Positive TPOAb Research Articles

Thyroid autoimmunity in different phenotypes of polycystic ovary syndrome: a single-center experience.

Polycystic ovary syndrome (PCOS) has been associated with Hashimoto's thyroiditis (HT) and 4 phenotypes have been described in this syndrome. The aim of this work was to investigate the frequency of anti-thyroid antibodies (TAb) and thyroid function in the 4 phenotypes of PCOS. This study included 448 patients with PCOS: 260 (58.0%) with phenotype A, 119 (26.6%) with phenotype B, 38 (8.5%) with phenotype C and 31 (6.9%) with phenotype D. TAb positivity was detected in 90/448 patients (20.1%) and was statistically significant higher (p = 0.03) in the grouped phenotypes A-B (83/379, 21.9%) than in phenotypes C-D (7/69, 10.1%). Positive anti-thyroglobulin antibodies (TgAb) were detected in 74/448 (16.5%) patients and positive anti-thyroperoxidase antibodies (TPOAb) in 66/448 (14.7%) patients. Both TgAb and TPOAb positivity was higher but not statistically significant in phenotype A-B than phenotype C-D. High titer TgAb (> 100UI/ml) frequency was significantly higher (p = 0.005) in grouped phenotypes A-B (39/379, 10.3%) than in phenotypes C-D (0/69, 0.0%), while no significant difference was observed for low titer TgAb (≤ 100UI/ml). According to a binary logistic regression analysis hypothyroidism was significantly associated with TAb positivity (OR 4.19; CI 2.25-7.79; p < 0.01) but not with PCOS phenotype. Androgen profile was not associated with TAb positivity. A higher frequency of positive TAb and of high titer TgAb and TPOAb have been detected in PCOS women with phenotypes A and B, probably in relation to the greater imbalances between estrogen and progesterone levels present in these phenotypes.

7729 Autoimmune Thyroid Disease And Risk of Premature Ovarian Failure - A Comprehensive Analysis Combining Observational Studies, Two-sample Mendelian Randomization Study, And Targeted Drug Forecast

Abstract Disclosure: R. Wang: None. T. Dou: None. L. Guan: None. X. Qi: None. X. Wang: None. C. Yu: None. Q. Guan: None. Premature ovarian failure (POF), a condition impacting women's fertility and physical well-being. Specifically, autoimmune thyroid disease (TAI) is recognized as an organ-specific autoimmune condition that may co-occur with POF in clinical scenarios, yet the precise nature of their relationship remains uncertain. The objective of this study is to investigate the influence of TAI on ovarian function, identify shared pathogenic genes, predict potentially effective drugs, and establish a foundation for clinical interventions. Firstly, a case-controlled study was conducted using the Nationwide Readmissions Database (NRD) in the United States. This involved identifying patients with Hashimoto's thyroiditis (HT) and Graves' disease (GD) as the study group, and those without deficiency as the control group, to explore the correlation with POF. Additionally, an Asian population-based case group comprising 897 patients with POF and a control group of 897 healthy women were gathered to analyze the association of POF with TAI-related antibodies, namely TGAb and TPOAb. Furthermore, a two-sample Mendelian randomization(MR) study was undertaken in European populations to investigate the causal relationship between TAI and POF. Lastly, genes associated with HT, GD, and POF were compiled from the GEO, GeneCards, and DisGeNET databases, and common genes were identified through intersection. Subsequent gene ontology and pathway enrichment analyses, protein-protein interaction analyses, and candidate drug predictions were performed based on the shared genes. The findings revealed a significant association between TAI and POF in the NRD, with patients exhibiting TAI being notably more prone to POF compared to the control group (OR 1.78, 1.34-2.35, P&amp;lt;0.001). Subgroup analysis further demonstrated an increased risk of POF in patients with HT (OR 1.51, 1.02-2.22, P&amp;lt;0.05) and GD (OR 2.18, 1.45-3.29, P&amp;lt;0.05). In the Asian population, a retrospective analysis indicated a positive correlation between TPOAB positivity and POF (OR 1.76, 1.24-2.51, P&amp;lt;0.05). MR analysis unveiled a causal relationship between GD and POF. Through a comprehensive examination of multiple gene databases, 47 common genes were identified between HT and POF, and 20 common genes between GD and POF. Enrichment analysis demonstrated relative similarities in cytokines and signal transduction, apoptosis, inflammatory response, and other aspects between HT and POF. GD was found to potentially influence ovarian function through pathways such as the PI3K-Akt signaling pathway and adhesive plaques. Dexamethasone, rapamycin, and other drugs emerged as potential therapeutic options for both diseases. In summary, our study suggests that TAI, particularly GD, may elevate the risk of POF. Additionally, we predict potential therapeutic drugs, and shed light on the potential biological mechanisms linking HT/GD and POF. Presentation: 6/3/2024

9303 Evaluation of The Consistency of Thyroid Indicators Tests in Minimally Invasive Peripheral Blood and Venous Blood

Abstract Disclosure: Z. Zhu: None. Y. Huang: None. Z. Cao: None. L. Zhang: None. D. Wang: None. S. Wang: None. J. Zhang: None. Y. Gao: None. Y. Zhang: None. Background The detection of thyroid indicators is of high demand in clinical and epidemiological screenings. Compared with existing venous blood tests, peripheral fingertip blood tests are less invasive and have a lower blood collection volume, which is the basis for point-of-care tests of thyroid indicators. Objective To explore the feasibility of minimally invasive and micro blood collection tests for thyroid disease (TD) patients by evaluating the consistency of thyroid indicators and TD diagnostic efficiency between fingertip blood tests and venous blood tests. Method 63 subjects with or without thyroid dysfunction were consecutively recruited. All subjects underwent serum, plasma and fingertip blood (same day collection) measurements for TSH and TT4 detection via the chemiluminescence method and for TPOAb detection via the electrochemiluminescence immunoassay method. The fingertip blood was centrifuged and diluted after EDTA anticoagulation. Bland–Altman plot, Passing–Bablok regression, and weighted kappa test were used for consistency test; AUC of ROC curve, sensitivity and specificity were used for authenticity evaluation among the three collection and testing methods. Results 43 subjects with euthyroidism and 20 subjects with thyroid dysfunction were included; including 29 (46.03%) females, the average age was 50.98±14.76 years. Bland-Altman plots showed more than 90% of the subjects had TSH and TT4 differences within the 95% limits of agreement between peripheral blood (PB) and venous blood (including serum and plasma). Passing–Bablok regression analyses revealed strong correlations between TSH levels in PB and serum (r=0.888) and plasma (r=0.894) (p&amp;lt;0.05); for TT4, there was a strong correlation between PB and serum (r=0.746), and there was also a moderate correlation between PB and plasma (r=0.664) (p&amp;lt;0.05 for both). Weighted kappa tests were performed for low, normal and high TSH values, indicating strong consistency between PB and serum and between PB and plasma, with coefficients of 0.901 and 0.881, respectively (P&amp;lt;0.001); for TT4, the coefficients between PB and serum, PB and plasma were 0.541 and 0.585 (P&amp;lt;0.001), indicating moderate consistency. Regardless of TPOAb positivity or negativity, the consistency among three blood sample sources was 100%. For euthyroidism (n=43), hyperthyroidism (n=6), subclinical hyperthyroidism (n=9), hypothyroidism (n=1), and subclinical hypothyroidism (n=4), the diagnostic sensitivities of PB were 97.06%, 83.33%, 87.50%, 100%, and 75.00%, respectively; the specificities were 94.74%, 97.87%, 95.74%, 98.11%, and 100.00%, respectively. The AUC of PB ROC curve for determining thyroid dysfunction was 0.944 (95% CI 0.867-1.000). Conclusion PB tests of thyroid indicators has high consistency with venous blood tests, offers sufficient diagnostic efficiency for TD, and is a feasible minimally invasive detection method. Presentation: 6/1/2024

7589 A Survey On the Current Status of Universal Screening Thyroid Indicators During Pregnancy in Real World Study

Abstract Disclosure: N. Zhou: None. W. Sun: None. H. Meng: None. Y. Huang: None. J. Zhao: None. Y. Gao: None. H. Yang: None. Y. Zhang: None. A Survey on the current status of universal screening thyroid indicators during pregnancy in real world study Background: Thyroid dysfunction and thyroid auto-immunity (TAI) are common in women of childbearing age, which have been proven to increase the risk of maternal and fetal adverse pregnancy outcomes. China has adhered to the strategy of universal screening for early pregnancy thyroid indicators since 2012, and is currently the only country that recommends universal screening. This study aimed to investigate the implementation situation of universal screening for thyroid indicators during pregnancy in real world study. Methods: We retrospectively collected medical record information from 18,932 women who underwent regular prenatal examinations at Peking University First Hospital from January 2014 to December 2016 until the end of pregnancy, grouping based on whether thyroid indicators were screened during pregnancy, and comparing the general characteristics and pregnancy outcomes. Furthermore, the treatment compliance status of women who took levothyroxine and antithyroid drugs (ATD) before pregnancy was also analyzed. Results: The screening rate for thyroid indicators in pregnancy was 88.7% in our hospital, 93.3% of pregnant women underwent screening in early pregnancy, with a median gestational age of 7.0 (6.6, 10.1) weeks. Non-screening ones were more inclined to be aged&amp;gt;40 years or &amp;lt;25 years, with a BMI ≥24 kg/m2, pluriparity (≥2), and without thyroid disease history prior to conception (P &amp;lt; 0.05). After correcting covariates, the risks of early miscarriage (8-12 weeks) (OR=21.96, 95% CI: 19.2, 25.1) and late miscarriage (12-28 weeks) (OR=3.0, 95% CI: 2.5, 3.6) were significantly higher in non-screening group than in the screening group, but there was no significant difference in the risk of preterm labor between the two groups (P=0.985). The achievement rate (0.23≤TSH&amp;lt;2.5uIU/mL, FT4 within normal range, 53.7%-64.2%) of early pregnancy thyroid function among levothyroxine intervention participants increased from 2014 to 2016. Compared with those in the thyroid function controlled group, the patients in the uncontrolled group had earlier screening gestational weeks (6.7 vs. 8.0 weeks), higher TPOAb positivity (58.6% vs. 44%), and a greater incidence of other autoimmune disorders (14.2% vs. 9.8%) (P&amp;lt;0.05). The achievement rate of early pregnancy thyroid function among ATD intervention participants ranged from 63.6 to 71.2%. Conclusions: The screening rate for thyroid indicators in pregnancy is nearly 90% in comprehensive hospitals. The lack of screening may be related to miscarriage to some extent. The current treatment compliance status pre-pregnancy neither for levothyroxine nor ATDs was not satisfactory. Presentation: 6/2/2024

7583 Evaluation of The Consistency of Thyroid Indicators Tests in Minimally Invasive Peripheral Blood and Venous Blood

Abstract Disclosure: Z. Zhu: None. Y. Huang: None. Z. Cao: None. L. Zhang: None. D. Wang: None. S. Wang: None. J. Zhang: None. Y. Gao: None. Y. Zhang: None. Background: The detection of thyroid indicators is of high demand in clinical and epidemiological screenings. Compared with existing venous blood tests, peripheral fingertip blood tests are less invasive and have a lower blood collection volume, which is the basis for point-of-care tests of thyroid indicators. Objective To explore the feasibility of minimally invasive and micro blood collection tests for thyroid disease (TD) patients by evaluating the consistency of thyroid indicators and TD diagnostic efficiency between fingertip blood tests and venous blood tests. Method 63 subjects with or without thyroid dysfunction were consecutively recruited. All subjects underwent serum, plasma and fingertip blood (same day collection) measurements for TSH and TT4 detection via the chemiluminescence method and for TPOAb detection via the electrochemiluminescence immunoassay method. The fingertip blood was centrifuged and diluted after EDTA anticoagulation. Bland–Altman plot, Passing–Bablok regression, and weighted kappa test were used for consistency test; AUC of ROC curve, sensitivity and specificity were used for authenticity evaluation among the three collection and testing methods. Results 43 subjects with euthyroidism and 20 subjects with thyroid dysfunction were included; including 29 (46.03%) females, the average age was 50.98±14.76 years. Bland-Altman plots showed more than 90% of the subjects had TSH and TT4 differences within the 95% limits of agreement between peripheral blood (PB) and venous blood (including serum and plasma). Passing–Bablok regression analyses revealed strong correlations between TSH levels in PB and serum (r=0.888) and plasma (r=0.894) (p&amp;lt;0.05); for TT4, there was a strong correlation between PB and serum (r=0.746), and there was also a moderate correlation between PB and plasma (r=0.664) (p&amp;lt;0.05 for both). Weighted kappa tests were performed for low, normal and high TSH values, indicating strong consistency between PB and serum and between PB and plasma, with coefficients of 0.901 and 0.881, respectively (P&amp;lt;0.001); for TT4, the coefficients between PB and serum, PB and plasma were 0.541 and 0.585 (P&amp;lt;0.001), indicating moderate consistency. Regardless of TPOAb positivity or negativity, the consistency among three blood sample sources was 100%. For euthyroidism (n=43), hyperthyroidism (n=6), subclinical hyperthyroidism (n=9), hypothyroidism (n=1), and subclinical hypothyroidism (n=4), the diagnostic sensitivities of PB were 97.06%, 83.33%, 87.50%, 100%, and 75.00%, respectively; the specificities were 94.74%, 97.87%, 95.74%, 98.11%, and 100.00%, respectively. The AUC of PB ROC curve for determining thyroid dysfunction was 0.944 (95% CI 0.867-1.000). Conclusion PB tests of thyroid indicators has high consistency with venous blood tests, offers sufficient diagnostic efficiency for TD, and is a feasible minimally invasive detection method. Presentation: 6/1/2024

The association of maternal thyroid function with offspring iq and brain morphology: persistency into early adolescence and relevance of tpoab positivity

The association of maternal thyroid function with offspring iq and brain morphology: persistency into early adolescence and relevance of tpoab positivity

Autoimmune thyroid disease modifies the clinical expression of hand osteoarthritis in older people: a third National Health and nutrition examination survey study.

The risk factors linked to hand osteoarthritis (OA) that contribute to its distinct symptoms and clinical presentation are not thoroughly understood. This study aimed to examine whether the autoimmune thyroid disease (AITD) autoantibodies, anti-thyroid peroxidase antibody (TPOAb), and anti-thyroglobulin antibody (TgAb), associate with hand OA and symptomatic hand OA in the Third National Health and Nutrition Examination Survey (NHANES III). We included 2,429 persons from NHANES III ≥60 years of age. Data on hand OA or symptomatic hand OA were examined with respect to their associations with TPOAb and TgAb. Log-binomial and modified Poisson regression models were fit to examine the associations between the anti-thyroid autoantibodies and hand OA or symptomatic hand OA. Higher levels of TPOAb were associated with a higher prevalence of symptomatic hand OA in the unadjusted (PR = 1.182, p = 0.024) and adjusted models after controlling for age, gender, and diabetes (PR = 1.174, p = 0.039). This association was no longer significant when positive TPOAb was considered a categorical variable with four levels and compared with negative TPOAb. TgAb showed a trend toward being positively associated with symptomatic hand OA (p < 0.10). When positive TgAb was considered a categorical variable with four levels and compared with negative TgAb, the highest quartile was associated with a higher prevalence of symptomatic hand OA than negative TgAb in the unadjusted (PR = 2.242, p = 0.008) and adjusted models (PR = 2.045, p = 0.038). There was no significant association between TPOAb or TgAb and hand OA. Higher levels of TPOAb may be associated with the presence of symptomatic hand OA in persons ≥60 years old. Persons ≥60 years old with the highest quartile levels of TgAb may be more likely to present with symptomatic hand OA.

Associations between thyroid function, thyroid diseases, and primary aldosteronism.

Previous studies focusing on primary aldosteronism (PA) and thyroid diseases were controversial. Hence, this study aimed to examine associations between thyroid function, thyroid diseases, and PA and its subtypes. This was a cross-sectional study, which enrolled 1023 patients with PA and 6138 patients with essential hypertension (EH) admitted to Hypertension Center of People's Hospital of Xinjiang Uygur Autonomous Region from August 2011 to June 2022. All patients with PA were accurately classified into aldosterone-producing adenoma (APA) and idiopathic hyperaldosteronism (IHA) by adrenal vein sampling (AVS). Multivariate logistic regression analysis was used to assess the relationship of thyroid function, thyroid nodules, and PA and its subtypes. A total of 7161 patients (327 APA and 696 IHA, and 6138 EH) were included with a mean age of 48.20 ± 8.83 years. PA patients and PA subtypes showed lower FT4, FT3, TT4, TT3, and prevalence of positive TPOAb, meanwhile higher prevalence of thyroid nodules than EH patients (PA: 56.10%, IHA: 56.90%, APA: 54.80%, and EH: 48.90%, respectively). PA (adjusted OR: 1.290, 95% CI: 1.035-1.607, P = .02) and its subtype (IHA) (adjusted OR: 1.316, 95% CI: 1.005-1.724, P = .04) were significantly associated with thyroid nodules. Compared to patients with lower plasma aldosterone concentration (PAC) levels (<12 ng/dL), patients with PAC levels ≥ 12 ng/dL presented a higher prevalence of thyroid nodules. PA patients had lower thyroid function and higher prevalence of thyroid nodules compared to EH patients. Therefore, the screening of thyroid function and thyroid nodules may be indispensable for PA patients.

Positive baseline thyroid autoantibodies as a predictive biomarker for thyroid immune-related adverse events: A systematic review and meta-analysis.

e24124 Background: Thyroid dysfunction is one of the most common immune-related adverse events (irAE) by immune checkpoint inhibitors (ICI). Given the known relationship between antithyroid autoantibodies (ATA), including antithyroid peroxidase (TPO Ab) and anti-thyroglobulin (Tg Ab), and autoimmune thyroid disease, they could also play a role as a predictive biomarker for thyroid irAE (T-irAE). We performed this meta-analysis to evaluate the association of positive baseline thyroid autoantibodies and T-irAE. Methods: Eligible studies were screened using Ovid Medline and Embase databases with search terms related to ATA and thyroid irAE. Studies must be case-control or cohort studies with patients who received ICI and report the numbers of patients who have thyroid dysfunction and do not have thyroid dysfunction by the pre-ICI treatment statuses of ATA, TPO Ab, or Tg Ab. The pooled odds ratio (OR) and the associated 95% confidence interval (95% CI) were calculated using the Mantel-Haenszel method. Subgroup analysis by types of ICI (anti-PD1, anti-PD-L1, or combination treatment) and study region were also performed. The presence of publication bias was assessed by direct visualization of funnel plots. Results: After two rounds of screening, 19 case-control and five retrospective cohort studies were included in the meta-analysis. Patients who had positive baseline ATA had increased odds of developing T-irAE, hypothyroidism, and hyperthyroidism (pooled OR 10.95, 95% CI 6.65-18.02, I2= 38%; 6.82, 95% CI 2.99-15.56, I2= 27%; and 7.59, 95% CI 2.51-22.96, I2= 42%; respectively). Positive pre-treatment TPO Ab and Tg Ab were also independently associated with higher odds of hypothyroidism (pooled OR 5.01, 95% CI 2.87-8.75, I2= 4%, and 18.73, 95% CI 9.04-38.80, I2= 0%, respectively) and hyperthyroidism (pooled OR 2.94, 95% CI 1.57-5.52, I2= 25%, and 8.36, 95% CI 1.18-59.31, I2= 82%, respectively). The associations did not significantly differ between the types of ICI utilized and the study region. Visualization of funnel plots did not reveal a presence of publication bias. Conclusions: Pre-ICI treatment statuses of ATA, TPO Ab, and Tg Ab are associated with both hypothyroidism and hyperthyroidism. Thyroid autoantibodies as a baseline predictive tool can be helpful for early detection of T-irAE in patients who receive ICI therapy.

EVALUATION OF THYROID FUNCTION AND THYROID DISEASES IN PATIENTS WITH PRIMARY ALDOSTERONISM

Objective: To explored the thyroid function and prevalence of thyroid diseases in primary aldosteronism (PA) and PA subtypes. Design and method: Patients with PA and Essential hypertension (EH) in our hypertension center between August 2011 to June 2022 were enrolled in this observational study. All PA patients underwent adrenal venous sampling (AVS), thus receiving the most accurate subtype diagnosis available. The differences of thyroid function and the prevalence of thyroid diseases between PA and EH patients were analyzed. Results: 7161 participants were included in the study with a mean age of 48.20±8.83 years and a mean BMI of 26.52±3.45 kg/m2. Two groups: PA patients showed lower FT4, FT3, TT4, TT3, positive TPOAb and higher prevalence of thyroid nodules (22.5%) than EH patients. PA was significantly associated with thyroid nodules (OR: 1.245, 95%CI: 1.052-1.473, P= 0.011). Three groups: statistical differences in FT4, FT3, TT4, TT3, and positive TPOAb levels were found in APA, IHA and EH. Thyroid nodules are most prevalent in APA (26.00%), followed by IHA (20.80%) and EH (17.80%). APA showed a significant association with thyroid nodules (OR: 1.345, 95%CI: 1.015-1.781, P=0.039). Additionally, it was found that FT4, FT3, TT4, and TT3 were negatively correlated with the PAC levels in patients. The stratification analysis showed that the prevalence of thyroid nodules was higher in subjects with PAC levels great than or equal to 12ng/dL. Conclusions: Compared to EH groups, PA patients had lower thyroid function and higher prevalence of thyroid nodules.

TO EXPLORED THE THYROID FUNCTION AND PREVALENCE OF THYROID DISEASES IN PRIMARY ALDOSTERONISM (PA) AND PA SUBTYPES

Objective: To explored the thyroid function and prevalence of thyroid diseases in primary aldosteronism (PA) and PA subtypes. Design and method: Patients with PA and Essential hypertension (EH) in our hypertension center between August 2011 to June 2022 were enrolled in this observational study. All PA patients underwent adrenal venous sampling (AVS), thus receiving the most accurate subtype diagnosis available. The differences of thyroid function and the prevalence of thyroid diseases between PA and EH patients were analyzed. Results: 7161 participants were included in the study with a mean age of 48.20±8.83 years and a mean BMI of 26.52±3.45 kg/m2. Two groups: PA patients showed lower FT4, FT3, TT4, TT3, positive TPOAb and higher prevalence of thyroid nodules (22.5%) than EH patients. PA was significantly associated with thyroid nodules (OR: 1.245, 95%CI: 1.052-1.473, P= 0.011). Three groups: statistical differences in FT4, FT3, TT4, TT3, and positive TPOAb levels were found in APA, IHA and EH. Thyroid nodules are most prevalent in APA (26.00%), followed by IHA (20.80%) and EH (17.80%). APA showed a significant association with thyroid nodules (OR: 1.345, 95%CI: 1.015-1.781, P=0.039). Additionally, it was found that FT4, FT3, TT4, and TT3 were negatively correlated with the PAC levels in patients. The stratification analysis showed that the prevalence of thyroid nodules was higher in subjects with PAC leve greater than or equal to 12ng/dL. Conclusions: Compared to EH groups, PA patients had lower thyroid function and higher prevalence of thyroid nodules.

Association of preexisting anti-thyroid antibodies and body mass index with prognosis of lung cancer patients treated with PD-1/PD-L1 inhibitors

Abstract Objectives Immune checkpoint inhibitors are a new beneficial medication in the treatment of cancer. Whether preexisting TPOAb was related to longer overall survival (OS) is controversial. This retrospective study analyzed the OS and progression-free survival (PFS) of patients with lung cancer, and explored predictive factors associated with the efficacy of PD-1/PD-L1 inhibitors treatment. Methods Patients with lung cancer who were hospitalized in the First Affiliated Hospital of Wenzhou Medical University between January 1, 2020 and December 30, 2020 were enrolled. Thyroid function, TPOAb, TGAb, and prognostic nutritional index levels and body mass index were analyzed. Supervising physicians independently assessed patient staging, OS, and PFS. Demographic data, pathological type, and previous treatment history were also collected. Results In total, this study enrolled 69 patients, with ages of 46–80 years old. Patients with lower weight showed reduced OS and PFS rates relative to those with normal weight and overweight (p&lt;0.05). The single patient with large cell neuroendocrine carcinoma (LCNEC) exhibited a 1-, 1.5- and 2-year OS rate lower than that of the patients diagnosed with squamous cell carcinoma, small cell lung cancer, or adenocarcinoma (p&lt;0.05). This LCNEC patient also had lower 1-, 1.5-, and 2-year PFS rates compared to adenocarcinoma patients (p&lt;0.05). TPOAb and TGAb levels were unrelated to OS or PFS. Multivariate Cox regression analyses revealed a positive association between body mass index, OS, and PFS. Conclusions Patients with lower body weight were predictive of poorer survival outcomes when receiving PD-1/PD-L1 inhibitors treatment as compared to patients with normal weight and overweight. However, positive baseline TGAb and TPOAb levels were not associated with increased OS or PFS in patients with lung cancer.

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

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. 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), 25µg levothyroxine intervention group (G25, 69 women), and 50µg 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. 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). For pregnant women with high-normal thyroid stimulating hormone levels and thyroid peroxidase antibodies positive during the first half of pregnancy, supplementation with 50µg 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 ≥ 117IU/mL proved more beneficial in mitigating the risk of spontaneous abortion.

Autoimmune thyroiditis in psoriatic disease

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.

Risk Factors for Thyroid Dysfunction in Pregnancy: An Individual Participant Data Meta-Analysis.

Background: International guidelines recommend targeted screening to identify gestational thyroid dysfunction. However, currently used risk factors have questionable discriminative ability. We quantified the risk for thyroid function test abnormalities for a subset of risk factors currently used in international guidelines. Methods: We included prospective cohort studies with data on gestational maternal thyroid function and potential risk factors (maternal age, body mass index [BMI], parity, smoking status, pregnancy through in vitro fertilization, twin pregnancy, gestational age, maternal education, and thyroid peroxidase antibody [TPOAb] or thyroglobulin antibody [TgAb] positivity). Exclusion criteria were pre-existing thyroid disease and use of thyroid interfering medication. We analyzed individual participant data using mixed-effects regression models. Primary outcomes were overt and subclinical hypothyroidism and a treatment indication (defined as overt hypothyroidism, subclinical hypothyroidism with thyrotropin >10 mU/L, or subclinical hypothyroidism with TPOAb positivity). Results: The study population comprised 65,559 participants in 25 cohorts. The screening rate in cohorts using risk factors currently recommended (age >30 years, parity ≥2, BMI ≥40) was 58%, with a detection rate for overt and subclinical hypothyroidism of 59%. The absolute risk for overt or subclinical hypothyroidism varied <2% over the full range of age and BMI and for any parity. Receiver operating characteristic curves, fitted using maternal age, BMI, smoking status, parity, and gestational age at blood sampling as explanatory variables, yielded areas under the curve ranging from 0.58 to 0.63 for the primary outcomes. TPOAbs/TgAbs positivity was associated with overt hypothyroidism (approximate risk for antibody negativity 0.1%, isolated TgAb positivity 2.4%, isolated TPOAb positivity 3.8%, combined antibody positivity 7.0%; p < 0.001), subclinical hypothyroidism (risk for antibody negativity 2.2%, isolated TgAb positivity 8.1%, isolated TPOAb positivity 14.2%, combined antibody positivity 20.0%; p < 0.001) and a treatment indication (risk for antibody negativity 0.2%, isolated TgAb positivity 2.2%, isolated TPOAb positivity 3.0%, and combined antibody positivity 5.1%; p < 0.001). Twin pregnancy was associated with a higher risk of overt hyperthyroidism (5.6% vs. 0.7%; p < 0.001). Conclusions: The risk factors assessed in this study had poor predictive ability for detecting thyroid function test abnormalities, questioning their clinical usability for targeted screening. As expected, TPOAb positivity (used as a benchmark) was a relevant risk factor for (subclinical) hypothyroidism. These results provide insights into different risk factors for gestational thyroid dysfunction.

The Ratio of Peripheral Blood Natural Killer Cells is not a Solid Surrogate Immune Index in Unexplained Recurrent Miscarriage.

Immunotherapies targeting peripheral natural killer (pbNK) cells in unexplained recurrent miscarriage (uRM) remain controversial. We hypothesized that the change in pbNK cell count might be a result of innate immune responses rather than a cause. To explore whether the pbNK count is significantly different in women testing positive than those testing negative for commonly studied autoimmune markers. Peripheral blood samples were collected from 302 eligible patients with uRM for the antinuclear antibody (ANA) testing determined by the enzyme-linked immunosorbent assay (ELISA), anti-thyroid peroxidase antibody (TPO-Ab) testing and anti-thyroglobulin antibody (Tg-Ab) testing determined by the chemiluminescent immunoassay, and pbNK cell testing determined by flow cytometry. The patients were divided into two groups according to the pbNK normal range, and the comparative analysis entailed an examination of the prevalence rates of autoantibodies within the high pbNK group and the normal pbNK group, followed by a comprehensive investigation into the potential correlations between autoantibodies and pbNK cells. There was a positive association between TPO-Ab positivity and high pbNK cells (p=0.016, OR=5.097, 95% CI 1.356-19.159), while there was a negative association between ANA positivity and high pbNK cells (p=0.013, OR=0.293, 95% CI 0.111-0.773). TPO-Ab-positive patients had a higher pbNK cell count compared with TPO-Ab-negative patients, while ANA-positive patients had a lower pbNK cell count compared with ANA-negative patients. The change in pbNK cell count may be a consequence of immune responses, and there should be careful consideration in applying it as an immunotherapeutic index.

Autoimmune thyroid disease and myasthenia gravis: a study bidirectional Mendelian randomization.

Previous studies have suggested a potential association between AITD and MG, but the evidence is limited and controversial, and the exact causal relationship remains uncertain. Therefore, we employed a Mendelian randomization (MR) analysis to investigate the causal relationship between AITD and MG. To explore the interplay between AITD and MG, We conducted MR studies utilizing GWAS-based summary statistics in the European ancestry. Several techniques were used to ensure the stability of the causal effect, such as random-effect inverse variance weighted, weighted median, MR-Egger regression, and MR-PRESSO. Heterogeneity was evaluated by calculating Cochran's Q value. Moreover, the presence of horizontal pleiotropy was investigated through MR-Egger regression and MR-PRESSO. The IVW method indicates a causal relationship between both GD(OR 1.31,95%CI 1.08 to 1.60,P=0.005) and autoimmune hypothyroidism (OR: 1.26, 95% CI: 1.08 to 1.47, P =0.002) with MG. However, there is no association found between FT4(OR 0.88,95%CI 0.65 to 1.18,P=0.406), TPOAb(OR: 1.34, 95% CI: 0.86 to 2.07, P =0.186), TSH(OR: 0.97, 95% CI: 0.77 to 1.23, P =0.846), and MG. The reverse MR analysis reveals a causal relationship between MG and GD(OR: 1.50, 95% CI: 1.14 to 1.98, P =3.57e-3), with stable results. On the other hand, there is a significant association with autoimmune hypothyroidism(OR: 1.29, 95% CI: 1.04 to 1.59, P =0.019), but it is considered unstable due to the influence of horizontal pleiotropy (MR PRESSO Distortion Test P < 0.001). MG has a higher prevalence of TPOAb(OR: 1.84, 95% CI: 1.39 to 2.42, P =1.47e-5) positivity and may be linked to elevated TSH levels(Beta:0.08,95% CI:0.01 to 0.14,P =0.011), while there is no correlation between MG and FT4(Beta:-9.03e-3,95% CI:-0.07 to 0.05,P =0.796). AITD patients are more susceptible to developing MG, and MG patients also have a higher incidence of GD.

Crossroads between Skin and Endocrine Glands: The Interplay of Lichen Planus with Thyroid Anomalies.

In this narrative review, we aimed to overview the interplay between lichen planus (LP) and thyroid conditions (TCs) from a dual perspective (dermatologic and endocrine), since a current gap in understanding LP-TC connections is found so far and the topic is still a matter of debate. We searched PubMed from Inception to October 2023 by using the key terms "lichen planus" and "thyroid", (alternatively, "endocrine" or "hormone"). We included original clinical studies in humans according to three sections: LP and TC in terms of dysfunction, autoimmunity, and neoplasia. Six studies confirmed an association between the thyroid dysfunction (exclusively hypothyroidism) and LP/OL (oral LP); of note, only one study addressed cutaneous LP. The sample size of LP/OLP groups varied from 12-14 to 1500 individuals. Hypothyroidism prevalence in OLP was of 30-50%. A higher rate of levothyroxine replacement was identified among OLP patients, at 10% versus 2.5% in controls. The highest OR (odd ratio) of treated hypothyroidism amid OLP was of 2.99 (p < 0.005). Hypothyroidism was confirmed to be associated with a milder OLP phenotype in two studies. A single cohort revealed a similar prevalence of hypothyroidism in LP versus non-LP. Non-confirmatory studies (only on OLP, not cutaneous LP) included five cohorts: a similar prevalence of hypothyroidism among OLP versus controls, and a single cohort showed that the subjects with OLP actually had a lower prevalence of hypothyroidism versus controls (1% versus 4%). Positive autoimmunity in LP/OLP was confirmed in eight studies; the size of the cohorts varied, for instance, with 619 persons with LP and with 76, 92, 105, 108, 192, 247, and 585 patients (a total of 1405) with OLP, respectively; notably, the largest control group was of 10,441 individuals. Four clusters of approaches with respect to the autoimmunity in LP/OLP were found: an analysis of HT/ATD (Hashimoto's thyroiditis/autoimmune thyroid diseases) prevalence; considerations over the specific antibody levels; sex-related features since females are more prone to autoimmunity; and associations (if any) with the clinical aspects of LP/OLP. HT prevalence in OLP versus controls was statistically significantly higher, as follows: 19% versus 5%; 12% versus 6%; and 20% versus 9.8%. A single study addressing LP found a 12% rate of ATDs. One study did not confirm a correlation between OLP-associated clinical elements (and OLP severity) and antibody values against the thyroid, and another showed that positive TPOAb (anti-thyroperoxidase antibodies) was more often found in erosive than non-erosive OLP (68% versus 33%). Just the reverse, one cohort found that OLP subjects had a statistically significantly lower rate of positive TPOAb versus controls (9% versus 15%). Five case-control studies addressed the issue of levothyroxine replacement for prior hypothyroidism in patients that were diagnosed with OLP (no study on LP was identified); three of them confirmed a higher rate of this treatment in OLP (at 8.9%, 9.7%, and 10.6%) versus controls. In conclusion, with regard to LP/OLP-TC, we note several main aspects as practical points for multidisciplinary practitioners: OLP rather than LP requires thyroid awareness; when it comes to the type of thyroid dysfunction, mostly, hypothyroidism should be expected; female patients are more prone to be associated with ATDs; a potential higher ratio of OLP subjects taking levothyroxine was found, thus a good collaboration with an endocrinology team is mandatory; and so far, OLP individuals have not been confirmed to be associated with a higher risk of thyroid nodules/cancer.

TPOAb positivity can impact ovarian reserve, embryo quality, and IVF/ICSI outcomes in euthyroid infertile women

The aim of this study was to investigate the effects of positive anti-thyroid peroxidase (TPO) antibodies on fertility, embryo quality, and pregnancy outcomes in women with normal thyroid function. A cross-sectional study of 1223 infertile women who received assisted reproductive technology (ART) treatment for the first time was conducted at our hospital from January 2019 to March 2022. Overall, 263 infertile women were included, comprising 263 cycles and 1813 embryos, and were divided into a positive group and a control group based on TPO antibody levels. The positive group was further divided into two subgroups according to the median antibody titer, and the therapeutic indices and pregnancy outcomes for each group were compared. The results showed that the AMH level in the positive group was significantly lower than that in the control group (2.37 (1.26-3.63) ng/ml vs. 3.54 (1.74-5.41) ng/ml, p < 0.001). The high-quality embryo rate (40.04% vs. 45.49%, p = 0.034) and live birth rate (23.26% vs. 36.16, p = 0.035) of the positive group were lower than those of the control group; the miscarriage rate was higher than that of the control group (37.50% vs. 17.95%, p = 0.035). The live birth rate in the low-titer group was significantly higher than that in the high-titer group (32.56% vs. 13.95%, p = 0.041). Studies have shown that positive anti-thyroid peroxidase antibodies are associated with a decreased ovarian reserve and decreased embryo quality. High titers of anti-thyroid peroxidase antibodies can reduce the live birth rate.

SAT456 Validation And Optimization Of TSH And FT4 Reference Interval Definitions During Pregnancy

Abstract Disclosure: J. Osinga: None. A. Derakhshan: None. W. Consortium on Thyroid and Pregnancy: None. T. Korevaar: None. Objective: While international guidelines recommend to diagnose gestational thyroid disease according to trimester specific TSH and FT4 reference intervals (RIs), most centers still rely on non-pregnancy RIs in combination with a fixed upper limit for TSH or by a deduction from this upper limit. Both strategies are based on expert opinion and have not been properly validated. We aimed to quantify the diagnostic accuracy of the alternative methods, and to identify the optimal diagnostic strategy to diagnose thyroid disease using a non-pregnancy TSH and FT4 RI. Methods: We performed an individual participant data meta-analysis of prospective birth cohorts. RIs and disease prevalences were calculated according to 1) trimester specific RIs, 2) non-pregnancy RIs, 3) non-pregnancy RIs with a fixed upper limit for TSH of 4.0mU/L and 4) non-pregnancy RIs with a 0.5mU/L subtraction from the TSH upper limit. Sensitivity and false discovery rates (FDR) of the alternative methods were calculated as compared to method 1), which is currently accepted as the best practice. We also varied non-pregnancy RIs with differing subtractions to identify the optimal diagnostic method. Participants with a treatment indication were defined as either overt hypothyroidism, subclinical hypothyroidism with TSH&amp;gt;10 or with concomitant TPOAb positivity. Results: The study population comprised 58,815 participants in 19 prospective cohorts. For first trimester overt hypothyroidism, sensitivity of all alternative methods (non-pregnancy RIs, fixed limit approach, subtraction approach) was similarly poor (0.43, 0.46 and 0.46) with a moderate FDR (0.22, 0.28 and 0.29). For first trimester subclinical hypothyroidism, results were slightly better for all methods, except for the FDR of the subtraction method; sensitivity (0.44, 0.54 and 0.55) and FDR (0.23, 0.23 and 0.35). Using the trimester specific approach, 2.01% of all women had a treatment indication in the first trimester. For this group, both the fixed limit and subtraction approach had a sensitivity of 0.65 and a FDR of 0.11 and 0.17 respectively. Furthermore, we leveraged our dataset to identify how non-pregnancy TSH and FT4 RIs can be used to approach pregnancy-specific RIs. We identified that for a treatment indication, subtraction of 20-25% of the non-pregnancy upper limit of TSH and subtracting 5-10% of the non-pregnancy lower limit of FT4 yielded a higher sensitivity (0.72-0.77) with a comparable FDR (0.20-0.25). Conclusion: Currently recommended alternative methods for defining RIs for TSH and FT4 in pregnancy have poor sensitivity when compared to the currently accepted trimester specific approach, and lead to substantial overdiagnosis. A relative subtraction from the non-pregnancy upper limit of TSH and lower limit of FT4 could considerably improve the diagnostic rates and would be directly available in daily practice. Presentation: Saturday, June 17, 2023