[Acupoint application for Hashimoto's thyroiditis with liver-qi stagnation: a randomized controlled trial].

OBJECTIVE: To observe the clinical efficacy and safety of acupoint application for Hashimoto's thyroiditis (HT) with liver-qi stagnation. METHODS: One hundred and fifty patients of HT with liver-qi stagnation were randomly divided into an acupoint application group (75 cases, 11 cases were excluded, 5 cases dropped out) and a control group (75 cases, 12 cases excluded, 3 cases dropped out). Based on the health education combined with conventional western medicine treatment, the patients in the acupoint application group were treated with acupoint application, while the patients in the control group were treated with placebo acupoint application. Shenque (CV 8), bilateral Yongquan (KI 1), Yeshi, and ashi point were selected in both groups, with Yeshi treated once a week and the remaining acupoints treated every other day, for a total of 4 weeks. The serum levels of thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb), free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH), as well as the thickness of thyroid left lobe, right lobe, and isthmus, TCM symptom score, hospital anxiety and depression scale (HADS) score, and MOS 36-item short form health survey (SF-36) score were compared between the two groups before and after treatment. Adverse reactions in both groups were observed. RESULTS: Compared with before treatment, in the acupoint application group, the serum levels of TgAb and TPOAb were reduced after treatment (P<0.05), and the scores of role physical (RP), body pain (BP), vitality (VT), role emotional (RE), and mental health (MH) in SF-36 were increased after treatment (P<0.01, P<0.001). The thickness of the thyroid isthmus after treatment was smaller than that before treatment (P<0.05), and the TCM symptom scores and HADS anxiety (HADS-A) scores after treatment were lower than those before treatment (P<0.001, P<0.01) in both groups. In the control group, the scores of physical function (PF), RP, BP, VT, and RE in SF-36 after treatment were higher than those before treatment (P<0.05, P<0.01, P<0.001). There was no statistically significant difference in serum FT3, FT4, and TSH levels within the groups (P>0.05). There was no statistically significant difference in the above indexes between the two groups (P>0.05). The incidence of adverse reactions in the acupoint application group and the control group was 20.0% (15/75) and 10.7% (8/75) respectively, with skin allergy being the main adverse reaction. CONCLUSION: Acupoint application could reduce the serum levels of TgAb and TPOAb in patients of HT with liver-qi stagnation, alleviate thyroid enlargement, improve TCM symptoms and anxiety, and improve quality of life, with safe and reliable clinical efficacy.

Prevalence of Selected Polymorphisms of Il7R, CD226, CAPSL, and CLEC16A Genes in Children and Adolescents with Autoimmune Thyroid Diseases.

Hashimoto's thyroiditis (HT) and Graves' disease (GD) are common autoimmune endocrine disorders in children. Studies indicate that apart from environmental factors, genetic background significantly contributes to the development of these diseases. This study aimed to assess the prevalence of selected single-nucleotide polymorphisms (SNPs) of Il7R, CD226, CAPSL, and CLEC16A genes in children with autoimmune thyroid diseases. We analyzed SNPs at the locus rs3194051, rs6897932 of IL7R, rs763361 of CD226, rs1010601 of CAPSL, and rs725613 of CLEC16A gene in 56 HT patients, 124 GD patients, and 156 healthy children. We observed significant differences in alleles IL7R (rs6897932) between HT males and the control group (C > T, p = 0.028) and between all GD patients and healthy children (C > T, p = 0.035) as well as GD females and controls (C > T, p = 0.018). Moreover, the C/T genotype was less frequent in GD patients at rs6897932 locus and in HT males at rs1010601 locus. The presence of the T allele in the IL7R (rs6897932) locus appears to have a protective effect against HT in males and GD in all children. Similarly, the presence of the T allele in the CAPSL locus (rs1010601) seems to reduce the risk of HT development in all patients.

Interaction of BANCR in the relationship between Hashimoto's thyroiditis and papillary thyroid carcinoma expression patterns and possible molecular mechanisms.

BACKGROUND: Previous studies have established a connection between Hashimoto's thyroiditis (HT) and an increased risk of papillary thyroid carcinoma (PTC). However, the molecular mechanisms driving this association are not well understood. The long non-coding RNA (lncRNA) BRAF-activated non-coding RNA (BANCR) has been implicated in various cancers, suggesting a potential role in the HT-PTC linkage. METHODS: This study investigated the expression levels of BANCR in PTC and HT samples, compared to control tissues. We also examined the association between BANCR expression and clinicopathological features, including lymph node metastasis. Furthermore, we explored the molecular mechanisms of BANCR in PTC pathogenesis and its potential as a therapeutic target. RESULTS: BANCR expression was significantly lower in PTC samples than in controls, while it was moderately increased in HT samples. In PTC cases with concurrent HT, BANCR expression was markedly reduced compared to normal tissues. Our analysis revealed BANCR's role as an oncogene in PTC, influencing various cancer-related signaling pathways. Interestingly, no significant correlation was found between BANCR expression and lymph node metastasis. CONCLUSION: Our findings underscore the involvement of BANCR in the connection between HT and PTC. The distinct expression patterns of BANCR in PTC and HT, especially in PTC with concurrent HT, provide new insights into the molecular interplay between these conditions. This study opens avenues for the development of innovative diagnostic and therapeutic strategies targeting BANCR in PTC and HT.

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

Background: The role of quantitative contrast-enhanced ultrasound (CEUS) in the evaluation of thyroid nodules with Hashimoto's thyroiditis (HT) has received little attention. Methods: 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. Results: 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). Conclusions: CEUS quantitative analysis could be valuable in differentiating thyroid malignancies in patients with HT.

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

Background: Whether 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. Methods: The 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. Results: Seven 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. Conclusions: The 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.

Exome sequencing to explore the possibility of predicting genetic susceptibility to the joint occurrence of polycystic ovary syndrome and Hashimoto's thyroiditis.

A large body of evidence indicates that women with polycystic ovary syndrome (PCOS) have a higher risk of developing Hashimoto's thyroiditis (HT) than healthy individuals. Given the strong genetic impact on both diseases, common predisposing genetic factors are possibly involved but are not fully understood. Here, we performed whole-exome sequencing (WES) for 250 women with sporadic PCOS, HT, combined PCOS and HT (PCOS+HT), and healthy controls to explore the genetic background of the joint occurrence of PCOS and HT. Based on relevant comparative analyses, multivariate logistic regression prediction modeling, and the most informative feature selection using the Monte Carlo feature selection and interdependency discovery algorithm, 77 variants were selected for further validation by TaqMan genotyping in a group of 533 patients. In the allele frequency test, variants in RAB6A, GBP3, and FNDC7 genes were found to significantly (padjusted < 0.05) differentiated the PCOS+HT and PCOS groups, variant in HIF3A differentiated the PCOS+HT and HT groups, whereas variants in CDK20 and CCDC71 differentiated the PCOS+HT and both single disorder groups. TaqMan genotyping data were used to create final prediction models, which differentiated between PCOS+HT and PCOS or HT with a prediction accuracy of AUC = 0.78. Using a 70% cutoff of the prediction score improved the model parameters, increasing the AUC value to 0.87. In summary, we demonstrated the polygenic burden of both PCOS and HT, and many common and intersecting signaling pathways and biological processes whose disorders mutually predispose patients to the development of both diseases.

Diagnostic value of a dynamic artificial intelligence ultrasonic intelligent auxiliary diagnosis system for benign and malignant thyroid nodules in patients with Hashimoto thyroiditis.

Background: A dynamic artificial intelligence (AI) ultrasonic intelligent assistant diagnosis system (dynamic AI) is a joint application of AI technology and medical imaging, which can conduct real-time synchronous dynamic analysis of nodules from multiple sectional views with different angles. This study explored the diagnostic value of dynamic AI for benign and malignant thyroid nodules in patients with Hashimoto thyroiditis (HT) and its significance in guiding surgical treatment strategies. Methods: Data of 487 patients (154 with and 333 without HT) with 829 thyroid nodules who underwent surgery were collected. Differentiation of benign and malignant nodules was performed using dynamic AI, and diagnostic effects (specificity, sensitivity, negative predictive value, positive predictive value, accuracy, misdiagnosis rate and missed diagnosis rate) was assessed. Differences in diagnostic efficacy were compared among AI, preoperative ultrasound based on the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS), and fine needle aspiration cytology (FNAC) diagnoses. Results: The accuracy, specificity and sensitivity of dynamic AI reached 88.06%, 80.19%, and 90.68%, respectively; besides, there was consistency with postoperative pathological consequences (κ=0.690; P<0.001). The diagnostic efficacy of dynamic AI was equivalent between patients with and without HT, and there were no significant differences in sensitivity, specificity, accuracy, positive predictive value, negative predictive value, missed diagnosis rate, and misdiagnosis rate. In patients with HT, dynamic AI had significantly higher specificity and a lower misdiagnosis rate than did preoperative ultrasound based on the ACR TI-RADS (P<0.05). Compared with FNAC diagnosis, dynamic AI had a significantly higher sensitivity and a lower missed diagnosis rate (P<0.05). Conclusions: Dynamic AI possessed an elevated diagnostic worth of malignant and benign thyroid nodules in patients with HT, which can provide a new method and valuable information for the diagnosis and development of management strategy of patients.

HTC-Net: Hashimoto's thyroiditis ultrasound image classification model based on residual network reinforced by channel attention mechanism.

Convolutional neural network (CNN) is efficient in extracting and aggregating local features in the spatial dimension of the images. However, obtaining the inapparent texture information of the low-echo area in the ultrasound images is not easy, and it is especially challenging for the early lesion recognition in Hashimoto's thyroiditis (HT) ultrasound images. In this paper, a HT ultrasound image classification model HTC-Net based on residual network reinforced by channel attention mechanism is proposed. HTC-Net strengthens the features of the important channels by reinforced channel attention mechanism through which the high-level semantic information is enchanced and the low-level semantic information is suppressed. Residual network assists HTC-Net focus on the key local areas of the ultrasound images while pay attention to the global semantic information. Furthermore, in order to solve the problem of uneven distribution caused by large amount of difficult-to-classify samples in the data sets, a new feature loss function TanCELoss with weight factor dynamically adjusting is constructed. TanCELoss function can better assist HTC-Net to transform difficult-to-classify samples into easy-to-classify samples gradually, and improve the balancing distribution of the samples. The experiments are implemented based on data sets collected by the Endocrinology Department of four branches from Guangdong Provincial Hospital of Chinese Medicine. Both quantitative testing and visualization results show that HTC-Net obtains STOA performance for early lesions recognition in HT ultrasound images. HTC-Net has great application value especially under the condition of owning only small data samples.

Hashimoto's thyroiditis, vitiligo, anemia, pituitary hyperplasia, and lupus nephritis-A case report of autoimmune polyglandular syndrome type III C + D and literature review.

Objective: This study aims to summarize the clinical characteristics of one teenager with autoimmune polyglandular syndrome (APS) type III C + D to improve the understanding of APS III C + D and its effect of thyroid function. Methods: This article reported the clinical manifestations, laboratory examinations, treatment methods, and outcomes of an adolescent with anemia admitted to the Pediatrics Department of Tianjin Medical University General Hospital in July 2020 and reviewed the literature. Results: A girl, aged 13 years and 1 month, was admitted to the hospital due to anemia for more than 4 years and episodic abdominal pain for 1 week. Four years ago, the girl went to a local hospital for "vitiligo", and a routine blood test revealed anemia. The lowest hemoglobin (HGB) was 61 g/L, and the blood test revealed iron deficiency anemia. She had no menstrual cramps for 2 months. Urine routine showed protein 3+∼4+ and 258 red blood cells (RBCs)/high-power field. Urine protein was 3,380 mg/24 h. Free thyroxine was low, thyroid-stimulating hormone was >100 uIU/ml, thyroid peroxidase antibody was >1,000 IU/ml, and thyroglobulin antibody and thyrotropin receptor antibody were negative. Pituitary magnetic resonance imaging showed a mass in the sellar region with a uniform signal and a maximum height of about 15.8 mm. The result of the antinuclear antibody was 1:80 homogeneous type, and anti-dsDNA and anticardiolipin antibodies IgA and IgM were slightly higher. Thyroxine and iron were given for 1 month, menstruation resumed, and urine protein and RBC count decreased. After 5 months of treatment, free thyroid function, HGB, RBCs in urine, and pituitary returned to normal. Later, a renal biopsy showed changes in focal proliferative glomerulonephritis, and the girl was diagnosed with lupus glomerulonephritis type III. After 3 days of shock therapy with methylprednisolone, prednisone, mycophenolate mofetil, and other treatments were administrated for 1 year. At the time of writing, urine protein was 280 mg/24 h. Conclusion: Co-occurrence of Hashimoto's thyroiditis, vitiligo, anemia, pituitary hyperplasia, and lupus nephritis is rare. It is very important to pay attention to the screening of thyroid function.

HDAC6-specific inhibitor alleviates hashimoto's thyroiditis through inhibition of Th17 cell differentiation.

OBJECTIVE: Hashimoto's thyroiditis (HT) is one of the commonest autoimmune disorders. This study was performed to investigate the potential effect of histone deacetylase 6-specific inhibitor (HDAC6i) on Th17 cell differentiation in animal model and the underlying mechanism. METHODS: Experimental autoimmune thyroiditis (EAT) mouse model was established by subcutaneously immunization of porcine thyroglobulin (pTg) and adjuvant, and the HDACi Tubastatin A (TSA) or HDAC6i (ACY-1215) was intraperitoneally injected into mice in the following. The histological examination and immune analysis in EAT mice were carried out. Next, the CD4+ T cells were isolated from peripheral blood mononuclear cells (PBMCs) of EAT mice followed by Th17 cell differentiation assay. The associated factor levels, and the protein interaction between HDAC6 and PKM2 were examined. Subsequently, the effect of STAT3 activation on Th17 cell differentiation was explored. RESULTS: ACY-1215 or TSA treatment reduced lymphocytic infiltration and alleviated thyroid tissue injury in EAT mice. Correspondingly, either ACY-1215 or TSA treatment reduced the levels of anti-thyroglobulin (Tg), anti-thyroid peroxidase (TPO), IL-17A, and IFN-γ in the serum, decreased Th17 cell differentiation, but enhanced TGF-ß level and promoted Treg cell differentiation. In vitro, after induction of Th17 cell differentiation from CD4+ T cells, HDAC6 activity and Th17 cell differentiation were significantly decreased when treated with ACY-1215 or TSA. HDAC6 could interact with PKM2, and HDAC6 overexpression promoted the phosphorylation of STAT3 and PKM2 nuclear translocation. Furthermore, the STAT3 activator treatment reversed the effects of ACY-1215 or TSA treatment. CONCLUSION: HDAC6i suppresses Th17 cell differentiation and attenuates HT via PKM2/STAT3 axis.

CTLA-4 POLYMORPHISM ALONG WITH PROINFLAMMATORY CYTOKINES IN AUTOIMMUNE THYROIDITIS DISEASE.

OBJECTIVE: The aim: Evaluating serum concentration of IL-17 and IL-23 in autoimmune thyroiditis patient and control group along with the role of CTLA-4 rs3087243 gene polymorphism. PATIENTS AND METHODS: Materials and methods: A case control study was conducted in 30 HT (Hashimoto's thyroiditis), 30 GD (Graves' disease) who attended the consultant clinic for thyroiditis in AL-Diwaniyah teaching hospital and in 30 people as control group. Blood samples were processed for measurement of serum IL-17 and IL-23 using ELISA test. The second part used for DNA extraction then CTLA-4 polymorphism was detected by Allele - specific PCR assay. RESULTS: Results: The level of IL-17, and IL23 was highest in patients with Hashimoto's thyroiditis and Graves' disease, followed by control group and the difference was highly significant (p< 0.001; p< 0.001) respectively; however, the difference between patients Hashimoto's thyroiditis and patients with Graves' disease was not significant (p > 0.05; p > 0.05) respectively. There was no significant association between rs3087243 gene polymorphism and Hashimoto's thyroiditis (p> 0.05), no significant association between rs3087243 gene polymorphism and Graves' disease (p> 0.05). Moreover, there was no significant difference in rs3087243 genotypes frequencies between Hashimoto's thyroiditis and Graves' disease (p> 0.05). CONCLUSION: Conclusions: Serum IL-17 and IL-23 level have been linked with autoimmune thyroiditis disease, while CTLA-4 rs3087243 polymorphism seem to have no role in disease susceptibility in Iraqi population.

Frequency of hashimoto thyroiditis in papillary thyroid cancer patients and its impact on their Outcome.

BACKGROUND: Hashimoto thyroiditis (HT) is an autoimmune disorder of thyroid gland and is the most common cause of hypothyroidism. Its association with thyroid lymphoma is well established but with papillary thyroid cancer (PTC), the studies have shown inconsistent results. METHODS: It is a retrospective review of papillary thyroid cancer patients and 213 participants were included for final analysis. They were divided in two groups, based on presence or absence of Hashimoto thyroiditis. We noted their demographic details, histopathological diagnosis, presence of thyroid autoantibodies, TNM staging, outcome and duration of follow up. RESULTS: The frequency of Hashimoto thyroiditis in papillary thyroid cancer patients was found to be 34.27% (73). In Hashimoto thyroiditis and PTC patients, more patients were in T1 and T2 stage, i.e., 27.4% and 38.4% as compared to PTC alone group, who had more patients with T3 and T4 disease 44.3% and 5% respectively. Although lymph node metastasis was more common in PTC with Hashimoto thyroiditis 56.2%, but distant metastasis was observed more in isolated PTC group 14.3%. Cure was observed in 75.3% and 47.1% in PTC patients with and without Hashimoto thyroiditis respectively. While 22.9% patients having isolated PTC had persistent disease as compared to 6.8% when PTC was accompanied with Hashimoto thyroiditis. CONCLUSIONS: The papillary thyroid cancer patient who had concomitant Hashimoto thyroiditis, had a less aggressive disease in terms of T stage and distant metastasis and they had a better outcome in terms of higher cure rate and less persistent disease as compared to the papillary thyroid cancer without Hashimoto thyroiditis.

Changes of IgG N-Glycosylation in Thyroid Autoimmunity: The Modulatory Effect of Methimazole in Graves' Disease and the Association With the Severity of Inflammation in Hashimoto's Thyroiditis.

The N-glycome of immunoglobulin G (IgG), the most abundant glycoprotein in human blood serum, reflects pathological conditions of autoimmunity and is sensitive to medicines applied in disease therapy. Due to the high sensitivity of N-glycosylation, the IgG N-glycan profile may serve as an indicator of an ongoing inflammatory process. The IgG structure and its effector functions are strongly dependent on the composition of N-glycans attached to the Fc fragment, and the binding of antigens is regulated by Fab sugar moieties. Because of the crucial role of N-glycans in IgG function, remodeling of its N-oligosaccharides can induce pathological changes that ultimately contribute to the development of autoimmunity; restoration of their physiological structure is critical to the reduction of disease symptoms. Our recently published data have shown that the pathology of autoimmune thyroid diseases (AITDs), including Hashimoto's thyroiditis (HT) and Graves' disease (GD), is accompanied by alterations of the composition of IgG N-glycans. The present study is a more in-depth investigation of IgG glycosylation in both AITDs, designed to determine the relationship between the severity of thyroid inflammation and IgG N-glycan structures in HT, and to assess the impact of immunosuppressive therapy on the N-glycan profile in GD patients. The study material consisted of human serum samples collected from donors with elevated anti-thyroglobulin (Tg) and/or anti-thyroperoxidase (TPO) IgGs without symptoms of hypothyroidism (n=68), HT patients characterized by high autoantibody titers and advanced destruction of the thyroid gland (n=113), GD patients with up-regulated IgG against thyroid-stimulating hormone receptor (TSHR) before (n=62) and after (n=47) stabilization of TSH level as a result of methimazole therapy (study groups), and healthy donors (control group, n=90). IgG was isolated from blood serum using protein G affinity chromatography. N-glycans were released from IgG by PNGase F digestion and analyzed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) after 2-aminobenzamide (2-AB) labeling. UPLC-MS chromatograms were integrated into 25 peaks (GP) in the Waters UNIFI Scientific Information System, and N-glycans were assigned based on the glucose unit values and mass-to-charge ratios (m/z) of the detected ions. The Kruskal-Wallis non-parametric test was used to determine the statistical significance of the results (p<0.05). The obtained results suggest that modifications of IgG sialylation, galactosylation and core-fucosylation are associated with the severity of HT symptoms. Methimazole therapy implemented in GD patients affected the IgG N-glycan profile; as a result, the content of the sialylated and galactosylated oligosaccharides with core fucose differed after treatment. Our results suggest that N-glycosylation of IgG undergoes dynamic changes during the intensification of thyroiditis in HT, and that in GD autoimmunity it is affected significantly by immunosuppressive therapy.

Hashimoto's Thyroiditis: A "Double-Edged Sword" in Thyroid Carcinoma.

Background: The prevalence of thyroid carcinoma (TC) and Hashimoto's thyroiditis (HT) has been increasing dramatically over the past decades. We investigated the relationship between HT and TC. Methods: We followed the Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines for carrying out and reporting this meta-analysis. The literature from January 1, 2010 to December 31, 2020, regardless of region and publication type, was searched comprehensively in PubMed, Embase, Web of Science, and Cochrane Library databases. After careful selection and data extraction, the pooled odds ratio of various clinical characteristics in 39 studies were calculated. Publication bias was analyzed using funnel plots. Results: Meta-analysis of 39 original research articles showed HT to be a risk factor of TC (pooled odds ratio = 1.71; 95% confidence interval, 1.57-1.80; p < 0.00001) and papillary thyroid carcinoma (1.67, 1.51-1.85, <0.00001). Patients with papillary thyroid carcinoma (PTC) combined with HT were more likely to have multifocal carcinomas. The prevalence of an extrathyroidal extension, metastasis, BRAFV600E mutation, and recurrence was significantly lower in patients with PTC combined with HT. Conclusions: HT is a "double-edged sword" in TC patients. HT increases the risk of TC and PTC but is a protective factor against PTC progression.

Thyroid Langerhans cell histiocytosis concurrent with papillary thyroid carcinoma: A case report and literature review.

Langerhans cell histiocytosis (LCH) is a clonal neoplasm of myeloid dendritic cells, rarely involving the thyroid gland. Papillary thyroid carcinoma (PTC) is the most common histological subtype of thyroid cancer. We report a rare case of a 34-year-old Chinese woman who has LCH with PTC and cervical lymph node metastasis of LCH, with a review of the literature. The patient has thyroid nodules and cervical lymph node enlargement detected by neck ultrasound during physical examination. Fine needle aspiration cytology (FNAC) showed PTC with Hashimoto's thyroiditis and BRAF V600E mutation after thyroidectomy and lymph node dissection. Histopathological examination suggests that LCH was concurrent with classical PTC, accompanied by LCH cervical lymph node metastasis. No BRAF, HRAS, and TERT promoter mutations were detected in LCH metastatic lesions. The patient is in stable clinical condition currently.

Association Between Gut Microbiota and Autoimmune Thyroid Disease: A Systematic Review and Meta-Analysis.

Background: Autoimmune thyroid disease (AITD) is characterized by thyroid dysfunction and deficits in the autoimmune system. Growing attention has been paid toward the field of gut microbiota over the last few decades. Several recent studies have found that gut microbiota composition in patients with AITD has altered, but no studies have conducted systematic reviews on the association between gut microbiota and ATID. Methods: We searched PubMed, Web of Science, Embase, and Cochrane databases without language restrictions and conducted a systematic review and meta-analysis of eight studies, including 196 patients with AITD. Results: The meta-analysis showed that the alpha diversity and abundance of certain gut microbiota were changed in patients with AITD compared to the controls. Chao1,the index of the microflora richness, was increased in the Hashimoto's thyroiditis group compared to controls (SMD, 0.68, 95%CI: 0.16 to 1.20), while it was decreased in the Graves' disease group (SMD, -0.87, 95%CI: -1.46 to -0.28). In addition, we found that some beneficial bacteria like Bifidobacterium and Lactobacillus were decreased in the AITD group, and harmful microbiota like Bacteroides fragilis was significantly increased compared with the controls. Furthermore, the percentage of relevant abundance of other commensal bacteria such as Bacteroidetes, Bacteroides, and Lachnospiraceae was increased compared with the controls. Conclusions: This meta-analysis indicates an association between AITD and alteration of microbiota composition at the family, genus, and species levels. Systematic Review Registration: PROSPERO, identifier CRD42021251557.

Circulating Exosome Involves in the Pathogenesis of Autoimmune Thyroid Diseases Through Immunomodulatory Proteins.

Autoimmune thyroid diseases (AITDs) are chronic organ-specific autoimmune diseases, mainly including Graves' disease (GD) and Hashimoto's thyroiditis (HT). Exosomes, as extracellular vesicles, contain a variety of biologically active substances that play a role in information exchange, thereby affecting the occurrence and progression of diseases. However, it is unclear whether exosomes are involved in the pathogenesis of AITDs. In this study, the role of exosomes in AITDs was explored from a proteomics perspective. Plasma exosomes were isolated from 12 patients with GD, 10 patients with HT, and seven normal controls (NC). Protein profiles were detected using the data-independent acquisition (DIA) method and analyzed to investigate changes in plasma exosome proteins. In the setting of GD, 11 proteins were upregulated while 197 proteins were downregulated compared with healthy people. Among them, MAP1S (log2 FC = 4.669, p = 0.009) and VAMP8 (log2 FC = 3.216, p = 0.003) were the most significantly upregulated, and RSU1 (log2 FC = -6.797, p = 0.001), ACTB (log2 FC = -4.795, p < 0.001), and CXCL7 (log2 FC = -4.674, p < 0.001) were the most significantly downregulated. In the cases of HT, HGFL (log2 FC = 2.766, p = 0.001), FAK1 (log2 FC = 2.213, p < 0.001), and PTN12 (log2 FC = 1.624, p < 0.001) were significantly upregulated, while PSMF1 (log2 FC = -3.591, p < 0.001), PXL2B (log2 FC = -2.622, p = 0.001), and CYTM (log2 FC = -1.609, p < 0.001) were the most downregulated. These differential proteins were mainly enriched in the immune system and metabolic system, indicating that plasma exosomes may play an important role in systemic immune imbalance in AITDs.

Non-Conventional Clinical Uses of TSH Receptor Antibodies: The Case of Chronic Autoimmune Thyroiditis.

Anti TSH receptor antibodies (TSHrAb) are a family of antibodies with different activity, some of them stimulating thyroid function (TSAb), others with blocking properties (TBAb), it is a common finding that antibodies with different function might coexist in the same patient and can modulate the function of the thyroid. However, most of the labs routinely detect all antibodies binding to the TSH receptor (TRAb, i.e. TSH-receptor antibodies detected by binding assay without definition of functional property). Classical use of TSHr-Ab assay is in Graves' disease where they are tested for diagnostic and prognostic issues; however, they can be used in specific settings of chronic autoimmune thyroiditis (CAT) as well. Aim of the present paper is to highlight these conditions where detection of TSHr-Ab can be of clinical relevance. Prevalence of TSHrAb is different in in the 2 main form of CAT, i.e. classical Hashimoto's thyroiditis and in atrophic thyroiditis, where TBAb play a major role. Simultaneous presence of both TSAb and TBAb in the serum of the same patient might have clinical implication and cause the shift from hyperthyroidism to hypothyroidism and vice versa. Evaluation of TRAb is recommended in case of patients with Thyroid Associated Orbitopathy not associated with hyperthyroidism. At present, however, the most relevant recommendation for the use of TRAb assay is in patients with CAT secondary to a known agent; in particular, after treatment with alemtuzumab for multiple sclerosis. In conclusion, the routine use of anti-TSH receptor antibodies (either TRAb or TSAb/TBAb) assay cannot be suggested at the present for diagnosis/follow up of patients affected by CAT; there are, however, several conditions where their detection can be clinically relevant.

Analysis of Expression of Different Histone Deacetylases in Autoimmune Thyroid Disease.

CONTEXT: Histone deacetylases (HDACs) and histone acetyltransferases (HAT) have an important role in the regulation of gene transcription as well as in the development and function of CD4+Foxp3+ T regulatory (Treg) cells. Our group and others have reported that patients with autoimmune thyroid disease (AITD) show abnormalities in the levels and function of different Treg cell subsets. OBJECTIVE: We aimed to analyze the levels of expression of several HDACs and the Tip60 HAT in the thyroid gland and immune cells from patients with AITD. METHODS: The expression of HDAC1-11 and the Tip60 HAT, at RNA and protein levels, were determined in thyroid tissue from 20 patients with AITD and 10 healthy controls and these findings were correlated with clinical data. HDAC9 and Tip60 levels were also analyzed in thyroid cell cultures, stimulated or not with proinflammatory cytokines, as well as in different cell subsets from peripheral blood mononuclear cells. RESULTS: Altered expression of different HDACs was observed in thyroid tissue from AITD patients, including a significant increase in HDAC9, at RNA and protein levels. Likewise, HDAC9 expression was increased in peripheral blood mononuclear cells particularly in Treg cells in patients with AITD. In contrast, Tip60 expression was reduced in thyroid gland samples from patients with Hashimoto thyroiditis. CONCLUSION: Our results indicate that HDAC expression is dysregulated in thyroid gland and immune cells from patients with AITD, suggesting involvement in the pathogenesis of this condition.