ACR in diabetic patients. However, gene-based thyroid hormones were not associated with DR, indicating a possible pathway involving the thyroid-islet-renal axis. However, larger population studies are needed to further validate this conclusion.