This study aims to explore the effects of Buzhong Yiqi Decoction(BYD) on the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon genes(STING) signaling pathway in the mouse model of autoimmune thyroiditis(AIT) and the mechanism of BYD in alleviating the immune injury. Forty-eight NOD.H-2~(h4) mice were assigned into normal, model, low-, medium-, and high-dose BYD, and selenium yeast tablets groups(n=8). Mice of 8 weeks old were treated with 0.05% sodium iodide solution for 8 weeks for the modeling of AIT and then administrated with corresponding drugs by gavage for 8 weeks before sampling. High performance liquid chromatography was employed to measure the astragaloside Ⅳ content in BYD. Hematoxylin-eosin staining was employed to observe the pathological changes in the mouse thyroid tissue. Enzyme-linked immunosorbent assay was employed to measure the serum levels of thyroid peroxidase antibody(TPO-Ab), thyroglobulin antibody(TgAb), and interferon-γ(IFN-γ). Flow cytometry was employed to detect the distribution of T cell subsets in the spleen. The immunohistochemical method was used to detect the expression of cGAS, STING, TANK-binding kinase 1(TBK1), and interferon regulatory factor 3(IRF3). Real-time PCR and Western blot were employed to determine the mRNA and protein levels, respectively, of markers related to the cGAS-STING signaling pathway in the thyroid tissue. The results showed that the content of astragaloside Ⅳ in BYD was(7.06±0.08) mg·mL~(-1). Compared with the normal group, the model group showed disrupted structures of thyroid follicular epithelial cells, massive infiltration of lymphocytes, and elevated levels of TgAb and TPO-Ab. Compared with the model group, the four treatment groups showed intact epithelial cells, reduced lymphocyte infiltration, and lowered levels of TgAb and TPO-Ab. Compared with the normal group, the model group showed increases in the proportions of Th1 and Th17 cells, a decrease in the proportion of Th2 cells, and an increase in the IFN-γ level. Compared with the model group, the four treatment groups presented decreased proportions of Th1 and Th17 cells and lowered levels of IFN-γ, and the medium-dose BYD group showed an increase in the proportion of Th2 cells. Compared with the normal group, the modeling up-regulated the mRNA levels of cGAS, STING, TBK1, and IRF3 and the protein levels of cGAS, p-STING, p-TBK1, and p-IRF3. Compared with the model group, the four treatment groups showed reduced levels of cGAS, STING, TBK1, and IRF3-positive products, down-regulated mRNA levels of cGAS, STING, and TBK1, and down-regulated protein levels of cGAS and p-STING. The high-dose BYD group showed down-regulations in the mRNA level of IRF3 and the protein levels of p-TBK1 and p-IRF3. The above results indicate that BYD can repair the imbalance of T cell subsets, alleviate immune injury, and reduce thyroid lymphocyte infiltration in AIT mice by inhibiting the cGAS-STING signaling pathway.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; Thyroiditis, Autoimmune/metabolism* ; Mice ; Membrane Proteins/metabolism* ; Mice, Inbred NOD ; Humans ; Female ; Nucleotidyltransferases/metabolism* ; Male ; Disease Models, Animal

BACKGROUND: This study aimed to analyze the association of low vitamin D status with thyroid autoimmunity and dysfunction in the Korean population according to sex and menopausal status in women. METHODS: This study was based on the data acquired from the 6th Korea National Health and Nutrition Examination Survey. We enrolled 4,356 subjects who had data of thyroid function, antithyroid peroxidase antibody (TPOAb), and serum 25-hydroxyvitamin D (25[OH]D) levels. We excluded subjects who were pregnant and who had a history of thyroid disease or thyroid cancer, and those with transient thyroid dysfunction who tested negative for TPOAb (TPOAb[−]). RESULTS: TPOAb positivity (TPOAb[+]) with thyroid dysfunction (subclinical and overt hypothyroidism) was more prevalent in the vitamin D deficient group than in the vitamin D insufficient and sufficient groups including premenopausal (P=0.046) and postmenopausal women (P=0.032), although no significant differences were observed in men. The mean serum 25(OH)D level was significantly lower in the TPOAb(+) with thyroid dysfunction group than in the TPOAb(+) with euthyroidism and TPOAb(−) groups of premenopausal women (P=0.001), although no significant differences were observed in men and postmenopausal women. Multivariate binary logistic regression analysis, adjusted for age, body mass index, and current smoking status, showed that vitamin D insufficiency and deficiency were significantly associated with TPOAb(+) with thyroid dysfunction in premenopausal women (P<0.001), although no significant associations were observed in men and postmenopausal women. CONCLUSION: Low vitamin D status was significantly associated with thyroid autoimmunity and dysfunction in the Korean population, especially in premenopausal women.
Autoimmunity ; Body Mass Index ; Female ; Humans ; Korea ; Logistic Models ; Male ; Nutrition Surveys ; Peroxidase ; Premenopause ; Smoke ; Smoking ; Thyroid Diseases ; Thyroid Gland ; Thyroid Neoplasms ; Thyroiditis, Autoimmune ; Vitamin D Deficiency ; Vitamin D ; Vitamins

PURPOSE: Type 1 diabetes mellitus (DM) is associated with autoimmune diseases such as thyroiditis. Therefore, we aimed to investigate the prevalence of autoimmune thyroiditis in patients with type 1 DM. METHODS: A total of 102 patients who were diagnosed and followed up (mean age, 8.1±4.0 years) in Ajou University Hospital were enrolled in this study. All the patients were evaluated for beta cell autoimmunity, including insulin autoantibody, glutamic acid decarboxylase antibodies (GADA), and islet cell antibody. Moreover, autoantibodies to thyroid peroxidase and thyroglobulin were assessed at initial diagnosis and annually thereafter. RESULTS: The mean patient age (49 men and 53 women) was 19.2±4.8 years. The prevalence of at least one thyroid antibody was 30.4%. Patients with thyroid anti­bodies had a significantly higher frequency of GADA at the time of the diagnosis. Autoimmune thyroiditis was more prevalent in the older age group. GADA was a significant risk factor for development of thyroid autoantibodies after diagnosis of type 1 DM (odds ratio, 4.45; 95% confidence interval, 1.399–14.153). CONCLUSIONS: In patients with type 1 DM, the prevalence of autoimmune thyroiditis was higher than in the general population. Moreover, GADA positivity at diagnosis was associated with thyroid autoimmunity.
Antibodies ; Autoantibodies ; Autoimmune Diseases ; Autoimmunity ; Diabetes Mellitus, Type 1 ; Diagnosis ; Follow-Up Studies* ; Glutamate Decarboxylase ; Humans ; Insulin ; Iodide Peroxidase ; Islets of Langerhans ; Male ; Prevalence* ; Risk Factors ; Thyroglobulin ; Thyroid Gland ; Thyroiditis ; Thyroiditis, Autoimmune*

Kikuchi-Fujimoto disease (KFD) is a benign and self-limited disease characterized by fever and lymphadenopathy. The etiology of KFD is unknown, but an autoimmune cause has been suggested. Hashimoto thyroiditis is the most common autoimmune thyroid disorder in children and is known to be associated with other autoimmune diseases. Only a few cases of Hashimoto thyroiditis associated with KFD have been documented. We report a case of a 16-year-old girl who was first diagnosed with KFD and developed Hashimoto thyroiditis 2 years and 6 months later during her follow-up period. Physicians of patients with KFD should consider the possibility of autoimmune diseases like Hashimoto’s thyroiditis.
Adolescent ; Autoimmune Diseases ; Child ; Female ; Fever ; Follow-Up Studies ; Hashimoto Disease* ; Histiocytic Necrotizing Lymphadenitis* ; Humans ; Lymphatic Diseases ; Thyroid Gland ; Thyroiditis

BACKGROUND: Warthin-like variant of papillary thyroid carcinoma (WLV-PTC) is a relatively rare variant of papillary thyroid carcinoma with favorable prognosis. However, preoperative diagnosis using fine-needle aspiration (FNA) specimens is challenging especially with lymphocytic thyroiditis characterized by Hürthle cells and lymphocytic background. To determine a helpful cytological differential point, we compared WLV-PTC FNA findings with conventional papillary thyroid carcinoma with lymphocytic thyroiditis (PTC-LT) and conventional papillary thyroid carcinoma without lymphocytic thyroiditis (PTC) regarding infiltrating inflammatory cells and their distribution. Preoperative diagnosis or potential for WLV-PTC will be helpful for surgeons to decide the scope of operation. METHODS: Of the 8,179 patients treated for papillary thyroid carcinoma between January 2007 and December 2012, 16 patients (0.2%) were pathologically confirmed as WLV-PTC and four cases were available for cytologic review. For comparison, we randomly selected six PTC-LT cases and five PTC cases during the same period. The number of intratumoral and background lymphocytes, histiocytes, neutrophils, and the presence of giant cells were evaluated and compared using conventional smear and ThinPrep preparations. RESULTS: WLV-PTC showed extensive lymphocytic smear with incorporation of thyroid follicular tumor cell clusters and frequent histiocytes. WLV-PTC was associated with higher intratumoral and background lymphocytes and histiocytes compared with PTC-LT or PTC. The difference was more distinct in liquid-based cytology. CONCLUSIONS: The lymphocytic smear pattern and the number of inflammatory cells of WLV-PTC are different from those of PTC-LT or PTC and will be helpful for the differential diagnosis of WLV-PTC in preoperative FNA.
Biopsy, Fine-Needle ; Diagnosis ; Diagnosis, Differential ; Giant Cells ; Hashimoto Disease ; Histiocytes ; Humans ; Lymphocytes ; Neutrophils ; Prognosis ; Surgeons ; Thyroid Gland ; Thyroid Neoplasms ; Thyroiditis, Autoimmune

Elephantiasis is a symptom characterized by the thickening of the skin and underlying tissues in the legs. Pretibial myxedema (PTM) is a non-frequent manifestation of autoimmune thyroiditis, particularly Graves' disease. Lesions of myxedema occur most commonly on the pretibial surfaces, also develop at sites of previous injury or scars and other areas. A 49-year-old male presented with severe elephantiasis on the both pretibial areas, dorsum of the feet, ankles and toes. Twenty years previously, he had received radioactive iodine treatment for thyrotoxicosis. Laboratory tests showed that the patient's thyroid function was normal, but the level of thyroid stimulating hormone (TSH) receptor antibodies was very high (>40 IU/L). The biopsy confirmed PTM. Interestingly, the connective tissue was stained with the TSH receptor antibodies in the deep dermis. Elephantiasic PTM is a severe form of the myxedema and there is few reported case. We report a rare case of PTM with appearance of severe elephantiasis.
Ankle ; Antibodies ; Biopsy ; Cicatrix ; Connective Tissue ; Dermis ; Elephantiasis* ; Foot ; Graves Disease ; Humans ; Iodine ; Leg ; Male ; Middle Aged ; Myxedema* ; Receptors, Thyrotropin ; Skin ; Thyroid Gland ; Thyroiditis, Autoimmune ; Thyrotoxicosis ; Thyrotropin ; Toes

BACKGROUND AND OBJECTIVES: This study aimed to identify a reliable preoperative predictive factor for the development of thyroid cancer in patients with atypia of undetermined significance (AUS) identified by fine needle aspiration biopsy (FNAB). SUBJECTS AND METHOD: This was a retrospective cohort study. Two hundred and ninety-nine patients diagnosed with AUS by preoperative FNAB who underwent curative thyroid surgery at our institution between September 2005 and February 2014 were analyzed. Clinical, radiological and molecular features were investigated as preoperative predictors for postoperative permanent malignant pathology. RESULTS: The final pathologic results revealed 36 benign tumors including nodular hyperplasia, follicular adenoma, adenomatous goiter, nontoxic goiter, and lymphocytic thyroiditis, as well as 263 malignant tumors including 1 follicular carcinoma and 1 invasive follicular carcinoma; the rest were papillary thyroid carcinomas. The malignancy rate was 87.9%. The following were identified as risk factors for malignancy by univariate analysis: BRAFV600E gene mutation, specific ultrasonographic findings including smaller nodule size, low echogenicity of the nodule, and irregular or spiculated margin (p < 0.05). Multivariate analysis revealed that only BRAFV600E mutation was a statistically significant risk factor for malignancy (p < 0.05). When BRAFV600E mutation was positive, 98.5% of enrolled patients developed malignant tumors. In addition, the diagnostic rate of malignancy in these cases was approximately 16-fold higher than BRAF-negative cases. CONCLUSION: Patients with AUS thyroid nodules should undergo BRAFV600E gene mutation analysis to improve diagnostic accuracy and if the mutation is confirmed, surgery is recommended due to the high risk of malignancy.
Adenoma ; Biopsy ; Biopsy, Fine-Needle* ; Cohort Studies ; Goiter ; Humans ; Hyperplasia ; Methods ; Multivariate Analysis ; Pathology ; Retrospective Studies ; Risk Factors ; Thyroid Gland* ; Thyroid Neoplasms ; Thyroid Nodule* ; Thyroiditis, Autoimmune

BACKGROUND AND OBJECTIVES: Sodium-iodine symporter (NIS) is a marker for the degree of differentiation in thyroid cancer. The genetic factors or microenvironment surrounding tumors can affect transcription of NIS. In this study, we investigated the NIS mRNA expression according to mutational status and coexistent lymphocytic thyroiditis in papillary thyroid cancer (PTC). MATERIALS AND METHODS: The RNA expression levels of NIS in the samples from database of The Caner Genome Atlas (TCGA; n=494) and our institute (n=125) were analyzed. RESULTS: The PTCs with the BRAFV600E mutation and the coexistence of BRAFV600E and TERT promoter mutations showed significantly lower expression of NIS (p < 0.001, respectively), and those with BRAF-like molecular subtype also had reduced expression of NIS (p < 0.001). NIS expression showed a positive correlation with thyroid differentiation score (r=0.593, p < 0.001) and negative correlations with expressions of genes involved in ERK signaling (r=−0.164, p < 0.001) and GLUT-1 gene (r=−0.204, p < 0.001). The PTCs with lymphocytic thyroiditis showed significantly higher NIS expression (p=0.013), regardless of mutational status. CONCLUSION: The NIS expression was reduced by the BRAFV600E mutation and MAPK/ERK pathway activation, but restored by the presence of lymphocytic thyroiditis.
Genome ; Ion Transport ; RNA ; RNA, Messenger ; Thyroid Gland ; Thyroid Neoplasms ; Thyroiditis, Autoimmune

Systemic lupus erythematosus (SLE) is a multiorgan-involved autoimmune disease, and it can overlap organ-specific autoimmune diseases such as autoimmune thyroid diseases, autoimmune hepatitis and inflammatory bowel disease. There may be some association between SLE and these autoimmune diseases, such as common immunological and genetic basis, but the pathogenic mechanism is still unclear. This review focuses on current knowledge regarding the prevalence and possible pathogenesis of SLE overlapping the above three autoimmune diseases.
Autoimmune Diseases ; complications ; epidemiology ; Hepatitis, Autoimmune ; complications ; epidemiology ; Humans ; Inflammatory Bowel Diseases ; complications ; epidemiology ; Lupus Erythematosus, Systemic ; complications ; epidemiology ; Prevalence ; Research ; trends ; Thyroiditis, Autoimmune ; complications ; epidemiology

Inflammatory pseudotumor is a benign disease entity, which is histologically composed of inflammatory cells and fibrotic stroma. It is mainly found in the respiratory tract, but it has also been reported in the liver, central nervous system, soft tissues, urological system, and gastrointestinal tract. It is extremely rare in the spleen and there have been no cases of splenic inflammatory pseudotumor associated with autoimmune thyroiditis in Korea. The pathogenesis or etiology is unknown, but hypotheses include infection, autoimmunity, and parenchymal necrosis with hemorrhage. Because inflammatory pseudotumor may mimic malignant tumors on radiologic findings, pathologic confirmation is necessary to distinguish it from lymphoproliferative disorders of the spleen and other malignant tumors. We report a case of inflammatory pseudotumor of the spleen associated with autoimmune thyroiditis in a patient who complained of periumbilical pain.
Autoimmunity ; Central Nervous System ; Gastrointestinal Tract ; Granuloma, Plasma Cell* ; Hemorrhage ; Humans ; Korea ; Liver ; Lymphoproliferative Disorders ; Necrosis ; Respiratory System ; Spleen* ; Thyroiditis, Autoimmune*