Hashimoto's Thyroiditis Group Research Articles

A machine learning-based diagnosis modeling of IgG4 Hashimoto's thyroiditis.

This study aims to develop a non-invasive diagnosis model using machine learning (ML) for identifying high-risk IgG4 Hashimoto's thyroiditis (HT) patients. A retrospective cohort of 93 HT patients and a prospective cohort of 179 HT patients were collected. According to the immunohistochemical and pathological results, the patients were divided into IgG4 HT group and non-IgG4 HT group. Serum TgAb IgG4 and TPOAb IgG4 were detected by ELISAs. A logistic regression model, support vector machine (SVM) and random forest (RF) were used to establish a clinical diagnosis model for IgG4 HT. Among these 272 patients, 40 (14.7%) were diagnosed with IgG4 HT. Patients with IgG4 HT were younger than those with non-IgG4 HT (P < 0.05). Serum levels of TgAb IgG4 and TPOAb IgG4 in IgG4 HT group were significantly higher than those in non-IgG4 HT group (P < 0.05). There were no significant differences in gender, disease duration, goiter, preoperative thyroid function status, preoperative TgAb or TPOAb levels, and thyroid ultrasound characteristics between the two groups (all P > 0.05). The accuracy, sensitivity, and specificity were 57%, 78%, and 79% for logistic regression model of IgG4 HT, 80 ± 7%, 84.7% ± 2.6%, and 75.4% ± 9.6% for the RF model and 78 ± 5%, 89.8% ± 5.7%, and 64.7% ± 5.7% for the SVM model. The RF model works better than SVM. The area under the ROC curve of RF ranged 0.87 to 0.92. A clinical diagnosis model for IgG4 HT established by RF model might help the early recognition of the high-risk patients of IgG4 HT.

The BRAF V600E Mutation and Clinicopathological Changes Among Patients With Hashimoto thyroiditis, Papillary Thyroid Carcinoma With Hashimoto Thyroiditis, and Nodular Goiter.

The study aimed to investigate the BRAF V600E mutation and clinicopathological changes among patients with Hashimoto thyroiditis (HT), papillary thyroid carcinoma (PTC) with Hashimoto thyroiditis (HT), or nodular goiter (NG). A total of 87 patients with the BRAF V600E mutation who were diagnosed with HT (including with hyperplasia dysplasia), PTC with HT, and PTC with NG were enrolled. Clinical data, concentrations of antithyroglobulin antibodies (TGAb) and thyroid microsomal antibodies (TMAb) in the serum thyroid-function levels, and the result presence of the BRAF V600E mutation were retrospectively analyzed. There were significant differences in the BRAF V600E mutation rates between the HT and PTC with HT groups (P <0.05) and the HT and PTC with NG groups (P <0.05), whereas no significant difference was found between the PTC with HT and PTC with NG groups. There was no difference in incidences of PTC between HT with elevated TGAb and TMAb group and those with baseline levels. The incidence of multifocal PTC was higher in the PTC with HT group; however, the difference was not significant. Our findings documented that BRAF mutation distinguished between the benign HT and the malignant PTC groups. The serum levels of TGAb and TMAb autoantibodies did not directly correlate with PTC in the background of HT. HT and NG may similarly contribute to the pathogenesis of PTC.

Utilizing Immunoglobulin IgG4 Immunohistochemistry for Risk Stratification in Patients with Papillary Thyroid Carcinoma Associated with Hashimoto Thyroiditis.

Hashimoto thyroiditis (HT) is suspected to correlate with papillary thyroid carcinoma (PTC) development. While some HT cases exhibit histologic features of immunoglobulin G4 (IgG4)-related disease, the relationship of HT with PTC progression remains unestablished. This cross-sectional study included 426 adult patients with PTC (≥1 cm) undergoing thyroidectomy at an academic thyroid center. HT was identified based on its typical histologic features. IgG4 and IgG immunohistochemistry were performed. Wholeslide images of immunostained slides were digitalized. Positive plasma cells per 2 mm2 were counted using QuPath and a pre-trained deep learning model. The primary outcome was tumor structural recurrence post-surgery. Among the 426 PTC patients, 79 were diagnosed with HT. With a 40% IgG4 positive/IgG plasma cell ratio as the threshold for diagnosing IgG4-related disease, a cutoff value of >150 IgG4 positive plasma cells per 2 mm2 was established. According to this criterion, 53% (43/79) of HT patients were classified as IgG4-related. The IgG4-related HT subgroup presented a more advanced cancer stage than the IgG4-non-related HT group (P=0.038). The median observation period was 109 months (range, 6 to 142). Initial assessment revealed 43 recurrence cases. Recurrence-free survival periods showed significant (P=0.023) differences, with patients with IgG4 non-related HT showing the longest period, followed by patients without HT and those with IgG4-related HT. This study effectively stratified recurrence risk in PTC patients based on HT status and IgG4-related subtypes. These findings may contribute to better-informed treatment decisions and patient care strategies.

Interleukin (IL)-23, IL-31, and IL-33 Play a Role in the Course of Autoimmune Endocrine Diseases.

Interleukins (IL)-23, 31, and 33 are involved in the regulation of T helper 17 (Th17)/regulatory T (Treg) cells balance. The role of IL-23, 31 and 33 in non-endocrine autoimmune diseases has been confirmed. Data on the involvement of these cytokines in endocrine autoimmune diseases are limited. This study aimed to determine the involvement of cytokines regulating the T helper 17 (Th17)/regulatory T (Treg) cells axis in the course of autoimmune endocrine diseases. A total number of 80 participants were divided into 4 groups: the autoimmune polyendocrine syndrome (APS) group consisting of APS type 2 (APS-2) and type 3 (APS-3) subgroups, the Hashimoto's thyroiditis (HT) group, the Graves' disease (GD) group and the control (C) group. Fifteen cytokines related to Th17 and Treg lymphocytes were determined in the serum of all participants. Higher levels of IL-23 and IL-31 were found in the APS, GD, and HT groups compared to the C group. Higher levels of IL-23 and IL-31 were also observed in the APS-2 group, in contrast to the APS-3 group. Correlation analysis of variables in the groups showed a statistically significant correlation between the cytokines IL-23, IL-31, and IL-33 in the APS and APS-2 groups, but no correlation in the APS-3 and C groups. IL-23 and IL-31 are independent factors in the course of HT, GD, and APS-2, in contrast to APS-3. The positive correlation between IL-23 and IL-31, IL-23 and IL-33, and between IL-31 and IL-33 in the APS, APS-2 groups, but the lack of correlation in the APS-3 and C groups may further suggest the involvement of these cytokines in the course of Addison's disease.

Coexistence of Hashimoto's Thyroiditis in Differentiated Thyroid Cancer: Post-Operative Monitoring of Anti-Thyroglobulin Antibodies and Assessment of Treatment Response.

Differentiated thyroid carcinoma (DTC) is frequently found in conjunction with autoimmune thyroid disorders, particularly Hashimoto's thyroiditis (HT). This study investigates the impact of coexisting HT on the persistence of an indeterminate response to therapy due to positive anti-thyroglobulin antibodies (AbTg), measured via competitive immunoassay, in a consecutive patient series from Calabria, Southern Italy. This retrospective longitudinal study analyzed 259 consecutive DTC patients managed at the Endocrinology Unit of Renato Dulbecco Hospital (Catanzaro, Italy) up to 2023. Patients with medullary and undifferentiated thyroid carcinoma, partial thyroidectomy, less than six months of post-operative monitoring, or missing clinical data were excluded. Demographic information, histological findings, initial tumor stage, and ATA risk category were collected. The response to therapy was assessed based on ATA guidelines. Among the 259 patients, 29% had coexisting HT. Patients with HT exhibited distinct characteristics: a higher proportion of females (87.0% vs. 74.7%), a shorter post-operative monitoring duration (median 3 vs. 5 years), and a higher prevalence of papillary thyroid carcinoma (PTC) (97.4% vs. 86.3%). The tumor size, lymph node involvement, and distant metastasis were similar between the groups, with patients without HT having a higher incidence of extrathyroidal tumor extension. However, the initial TNM stage and ATA risk category did not differ significantly. At the six-month follow-up, HT patients showed a higher rate of indeterminate responses, primarily due to positive AbTg. After 12 months, the response categories aligned, with decreasing AbTg levels in the HT group. After 24 months, most patients with long-term follow-up demonstrated an excellent response to DTC therapy, irrespective of HT coexistence. While HT does not worsen DTC prognosis, it may result in indeterminate responses. AbTg measurements in the peri-operative period should be encouraged to facilitate post-operative monitoring, emphasizing the importance of using standardized assays. Further research in larger populations with extended follow-up is needed to comprehensively understand the HT-DTC relationship.

Clinical value of contrast-enhanced ultrasound quantitative analysis for differentiating thyroid lesions in Hashimoto's thyroiditis patients.

The role of quantitative contrast-enhanced ultrasound (CEUS) in the evaluation of thyroid nodules with Hashimoto's thyroiditis (HT) has received little attention. This was a retrospective cohort study. We consecutively enrolled 242 patients (49 males, 193 females, average age 52 years) with a combined total of 248 thyroid nodules coexisting with HT who underwent biopsy/resection-proven pathology from December 2016 to June 2021. All patients underwent preoperative ultrasound (US) and CEUS examinations performed by 2 radiologists independently. Quantitative analysis of CEUS using time-intensity curves (TIC) was measured by an expert radiologist from the thyroid intra-nodule and the surrounding parenchyma and their ratios. Receiver operating characteristic (ROC) analysis was performed to evaluate their diagnostic performance. The patients were divided into the nodular HT (NHT) group (n=42), the papillary thyroid carcinoma (PTC) group (n=154), and the primary thyroid lymphoma (PTL) group (n=52) according to their pathological results. TIC parameters revealed that PTC and PTL showed faster time to peak (TTP) (P=0.044, P=0.049), lower peak intensity (PI) (both P<0.001), and smaller areas under the curve (both P<0.001) than those of NHT. The intra nodule of PTL showed an obviously slower perfusion (ratio =0.90, P<0.001) and lower PI (ratio =0.84, P<0.001) compared with the thyroid parenchyma. TIC improved performance in distinguishing PTL from NHT [area under the curve (AUC): 0.947, 95% confidence interval (CI): 0.903-0.991], but inferior performance in differentiating PTC and NHT (AUC: 0.838, 95% CI: 0.759-0.917). CEUS quantitative analysis could be valuable in differentiating thyroid malignancies in patients with HT.

Increased Thyroid DPP4 Expression Is Associated With Inflammatory Process in Patients With Hashimoto Thyroiditis.

Dipeptidyl peptidase-4 (DPP4) is originally described as a surface protein in lymphocytes. Lymphocyte infiltration and subsequent destruction of thyroid tissue have been considered as the central pathological mechanism in Hashimoto thyroiditis (HT). The present study aimed to investigate DPP4 expression in peripheral blood and thyroid tissue in HT patients, and explore the role of DPP4 in the pathophysiological process of HT. This case-control study recruited 40 drug-naive HT patients and 81 control individuals. Peripheral blood and thyroid specimens were collected for assessing the expression and activity of DPP4. Moreover, single-cell RNA sequencing (scRNA-seq) analysis of 6 "para-tumor tissues" samples from scRNA-seq data set GSE184362 and in vitro cell experiments were also conducted. The HT patients had similar DPP4 serum concentration and activity as the controls. However, the expression and activity of DPP4 was significantly increased in the thyroid of the HT group than in the control group. The scRNA-seq analysis showed that DPP4 expression was significantly increased in the HT group, and mainly expressed in T cells. Further in vitro studies showed that inhibition of lymphocyte DPP4 activity with sitagliptin downregulated the production of inflammatory factors in co-cultured thyroid cells. DPP4 expression was significantly increased in the thyroid of the HT group compared with the control group, and was mainly localized in the lymphocytes. Inhibition of lymphocyte DPP4 activity reduced the production of inflammatory factors in co-cultured thyroid cells. Therefore, inhibition of DPP4 may have a beneficial effect by alleviating inflammatory reactions in HT patients.

The expression of GADA, ZnT8A and IA-2A in patients with type 1 diabetes mellitus with thyroid disease and their correlation with thyroid autoantibodies.

The aim of this research was to study the expression of anti-glutamate decarboxylase antibody (GADA), zinc transporter-8 autoantibody (ZnT8A), and insulinoma-associated protein-2 antibody (IA-2A) in patients with type 1 diabetes (T1DM) with thyroid disease (TD) and its correlation with thyroid autoantibodies. 380 patients with T1DM were included in the study, of which 313 patients with T1DM alone were included in the control group. In the TD group, 41 patients with T1DM and Hashimoto's thyroiditis (HT) were included, and 26 cases of T1DM patients with Graves' disease were included in the Graves group. The clinical features of the control group, the HT group, and the Graves group were compared. The positive rates of insulin autoantibodies in the control group and the TD group were analyzed. The clinical characteristics of patients with and without insulin autoantibody positivity were compared. The positive rates of thyroid autoantibodies in T1DM patients with positive GADA, ZnT8A, IA-2A, and different numbers of positive insulin autoantibodies were analyzed. The levels of total cholesterol (TC) and thyroid stimulating hormone (TSH) in the HT group were significantly higher than those in the control and Graves groups, and the levels of free thyroid hormone (FT4) and low-density lipoprotein cholesterol (LDL-C) were significantly lower than those in the control and Graves groups (p<0.001). The levels of TC and TSH in the Graves group were significantly lower than those in the control group, the levels of HbA1c, LDL-C, and FT4 were significantly higher than those in the control group, and the levels of FT3 were significantly higher than those in the control and HT groups (p<0.001). The levels of C peptide, triglyceride (TG), and LDL-C of insulin autoantibodies positive patients were significantly lower than those of negative patients (p<0.05). The positive rates of GADA, ZnT8A, and IA-2A in the TD group, as well as the positive rates of double antibodies and triple antibodies, were significantly higher than those of the control group (p<0.05). In T1DM patients, the positive rates of thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TGAb) in GADA and IA-2A-positive patients were significantly higher than those in GADA and IA-2A-negative patients (p<0.05). The positive rate of TPOAb in ZnT8A-positive patients was significantly higher than that in ZnT8A-negative patients (p<0.05). The positive rates of TRAb, TPOAb, and TGAb in T1DM patients positive for two of the three insulin autoantibodies and three insulin autoantibodies were significantly higher than those positive for one of the three insulin autoantibodies (p<0.001). TD can exacerbate the disorder of glucose and lipid metabolism in patients with T1DM, and multiple insulin autoantibodies positive T1DM patients it is more likely to have thyroid autoantibody positivity. It is suggested that patients with aggravated glucose and lipid metabolism and multiple insulin autoantibody positivity should be routinely screened for thyroid antibodies to help early diagnosis of TD.

Association of Mitochondrial Variants with the Joint Occurrence of Polycystic Ovary Syndrome and Hashimoto's Thyroiditis.

The prevalence of Hashimoto's thyroiditis (HT) among women with polycystic ovary syndrome (PCOS) is higher than in the general female population, but the factors predisposing to the coexistence of these disorders remain unclear. This study employed whole genome sequencing of mitochondrial DNA to identify genetic variants potentially associated with the development of PCOS and HT and predisposing to their joint occurrence. A total of 84 women participated, including patients with PCOS, HT, coexisting PCOS and HT (PCOS + HT) and healthy women. Both Fisher's exact and Mann-Whitney U statistical analyses were performed to compare the frequency of variants between groups. Ten differentiating variants were common to both analyses in PCOS + HT vs. PCOS, one in PCOS + HT vs. HT, and six in PCOS + HT vs. control. Several variants differentiating the PCOS + HT group from PCOS and controls were identified, located both in the mitochondrial genes (including the MT-CYB, MT-ND1, MT-ND2, MT-ND4, MT-ND6, MT-CO1, MT-CO3) and the D-loop region. Only two variants differentiated PCOS + HT and HT groups. One variant (13237a in MT-ND5) was common for all three comparisons and underrepresented in the PCOS + HT group. Functional enrichment analysis showed 10 pathways that were unique for the comparison of PCOS + HT and PCOS groups, especially related to ATP production and oxidative phosphorylation, and one pathway, the NADH-quinone oxidoreductase, chain M/4, that was unique for the comparison of PCOS + HT and control groups. Notably, nine pathways shared commonality between PCOS + HT vs. PCOS and PCOS + HT vs. control, related to the biogenesis and assembly of Complex I. This study provides novel insights into the genetic variants associated with oxidative stress in women with coexisting PCOS and HT. Mitochondrial dysfunction and oxidative stress appear to play a role in the pathogenesis of both conditions. However, more mitochondrial variants were found to differentiate women with both PCOS and HT from those with PCOS alone than from those with HT alone.

Experimental study on changes in metabolic mechanism of papillary thyroid carcinoma complicated with Hashimoto’s thyroiditis

BackgroundWhether the mechanism of thyroid papillary carcinoma (PTC) is the same in patients with a Hashimoto's thyroiditis (HT) background as compared with patients with a normal background remains a highly debated and controversial issue. In this study, we aimed to analyze the differences and similarities of the metabolic mechanism of PTC in normal and HT background, and to explore the relationship between HT and PTC. MethodsThe ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometry (UPLC-Q-TOF/MS) technology was used to analyze 61 PTC patient tissues (31 HT background and 30 normal tissue (NC) background). Potential biomarkers were screened from principal component analysis (PCA) to orthogonal partial least square (OPLS) discriminant analysis. HMDB was searched to identify potential differential metabolites and final metabolic pathway analysis was performed by MetaboAnalyst 5.0. We analyzed the differential metabolites diagnostic accuracy through receiver operating characteristic (ROC) curves analysis. ResultsSeven different metabolites were screened from HT group and NC group, including arginine, glutamic acid, cysteine, citric acid, malic acid, uracil and taurine. Logistic regression model combined with ROC analysis of these 7 biomarkers had good discriminability for PTC (area under operating characteristic curve of HT group and NC group were 0.867 and 0.973, respectively). The HT group had specific metabolic pathways, including aminoacyl-tRNA biosynthesis, glycine, serine and threonine metabolism. ConclusionsThe metabolic profiles of the NC and HT groups had important similarities and differences in PTC. The correlation of PTC with HT may be related to aminoacyl-tRNA biosynthesis, serine and threonine metabolism.

Ultrasound characteristics of Hashimoto’s thyroiditis in the subclinical stages of the disease

ObjectiveTo investigate the prognostic value of indicators from b-mode ultrasound, color Doppler ultrasound, and strain elastography of the thyroid gland in the diagnosis of Hashimoto's thyroiditis (HT). MethodsIn 70 euthyroidal patients with HT, demographic characteristics, serum thyroid profile and ultrasound parameters, including thyroid gland size, vascularity and stiffness (elastography strain index) of the parenchyma, and flow indices of the superior and inferior thyroid artery were recorded. The control group consisted of 70 age and weight matched euthyroid individuals with negative anti-thyroid antibodies (anti-TPO and anti-Tg). ResultsA significant difference was observed between the two groups in total thyroid size (ml, median ± standard deviation, SD) 7.86 ± 2.9 in HT vs. 6.35 ± 2.7 ml in controls, p = 0.003) and parenchymal vascularity which was increased in patients with HT (p < 0.001). Tissue strain index was higher in the HT group but without reaching statistical significance In logistic regression, thyroid size (odds ratio 1.20, 95% confidence interval: 1.02–1.41, p = 0.022) demonstrated significant prognostic value for the presence of HT. No differences were found between the two groups, regarding the peak systolic velocity (PSV), end-diastolic volume (EDV), pulsatility index (PI) and resistive index (RI) values of the thyroid arteries. In the ROC analysis (AUC 0.653, p = 0.002), a thyroid size >7.3 ml exhibited sensitivity of 61.43% and specificity of 72.6% for the diagnosis of HT. ConclusionPatients with HT exhibit larger thyroid size and increased intrathyroidal vascularity on ultrasound prior to the manifestation of hypothyroidism compared to the healthy population. Flow indices of the superior thyroid artery do not have prognostic value in the diagnosis of HT.

Evaluation of the ovarian reserve in women and adolescent girls with Hashimoto's thyroiditis by serum anti-Müllerian hormone level: A systematic review and meta-analysis

ObjectivesSeveral researchers performed case-control studies to explore the relationship between Hashimoto's thyroiditis(HT) and ovarian reserve using anti-Müllerian hormone(AMH) in adolescent girls and women. But the results among these studies are inconsistent and the relationship between HT and ovarian reserve is still controversial. The study aimed to conduct the meta analysis of case-control studies to confirm the relationship between HT and ovarian reserve using AMH. Methods6 electronic databases including PubMed, EMBASE, the Cochrane Library, China National Knowledge Internet(CNKI), SinoMed and Wanfang were searched from inception to December 2021. Endnote X7.0 software was applied to managing all the relevant records. Then data extraction and evaluation of methodological quality of included studies were conducted after two-step selection.Review manager 5.4 version software and Stata 12.0 version software were used to perform all statistical analyses. Results10 case-control studies involving 1202 individuals were included in the present study. The preliminary results revealed AMH values were significantly higher in adolescent girls with euthyroid HT compared with healthy adolescent girls(MD = 1.97; 95%CI, 1.43–2.51; P < 0.001; I2 = 0%). The pooled results in the subgroup of female adults with euthyroid HT showed AMH values were not significantly different between patients with HT and healthy women(MD = −0.21; 95%CI, −0.51-0.09; P = 0.18; I2 = 38%). The pooled results in the two subgroups of female adults with subclinical hypothyroidism and overt hypothyroidism both showed AMH values were significantly lower in the HT group compared with healthy women [(MD = −0.60; 95%CI, −0.86 to −0.34; P < 0.001; I2 = 0%), (MD = −1.34; 95%CI, −1.94 to −0.74; P < 0.001; I2 = 65%)]. ConclusionsOvarian reserve evaluated by serum AMH concentration is affected by female adults with subclinical hypothyroidism and overt hypothyroidism. The AMH level was significantly higher in euthyroid adolescent girls.

Association Between NEAT1 rs512715 Gene polymorphism and Hashimoto Thyroiditis and Graves’ Disease: A Case-Control Study

Background: Some evidence demonstrated the relationship between long non-coding RNA and autoimmune disease development. The current study assessed the possible association between the nuclear enriched abundant transcript 1 (NEAT1) gene rs512715 polymorphism and Hashimoto and Graves’ diseases. Methods: Two hundred forty-eight participants with autoimmune thyroid disease (133 Hashimoto thyroiditis (HT) patients and 115 Graves’ disease (GD) patients) and 135 age- and sex-matched controls were enrolled in the study. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used for genotyping NEAT1 rs512715 polymorphism. Results: Significant differences were observed in the frequency of the CC genotype of rs512715 in the HT group compared to the controls; the CC genotype may act as a risk factor for HT development. Also, the dominant and recessive genetic models showed the same results. Regarding the frequency of alleles, the C allele frequency was higher in the HT group than in the controls. In the GD group, there was no significant difference in the distribution of genotypes and the genetic models. Also, no significant difference was observed in the frequencies of alleles in Graves’ patients. Conclusions: Our findings indicated that NEAT1 rs512715polymorphism might play an influential role in Hashimoto’s disease development as the risk factor.

Altered profile of glycosylated proteins in serum samples obtained from patients with Hashimoto's thyroiditis following depletion of highly abundant proteins.

Hashimoto's thyroiditis (HT) is one of the most common autoimmune disorders; however, its underlying pathological mechanisms remain unclear. Although aberrant glycosylation has been implicated in the N-glycome of immunoglobulin G (IgG), changes in serum proteins have not been comprehensively characterized. This study aimed to investigate glycosylation profiles in serum samples depleted of highly abundant proteins from patients with HT and propose the potential functions of glycoproteins for further studies on the pathological mechanisms of HT. A lectin microarray containing 70 lectins was used to detect and analyze glycosylation of serum proteins using serum samples (N=27 HT; N=26 healthy control [HC]) depleted of abundant proteins. Significant differences in glycosylation status between HT patients and the HC group were verified using lectin blot analysis. A lectin-based pull-down assay combined with mass spectrometry was used to investigate potential glycoproteins combined with differentially present lectins, and an enzyme-linked immunosorbent assay (ELISA) was used to identify the expression of targeted glycoproteins in 131 patients with papillary thyroid carcinoma (PTC), 131 patients with benign thyroid nodules (BTN) patients, 130 patients with HT, and 128 HCs. Compared with the HC group, the majority of the lectin binding signals in HT group were weakened, while the Vicia villosa agglutinin (VVA) binding signal was increased. The difference in VVA binding signals verified by lectin blotting was consistent with the results of the lectin microarray. A total of 113 potential VVA-binding glycoproteins were identified by mass spectrometry and classified by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) analyses. Using ELISA, we confirmed that lactoferrin (LTF) and mannan-binding lectin-associated serine protease 1 (MASP-1) levels were elevated in the serum of patients with HT and PTC. Following depletion of abundant proteins, remaining serum proteins in HT patients exhibited lower glycosylation levels than those observed in HCs. An increased level of potential VVA-binding glycoproteins may play an important role in HT development. LTF and MASP-1 expression was significantly higher in the serum of HT and PTC patients, providing novel insight into HT and PTC.

De Ritis score as an inflammatory marker in Hashimoto's thyroiditis

AbstractBackgroundThe aim of the study was assessing the De Ritis score, an inflammatory marker, in Hashimoto's thyroiditis (HT) patients which is characterized with autoimmunity and chronic inflammation.MethodsBetween October 2021 and October 2022, the subjects in our outpatient clinics diagnosed with thyroiditis and healthy controls enrolled to the study. Age, gender, and laboratory parameters including C‐reactive protein (CRP), alanine (ALT), and aspartate (AST) transaminases, thyroid stimulating hormone (TSH), free T4 (FT4), were obtained and recorded for all participants, retrospectively. Division of AST by ALT was the formula to calculate the De Ritis score. Characteristics and laboratory data of the study and healthy controls were compared.ResultsMedian de Ritis ratio of the HT group (1.11 (0.56)%) was significantly higher than that of the control group (0.91 (0.41)%), (p &lt; .001). A positive and significant correlation between De Ritis score and CRP (r = 0.46, p &lt; .001) values. ROC analysis revealed the sensitivity and the specificity of CRP in predicting HT were higher than those of the De Ritis score. A De Ritis score higher than 0.9% has 67% sensitivity and 50% specificity in selecting patients with thyroiditis (AUC: 0.69, p &lt; .001, 95% CI: 0.63–0.76).ConclusionsWe think that elevated De Ritis score can be used as an adjunctive tool in the diagnosis of HT.

Histophysiology study of interleukin-4 in thyroid cancer patients

Introduction. Interleukins have promising prospects in the clinical treatment of cancer. Interleukin-4 (IL-4) is an an­ti-inflammatory cytokine with an immunosuppressive effect on antitumor activity by immune cells, but the mechanical action of IL-4 in thyroid cancer is unknown. Aim: to investigate the effect of IL-4 expression in thyroid cancer patients. Furthermore, to clarify the association between obesity and thyroid cancer. Material and methods. The present study was conducted on 115 subjects with thyroid nodules (36 with thyroid cancer and 79 with benign lesions) in Basrah, Iraq, from November 2019 to April 2022. To conduct a histophysiology study of IL-4. Results. There was a significant difference in serum IL-4 between the thyroid cancer and control subjects. A higher level of serum IL-4 was observed in the Hashimoto thyroiditis group. There was no significant difference in body mass index (BMI) between thyroid cancer and control subjects. The expression of tissue IL-4 in thyroid cancer patients was strong in 8 (22.22%) slides, moderate in 7 slides (19.44%), weak in 8 slides (22.22%), and negative in 13 slides (36.11%), while in the control group, it was strong in 7 (30.44%) slides, moderate in 8 slides (34.79%), weak in 5 slides (21.74%) and neg­ative in 3 slides (13.03%). Conclusions. These findings indicate that serum levels of IL-4 may help diagnose thyroid cancer and identify patients with active disease who deserve closer medical attention. Furthermore, the secretion of IL-4 was systematic and not localized in thyroid cancer tissues. Obesity was not associated with a prevalence of thyroid cancer.

Clinical Significance of Elevated Serum IL-36γ Levels in Patients with Early-Stage Hashimoto’s Thyroiditis

Background: Hypothyroidism was the diagnosed and treated as a result of health related quality of life issues. The aim of this study was that to evaluate the effect of IL-36 γ, Tg-Ab and TOP-Ab in the Hashimoto’s Thyroiditis (HT). Study design: This was a cross sectional study conducted at Rawal Institute of health sciences, Islamabad duration of study was six month, from April 2022 to September 2022. Methods: A total number of the patients was n=150 which divided into two group, control and HT group. To perform EISA for the estimation of free triiodothyronine 3, 4 (FT3, FT4), thyroid stimulating hormone (TSH), thyroid peroxidase antibody (TOP-Ab) and thyroid globulin antibody (Tg-Ab). The data was analyzed by SPSS 21. Results: The serum IL-36γ show correlation with the TOP-Ab and FT3 in HT. The IL-36γ was significantly higher in HT as compared to the control group; p&lt;0.001**. The IL-36γ show significant negative correlation with TOP-Ab (&lt;0.001**, r-0.126) and non- significant positive correlation with FT3 (0.321, r= + 0.28) in HT patients. The Tg-Ab was show non- significant correlation with IL-36 γ; (P&lt;=0. 928, r = 0.323). Conclusions: IL-36 γ is diagnostic marker and show negative correlation with TPO-Ab in the patient serum of HT. Il-36 γ had significantly high in the HT patients. IL-36 γ may involve to the progression of pathogenesis and enhance the inflammatory responses. In HT, Tg-Ab was significantly reduced than TPO-Ab but both contribute to the production of thyroid hormones. Keywords: Interleukin, Thyroxin, Thyroid stimulating hormone, Peroxidase.

Clinical and Pathological Characteristics of Patients With Papillary Thyroid Carcinoma Coexisting With Hashimoto's Thyroiditis: A Retrospective Cohort Study.

Papillary thyroid carcinoma (PTC) is the most common subtype of thyroid carcinoma, and Hashimoto's thyroiditis (HT) has been postulated to have a relationship with PTC. This study aims to assess clinical and pathological characteristics of patients with papillary thyroid carcinoma coexisting with Hashimoto's thyroiditis. A retrospective study was conducted in a cohort of patients with thyroid carcinoma at the Department of Surgery, Shanghai General Hospital from January 2017 to December 2018. Medical records of patients who had PTC with or without HT were reviewed and clinical and histopathological characteristics of these patients were analyzed. A total of 632 patients with thyroid carcinoma were identified. Among them, 614 (97.15%) had PTC and 120/614 (19.0%) harbored PTC together with HT. PTC was significantly associated with HT, as compared with other histological subtypes (P < .001). Patients with coexisting PTC and HT (PTC + HT group) were significantly younger than patients with PTC alone (PTC group) (P = .008). There were more women in the PTC + HT group than in the PTC group (88.3% vs. 73.1%, P < .001). TSH, TGAb, and TPOAb levels were significantly higher in the PTC + HT group than in the PTC group (P ≤ .001). In addition, tumor diameter was smaller in the PTC + HT group than in the PTC group (P = .034). The PTC + HT group showed a significant better recurrence-free survival than the PTC group. Furthermore, immunohistochemical analysis revealed that patients in the PTC + HT group had a higher positive rate and higher expression intensity of Ki67 than patients in the PTC group. Our study revealed that patients with coexisting PTC and HT were younger, had smaller tumor diameters, a better prognosis, and higher positive rates and expression intensity of Ki67, than did patients with PTC alone.

Oral Microbiota Signatures in the Pathogenesis of Euthyroid Hashimoto's Thyroiditis.

One of the most prevalent autoimmune illnesses in the world is Hashimoto's thyroiditis, whose pathogenesis is still unknown. The gut-thyroid axis is frequently examined, and although oral health affects thyroid functions, there are limited data on how oral microbiota is linked to Hashimoto's thyroiditis. The study aims to identify the oral microbiota from saliva samples taken from treated (with levothyroxine) and untreated female euthyroid Hashimoto's thyroiditis patients as well as healthy controls who were age- and sex-matched to compare the oral microbiota across the groups and to contribute preliminary data to the literature. This study was designed as a single-center cross-sectional observational study. Sixty (60) female patients with euthyroid Hashimoto's thyroiditis (HT) and eighteen (18) age- and gender-matched healthy controls were included in this study. Unstimulated saliva samples were collected. After DNA isolation, sequencing was performed by targeting the V3-V4 gene regions of the 16S rRNA on the MiSeq instrument. R scripts and SPSS were used for bioinformatic and statistical analysis. No significant differences were found in the diversity indices. However, Patescibacteria phylum showed a significantly higher abundance (3.59 vs. 1.12; p = 0.022) in the oral microbiota of HT patients compared to HC. In the oral microbiota, the euthyroid HT group had approximately 7, 9, and 10-fold higher levels of the Gemella, Enterococcus, and Bacillus genera levels than healthy controls, respectively. In conclusion, the results of our study demonstrated that Hashimoto's thyroiditis causes changes in the oral microbiota, whereas the medicine used to treat the condition had no such effects. Therefore, revealing the core oral microbiota and long-term follow-up of the HT process by conducting extensive and multicenter studies might provide some important data for understanding the pathogenesis of the disease.

Assessment of glucose and lipid metabolism in patients with polycystic ovary syndrome with and without Hashimoto's thyroiditis.

To investigate glucose and lipid metabolism in patients with polycystic ovary syndrome (PCOS) with and without Hashimoto's thyroiditis (HT). In the present study, 103 women were included as controls and a total of 213 patients (49 patients with HT and 164 patients without HT) diagnosed with PCOS. The oral glucose tolerance, insulin release, thyroid function, and lipid levels were measured. PCOS patients had significantly higher levels of fasting insulin (FINS), hemostasis of model assessment-insulin resistance, low-lipoprotein cholesterol, triglyceride, apolipoprotein B, apolipoprotein B/apolipoprotein A1, and homocysteine than the controls. PCOS Patients with HT + had higher FINS, 60FINS, 120FINS, and insulin resistance levels than those without Hashimoto's thyroiditis group. HT + group had higher total cholesterol, and thyroid-stimulating hormone levels, while free triiodothyronine, and free thyroxine levels were significantly lower. PCOS can lead to disorders of glucolipid metabolism, PCOS with Hashimoto's thyroiditis may further exacerbate disorders of glucose and lipid metabolism, and therefore thyroid function assessment in patients with PCOS needs to be emphasized.