Serum TgAb Levels Research Articles

6644 Glycosylation Patterns of the IgG Variable Region in Thyroglobulin Antibodies and Their Impact on Antigen Binding Affinity

Abstract Disclosure: S. Wang: None. Y. Cao: None. C. Zhao: None. C. Huang: None. K. Zhao: None. Y. Li: None. Y. Huang: None. Z. Ying: None. Y. Zhang: None. Y. Gao: None. Objective: Thyroglobulin antibodies (TgAb), key serological markers in Hashimoto's thyroiditis (HT) patients, are predominantly in immunoglobulin G (IgG) form. Prior research has highlighted the importance of increased glycosylation in TgAb IgG from HT patients. This study investigates the unique glycosylation patterns of F(ab')₂ fragments in TgAb IgG in HT patients, compared to healthy individuals. It focuses on how these patterns differ and their impact on binding to thyroglobulin (Tg). Exploring the role of N-glycosylation in the F(ab')₂ segment of TgAb IgG is crucial for understanding its effect on immune responses in HT, potentially unveiling key mechanisms of the disease. Methods: To assess serum TgAb levels in HT patients (n≥28), we used an electrochemiluminescence immunoassay, dividing patients into medium-level (mHT, n≥14) and high-level (hHT, n≥14) groups. TgAb IgG was isolated from serum of both HT and control groups (n = 14) using affinity chromatography. TgAb IgG was then cleaved with Ides enzyme to yield TgAb IgG F(ab’)2 and Fc fragments. The F(ab')2 fragment of TgAb IgG underwent MALDI-QIT-TOF-MS mass spectrometry for glycosylation profiling. Additionally, mixed TgAb IgG was separated using columns that recognize mannose and terminal sialic acid, yielding high mannose and high terminal sialic acid TgAb IgG. Different TgAb IgG glycoforms were prepared through enzymatic treatment with peptide-N-glycosidase F, β1-4 galactosidase, and α2-3,6,8 neuraminidase. The binding affinity of these TgAb IgG to Tg antigen was measured using Tg specific ELISA and surface plasmon resonance (SPR). Results: Using MALDI-TOF MS, we identified 22 IgG glycan types in both HT and control (Con) groups. In the hHT group, six glycan types (G0F, G1F, G2F, M5A1, A3G1F, A3F) were upregulated compared to Con, with statistical significance (p < 0.05). The mHT group showed increased levels of G1F and G2F compared to Con (p < 0.05). Between hHT and mHT, only A3F was significantly elevated (p < 0.05). Removal of N-glycosylation from IgG TgAb F(ab)2 reduced binding to Tg antigen. Presence of both mannose and terminal sialic acid in TgAb enhanced the binding to Tg. Conclusions: Most TgAb IgG in the variable region of HT patients contain N-glycans. The glycosylation patterns of TgAb IgG F(ab)2 in HT differ significantly from healthy controls, affecting antibody binding affinity. Our findings reveal the complex role of glycosylation patterns in TgAb IgG, providing new insights into HT pathogenesis and potential research directions. Presentation: 6/1/2024

Clinical Significance of Thyroid Autoantibodies in Differential Diagnosis and Predicting the Course of Programmed Cell Death Protein-1 Inhibitor-Induced Thyroid Dysfunction

ObjectiveThyroid immune-related thyrotoxicosis is one of the most common adverse effects in patients treated with programmed cell death protein-1 (PD-1) inhibitors. We investigated the significance of levels of serum anti-thyroglobulin antibodies (TgAbs), anti-thyroid peroxidase antibodies (TPOAbs), and thyroid-stimulating hormone receptor antibodies (TRAbs) in the identification of anti-PD-1-induced thyroid thyrotoxicosis. MethodsWe divided 161 patients with thyroid dysfunction who received PD-1 inhibitors at our hospital between January 2022 and June 2024 into 3 groups: primary hypothyroidism group, primary hyperthyroidism group, and destructive thyroiditis group. The characteristics of the 3 groups were determined, and the positivity rates of serum TgAbs, TPOAbs, and TRAbs were assessed. An additional 42 patients diagnosed with Hashimoto’s thyroiditis were selected as the control group for PD-1 inhibition-induced destructive thyroiditis. Age, sex, and time of transition from thyrotoxicosis to hypothyroidism in the 2 groups were compared. ResultsIn the primary hypothyroidism group, only 1 case was TPOAbs-positive (1/1%). In the destructive thyroiditis group, the positivity rate for TPOAbs or TgAbs was 92.9%, and TPOAbs and TgAbs were negative in the primary hyperthyroidism group. TRAbs were undetectable in all 3 groups. There were statistically significant differences in age, sex, and time from thyrotoxicosis to hypothyroidism in the PD-1 induced destructive thyroiditis and Hashimoto’s thyroiditis groups. ConclusionsIn patients with thyrotoxicosis caused by PD-1 inhibitors, serum TgAb, and TPOAb levels can be used to distinguish between primary hyperthyroidism and destructive thyroiditis. This study provides insights into novel treatment targets and effective management strategies for PD-1-induced thyrotoxicosis.

Effect of acupuncture on Hashimoto thyroiditis: A systematic review and meta-analysis.

Hashimoto thyroiditis (HT) is a common autoimmune thyroid disease for which there is no specific treatment. Oral levothyroxine sodium tablets significantly improved thyroid function but did not promote a reduction in thyroid-related antibody concentrations. Acupuncture can improve clinical symptoms and thyroid function in HT patients, reduce serum TPOAb and TGAb levels in HT patients, and improve patients' quality of life. We conducted a systematic review and meta-analysis to evaluate the effect of acupuncture versus levothyroxine sodium tablets on Hashimoto thyroiditis. We searched Web of Science, Embase, China National Knowledge Infrastructure, WanFang, VIP, SinoMed and the Cochrane Central Registry of Controlled Trials to identify candidate randomized controlled trials (RCTs). A total of 1020 patients participated in 14 randomized controlled trials. The results of meta-analysis showed that acupuncture regulated TPOAb content (mean difference [MD] = -63.18, 95%CI = -91.73 to -34.62, P < .00001), TGAb content (MD = -68.56, 95%CI = -101.55 to -35.57, P < .00001), serum free triiodothyronine (FT3) content (MD = 0.74, 95%CI = 0.20 to 1.27, P < .00001), serum free thyroxine (FT4) content (MD = 1.10, 95%CI = 0.29 to 1.92, P < .00001), TSH content (MD = -2.16, 95%CI = -3.14 to -1.19, P < .00001) had a significant effect. Compared with levothyroxine sodium tablets alone, acupuncture can significantly regulate the contents of TPOAb, TGAb, FT3, FT4 and TSH.

The association of plasma connective tissue growth factor levels with left ventricular diastolic dysfunction in patients with overt hyperthyroidism.

Left ventricular (LV) diastolic dysfunction is an independent predictor of future cardiovascular events. Early detection of patients with LV diastolic dysfunction can improve clinical outcomes through active management. However, the assessment of diastolic function is very complicated, and there are currently lack of effective biomarkers to assess the risk of LV diastolic dysfunction. Connective tissue growth factor (CTGF) plays a significant role in cardiac remodeling and dysfunction. We aimed to investigate the associations between plasma CTGF level and the risk of LV diastolic dysfunction in this study and judge its effectiveness in diagnosing LV diastolic dysfunction. A total of 169 patients with overt hyperthyroidism were included. LV diastolic function was evaluated and the subjects were divided into normal LV diastolic function group and LV diastolic dysfunction group. Routine clinical medical data, biochemical data, thyroid related parameters and echocardiographic parameters were recorded for analysis. Compared with normal LV diastolic function group, the LV diastolic dysfunction group had higher age and BMI, as well as lower heart rate, lower serum albumin, lower eGFR, higher serum TgAb and BNP level, and the incidences of hypertension were also higher (all P <0.05). Circulating plasma CTGF levels in the LV diastolic dysfunction group were significantly higher (normal LV diastolic function group: 7.026 [5.567-8.895], LV diastolic dysfunction group: 8.290 [7.054-9.225] ng/ml, median [(Interquartile range)], P = 0.004); Compared with the lowest quartile group, the crude odds ratios (OR) of LV diastolic dysfunction in the second, third, and fourth quartile group were 3.207, 5.032 and 4.554, respectively (all P<0.05). After adjustment for the potentially confounding variables, the adjusted OR values of the third and fourth quartile group had no obvious change. The results of ROC showed that the plasma CTGF had the largest area under the ROC curve, and the value was 0.659 (P = 0.005). The level of circulating plasma CTGF in the LV diastolic dysfunction group was significantly increased. Plasma CTGF level is an independent risk factor for LV diastolic dysfunction. Compared with serum BNP level, the plasma CTGF level may have auxiliary diagnostic value for LV diastolic dysfunction in hyperthyroid patients.

Gut Microecology May Be Involved in the Pathogenesis of Hashimoto Thyroiditis by Reducing Production of Hydrogen Sulfide.

Hashimoto thyroiditis (HT) is related to intestinal microbiota alteration, but the causal relationship remains unclear. Hydrogen sulfide (H2S) is a microbiota-derived metabolite. We speculated that abnormal intestinal microbiota might limit H2S production capacity, promoting HT pathogenesis. This work aimed to illustrate that the intestinal microbiota plays important roles in HT pathogenesis via microbiota-derived H2S levels. We collected feces from HT patients and healthy donors for fecal microbiota transplantation (FMT). Thirty-six female CBA/J mice were randomly assigned to 4 groups: experimental autoimmune thyroiditis (EAT) group, EAT + Healthy group, EAT + HT group, and EAT + HT + H2S group. 16S ribosomal RNA sequencing was performed to examine gut microbiota alterations and the H2S production pathway. Serum TgAb and H2S levels were assayed by enzyme-linked immunosorbent assay and H2S-selective sensors, respectively. T-cell subpopulations in the spleen were detected by flow cytometry. The gut microbiota was different after FMT among the EAT, EAT + Healthy, and EAT + HT groups. The thyroiditis score assessed by hematoxylin and eosin staining was higher in the EAT + HT group than that in the EAT and EAT + HT + H2S groups. Helper T (Th1) and Th17 cell differentiation ratios were increased in the EAT + HT group compared to the other 3 groups. Serum H2S levels were decreased and the dissimilatory sulfate reduction (DSR) pathway was attenuated in the EAT + HT group compared to the EAT + Healthy group. H2S alleviated thyroiditis severity and related immune disorders, which were aggravated by the FMT from HT patients. The attenuated DSR pathway in the gut microbiota from HT patients might be involved in thyroiditis pathogenesis.

The Diagnostic Value of 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Differentiated Thyroid Cancer Patients with Elevated Thyroglobulin/Thyroglobulin Antibody Levels and Negative Iodine Scintigraphy: A Systematic Review and Meta-Analysis.

Background: The objective of this study is to evaluate the diagnostic accuracy of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in detecting recurrence in patients with differentiated thyroid cancer (DTC) who have negative whole-body scans (WBSs) but elevated serum thyroglobulin (Tg) or thyroglobulin antibody (TgAb) levels. Methods: This systematic review/meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Diagnostic Test Accuracy criteria (International Prospective Register of Systematic Reviews registration number: CRD42022340924). A comprehensive search of the MEDLINE, EMBASE, and Cochrane databases identified articles reporting the diagnostic accuracy of FDG PET/CT for the detection of recurrence in patients with DTC with negative WBS and elevated serum Tg or TgAb levels published between January 2012 and June 2023. Meta-analyses were performed to determine the diagnostic accuracy of FDG PET/CT on the total target population as well as on subgroups stratified by serum Tg or TgAb, and thyrotropin (TSH) stimulation status at the time of FDG PET/CT. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework was applied to evaluate the quality of evidence and the strength of recommendations to facilitate translation of the meta-analysis results into practical recommendations for clinical guidelines. Results: A total of 24 studies involving 1988 patients were included for analysis. The overall pooled sensitivity and specificity values were 0.87 (95% confidence interval [CI] = 0.83-0.92; I2 = 75%) and 0.84 (CI = 0.80-0.89; I2 = 44%), respectively. Subgroup analyses revealed no significant differences in the diagnostic accuracy of FDG PET/CT in patients stratified by serum Tg or TgAb levels, and TSH stimulation status at the time of PET/CT. Treatment plans were changed following FDG PET/CT imaging in 40% (CI = 34-47%; I2 = 39%) of cases. The quality level of evidence for using FDG PET/CT was moderate in both sensitivity and specificity according to the GRADE system. Conclusion: There is moderate quality evidence demonstrating the high diagnostic accuracy of FDG PET/CT in detecting recurrence in patients with DTC with negative WBS and elevated serum Tg or TgAb levels. This evidence corroborates the current guidelines' endorsement of FDG PET/CT as a diagnostic tool in such patients.

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.

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.

Thyroid Cancer Persistence in Patients with Unreliable Thyroglobulin Measurement: Circulating microRNA as Candidate Alternative Biomarkers.

We aimed to evaluate the role of circulating miRNAs as a biomarker of the persistence of papillary thyroid cancer (PTC) in patients with an "uninformative" thyroglobulin (Tg) measurement. We prospectively enrolled 49 consecutive PTC patients with Tg-positive antibodies (TgAb) who had undergone a (near)-total thyroidectomy and 131I therapy (RIT). The serum thyroid stimulating hormone (TSH), Tg, and TgAb levels were measured before and at 6 and 12 months after RIT, respectively. The serum miRNA (221, 222, 375, 155, and 146b) levels were measured simultaneously. The response to the initial therapy was assessed according to the 2015 ATA criteria. A decrease in 50% or more of serum miRNA over time was observed in 41/49 PTC patients, who showed an excellent response (ER), but six and two patients were classified to have an indeterminate/incomplete biochemical or incomplete structural response to initial therapy. Serum miRNA kinetics emerge as a promising biomarker for the early detection of a persistent disease in PTC patients with uninformative Tg results.

Effectiveness and Safety of Levothyroxine Tablets Combined with Iodine-131 in the Treatment of Thyroid Cancer

Objective To explore the effectiveness of levothyroxine tablets combined with iodine-131 in thyroid cancer patients after radical thyroidectomy and the effect on their serum thyroglobulin (Tg) and thyroglobulin antibody (TgAb) levels. Methods A total of 70 thyroid cancer patients receiving radical thyroidectomy in our hospital from July 2015 to April 2016 were recruited and were assigned via different treatment methods (1 : 1) to receive either levothyroxine tablets (observation group) or levothyroxine tablets plus iodine-131 (control group). Outcome measures included treatment efficiency, 1, 3, and 5-year recurrence and metastasis, serum Tg and TgAb levels, postoperative survival, and adverse reactions. Results The total effective rate of treatment in the control group was significantly higher than that in the observation group (P < 0.05). There was no significant difference in cancer recurrence and metastasis rate between the two groups one year postoperatively (P > 0.05). The rate of cancer recurrence and metastasis in the control group was significantly lower than that in the observation group 3 and 5 years after surgery (P < 0.05). Before treatment, there was no significant difference in serum Tg and TgAb levels between the two groups (P > 0.05). After treatment, serum Tg and TgAb levels decreased in both groups, with lower results in the control group (P < 0.05). There was no significant difference in the 1 and 3-year survival rates between the two groups (P > 0.05). The 5-year survival rate in the control group was significantly higher than that in the observation group (P < 0.05). There was no significant difference in adverse reactions between the two groups (P > 0.05). Conclusion Levothyroxine tablets combined with iodine-131 for thyroid cancer patients undergoing radical thyroidectomy effectively could improve the treatment efficiency, reduce the risk of cancer recurrence and metastasis after surgery, lower the serum Tg and TgAb levels of patients, and prolong the survival of patients, with a high safety profile. Further trials are, however, required prior to clinical promotion.

A Predictive Role of Autoantibodies Against the Epitope aa168–183 of ENO1 in the Occurrence of Miscarriage Related to Thyroid Autoimmunity

ObjectiveThe aim of the research is to study the association between the serum levels of autoantibodies against one important epitope (168FMILPVGAANFREAMR183, designated as P6) of α-enolase (ENO1-P6Abs) and miscarriage among euthyroid females with thyroid autoimmunity (TAI).MethodsAnti-ENO1-P6 total IgG was investigated in 432 euthyroid women, and its four subclasses were analyzed in 184 euthyroid women. The serum FT4, TSH, TgAb, and TPOAb levels were determined using an electrochemiluminescence immunoassay. The serum ENO1-P6Ab and anti-protein disulfide isomerase A3 autoantibody (PDIA3Ab) levels were determined using an enzyme-linked immunosorbent assay.ResultsThe serum levels of anti-ENO1-P6 total IgG, IgG2, IgG3, and IgG4 were significantly higher in euthyroid TAI females than in non-TAI controls. Additionally, anti-ENO1-P6 total IgG and its 4 subtypes were all markedly higher in euthyroid TAI females with pregnancy loss than those without miscarriage. Moreover, logistic regression analysis showed that highly expressed anti-ENO1-P6 total IgG, IgG1, IgG2, and IgG3 subtypes in the serum were all independent risk factors for euthyroid TAI-related miscarriage, and its IgG1 was also for non-TAI-related abortion. According to the trend test, the prevalence of miscarriage was increased in a titer-dependent manner with the raised levels of serum anti-ENO1-P6 total IgG and IgG1, IgG2, and IgG3 subtypes among euthyroid TAI females. The receiver operating characteristic curve analysis of anti-ENO1-P6 total IgG and IgG1, IgG2, and IgG3 subclass expressions in the serum for miscarriage prediction in euthyroid TAI females exhibited that the total areas under the curves were 0.773 ± 0.041, 0.761 ± 0.053, 0.827 ± 0.043, and 0.760 ± 0.050, respectively (all P <0.0001). Their corresponding optimal cut-off OD450 values were 0.68 (total IgG), 0.26 (IgG1), 0.97 (IgG2), and 0.48 (IgG3), with sensitivities of 70.8, 87.5, 83.3, and 85.4%, and specificities of 70.8, 59.1, 77.3, and 56.8%, respectively. There was an additive interaction between serum anti-ENO1-P6 and anti-PDIA3 total IgGs on the development of miscarriage (RERI = 23.6, AP = 0.79, SI = 5.37).ConclusionThe highly expressed ENO1-P6Abs may be important risk factors for euthyroid TAI-related miscarriage. The serum levels of ENO1-P6Abs may become good predictive markers for pregnancy loss in euthyroid TAI females, especially its IgG2 subclass expression.

Clinical Application Value of High-Frequency Ultrasound Combined with Detection of Serum High Mobility Group Box 1, Soluble IL-2 Receptor, and Thyroglobulin Antibody in Diagnosing Thyroid Cancer.

Objective The aim of this study is to explore the clinical application value of high-frequency ultrasound combined with detection of serum high mobility group box (HMGB-1), soluble IL-2 receptor (SIL-2R), and thyroglobulin antibody (TgAb) in diagnosing thyroid cancer. Methods By means of retrospective study, 50 thyroid cancer patients treated in our hospital from January 2019 to January 2021 were selected as the thyroid cancer group, 50 patients with benign thyroid lesions were included in the benign lesion group, and 50 healthy individuals examined in our hospital in the same period were included in the control group. All study objects received high-frequency ultrasound examination, and at the same time, their serum HMGB-1, SIL-2R, and TgAb levels were measured. After that, the results of high-frequency ultrasound examination were analyzed, the diagnostic efficacy of different diagnosis methods was explored, and receiver operating characteristic (ROC) curves were plotted. Results According to the results of high-frequency ultrasound examination, there were significant differences in echogenicity surrounding and inside the lesion, calcification, blood flow distribution, and blood flow parameters between the thyroid cancer group and the benign lesion group (P < 0.001); the HMGB-1, SIL-2R, and TgAb levels were statistically different among the three groups (P < 0.001), and the level values of HMGB-1, SIL-2R, and TgAb of the thyroid cancer group were, respectively, (12.26 ± 1.32) ng/ml, (108.65 ± 9.75) pmol/L, and (690.65 ± 34.47) IU/mL; the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of high-frequency ultrasound combined with detection of serum HMGB-1, SIL-2R, and TgAb were, respectively, 98.0%, 95.0%, 90.7%, and 99.0%, and AUC (95%CI) = 0.965 (0.931–0.999). Conclusion High-frequency ultrasound combined with detection of serum HMGB-1, SIL-2R, and TgAb has a good value in diagnosing thyroid cancer, which should be promoted in practice.

Serum Thyroglobulin Antibody as a Tumor Marker in Differentiated Thyroid Carcinoma and its Correlation with FNAC and Histopathology

Background: This longitudinal descriptive study was conducted for the first time in the department of Pathology, Rajshahi Medical College in order to evaluate the prognostic significance of serum TgAb as a tumor marker for differentiated thyroid carcinoma. Objective: The aim of this study to detect the antibody positive differentiated thyroid carcinoma using serum TgAb and compare with the FNAC and histopathological findings. Method: A total forty patients of clinically, radiologically and by FNAC diagnosed as differentiated thyroid carcinoma were selected attending in the department of Otolaryngology, Rajshahi Medical College Hospital from January 2010 to December 2011. Preoperative serum TgAb level (TgAbl) was measured in all patients taking cut off value as 40 IU/ml. Biopsy material were examined for histopathological diagnosis. 3-6 months after thyroidectomy postoperative serum TgAb level (TgAb2) was measured in those patients only who were TgAbl positive. Result: The correlation, association and statistical analysis of preoperative and postoperative serum TgAb level were computed against histopathological diagnosis. Out of forty cases, 35 were papillary and 5 were follicular carcinoma. Mean age was 25.48+9.70 years and Male: Female was 1:6. In this study, 9 cases (22.5%) were TgAb positive preoperatively and 2 cases showed highest level 3000 and 2200 IU/ml. Post operative TgAb level of 9 cases showed significant reduction. Statistical analysis demonstrates significant correlation (P=&lt;0.01) and association (P=&lt;0.05) between preoperative and postoperative TgAb level. Conclusion: So, it is concluded that serum TgAb level can be used as a tumor marker in antibody positive differentiated thyroid carcinoma.

A New Dynamic Response to Therapy Assessment in Postoperative Patients With Low-Risk Differentiated Thyroid Cancer Treated Without Radioactive Iodine.

BackgroundTotal thyroidectomy (TT) or lobectomy without radioactive iodine (RAI) is becoming a common management for patients with low-risk differentiated thyroid cancer (DTC). However, the assessment of response to therapy for these patients remains controversial. The aim of this study was to propose and validate a new dynamic evaluation strategy to assess the response to therapy in patients with low-risk DTC treated with TT or lobectomy but without RAI.MethodsWe performed a retrospective analysis of 543 adult patients with low-risk DTC who underwent TT or lobectomy without RAI therapy. Follow-up consisted of trends of serum thyroglobulin (Tg), anti-thyroglobulin antibody (TgAb) levels and neck ultrasonography (US) were conducted every 6–24 months. Response to therapy assessments were defined as excellent response, biochemical incomplete response, structural incomplete response, and indeterminate response according to the follow-up findings.ResultsAt a median follow-up of 51 months (range 33–66 months), 517 (95%) had excellent response, while the other 26 had either biochemical incomplete response (an increasing trend of suppressed serum Tg levels, n=9; an increasing trend of TgAb levels, n=3) or indeterminate response (a stable or decreasing trend of suppressed serum Tg levels, but a stable positive trend of TgAb levels, n=14). No patients had structural incomplete response or no deaths related to thyroid cancer. The risk of incomplete response was significantly higher in lobectomy than in TT (p<0.001).ConclusionOur study proposed and validated a new dynamic response to therapy assessment depending on trends of suppressed serum Tg, TgAb levels, and neck US findings which could be an appropriate tool for postoperative follow-up in low-risk DTC patients without RAI therapy. Our findings provided further evidence to support no routine recommendation of RAI after surgery in low-risk DTC.

Antithyroid Antibody Status During Pregnancy

Background: Gradual alteration of antithyroid antibody level occurs during different trimesters of gestation. The study finds the type of alteration in Bangladeshi population. Objective: The present study was carried out to find out the alterations of antithyroid antibody levels during each trimester in normal pregnant women in Bangladesh. Materials and Methods: This cross sectional study was carried out in the Department of Physiology, Sir Salimullah Medical College (SSMC), Dhaka from July 2016 to June 2017. Total 90 apparently healthy pregnant women of different trimesters, age ranged from 20 to 35 years were selected as study group (Group I). Again according to gestational age, study group was subdivided into 1st trimester of gestation (Group Ia, n=30), 2nd trimester of gestation (Group Ib, n=30) and 3rd trimester of gestation (Group Ic, n=30) respectively for comparison. For assessment of antithyroid antibody status, serum TPO-Ab and Tg-Ab levels were measured by chemiluminescent microparticle immunoassay (CMIA) method in Bangabandhu Sheikh Mujib Medical University (BSMMU). The statistical analysis was done by ANOVA test and Bonferroni test. Results: In this study, mean serum TPO-Ab level was significantly (p≤0.05, p&lt;0.001) lower in 2nd and 3rd trimester in comparison to that of 1st trimester. On the other hand, mean serum Tg-Ab level was significantly (p&lt;0.01, p&lt;0.001) lower in 2nd and 3rd trimester in comparison to that of 1st trimester. Again, this value was significantly (p≤0.05) lower in 3rd trimester than that of 2nd trimester. Conclusion: Antithyroid antibody titre gradually decreases with the progression of trimesters of gestation. KYAMC Journal.2021;12(02): 98-100

P–645 Abnormal thyroid hormone levels are associated with biochemical primary ovarian insufficiency and low ovarian reserve: a cross-sectional study

Abstract Study question To address whether there was a correlation between thyroid parameters and primary ovarian insufficiency. Summary answer Thyroid dysfunction was related with bPOI and LOR. What is known already In our daily clinical work, there seems to be a link between thyroid disease and POI. A recent study reported that subclinical hypothyroidism was associated with lower ovarian reserve during later reproductive age. Animal studies demonstrated that thyroid hormones played important roles in ovarian functions, and both maternal hypothyroidism and hyperthyroidism were related with reduced primordial, primary and secondary follicle number in rats. However, others reported that thyroid autoimmunity (TAI) and hypothyroidism were not associated with DOR. In all, accumulative animal and epidemiological studies indicated the connection between thyroid function and ovarian reserve, but the results were still inconsistent. Study design, size, duration This is a cross-sectional study with consecutive women performed ovarian reserve assessment and thyroid test in the Second Hospital of Zhejiang University School of Medicine from April 2016 to March 2019. A total of 2109 women were included, with 111 with bPOI and 1771 without bPOI. To exclude the influence of age the participants were categorized into low ovarian reserve (LOR) and non-LOR groups based on age-specific AMH, including 78 LOR and 2031 non-LOR. Participants/materials, setting, methods At the outpatient, a doctor carried out an interview, recorded age, body mass index (BMI), past history, and current treatment, and made a diagnosis. Serum AMH, FSH, TPOAb, TgAb, Tg, TT3, FT3, TT4, FT4, and TSH levels were measured with electrochemiluminescence method. Main results and the role of chance TT3, FT3, FT4 was significantly positively correlated with serum AMH level. Further logistic regression analysis found that abnormal TT3, FT3 and TT4 levels were related to increased risks of bPOI and LOR. Chi-square analysis also proved that the incidence of abnormal TT3, FT3 and TT4 increased significantly in women with bPOI or LOR. The incidence of bPOI and LOR increased significantly in women with 2 or 3 abnormal thyroid hormones. The above analyses demonstrate in multiple aspects that thyroid dysfunction is related with decreased ovarian reserve. Limitations, reasons for caution Since this is a retrospective cross-sectional study, we only got the correlation between factors, and we could not achieve causal relationship. Further prospective cohort or randomized controlled trial (RCT) studies are required to make the results more robust. Wider implications of the findings: The present study demonstrated that thyroid dysfunction was related with bPOI and LOR. It might be thyroid hormones, not TSH or thyroid antibodies, played the major role in ovarian reserve impairment. The treatment of euthyroxine may improve the ovarian reserve function. Trial registration number Not applicable

Preoperatively Predicting the Central Lymph Node Metastasis for Papillary Thyroid Cancer Patients With Hashimoto's Thyroiditis.

BackgroundThe preoperative distinguishment of lymph nodes with reactive hyperplasia or tumor metastasis plays a pivotal role in guiding the surgical extension for papillary thyroid carcinoma (PTC) with Hashimoto’s thyroiditis (HT), especially in terms of the central lymph node (CLN) dissection. We aim to identify the preparative risk factors for CLN metastasis in PTC patients concurrent with HT.Materials and MethodsWe retrospectively reviewed and analyzed the data including the basic information, preoperative sonographic characteristics, and thyroid function of consecutive PTC patients with HT in our medical center between Jan 2019 and Apr 2021. The Chi-square and Fisher’s exact tests were used for comparison of qualitative variables among patients with or without CLN metastasis. Univariate and multivariate logistic regression analyses were used to determine the risk factors for CLN metastasis. The nomogram was constructed and further evaluated by two cohorts produced by 1,000 resampling bootstrap analysis.ResultsA total of 98 in 214 (45.8%) PTC patients were identified with CLN metastasis. In multivariate analysis, four variables including high serum thyroglobulin antibody (TgAb) level (>1,150 IU/ml), lower tumor location, irregular margin of CLN, and micro-calcification in the CLN were determined to be significantly associated with the CLN metastasis in PTC patients with HT. An individualized nomogram was consequently established with a favorable C-index of 0.815 and verified via two internal validation cohorts.ConclusionsOur results indicated that preoperatively sonographic characteristics of the tumor and lymph node condition combined with serum TgAb level can significantly predict the CLN in PTC patients with HT and the novel nomogram may further help surgeons to manage the CLN in this subpopulation.

Yanghe Decoction Suppresses the Experimental Autoimmune Thyroiditis in Rats by Improving NLRP3 Inflammasome and Immune Dysregulation.

Inflammation is an important contributor to autoimmune thyroiditis. Yanghe decoction (YH) is a traditional Chinese herbal formulation which has various anti-inflammatory effects. It has been used for the treatment of autoimmune diseases such as ankylosing spondylitis In this study we aimed to investigate the effects of YH on autoimmune thyroiditis in a rat model and elucidate the underlying mechanisms. The experimental autoimmune thyroiditis (EAT) model was established by thyroglobulin (pTG) injections and excessive iodine intake. Thyroid lesions were observed using hematoxylin and eosin (H and E) staining and serum TgAb, TPOAb, TSH, T3, and T4 levels were measured by enzyme-linked immunosorbent assay IL-35 levels were evaluated using real-time polymerase chain reaction (RT-PCR) and Th17/Treg balance in peripheral blood mononuclear cells (PBMCs) was determined by flow cytometry and RT-PCR. Changes in Wnt/β-catenin signaling were evaluated using Western blot. Immunofluorescence staining and western blot were employed to examine NLRP3 inflammasome activation in the thyroid. YH minimized thyroid follicle injury and decreased concentrations of serum TgAb, TPOAb, TSH, T3, and T4 in EAT model. The mRNA of IL-35 was increased after YH treatment. YH also increased the percentage of Treg cells, and decreased Th17 proportion as well as Th17/Treg ratio in PBMCs. Meanwhile, the mRNA levels of Th17 related cytokines (RORγt, IL-17A, IL-21, and IL-22) were suppressed and Treg related cytokines (FoxP3, TGF-β, and IL-10) were promoted in PBMCs. Additionally, the protein expressions of Wnt-1 and β-catenin were unregulated after YH treatment. NLRP3 immunostaining signal and protein levels of IL-17, p-NF-κB, NLRP3, ASC, cleaved-Caspase-1, cleaved-IL-1β, and IL-18 were downregulated in the thyroid after YH intervention. Overall, the present study demonstrated that YH alleviated autoimmune thyroiditis in rats by improving NLRP3 inflammasome and immune dysregulation.

Long-Term Oncological Outcome Comparison between Intermediate- and High-Dose Radioactive Iodine Ablation in Patients with Differentiated Thyroid Carcinoma: A Propensity Score Matching Study.

Background Radioactive iodine (RAI) ablation is recommended for most patients with differentiated thyroid carcinoma (DTC) after total thyroidectomy (TT). We aimed to compare long-term outcomes between intermediate-dose (100 mCi) and high-dose (150 mCi) RAI ablation therapy in patients with DTC using propensity score matching analysis. Methods This was a retrospective study of 1448 patients with DTC who underwent RAI ablation after TT. Propensity score matching was performed using the extent of operation, tumor size, extrathyroidal extension, multifocality, lymphatic invasion, vascular invasion, perineural invasion, number of positive lymph nodes (LNs), ATA risk stratification system, T stage, N stage, TNM stage, preoperative serum Tg and TgAb levels, and post-RAI serum Tg and TgAb levels. Results Recurrence rates in the intermediate- and high-dose groups were 3.1% and 5.6%, respectively. After propensity score matching, LN ratio >0.22 (HR, 2.915; 95% CI, 1.228–6.918; p=0.015) and serum Tg >10 ng/mL after RAI (HR, 3.976; 95% CI, 1.839–8.595; p < 0.001) were significant predictors of recurrence. Kaplan–Meier analysis showed no significant difference in DFS before or after propensity score matching (p=0.074 and p=0.378, respectively). Conclusions Intermediate-dose RAI ablation for the adjuvant treatment of DTC is sufficient as compared to high-dose RAI ablation. Further prospective or multicenter studies should be conducted to clarify the prognosis of intermediate-dose RAI ablation.

The role of thyroid-stimulating hormone and thyroglobulin antibody in abnormally invasive placenta

Purpose Thyroid hormones and antibodies are known to participate in angiogenesis and invasion and also thyroid hormone receptors are expressed in the placenta. We aimed to evaluate the relationship of serum levels of thyroid-stimulating hormone (TSH), thyroid hormones (TH), and anti-thyroid antibodies with abnormally invasive placenta (AIP). We also aimed to investigate whether they are related with cesarean hysterectomy and massive blood transfusion need in AIP cases. Methods A total of 88 pregnant patients were enrolled in this prospective case-control study (30 with AIP, 28 with non-adherent placenta previa totalis (PPT) and 30 controls). Serum TSH, thyroid hormone [T3 (triiodothyronine) and T4 (thyroxine)] and thyroid antibodies against thyroglobulin (TgAb) and thyroid peroxidase (TPOAb) levels were studied in maternal serum at initial admission to our Perinatology Unit (at early third trimester). The factors associated with increased risk of AIP, cesarean hysterectomy, massive blood transfusion, and adverse perinatal outcomes were evaluated with multiple logistic regression analysis. Adjusted odds ratios and 95% confidence intervals were also calculated. Results Serum TSH and TgAb levels were significantly lower in the AIP group than both PPT and control groups (p = .01, p < .001 and p < .001, p < .001 respectively). Decreased serum levels of TSH (<2.16 mIU/L) and TgAb (<2.70 mIU/L) levels and high previous cesarean section rates were found to be independently associated with AIP in pregnant women with PPT (OR: 0.4, 95% CI: 0.1–0.9; p = .04, OR: 0.7, 95%CI: 0.4–1.3, p = .02 and OR: 0.1, 95% CI: 0.1–0.5, p = .01). Decreased serum TSH and TgAb levels were found to be independently associated with an increased rate of cesarean hysterectomy and massive blood transfusion in AIP cases (OR: 3.7, 95% CI: 1.4–9.8; p = .01, OR: 1.8, 95% CI: 1.1–3.1; p = .03 and OR: 2.6, 95% CI: 1.0–6.5; p = .05, OR: 2.2, 95% CI: 1.1–4.1 p = .02). Decreased TSH and TgAb serum levels were also found to be independently associated with adverse perinatal outcomes in AIP cases (OR: 3.4, 95% CI: 1.3–11.0; p = .01 and OR: 1.978, 95% CI: 2–3.6; p = .03). Conclusion Decreased serum TSH and TgAb levels, and previous history of cesarean section were all found to be significantly associated with AIP in cases with PPT. We suggest that maternal serum TSH and TgAb levels can provide additional contribution to obstetric Doppler ultrasound in the diagnosis of AIP and thus can reduce the risks of unplanned cesarean hysterectomy in cases with PPT.