Thyroid autoantibodies at baseline predict longer survival in non-small cell lung cancer patients treated with anti-programmed cell death-1 blockade: a prospective study.

The presence of anti-thyroid antibodies (ATAs) is a biomarker for the development of thyroid dysfunction induced by anti-programmed cell death-1 antibodies (PD-1-Abs). While patients with thyroid dysfunction reportedly showed better overall survival (OS), it remains unknown if ATAs at baseline can predict OS. Therefore, in this study, we examined the association of ATAs at baseline with OS in non-small cell lung cancer (NSCLC) patients with different levels of programmed cell death-1 ligand 1 (PD-L1) positivity associated with PD-1-Ab treatment efficacy. A total of 81 NSCLC patients treated with PD-1-Abs were evaluated for ATAs at baseline and prospectively for OS. Among the 81 patients, 49 and 32 patients had ≥50% (group A) and <50% (group B) PD-L1 positivity, respectively. Median OS did not differ significantly between patients with (n = 13) and without (n = 36) ATAs at baseline in group A. In contrast, median OS was significantly longer in patients with (n = 10) versus without (n = 22) ATAs at baseline in group B (not reached vs 378 days, respectively; 95% CI, 182 to 574 days, p = 0.049). These findings suggest that the presence of ATAs at baseline is a biomarker to predict better treatment efficacy of PD-1-Abs in NSCLC patients with low PD-L1 positivity, while the difference in OS in those with high PD-L1 positivity may be masked by increased tumor expression of PD-L1.

Zinc and Ferritin Levels and Their Associations with Functional Disorders and/or Thyroid Autoimmunity: A Population-Based Case-Control Study.

Population zinc and iron status appear to be associated with an increased risk of thyroid function abnormalities and thyroid autoimmunity (AITD). In the present study, we aimed to determine whether zinc and/or iron levels (assessed by ferritin levels) were associated with the presence of AITD and with alterations in thyroid function. A population-based case-control study (n = 1048) was conducted (cases: n = 524; controls: n = 524). Participants were measured for blood concentrations of zinc and ferritin, TSH, FT4, FT3, and thyroid autoantibodies. No significant differences were found in relation to ferritin levels between cases and controls. Among cases, the prevalence of low zinc levels in those with hypothyroidism (both subclinical and overt) was 49.1% [odds ratio (OR) of low zinc levels: 5.926; 95% CI: 3.756-9.351]. The prevalence of low zinc levels in participants with hyperthyroidism (both subclinical and overt) was 37.5% [OR of low zinc levels: 3.683; 95% CI: 1.628-8.33]. The zinc value that best discriminated the highest frequency of AITD was 70.4 µg/dL [sensitivity: 0.947, 1-specificity: 0.655, specificity: 0.345]. The highest frequency of AITD was calculated based on a zinc value <70 µg/dL (relative to a normal value), with this frequency being significantly higher in cases than in controls [OR: 9.3; 95% CI: 6.1-14.3 (p = 0.001)]. In conclusion, the results of our study suggest that zinc deficiency is associated with an increased frequency of functional thyroid disorders and thyroid autoimmunity.

Genome-wide association studies of thyroid-related hormones, dysfunction, and autoimmunity among 85,421 Chinese pregnancies.

Maintaining normal thyroid function is crucial in pregnancy, yet thyroid dysfunction and the presence of thyroid peroxidase antibodies (TPOAb) affect 0.5% to 18% of pregnant women. Here, we conducted a genome-wide association study (GWAS) of eight thyroid traits, including two thyroid-related hormones, four thyroid dysfunctions, and two thyroid autoimmunity measurements among 85,421 Chinese pregnant women to investigate the genetic basis of thyroid function during pregnancy. Our study identified 176 genetic loci, including 125 previously unknown genome-wide associations. Joint epidemiological and Mendelian randomization analyses revealed significant associations between the gestational thyroid phenotypes and gestational complications, birth outcomes, and later-age health outcomes. Specifically, genetically elevated thyroid-stimulating hormone (TSH) levels during pregnancy correlated with lower glycemic levels, reduced blood pressure, and longer gestational duration. Additionally, TPOAb and thyroid functions during pregnancy share genetic correlations with later-age thyroid and cardiac disorders. These findings provide insights into the genetic determinants of thyroid traits during pregnancy, which may lead to new therapeutics, early pre-diagnosis and preventive strategies starting from early adulthood.

Development and Validation of a Prediction Model for Thyroid Dysfunction in Patients During Immunotherapy.

OBJECTIVE: This study was designed to develop and validate a predictive model for assessing the risk of thyroid toxicity following treatment with immune checkpoint inhibitors. METHODS: A retrospective analysis was conducted on a cohort of 586 patients diagnosed with malignant tumors who received programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors. The patients were randomly divided into training and validation cohorts in a 7:3 ratio. Logistic regression analyses were performed on the training set to identify risk factors of thyroid dysfunction, and a nomogram was developed based on these findings. Internal validation was performed using K-fold cross-validation on the validation set. The performance of the nomogram was assessed in terms of discrimination and calibration. Additionally, decision curve analysis was utilized to demonstrate the decision efficiency of the model. RESULTS: Our clinical prediction model consisted of 4 independent predictors of thyroid immune-related adverse events, namely baseline thyrotropin (TSH, OR = 1.427, 95%CI:1.163-1.876), baseline thyroglobulin antibody (TgAb, OR = 1.105, 95%CI:1.035-1.180), baseline thyroid peroxidase antibody (TPOAb, OR = 1.172, 95%CI:1.110-1.237), and baseline platelet count (platelet, OR = 1.004, 95%CI:1.000-1.007). The developed nomogram achieved excellent discrimination with an area under the curve of 0.863 (95%CI: 0.817-0.909) and 0.885 (95%CI: 0.827-0.944) in the training and internal validation cohorts respectively. Calibration curves exhibited a good fit, and the decision curve indicated favorable clinical benefits. CONCLUSION: The proposed nomogram serves as an effective and intuitive tool for predicting the risk of thyroid immune-related adverse events, facilitating clinicians making individualized decisions based on patient-specific information.

Association between thyroid autoimmunity and antinuclear antibody prevalence among pregnant women: a cross-sectional study in Qingdao, China.

Objective: To identify the relationship between thyroid autoimmunity and antinuclear antibody (ANA) prevalence in Chinese pregnant women. Methods: The study involved 1923 first-trimester women who were measured for thyroid stimulating hormone (TSH) level, thyroid autoantibodies (thyroperoxidase antibody [TPOAb] and thyroglobulin antibody [TgAb]) and ANA titer. Social demographic data were collected through standardized questionnaires. Results: In this study, 23.3% of pregnant women tested positive for TPOAb and 9.9% tested positive for TgAb. Women with a positive ANA were more likely to be TPOAb-positive or TgAb-positive than women with a negative ANA (adjusted odds ratio [AOR] 1.96, 95% confidence interval [CI] 1.47-2.62 for TPOAb [+]; AOR 3.12, 95% CI 2.18-4.48 for TgAb[+]). In addition, ANA titers were closely associated with thyroid autoimmunity. Women with an ANA titer of >1:320 had a significant higher risk of being TPOAb positive or TgAb positive (AOR 4.49, 95% CI 1.48-13.66 for TPOAb [+]; AOR 5.51, 95% CI 1.65-18.49 for TgAb [+]). The higher the ANA titer, the greater the risk of developing thyroid autoimmunity, especially for those with a high ANA titer. Conclusions: ANA positivity is strongly correlated with thyroid autoimmunity. Further study is warranted to clarify the causal relationship between thyroid autoimmunity and ANA in pregnant women.This research is essential to evaluate and predict the risk of co-existing autoimmune disorders,leading to improved care for pregnancy and neonatal health.

Impaired embryo development potential associated with thyroid autoimmunity in euthyroid infertile women with diminished ovarian reserve.

Purpose: The aim of this study was to evaluate the associations of thyroid autoimmunity (TAI) with the number of oocytes retrieved (NOR), fertilization rate (FR), and embryo quality (EQ) in euthyroid women with infertility and diminished ovarian reserve (DOR). Methods: This retrospective cohort study involved 1,172 euthyroid women aged 20-40 years with infertility and DOR who underwent an oocyte retrieval cycle. TAI was diagnosed in the presence of serum thyroperoxidase antibody (TPOAb) concentrations higher than 34 IU/ml and/or serum thyroglobulin antibody (TgAb) concentrations exceeding 115.0 IU/ml. Among these women, 147 patients with TAI were classified as the TAI-positive group, while 1,025 patients without TAI were classified as the TAI-negative group. Using generalized linear models (GLMs) adjusted for confounding factors, we evaluated the associations of TAI and the serum TPOAb and TgAb concentrations and NOR, FR, and EQ in this study's subjects. The TPOAb and TGAb values were subjected to log10 transformation to reduce skewness. Logistic regression models were used to estimate the effects of TPOAb and TgAb concentrations on the probabilities of achieving a high NOR (≥7) and high FR (>60%). Results: For the whole study population, women with TAI had a significantly lower NOR and poorer EQ than women without TAI (P < 0.001 for both). Interestingly, in the TSH ≤2.5 subgroup, the TAI-positive group also had a significantly lower NOR and poorer EQ than the TAI-negative group (P < 0.001 for both). Furthermore, negative associations were observed between log10(TPOAb) concentrations and NOR and the number of high-quality embryos and available embryos (P < 0.05 for all). The log10(TgAb) concentrations were inversely associated with NOR and the number of high-quality embryos (P < 0.05 for all). In the regression analysis, the log10(TPOAb) concentrations had lower probabilities of achieving a high NOR [adjusted odds ratio (aOR): 0.56; 95% confidence interval (95% CI) 0.37, 0.85; P = 0.007]. Conclusions: TAI and higher TPOAb and TgAb concentrations were shown to be associated with reductions in the NOR and EQ in the study population. Our findings provide further evidence to support systematic screening and treatment for TAI in euthyroid women with infertility and DOR.

Association of exposure to a mixture of phenols, parabens, and phthalates with altered serum thyroid hormone levels and the roles of iodine status and thyroid autoantibody status: A study among American adults.

BACKGROUND: Toxicological and epidemiological studies have shown that environmental endocrine disruptors interfere with hormonal homeostasis. However, there is limited research on the effects of mixed exposure to nonpersistent endocrine disruptors on thyroid hormones and the factors (e.g., presence status of thyroid autoantibodies or nutritional status of organismal iodine) that may influence this association. METHODS: Data were collected from the National Health and Nutrition Examination Survey (NHANES) 2007-2008 and 2011-2012. Relationships between single pollutants and thyroid hormone and thyroid autoantibody levels were assessed using generalized linear (GLM) and restricted cubic spline (RCS) regression models. Weighted quantile sum regression (WQS), group-weighted quantile sum regression (GWQS), quantile-based g-computation (qgcomp), and adaptive elasticity network (AENET) were applied to assess the mixed exposure effect. Next, subgroup analyses were performed on the basis of the urinary iodine concentration or thyroid autoantibody status to assess the modifying role of urinary iodine and thyroid autoantibodies. RESULTS: A total of 2385 study participants were included in this study. Both the single-pollutant model and the multipollutant mixed model revealed that parabens and bis(2-ethylhexyl) phthalate (DEHP) metabolites were significantly and negatively associated with serum thyroxine (T4) levels. However, no associations were found between the target pollutants and thyroid autoantibodies (thyroglobulin antibodies (TgAb) and thyroid peroxidase antibodies (TPOAb)). In addition, this study revealed that urinary iodine or thyroid autoantibody status altered the associations of some of the target pollutants with thyroid hormones. WQS and qgcomp analyses, revealed that the associations of mixed pollutants with hormones differed depending on the urinary iodine or antibody status, especially T4 and thyroid-stimulating hormone (TSH). CONCLUSION: Significant associations were found between phenols, parabens, and phthalates and serum thyroid hormone levels, with parabens and DEHP metabolites playing major roles. Urinary iodine and thyroid autoantibody status act as modifiers between environmental endocrine-disrupting pollutants and thyroid hormones.

Thyroid ultrasonic changes relate to implantation failure in euthyroid women with thyroid autoimmunity undergoing in vitro fertilization/intracytoplasmic sperm injection.

OBJECTIVE: To determine whether ultrasonic manifestations of Hashimoto's thyroiditis (HT) related to embryo qualities or pregnancy outcomes in women with thyroid autoimmunity (TAI) undergoing in vitro fertilization/intracytoplasmic sperm injection. METHODS: Our study was a retrospective cohort study. A total of 589 euthyroid women enrolled from January 2017 to December 2019. 214 TAI women and 375 control women were allocated in each group according to serum levels of thyroid peroxidase antibodies (TPOAb) and/or anti-thyroglobulin antibodies (TgAb). Basal serum hormone levels and thyroid ultrasound were assessed, embryo qualities, pregnancy outcomes were collected from medical records. Diagnosis of thyroid ultrasound was used for subanalysis. Logistic regression was used to evaluate outcomes of embryo development and pregnancy. RESULTS: Implantation rate was significantly lower in euthyroid women with TAI compared with control group (TAI group: 65.5% vs. Control group: 73.0%, adjusted OR (95% CI): 0.65 (0.44, 0.97), p = 0.04). We further stratified TAI group into two groups: one group with HT features under ultrasound and another group with normal thyroid ultrasound. After regression analysis, TAI women with HT morphological changes had a lower chance of implantation compared with control group (TAI group with HT: 64.1% vs. Control group: 73.0%, adjusted OR (95% CI): 0.63 (0.41, 0.99), p = 0.04), while there was no significant difference on implantation rate between TAI women with normal thyroid ultrasound and control group. Other outcomes, such as embryo qualities and pregnancy rate, were comparable between TAI and control groups. CONCLUSIONS: A higher risk of implantation failure was seen among euthyroid women with TAI, especially women with HT morphological changes under ultrasound. The underlying mechanisms of implantation failure among euthyroid HT patients need further research.

Identification and functionalization of thyrotropin receptor antibodies with different antigenic epitopes.

One of the sensitive markers for autoimmune thyroid disease (AITD) clinical identification is thyroid-stimulating hormone receptor antibodies (TRAbs). To quickly distinguish TRAb with distinct antigenic epitopes, a straightforward and uncomplicated technique has not yet been created. The objective of this study is to search for molecular diagnostic targets for different types of AITD {Graves' disease (GD), Graves' orbitopathy (GO), GD with third-degree goiter [GD(3)], hypothyroidism combined with positive TRAb [HT(TRAb+)]} as molecular diagnostic targets. Following action on thyroid cells, differential genes (DEGs) generated by TRAb with distinct antigenic epitopes were detected and identified by RNA sequencing (RNA-Seq), bioinformatics analysis, and quantitative reverse transcription-polymerase chain reaction (RT-qPCR) in the serum of patients with AITD. Using the 5-ethynyl-2'-deoxyuridine (EdU) assay, the effect of coculturing thyroid cells with different antigenic TRAb epitopes on the cells' capacity to proliferate was investigated. Bioinformatics analysis and RT-qPCR validation identified one GD key gene alpha 2-HS glycoprotein (AHSG), two GO key genes [adrenoceptor alpha 1D (ADRA1D) and H2B clustered histone 18 (H2BC18)], two GD(3) key genes [suppressor of cytokine signaling 1 (SOCS1) and cytochrome b-245 beta (CYBB)], and one HT(TRAb+) key gene (MASP2). Correlation analysis and ROC curves showed that the abovementioned genes could be used as molecular diagnostic targets for different types of AITD. Finally, EdU results showed that TRAb inhibited thyroid cell proliferation in the HT(TRAb+) group compared with the normal control group, whereas the remaining three groups promoted thyroid cell proliferation, with a statistically significant difference (P < 0.05). We identified six key genes for different types of AITD, which have diagnostic value for different types of AITD. Meanwhile, we found that TRAbs with different antigenic epitopes in AITD have different biological functions.NEW & NOTEWORTHY We identified six molecular targets of different types of AITD [GD, GO, GD(3), and HT(TRAb+)], which have diagnostic value for different types of AITD. Meanwhile, we found that TRAb with different antigenic epitopes extracted from the sera of patients with AITD had different biological functions, which also provided a new idea for further research on the mechanism of action of TRAb with different antigenic epitopes in AITD.

Association between specific human leukocyte antigen alleles and development of thyroid immune-related adverse event.

Aim: Inherent variations in human leukocyte antigen (HLA) alleles have been revealed epidemiologically to influence the development of autoimmune diseases. HLA alleles may thus also be associated with the development of immune-related adverse events (irAEs), such as thyroid irAE.Materials & methods: In this case-control study, 71 cancer patients who received immune checkpoint inhibitors were enrolled and HLA-genotyped and the frequency of HLA alleles was compared.Results: A*26:01, DPA1*01:03 and DPB1*02:01 were significantly more frequent in patients with thyroid irAE than in patients without any irAEs (35.0 vs 3.2% [p = 0.004], 80.0 vs 45.2% [p = 0.020] and 55.0 vs 25.8% [p = 0.044], respectively).Conclusion: A*26:01, DPA1*01:03 and DPB1*02:01 appear to be associated with thyroid irAE.

Everyone has a unique combination of human leukocyte antigens (HLAs) in their body that help the immune system identify threats. HLAs were named from the fact that they were first identified on the surface of human leukocytes. Afterward, HLAs were also found on all human cells. HLAs present antigens to immune cells. These HLAs also influence how the immune system attacks cancer cells. Immune checkpoint inhibitors are drugs that can help the immune system fight cancer, but they sometimes cause severe adverse events. In this study, we investigated whether specific HLA genes are related to the development of an adverse event that affects the thyroid in cancer patients treated with immune checkpoint inhibitors. We found an association between three HLA genes (A*26:01, DPA1*01:03 and DPB1*02:01) and the development of the thyroid adverse event. However, larger studies are needed to confirm and generalize these initial exploratory findings.

Characterization of Immune Infiltrate Along the Leading Edge of Differentiated Thyroid Cancer.

Background: Although the impact of tumor-immune infiltrate has been reported on differentiated thyroid cancer (DTC) behavior, the expression of immune checkpoints [programmed cell death protein 1 (PD-1) and its ligand (PD-L1)] alone has not been able to predict response to immunotherapies. We aimed to identify tumor-infiltrating immune cells and checkpoints associated with DTC. Methods: We performed multiplex immunofluorescence on deparaffinized thyroid tissue collected at thyroidectomy from 17 adults with DTC to characterize the tumor immune microenvironment for leukocytes (CD45+), T cells (CD3+), T regulatory cells (Tregs) (CD3+FOXP3+), CD4+ T cells (CD3+CD4+), CD8+ T cells (CD3+CD8+), macrophages (CD68+), M2 macrophages (CD68+CD163+), M1 Macrophages (CD68+ inducible nitric oxide synthase [iNOS]+), and immune checkpoints PD-1 and PD-L1. We compared the mean percentage expression of immune markers between tumor and adjacent thyroid tissue from the same patient by paired t-test and performed spatial analysis along the tumor's leading edge. Results: Immune checkpoints PD-1 and PD-L1 showed a significant increase in expression intratumorally as compared to adjacent thyroid tissue (p < 0.05). A higher trend for M2 macrophages was observed intratumorally compared to adjacent tissue. Along the leading edge, PD-L1 expression correlated negatively with CD45 and positively with CD163 intratumorally. On exploratory analysis, there was a nonsignificant trend for higher FOXP3 but less CD8 and iNOS expression in tumor from DTC with (n = 3) versus without distant metastases (n = 14). There was a nonsignificant trend for higher CD58 and iNOS expression in DTC with (n = 7) than without thyroiditis (n = 10). Conclusions: Higher tumoral PD-1 and PD-L1 expression indicate their role in DTC occurrence. A trend for more Tregs and M2 macrophages but less M1 macrophages intratumorally in patients with distant metastatic DTC, suggests their potential role as prognostic biomarkers. Future studies with larger sample sizes are needed to compare various clinicopathologic severities to harness tumor microenvironment for cancer prognostication and therapy.

The association of thyroid autoimmunity with ovarian reserve in women with type 1 diabetes with and without polycystic ovary syndrome.

The aim of the study was to investigate the relation between thyroid autoimmunity (TAI), reflected as the presence of thyroid peroxidase antibodies (TPOAb), and parameters of ovarian reserve in women with type 1 diabetes (T1DM) and polycystic ovary syndrome (PCOS). We studied 83 euthyroid women with T1DM (age - 26 ± 5 years, BMI - 24 ± 3 kg/m2) - 12 with PCOS and positive TPOAb (PCOS + TPOAb), 29 with PCOS with negative TPOAb (PCOS + noTPOAb), 18 without PCOS with positive TPOAb (noPCOS + TPOAb), 24 without PCOS with negative TPOAb (noPCOS + noTPOAb). Serum concentrations of anti-Müllerian hormone (AMH), sex hormones, TSH, thyroid hormones and TPOAb were assessed. The prevalence of TAI was comparable between PCOS and noPCOS. We did not observe differences in hormonal profile or AMH concentration between two PCOS groups-PCOS + TPOAb and PCOS + noTPOAb (p > 0.05). Women with PCOS + TPOAb had lower FSH concentration and higher LH/FSH index than noPCOS + noTPOAb (p = 0.027; p = 0.019, respectively). Moreover, PCOS + TPOAb had lower oestradiol level than noPCOS + TPOAb (p = 0.041). AMH concentration was higher in both groups with PCOS, independent of TPOAb presence, than in noPCOS + noTPOAb (both p < 0.001). The presence of positive TPOAb titre was not related to the studied parameters of ovarian reserve - AMH and ovarian follicle number. In multiple linear regression analysis, the only significant predictor of AMH in the whole studied group with T1DM was total daily insulin dose U/kg (ß = - 0.264; p = 0.022). The presence of TAI did not affect the hormonal profile or ovarian reserve in women with T1DM with and without PCOS.

The relationship between thyroid autoantibodies and X chromosome monosomy in the chorionic tissue of patients with missed miscarriage.

OBJECTIVE: The aim of this study was to investigate the relationship between thyroid autoantibodies (TGAb and TPOAb) and X chromosome monosomy in the chorionic tissue of patients with missed early miscarriage. METHODS: The baseline data, thyroid function, thyroid antibody and the chromosomes from the chorionic tissue of 228 patients with missed early miscarriage were examined. RESULTS: (1) Among the 228 patients, 121 had a normal chromosome number, and 107 had an abnormal chromosome number. The majority of them were autosomal trisomy, of which trisomy 16 (40.19%) was predominant. Sex chromosome monosomy (28.04%) was secondary. (2) Among the 228 patients, 208 patients in this study had normal thyroid function (including 134 cases of negative thyroid antibodies and 74 cases of positive thyroid antibodies alone); 6 patients had abnormal thyroid function (including 2 cases of clinical hyperthyroidism, 3 cases of subclinical hypothyroidism, 1 case of hypothyroxinemia); and 14 patients had normal TSH and elevated T4 alone.(3) After exclusion of patients with thyroid function abnormalities, there were no significant differences in baseline data between the normal chromosome group and the abnormal chromosome group (P > 0.05). However, there was a significant difference in TGAb and TPOAb between the normal chromosome and abnormal chromosome group with 45, X karyotype, with a higher proportion of TGAb and/or TPOAb positivity in the 45, X karyotype group (P < 0.05). Additionally, compared to TGAb and/or TPOAb-positive patients, the risk of X chromosome monosomy was significantly reduced in TGAb and TPOAb-negative patients (P < 0.05). Moreover, both TGAb and TPOAb titer values in the X chromosome monosomy group were higher than those in the chromosomally normal group (P < 0.05). CONCLUSION: There is a correlation between TGAb, TPOAb and X chromosome monosomy in the chorionic tissue of patients with missed early miscarriage, although the mechanism remains to be further investigated.

Prevalence and factors associated with thyroid autoimmunity among children newly diagnosed with type 1 diabetes before and during the COVID-19 pandemic: Evidence from Kuwait.

AIMS: This study reports the prevalence and characteristics related to the development of thyroid autoimmunity among children newly diagnosed with type I diabetes (T1D) during the COVID-19 pandemic in Kuwait. MATERIALS AND METHODS: This is a prospective observational study of all children under age 14 years newly diagnosed with T1D in Kuwait. We define the duration of the COVID-19 pandemic from the official declaration of the first identified positive COVID-19 case on 24 February 2020 until 31 December 2022. For comparison, we use the time period directly before the COVID-19 pandemic, 1 January 2017 to 23 February 2020. RESULTS: One thousand twenty-four (1024) children newly diagnosed with T1D in Kuwait during the study period were included. Among newly diagnosed children, 20.3% tested positive for thyroid antibodies during the COVID-19 pandemic, compared with 14.5% during the pre-pandemic period (p = 0.015). Children with positive COVID-19 status were more likely to present with thyroid antibodies (p = 0.035). After adjusting for other characteristics, patients diagnosed with T1D during the COVID-19 pandemic had double the odds of testing positive for thyroid antibodies (Adjusted odds ratio = 2.173, 95%CI: 1.108, 4.261, p = 0.024). CONCLUSIONS: Incident cases of T1D during the COVID-19 pandemic may be different in aetiology or contextual factors leading to a higher risk of thyroid autoimmunity. Longitudinal studies are needed to understand the role of COVID-19 in the onset and progression of T1D and on thyroid autoimmunity and disease.

Evaluation of ovarian reserve in women with thyroid autoimmunity.

OBJECTIVE: To compare the ovarian reserve of women of reproductive age with and without thyroid autoimmunity (TAI). METHODS: We performed a retrospective analysis of medical records from an assisted reproduction clinic from February 2017 to December 2021. Women aged between18 and 47 years with data on antithyroperoxidase and antithyroglobulin (anti-Tg) antibodies and assessment of ovarian reserve by anti-müllerian hormone (AMH) and antral follicle count (AFC) were included. Among the 188 participants included, 63 were diagnosed with TAI, and 125 had both antibodies negative. AMH and AFC were compared between groups. Subanalysis based on age, types of antibodies, and thyroid function markers were performed. In addition, bivariate analysis and regression models were used. RESULTS: Overall, there was no difference in the median levels of AMH or AFC between the two groups. However, in the subgroup analysis by age, we observed a trend towards lower median levels of AMH in women over 39 years with TAI (0.9 ng/mL vs. 1.5 ng/mL, p=0.08). In a subanalysis according to antibodies, we found a significantly lower median AFC in the group with anti-Tg than in the group without this antibody (8.0 follicles vs. 11.5 follicles, p=0.036). We also found a significantly higher prevalence of anti-Tg in patients with low ovarian reserve compared to those with normal reserve (60.7% vs. 39.3%, p=0.038). CONCLUSIONS: The ovarian reserve of women with TAI appears to be insidiously compromised over the years, with a decreased ovarian reserve in women with anti-Tg.

Selenium levels and their association with thyroid autoimmunity and severe preeclampsia in pregnancy: Insights from a prospective ideal breast milk cohort study.

Objective: This study aimed to assess selenium status in South Korean pregnant women and its impact on maternal thyroid function and pregnancy outcomes. Methods: 'Ideal Breast Milk (IBM) Cohort Study' included 367 pregnant women out of 442 participants and categorized into three groups based on plasma selenium levels: deficient (< 70 µg/L), suboptimal (70-99 µg/L), and optimal (≥ 100 µg/L). During the second or third trimester, various blood parameters, including selenium, thyroid-stimulating hormone, free T4, free T3, and anti-thyroid peroxidase antibody levels, were measured. Thyroid parenchymal echogenicity was assessed as another surrogate marker for thyroid autoimmunity using ultrasonography. Results: The median plasma selenium was 98.8 (range: 46.7-206.4) µg/L, and 30 individuals (8%) were categorized as deficient, while 164 (45%) were classified in the suboptimal group. Selenium deficiency was associated with markers of autoimmune thyroiditis, including positive anti-thyroid peroxidase antibody results (13.3 (deficient) vs 4.6 (optimal) %, P = 0.031) and thyroid parenchymal heterogeneity on ultrasound (33.3 (deficient) vs 14.6 (suboptimal) vs 17.3 (optimal) %, P = 0.042), independently of gestational age. The incidence of severe preeclampsia was higher in the group not taking selenium supplements, particularly among those with twin pregnancies, compared to the group taking selenium supplements (0 (selenium supplement) vs 9.0 (no supplement) %, P = 0.015). Conclusion: Pregnant women experience mild selenium deficiency, which can lead to significant health issues including maternal thyroid autoimmunity and obstetrical complications during pregnancy. Guidelines for appropriate selenium intake according to the stage of pregnancy and the number of fetuses are needed.

The interlink between thyroid autoimmunity and type 1 diabetes and the impact on male and female fertility.

The aim of this review is to discuss the several interconnections between thyroid autoimmunity and type 1 diabetes in terms of epidemiology, immunoserology, genetic predisposition, and pathogenic mechanisms. We will also analyze the impact of these conditions on both male and female fertility. A literature search was carried out using the MEDLINE/PubMed, Scopus, Google Scholar, ResearchGate, and Clinical Trials Registry databases with a combination of keywords. It was found that the prevalence of thyroid autoantibodies in individuals with type 1 diabetes (T1DM) varied in different countries and ethnic groups from 7 to 35% in both sexes. There are several types of autoantibodies responsible for the immunoserological presentation of autoimmune thyroid diseases (AITDs) which can be either stimulating or inhibiting, which results in AITD being in the plus phase (thyrotoxicosis) or the minus phase (hypothyroidism). Different types of immune cells such as T cells, B cells, natural killer (NK) cells, antigen presenting cells (APCs), and other innate immune cells participate in the damage of the beta cells of the islets of Langerhans, which inevitably leads to T1D. Multiple genetic and environmental factors found in variable combinations are involved in the pathogenesis of AITD and T1D. In conclusion, although it is now well-known that both diabetes and thyroid diseases can affect fertility, only a few data are available on possible effects of autoimmune conditions. Recent findings nevertheless point to the importance of screening patients with immunologic infertility for AITDs and T1D, and vice versa.

Clinical biomarkers for thyroid immune-related adverse events in patients with stage III and IV gastrointestinal tumors.

Background: Thyroid immune-related adverse events (irAEs) associated with immune checkpoint inhibitor (ICI) treatment appear to correlate with a better prognosis. We aimed to investigate clinical biomarkers associated with thyroid irAEs. Methods: We retrospectively analyzed data from 129 patients receiving programmed cell death protein 1 (PD-1) inhibitors for stage III and IV gastrointestinal tumors. Patients were divided into two groups: "thyroid irAEs" group and "no thyroid irAEs" group. We compared continuous variables using Mann-Whitney U and Kruskal-Wallis tests and categorical variables using Pearson's chi-square test. Survival curves were generated using the Kaplan-Meier method, and associations between clinical features and thyroid irAEs were assessed using univariate and multivariate logistic regression models. Associations for thyroid irAEs and outcomes [progression-free survival (PFS), overall survival (OS)] of the patients were performed with a Cox proportional hazard model. Results: A total of 129 patients, including 66 gastric cancer, 30 esophageal squamous cell carcinoma, and 33 hepatocellular carcinoma (HCC), were involved in this analysis with 47 cases of thyroid irAEs occurrence. The Cox proportional hazard model analysis confirmed the extended PFS [hazard rate (HR) = 0.447, 95% confidence interval (CI): 0.215 to 0.931, p = 0.031] and OS (HR = 0.424, 95% CI: 0.201 to 0.893, p = 0.024) for thyroid irAEs group when compared with those of the no thyroid irAEs group. Association between thyroid irAEs and clinical characteristics at baseline was analyzed subsequently by univariate analysis. Higher body mass index (p = 0.005), increased eosinophil count (p = 0.014), increased lactate dehydrogenase (p = 0.008), higher baseline thyroid stimulating hormone (TSH) (p = 0.001), HCC (p = 0.001) and increased adenosine deaminase (ADA) (p = 0.001) were linked with thyroid irAEs occurrence. The multivariable logistic regression model indicated that ADA [odds rate (OR) = 4.756, 95% CI: 1.147 to 19.729, p = 0.032] was independently associated with thyroid irAEs occurrence. Conclusions: Increased baseline level of ADA was associated with thyroid irAEs occurrence in patients with advanced gastrointestinal tumors who received ICI treatment. In the case of abnormal ADA, attention should be paid to the risk of thyroid irAEs.