Serum Thyroid Peroxidase Antibody Research Articles

Sex-specific associations between maternal thyroid peroxidase antibodies and cognitive development in preschool children: A prospective cohort study.

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

Early-pregnancy sex steroid and thyroid function hormones, thyroid autoimmunity, and maternal papillary thyroid cancer incidence in the Finnish Maternity Cohort.

Thyroid cancer more commonly affects women than men and is the third most frequently diagnosed cancer among women of reproductive age. We conducted a nested case-control study within the Finnish Maternity Cohort to evaluate pre-diagnostic sex steroid and thyroid function markers in relation to subsequent maternal papillary thyroid cancer. Cases (n = 605) were women ages 18-44 years, who provided an early-pregnancy (<20 weeks gestation) blood sample and were diagnosed with papillary thyroid cancer up to 11 years afterward. Controls (n = 1185) were matched to cases 2:1 by gestational age, mother's age, and date at blood draw. Odds ratios (ORs) for the associations of serum thyroid peroxidase antibodies (TPO-Ab), thyroglobulin antibodies (Tg-Ab), thyroid stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), progesterone, and estradiol with papillary thyroid cancer were estimated using conditional logistic regression. TPO-Ab and Tg-Ab positivity (>95th percentile among controls) were associated with more than 3-fold (OR = 3.32, 95% confidence interval [CI] 2.33-4.72) and 2-fold (OR = 2.03, 95% CI 1.41-2.93) increased odds of papillary thyroid cancer, respectively. These associations were similar by time since blood draw, parity, gestational age, smoking status, and age and stage at diagnosis. In models excluding TPO-Ab or Tg-Ab positivity, TPO-Ab (quartile 4 vs. 1: OR = 1.66, 95% CI 1.17-2.37, p-trend = .002) and Tg-Ab (quartile 4 vs. 1: OR = 1.74, 95% CI 1.22-2.49, p-trend = .01) levels were positively associated with papillary thyroid cancer. No associations were observed for estradiol, progesterone, TSH, fT3, or fT4 overall. Our results suggest that thyroid autoimmunity in early pregnancy may increase the risk of maternal papillary thyroid cancer.

Selenium supplementation and placebo are equally effective in improving quality of life in patients with hypothyroidism.

We investigated whether selenium supplementation improves quality-of-life (QoL) in patients with autoimmune thyroiditis (ID:NCT02013479). We included 412 patients ≥18 years with serum thyroid peroxidase antibody (TPOAb) level ≥100 IU/mL in a multicentre double-blinded randomised clinical trial. The patients were allocated 1:1 to daily supplementation with either 200 μg selenium as selenium-enriched yeast or matching placebo tablets for 12 months, as add-on to levothyroxine (LT4) treatment. QoL, assessed by the Thyroid-related Patient-Reported-Outcome questionnaire (ThyPRO-39), was measured at baseline, after six weeks, three, six, 12, and 18 months. In total, 332 patients (81%) completed the intervention period, of whom 82% were women. Although QoL improved during the trial, no difference in any of the ThyPRO-39 scales was found between the selenium group and the placebo group after 12 months of intervention. In addition, employing linear mixed model regression no difference between the two groups was observed in the ThyPRO-39 composite score (28.8 [95%CI:24.5-33.6] and 28.0 [24.5-33.1], respectively; P=0.602). Stratifying the patients according to duration of the disease at inclusion, ThyPRO-39 composite score, TPOAb level, or selenium status at baseline did not significantly change the results. TPOAb levels after 12 months of intervention were lower in the selenium group than in the placebo group (1995 [95%CI:1512-2512] vs. 2344 kIU/L [1862-2951]; P=0.016) but did not influence LT4 dosage or free triiodothyronine/free thyroxin ratio. In hypothyroid patients on LT4 therapy due to autoimmune thyroiditis, daily supplementation with 200 μg selenium or placebo for 12 months improved QoL to the same extent.

Effects of altitude on thyroid disorders according to Chinese three-rung, ladder-like topography: national cross-sectional study

BackgroundChinese topography appears a three-rung ladder-like distribution of decreasing elevation from northwest to southeast, which is divided by two sloping edges. Previous studies have reported that prevalence of thyroid diseases differed by altitude, and geographical factors were associated with thyroid disorders. To explore the association between three-rung ladder-like regions and thyroid disorders according to unique Chinese topographic features, we conducted an epidemiological cross-sectional study from 2015–2017 that covered all 31 mainland Chinese provinces.MethodsA total of 78,470 participants aged ≥ 18 years from a nationally representative cross-sectional study were included. Serum thyroid peroxidase antibody, thyroglobulin antibody, and thyroid-stimulating hormone levels; urine iodine concentration; and thyroid volume were measured. The three-rung ladder-like distribution of decreasing elevation from northwest to southeast in China was categorized into three topographic groups according to elevation: first ladder, > 3000 m above sea level; second ladder, descending from 3000—500 m; and third ladder, descending from 500 m to sea level. The third ladder was further divided into groups A (500–100 m) and B (< 100 m). Associations between geographic factors and thyroid disorders were assessed using linear and binary logistic regression analyses.ResultsParticipants in the first ladder group were associated with lower thyroid peroxidase (β = -4.69; P = 0.00), thyroglobulin antibody levels (β = -11.08; P = 0.01), and the largest thyroid volume (β = 1.74; P = 0.00), compared with the other groups. The second ladder group was associated with autoimmune thyroiditis (odds ratio = 1.30, 95% confidence interval [1.18–1.43]) and subclinical hypothyroidism (odds ratio = 0.61, 95%confidence interval [0.57–0.66]) (P < 0.05) compared with the first ladder group. Group A (third ladder) (500–100 m) was associated with thyroid nodules and subclinical hypothyroidism (P < 0.05). Furthermore, group B (< 100 m) was positively associated with autoimmune thyroiditis, thyroid peroxidase and thyroglobulin antibody positivity, and negatively associated with overt hypothyroidism, subclinical hypothyroidism, and goiter compared with the first ladder group(P < 0.05).ConclusionWe are the first to investigate the association between different ladder regions and thyroid disorders according to unique Chinese topographic features. The prevalence of thyroid disorders varied among the three-rung ladder-like topography groups in China, with the exception of overt hyperthyroidism.

The Cross-sectional and Longitudinal Association Between Thyroid Function and Depression: A Population-Based Study.

An association of thyroid function with mood disorders has been widely suggested, but very few studies have examined this association longitudinally. We assessed the cross-sectional and longitudinal association between thyroid function and depression in a population-based cohort. A total of 9471 individuals were included in cross-sectional analyses, of whom 8366 had longitudinal data. At baseline, we assessed thyroid function using serum samples (thyrotropin [TSH], free thyroxine (FT4), and thyroid peroxidase antibodies) and depressive symptoms using the Centre for Epidemiologic Studies Depression (CES-D) scale. Incident depressive events (n = 1366) were continuously followed up with the CES-D and clinical interviews. We analyzed the cross-sectional association of thyroid function and thyroid disease with depressive symptoms using linear and logistic regression, and the longitudinal association with Cox proportional hazard models for depressive events. Lower TSH levels and lower and higher FT4 levels were cross-sectionally associated with more depressive symptoms with a B value of -0.07 per 1 unit increase of natural log-transformed TSH (95% CI -0.11; -0.04). Furthermore, hypothyroidism was cross-sectionally associated with less depressive symptoms and hyperthyroidism with more depressive symptoms. Longitudinally, there was a U-shaped association between FT4 and incident depressive events but only in euthyroid participants. We show a cross-sectional association between thyroid (dys)function with depressive symptoms, and a U-shaped association between FT4 and incident depressive events in euthyroid individuals. Our findings suggest an association of thyroid function with the risk of developing depression, albeit small. Reverse causation and additional underlying factors may also contribute to the association.

Effect of hypothyroidism on ovarian reserve status in Iraqi women: hormonal study

Background: Hypothyroidism is a clinical syndrome prevalent in women, even those of reproductive age. Ovarian reserve can be defined as the number and quality of follicles in the ovary at any given time. Evaluation of ovarian reserve is recommended for patients at risk of decreased ovarian reserve. Objective: This study aims to evaluate the effect of hypothyroidism on ovarian reserve in Iraqi women by hormonal measurements of serum anti-mullerian hormones AMH, FSH, and LH. Subjects and methods: This case–control study was carried out at the Department of Biochemistry, College of Medicine, University of Baghdad, in collaboration with Endocrinology and Diabetes Clinic, Baghdad Teaching Hospital, and National Center for Teaching Laboratories, Medical City, during the period from November 2021 to March 2022. This study involved 88 women, age range (20-40 years). Fifty-one of them [Group I (GI)] had primary hypothyroidism and were diagnosed by an endocrinologist based on clinical analysis and thyroid function tests, including serum TSH, T4 and T3. Patients with symptoms and signs suggestive of hypothyroidism and elevated TSH with T4 less than the reference level were considered overt hypothyroidism. While patients with elevated TSH with standard T4 and T3 were considered subclinical hypothyroidism 1 , serum thyroid peroxidase antibody (TPOAb) was used to differentiate hypothyroidism patients with Hashimoto`s disease 2 . Thirty-seven of the included women were healthy and served as a control group and referred to group II (GII). Results: The mean (±SD) value of serum AMH of hypothyroidism women was significantly lower than that of controls (p &lt; 0.0001). However, the mean value of AMH did not differ significantly between women who had overt and subclinical hypothyroidism, regular and irregular menstrual cycle, well and poorly controlled thyroid status, and who had positive and negative anti-TPO. The mean (±SD) value of serum LH of hypothyroidism women was significantly higher than that of the control group (p &lt; 0.004), while that of FSH did not differ significantly. Serum TSH levels positively correlated with LH levels (r=0.3, p 0.03). In addition, BMI values were significantly positively correlated with FSH levels (r= 0.3, p 0.04). Conclusions: This study suggested the need for serum measurement of AMH in women suffering from hypothyroidism. Keywords: hypothyroidism, ovarian reserve, AMH.

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.

Thyroid function test abnormalities-isolated TPOAb+, SCH and hypothyroxinemiaand preschool children's neurodevelopment.

Thyroid function test abnormalities are frequent and associated with the offspring's adverse neurodevelopment. This study aimed to examine the relationship between maternal thyroid function test abnormalities before 20 gestational weeks and children's cognitive, emotional and behavioural development at 3-6 years of age. A total of 2243 mother-child pairs were included in the final analysis. Maternal thyroid function was evaluated retrospectively during the children's preschool period. The serum thyrotrophin, free thyroxine and thyroid peroxidase antibodies(TPOAb) were detected by chemiluminescence immunoassay during the follow-up period. The neurodevelopmental status of preschoolers aged 3-6 years was evaluated by parental versions of The Behavior Rating Inventory of Executive Function-Preschool and The Strengths and Difficulties Questionnaires. The associations between maternal thyroid function test abnormalities and preschoolers'neurodevelopment were examined using Poisson regression models. After adjusting for potential confounders in Poisson regression analyses, it showed that maternal isolated TPOAb positivity before 20 gestational weeks may be associated with the increased risk of abnormalities in peer problems (odds ratio [OR] = 1.90, 95% confidence interval[CI]: 1.26, 287). Maternal isolated SCH before 20 gestational weeks was observed to be related with increased risk of abnormalities in inhibition (OR = 2.73, 95%CI: 1.37, 5.41), working memory (OR = 1.67, 95%CI: 1.04, 2.70), conduct problems (OR = 1.80, 95%CI: 1.05, 3.09), hyperactivity (OR = 1.94, 95% CI:1.08, 3.49)and total difficulties (OR = 1.94, 95%CI: 1.13, 3.34). Maternal isolated hypothyroxinemia before 20 gestational was observed to be related with increased risk of abnormalities in peer problems (OR = 2.71, 95%CI: 1.17, 6.27). Thyroid function test abnormalities before 20 gestational weeks may be associated with children's neurodevelopment at 3-6 years of age.

Spectrum of Thyroid Dysfunction in Patients with Chronic Kidney Disease in Benin City, Nigeria.

There is an indication of abrupt rise in chronic kidney disease (CKD) in Nigeria and thyroid function involvement has not been sufficiently evaluated. This study determined thyroid gland function among subjects with CKD in Benin City, Nigeria. A total of 184 randomized CKD patients attending specialist clinic and 80 healthy control subjects were recruited for this study. A well-structured questionnaire was used to obtain data on socio-demography. Blood specimens were collected and used for the determination of thyroid function parameters; thyroid stimulating hormone (TSH), triiodothyronine (T3), free triiodothyronine (fT3), thyroxine (T4), free thyroxine (fT4), thyroid peroxidase antibody (TPO-Abs), thyroid globulin antibody (Tg-Abs) and Deiodinase enzyme Type 1 (D1). SPINA GD and SPINA GT were calculated using Michaelis-Menten model. The CKD was classified into stages using Modification of Drug in Renal Disease (MDRD) formula. Thyroid dysfunctions observed were clinical hyperthyroidism 1 (0.54%), non-thyroidal illness 78 (42.4%), clinical hypothyroidism 11 (6.0%), sub-clinical hyperthyroidism 3 (1.60%), and sub-clinical hypothyroidism 11 (6.0%), while euthyroid were 80 (43.5%). SPINA GD of CKD patients (33.85 ± 10.94) was not significantly different when compared with controls (24.85 ± 1.57), whereas, SPINA GT was significantly higher (p < 0.01) among CKD patients (3.74 ± 0.31) than controls (2.68 ± 0.11). Autoimmune thyroid disease demonstrated by positive Tg-Abs and TPO-Abs were observed among approximately 7.9% of CKD patients. Serum TPO-Abs concentration increased with CKD progression. Thyroid dysfunction is involved in the pathogenesis of CKD patients. The etiologies are multifactorial and immunological mechanisms of autoimmune thyroid disease may be a contributing factor.

Comprehensive analysis of hub biomarkers associated with immune and oxidative stress in Hashimoto's thyroiditis

Hashimoto's thyroiditis (HT) is a type of autoimmune disorder with a complex interplay between immune disorder and oxidative stress (OS). This research aimed to discover biomarkers and potential treatment targets associated with immune and OS dysregulation in HT through integrated bioinformatics analysis and clinical validations. Differential gene expression analysis of GSE138198 dataset from the GEO database identified 1490 differentially expressed genes (DEGs) in HT, including 883 upregulated and 607 downregulated genes. Weighted gene co-expression network analysis explored module genes associated with HT. Overlapping the differentially expressed module genes with immune-related and OS-related genes identified eight differentially expressed module genes associated with immune and OS (DEIOGs) in HT. Protein-protein interaction network analysis identified five hub genes (TNFAIP3, FOS, PTK2B, STAT1, and MMP9). We confirmed four hub genes (TNFAIP3, PTK2B, STAT1 and MMP9) in GSE29315 dataset and clinical thyroid samples, which showed high diagnostic accuracy (AUC >0.7) for HT. The expression of these four genes was positively correlated with serum thyroid peroxidase antibody, thyroglobulin antibody levels, and inflammatory infiltration scores in clinical thyroid samples. Immune profiling revealed distinct profiles in HT, such as B cells memory, monocytes and macrophages. Additionally, all hub genes were inversely associated with monocytes. Further, miRNA-mRNA network analysis was conducted, and a regulatory network comprising four hub genes, 238 miRNAs and 32 TFs was established. These findings suggest that immune cells play a crucial role in the development of HT, and the hub genes TNFAIP3, PTK2B, STAT1, and MMP9 may be key players in HT through immune- and OS-related signaling pathways. Our results may provide valuable insights into the pathogenesis and therapeutic monitoring of HT.

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

An Evaluation of the Second Trimester Thyroid Function Test in Gestational Diabetes Mellitus: A Case-Control Study.

Gestational diabetes mellitus (GDM) is defined as glucose intolerance in a female with its onset or first recognition during pregnancy. Females with GDM are at higher risk of developing antenatal complications like preeclampsia during pregnancy and increased risk of type 2 diabetes as well as cardiovascular disorders later in their life. Maternal thyroid changes in the first and second trimesters of pregnancy have been widely related to the risk of GDM.Hypothyroidism during pregnancy is associated with early and late complications like abortions, anaemia, gestational hypertension, placental abruption and postpartum haemorrhage, impaired infant neurodevelopment, and low birth weight. This study aims to compare the thyroid function test (TFT) (serum fT3, fT4, TSH)and thyroid peroxidase antibody (anti TPO) between GDM and non GDM pregnant women in the second trimester and to correlate the adverse pregnancy outcomes with TFT in GDM and non GDM women. A nested case-control study was done in the Department of Obstetrics and Gynaecology, Department of Endocrinology, Department of Paediatrics, University College of Medical Sciences, and Guru Teg Bahadur (GTB) Hospital, Delhi. About 350 pregnant women from 13 weeks till 28 weeks period of gestation were screened out of which 40 GDM and 40 non GDM women were selected after performing an oral glucose tolerance test (OGTT). A TFT and anti TPO test were compared between GDM and non GDM participants. Furthermore, various parameters like sociodemographic profile, mode of delivery, pregnancy outcomes, and adverse maternal and adverse neonatal outcomes were compared. The mean age of GDM women is found to be more than non GDM women. The mean TFTvalues are significantly lower in women with GDM as compared to non GDM women. In addition, higher values of anti TPO antibody (thyroid autoantibody) were found in the GDM group which aidsin insulin resistance. Maternal complications like polyhydramnios, preterm labour, and pregnancy-induced hypertension were found to be more frequent in the GDM group compared to the non GDM group, but the results were statistically not significant. There was a higher incidence of caesarean delivery in the GDM group. Thus, we recommend the implementation of routine thyroid function profile testing in all antenatal females especially those who are at risk of developing GDM. Our study is one of the few Indian studies to evaluate the association of TFT in GDM, and we recommend similar research with a larger sample size and postnatal follow-up.

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.

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.

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.

Abstract P662: Thyroid Peroxidase Antibodies is Associated With Carotid Intima-Media Thickness in the Brazilian Longitudinal Study of Adult Health

Introduction: There is an association between thyroid autoimmunity and the cardiovascular system, however, it remains unclear whether detectability and positivity of thyroid peroxidase antibodies (TPOAb) could contribute to the development of atherosclerosis. Hypothesis: We assessed the hypothesis that there is an association of multiple categories of TPOAb with increased carotid intima-media thickness (cIMT) in participants from the ELSA-Brasil study. Methods: This is a cross-sectional study using baseline data of 9651 participants (mean age of 51.5 years-old, 55.8% women), without a history of cardiovascular disease. Fasting serum TPOAb levels were determined (Roche Diagnostics) and categorized as undetectable (≤ 5.00 IU/mL), low detectable (5.01-14.99 IU/mL), high detectable (15.00-33.99 IU/mL), and positive (34.00-600.00 IU/mL). Values of cIMT above the 75th percentile (≥0.68) were classified as “increased cIMT”. We performed logistic regression models, univariate and adjusted (for sex, age, BMI, smoking, alcohol consumption, diabetes, hypertension, dyslipidemia, and family history of cardiovascular disease), to determine odds ratio (OR) and 95% confidence intervals (CI). Results: Increased cIMT was prevalent in 24.4% of our sample, without statistically significant difference among the categories of TPOAb (p=0.066). Compared to undetectable TPOAb, low detectable category was associated with higher odds of having increased cIMT in univariate (OR=1.37, CI= 1.04-1.82) and remained associated after the adjustment for all confounders (OR=1.39, CI= 1.01-1.91). TPOAb high detectability was associated with increased cIMT only in the univariate (OR=1.40, CI= 1.04-1.88) and after adjustment for sex, age and BMI (OR=1.42, CI= 1.02-1.97). No association was seen for TPOAb positivity and cIMT (OR= 1.29, CI= 0.91-1.83). Conclusions: In conclusion, the modest association of low detectable TPOAb with cIMT may suggest a possible role of TPOAb in the atherosclerotic process.

Correlation between Serum Beta-Human Chorionic Gonadotropin Levels and Thyroid Metabolic Function in Pregnant Women with Hyperemesis Gravidarum

As previously demonstrated, serum beta-human chorionic gonadotropin (β-hCG) is linked to identifying early gestational abnormalities. This research was aimed at investigating the correlation between serum β-hCG levels and thyroid metabolic function in pregnant women with hyperemesis gravidarum (HG). Ninety-one pregnant women with HG were selected as the study group and divided into early pregnancy (EP), mid-pregnancy (MP), and late pregnancy (LP) groups according to their gestational weeks, while 84 normal pregnant women were selected as the control group. Venous blood was collected from pregnant women in both groups and serum β-hCG levels were measured by chemiluminescent immunoassay. The levels of free thyroxine (FT4), free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), thyroid-stimulating hormone receptor antibody (TRAb), and thyroglobulin antibody (TgAb) were tested by chemiluminescent microparticle immunoassay. Visual analog scale (VAS) scores were utilized to assess the degree of HG. Pearson analysis was implemented to measure the correlations between serum β-hCG levels and serum FT3, FT4, TSH, TPOAb, TRAb, TgAb, as well as VAS scores and the correlations between β-hCG, FT3, FT4, TSH, TPOAb, TRAb, TgAb, as well as VAS scores and gestation period. The receiver operating characteristic (ROC) curve was plotted to analyze the diagnostic values of thyroid hormones, thyroid-related antibodies, and β-hCG levels for HG. Versus those in the control group, β-hCG, FT3, FT4, TPOAb, TRAb, TgAb levels, and VAS scores were higher and TSH levels were lower in the study group. Versus those in the EP group, β-hCG, FT3, FT4, TPOAb, TRAb, TgAb levels, and VAS scores of pregnant women in the MP and LP groups were decreased, and TSH levels were increased. Serum β-hCG levels of pregnant women with HG were positively correlated with FT3, FT4, TPOAb, TRAb, TgAb, and VAS scores and negatively correlated with TSH levels. Serum β-hCG, FT3, FT4, TPOAb, TRAb, TgAb levels, and VAS scores of pregnant women with HG had a negative correlation with the gestation period, while TSH levels had a positive correlation with the gestation period. The ROC curve analysis showed that β-hCG and thyroid function-related indicators were of high clinical values in the diagnosis of HG. Collectively, our article suggests that serum β-hCG expression of pregnant women with HG is abnormally elevated and closely related to the degree of HG and hyperthyroidism. In addition, β-hCG and thyroid function-related indicators have certain diagnostic efficacy for HG.

Nomogram for predicting prognosis of patients with metastatic melanoma after immunotherapy: A Chinese population-based analysis.

Previous studies indicated the evidence that baseline levels of thyroid antibodies, thyroid status, and serum lactate dehydrogenase (LDH) and M stage may influence the prognosis of patients with advanced or metastatic melanoma treated with immune checkpoint inhibitors that targets programmed cell death-1 (PD-1) or programmed death ligand 1, which reported that dramatic improvements in survival rates were observed; however, the presence of controversy has prevented consensus from being reached. Study objectives were to develop a nomogram to identify several prognostic factors in Chinese patients with metastatic melanoma receiving immunotherapy. This retrospective study included 231 patients from Sun Yat-sen University Cancer Center, and patients were split into internal cohort (n = 165) and external validation cohort (n = 66). We developed a nomogram for the prediction of response and prognosis on the basis of the levels of serum thyroid peroxidase antibody (A-TPO), free T3 (FT3), and LDH and M stage that were measured at the baseline of anti-PD-1 infusion. In addition, the follow-up lasted at least until 5 years after the treatment or mortality. RECIST v1.1 was used to classify treatment responses. Chi-square test showed that PD-1 antibody was more effective in patients with melanoma with high level baseline FT4 or earlier M stage. A multivariate Cox analysis showed that baseline FT3 (P = 0.009), baseline A-TPO (P = 0.016), and LDH (P = 0.013) levels and M stage (P < 0.001) independently predicted overall survival (OS) in patients with melanoma. The above factors are integrated, and a prediction model is established, i.e., nomogram. Survival probability area-under-the-curve values of 1, 2, and 3 years in the training, internal validation, and external validation cohorts showed the prognostic accuracy and clinical applicability of nomogram (training: 0.714, 0.757, and 0.764; internal validation: 0.7171963, 0.756549, and 0.7651486; external validation: 0.748, 0.710, and 0.856). In addition, the OS of low-risk (total score ≤ 142.65) versus high-risk (total score > 142.65) patients varied significantly in both training group (P < 0.0001) and external validation cohort (P = 0.0012). According to this study, baseline biomarkers are associated with response to immunotherapy and prognosis among patients with metastatic melanoma. Treatment regimens can be tailor-made on the basis of these biomarkers.

Relationship between serum NDRG3 and papillary thyroid carcinoma.

In recent years, papillary thyroid carcinoma is considered to be one of the fastest increaseing cancer. NDRG family member 3 (NDRG3) has been proposed as a molecular marker of tumor, and is expected to be used in clinic. Enzyme-linked immunosorbent assay was used to detect the serum NDRG3 expression in 81 papillary thyroid carcinoma cases, 75 benign thyroid nodules cases and 77 healthy control cases, respectively. Electrochemiluminescence method was applied to measure the levels of triiodothyronine, tetraiodothyronine, thyrotropin, thyroglobulin antibody and thyroid peroxidase antibody. Immunohistochemical staining was used to detect the expression of NDRG3 in papillary thyroid carcinoma, benign thyroid nodules and normal tissues adjacent to cancer. The expression of serum triiodothyronine, tetraiodothyronine, thyrotropin, thyroglobulin antibody and thyroid peroxidase antibody and NDRG3 were significantly different among benign thyroid nodules, papillary thyroid carcinoma cases and healthy control groups (P <0.001). Only the expression of serum NDRG3 was significantly different between benign thyroid nodules and papillary thyroid carcinoma groups (P <0.001). Immunohistochemistry showed that NDRG3 was expressed in all three groups, the lowest in papillary thyroid carcinoma, the second in benign thyroid nodules, and the highest in normal tissues adjacent to cancer. Logistic regression analysis showed that serum NDRG3 was an independent protective factor for papillary thyroid carcinoma (OR =0.964, 95%CI =0.953 to 0.974, P <0.001). The ROC curve of non-papillary thyroid carcinoma diagnosed by serum NDRG3 showed the optimal cut-off value of 481.38 pg/ml, sensitivity of 72.4%, specificity of 90.1%, and the maximum area under the curve (AUC =0.902, 95%CI =0.863 to 0.940, P <0.001). The ROC curve of benign thyroid nodules diagnosed by serum NDRG3 showed the optimal critical value of 459.28 pg/ml, sensitivity of 81.3%, and specificity of 74.1% (AUC =0.863, 95%CI =0.808 to 0.919, P <0.001). The expression level of serum NDRG3 was significantly correlated with extrathyroid extensionand (P =0.007) and lymphatic metastasis of papillary thyroid carcinoma (P =0.019). The decrease of NDRG3 expression can not only differential diagnosis benign thyroid nodules and papillary thyroid carcinoma, but also serve as a molecular marker for the diagnosis of papillary thyroid carcinoma.

Correlations of serum TgAb and TPOAb and clinicopathological features of PTC in children and adolescents

Objective: To analyze the correlations between serum thyroglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb) and clinicopathological features in children and adolescents with papillary thyroid carcinoma (PTC). Methods: A retrospective analysis was conduced on the clinicopathological data of children and adolescents (age≤21 years old) with PTC admitted to Tianjin Medical University Cancer Hospital from 2011 to 2019, and then, we used χ2 test or Fisher's exact probability test to compare the differences in clinicopathological characteristics between groups with different TgAb and TPOAb status and multivariate logistic regression model analysis to evaluate independent predictors of cervical lymph node metastasis. Results: A total of 304 patients, including 89 males and 215 females, aged 5-21 years (median age 19 years), were enrolled in this study. The comparison between groups with different TgAb and TPOAb status showed that there were significant differences in gender, preoperative thyroglobulin (Tg) level, primary tumor location, number of primary tumors and maximum tumor diameter (all P<0.05), which suggested that TgAb+group (n=81) and TPOAb+group (n=84) had relatively better primary tumor characteristics. Patitents with TgAb+and TPOAb+were more common in females and their preoperative Tg level was mostly within the normal range, and there were significant differences in primary tumor location, number of primary tumors and maximum tumor diameter between TgAb+and TgAb-(223 cases) groups (all P<0.05). There was significant difference in the maximum tumor diameter between TPOAb+and TPOAb-(220 cases) groups (P<0.05). Analysis of risk factors for cervical lymph node metastasis showed that independent risk factors for central lymph node metastasis were maximum tumor diameter>2 cm (OR=2.84, 95%CI: 1.59-5.07, P<0.001) and extra-thyroid extension (OR=0.32, 95%CI: 0.17-0.60, P<0.001), and independent risk factors for lateral neck lymph node metastasis included age≤14 years old (OR=0.34, 95%CI: 0.18-0.67, P=0.002), preoperative Tg+(OR=2.16, 95%CI: 1.10-4.24, P=0.026) and maximum tumor diameter>2 cm (OR=3.99, 95%CI: 2.33-6.82, P<0.001). Conclusion: It is recommended to test routinely serum TgAb and TPOAb before surgery in children and adolescents with PTC. Preoperative Tg+, age≤14 years, maximum tumor diameter>2 cm, and extra-thyroid extension are risk factors for cervical lymph node metastasis.