Bioinformatics-Based Study to Investigate Potential Differentially Expressed Genes and miRNAs in Hashimoto’s Thyroiditis

BackgroundHashimoto's thyroiditis (HT), also known as chronic lymphocytic thyroiditis, is a common autoimmune disease, which mainly occurs in women. The early manifestation was hyperthyroidism, however, hypothyroidism may occur if HT was not controlled for a long time. Numerous studies have shown that multiple factors, including genetic, environmental, and autoimmune factors, were involved in the pathogenesis of the disease, but the exact mechanisms were not yet clear. The aim of this study was to identify differentially expressed genes (DEGs) by comprehensive analysis and to provide specific insights into HT. MethodsTwo gene expression profiles (GSE6339, GSE138198) about HT were downloaded from the Gene Expression Omnibus (GEO) database. The DEGs were assessed between the HT and normal groups using the GEO2R. The DEGs were then sent to the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The hub genes were discovered using Cytoscape and CytoHubba. Finally, NetworkAnalyst was utilized to create the hub genes' targeted microRNAs (miRNAs). ResultsA total of 62 DEGs were discovered, including 60 up-regulated and 2 down-regulated DEGs. The signaling pathways were mainly engaged in cytokine interaction and cytotoxicity, and the DEGs were mostly enriched in immunological and inflammatory responses. IL2RA, CXCL9, IL10RA, CCL3, CCL4, CCL2, STAT1, CD4, CSF1R, and ITGAX were chosen as hub genes based on the results of the protein-protein interaction (PPI) network and CytoHubba. Five miRNAs, including mir-24-3p, mir-223-3p, mir-155-5p, mir-34a-5p, mir-26b-5p, and mir-6499-3p, were suggested as likely important miRNAs in HT. ConclusionsThese hub genes, pathways and miRNAs contribute to a better understanding of the pathophysiology of HT and offer potential treatment options for HT.

Clinical Observation of Levothyroxine Sodium Combined with Selenium in the Treatment of Patients with Chronic Lymphocytic Thyroiditis and Hypothyroidism and the Effects on Thyroid Function, Mood, and Inflammatory Factors

The purpose of this study was to investigate the therapeutic effects of levothyroxine sodium combined with selenium treatment and single levothyroxine sodium treatment on patients with chronic lymphocytic thyroiditis and hypothyroidism and to analyze the effects of different treatment regimens on patients’ thyroid function, mood, and inflammatory factors, with the aim of providing a reference for clinical treatment. The subjects of the current study were 138 chronic lymphocytic thyroiditis (CLT) patients with hypothyroidism admitted to our hospital from May 2016 to September 2019 and were randomly divided into a control group taking levothyroxine sodium (LT4) treatment and a combined group of LT4 combined with selenium treatment, with 69 cases each. Patients in both groups were evaluated for efficacy after 3 months of treatment, and their thyroid function was observed by total triiodothyronine (TT3), total thyroxine (TT4), thyroid stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), and thyroid globulin antibody (TGAb), and their mood changes were observed by Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) scores. The levels of inflammatory factors such as interleukin-2 (IL-2), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α) were measured, and the occurrence of adverse drug reactions during the treatment period was observed and recorded in all patients. The results showed that the total effective rate of the combined group was significantly higher than that of the control group. The levels of TT3, TT4, TSH, TgAb, and TPOAb, SAS and SDS scores, and levels of inflammatory factors such as IL-2, IL-10, and TNF-α were significantly improved in both groups after treatment. Compared with the control group, TGAb, TPOAb, IL-2, TNF-α levels, and SAS and SDS scores decreased more and IL-10 levels increased more in the combined group, while the differences of other indexes were not statistically significant. This suggests that LT4 has certain efficacy in treating CLT with hypothyroidism, and the combined selenium treatment can improve the therapeutic effect of LT4 and can play a greater role in improving patients’ mood and immune and inflammatory responses.

An aggressive case of Warthin-like variant of papillary thyroid carcinoma (PTC)

Introduction/Objective Warthin-like variant of PTC is a rare subtype of PTC, characterized by papillary growth lined with oncocytic neoplastic cells and lymphocytic rich stroma in the stalks of the papillae. It is frequently associated with Hashimoto thyroiditis and has good prognosis due to lower risk of metastasis. An association with BRAF V600E mutation has been reported. Here we report an aggressive case of Warthin-like variant of PTC. Methods/Case Report A 33-year-old Hispanic female presented with a progressively expanding neck mass, difficulty swallowing, voice hoarseness, and neck pain. Ultrasound showed a 3.8 cm left thyroid nodule which on biopsy was positive for PTC. Laboratory tests were positive for anti-peroxidase and anti-thyroglobulin antibodies. A total thyroidectomy was performed. Grossly, the left thyroid lobe nodule was well-circumscribed, unencapsulated, and firm with solid homogenous gray-tan cut surface. Microscopically, the nodule consisted of large eosinophilic cells demonstrating characteristic PTC nuclear features, arranged in papillary structures with the cores packed with prominent lymphoplasmacytic infiltrate consistent with Warthin-like variant of PTC (figure). Separate sub-centimeter foci of PTC with similar features were identified in a background of chronic lymphocytic thyroiditis. Central and left neck dissection showed extensive lymph node metastasis which had features similar to the primary tumor but with less pronounced lymphoplasmacytic cores. The patient is currently 6-month post operation and is receiving iodine ablative therapy. Results (if a Case Study enter NA) NA Conclusion Molecular analysis of the tumor may aid in identifying molecular aberrations responsible for the aggressive nature in this case and potentially guide treatment.

Malignancy Rate of Bethesda Class III Thyroid Nodules Based on the Presence of Chronic Lymphocytic Thyroiditis in Surgical Patients

BackgroundHashimoto’s thyroiditis (HT), also known as chronic lymphocytic thyroiditis (CLT), may interfere with the accurate cytological diagnosis of thyroid nodules. Recently, HT has been considered a premalignant condition for thyroid cancer development. The diagnosis of atypia of undetermined significance/follicular lesions of undetermined significance (AUS/FLUS) thyroid nodules is challenging and evidence for the malignancy risk of AUS/FLUS thyroid nodules coexisting with CLT is scarce. Therefore, we assessed the malignancy risk of AUS/FLUS thyroid nodules according to the presence of background CLT.MethodsThis study included 357 surgically resected thyroid nodules with AUS/FLUS cytology. Cases with concomitant malignant nodules were excluded. CLT was defined based on the pathologic report after thyroid surgery.ResultsAmong 357 tumors, 130 tumors (36%) were confirmed to have coexisting CLT, and 170 tumors (48%) were determined to be malignant after thyroidectomy. Malignancy rates were similar in both groups (48% in each) regardless of background CLT (62/130 with CLT vs. 108/227 without CLT). In the group with CLT, thyroiditis was more frequent in the final pathology (12% with CLT vs. 1% without CLT, P = 0.003). In multivariate analysis, positive BRAFV600E mutation, highly suspicious sonographic features (K-TIRADS 5), and smaller thyroid nodules were significant factors for thyroid malignancies.ConclusionThe malignancy rate of thyroid nodules with AUS/FLUS cytology was comparable irrespective of the presence of underlying CLT.

Hashimoto’s thyroiditis and coexisting disorders in correlation with HLA status—an overview

SummaryHashimoto’s thyroiditis (HT), also known as chronic lymphocytic thyroiditis, is a frequent disorder of the thyroid gland caused by autoimmune-trigged lymphocytic infiltration and destruction of the thyroid gland. With the progressive destruction of the organ, the thyroid gland shrinks in size, thus commonly leading to hypothyroidism. Therapy of HT is mainly focused on managing the thyroid dysfunction by oral substitution of L‑thyroxine. However, patients with HT often complain about a broad spectrum of symptoms, with some of them hardly explained by HT itself. Several other disorders are known to be associated with HT. The etiology of HT seems to be multifactorial, including environmental influences such as iodine supply, infections, and stress as triggers of immune modulation. In addition, also a genetic background based on changes of the human leukocyte antigen (HLA) status seems to be evident. The paper will provide an overview of diseases related to HT, including their correlation to certain HLA patterns. This presentation should give a broader view on HT-related disorders and facilitate detailed examination and management of patients with HT.

Integrative Analyses of Genes Associated with Hashimoto’s Thyroiditis

Objective. Hashimoto’s thyroiditis, also known as chronic lymphocytic thyroiditis, is a common autoimmune thyroiditis, which mostly occurs in young and middle-aged women. It can be manifested as hyperthyroidism in the early stage; hypothyroidism may appear with the progression of the disease. Studies have shown that multiple factors such as heredity, environment, and autoimmunity are involved in the pathogenesis, but the specific mechanism is not clear. In our study, we tried to find key genes and potential molecular mechanisms of Hashimoto’s thyroiditis to provide new ideas for the therapeutic targets of Hashimoto’s thyroiditis. Method. GSE138198 and GSE54958 were downloaded from the GEO database, and two datasets were combined for analysis. The combined data were normalized to identify the differentially expressed genes (DEGs), and GO and KEGG enrichment analyses were performed. Protein-protein interaction (PPI) networks and hub genes between DEGs were identified. We also used the miRWalk database to identify regulatory miRNAs associated with expressions of DEGs. Result. We identified 182 DEGs (160 upregulated and 22 downregulated) between Hashimoto’s disease patients and the healthy control group. GO analysis showed that DEGs were mostly concentrated in detection of chemical stimulus involved in sensory perception, intermediate filament cytoskeleton, and olfactory receptor activity. KEGG pathway analysis showed that DEGs were mainly related to olfactory transduction. Some members of the KRTAP family and HTR5A, KNG1, DRD3, HTR1D, TAS2R16, INSL5, TAS2R42, and GRM7 are the most important hub genes in the PPI network. In addition, we recognized that OTUD4, LLPH, and ECHDC1 were the most important hub genes in the miRNA-target gene network. Conclusion. In this study, a series of bioinformatics analyses of DEGs were performed to identify the key genes and pathways associated with Hashimoto’s thyroiditis. These genes and pathways provide a more detailed understanding of the pathogenesis of Hashimoto’s disease and provide new ideas for the therapeutic targets of Hashimoto’s thyroiditis.

Hashimoto's Thyroiditis Autoimmune Disease: Background and Current Status, Update Overview of Biotechnological and Biomedical Fields and Future Trends for 3D Models

Hashimoto thyroiditis, also known as chronic autoimmune thyroiditis or chronic lymphocytic thyroiditis, is an autoimmune illness in which thyroid cells are damaged by immunological mechanisms involving cells and antibodies. Thyroid peroxidase and/or thyroglobulin autoantibodies in the serum are biochemical indicators of the condition, with females having a higher incidence than males and increasing with age. It's the leading cause of hypothyroidism in affluent countries. Inadequate dietary iodine intake, on the other hand, is the most common cause of hypothyroidism worldwide. The development of antithyroid antibodies that target the thyroid tissue, causing gradual fibrosis, is the pathogenesis of Hashimoto thyroiditis. The diagnosis can be difficult, and as a result, the problem is frequently not detected until late in the disease process. The most prevalent laboratory findings are raised TSH and low thyroxine (T4) levels, as well as enhanced antithyroid peroxidase (anti-TPO) antibodies. The pathogenesis, diagnosis, and management of Hashimoto thyroiditis are discussed in this article.

Spontaneous (Hashimoto-like) chronic lymphocytic thyroiditis in a rhesus macaque (<i>Macaca mulatta</i>)

A case of a female, 10-year-old rhesus macaque (Macaca mulatta) with spontaneous chronic lymphocytic thyroiditis is presented. At necropsy, the thyroid gland was slightly enlarged, with up to 2 mm large, round, confluent, beige foci on the surface of both lobes. Histopathologic features resembled human Hashimoto's thyroiditis: multifocally, the interstitium was infiltrated by lymphocytes and variably sized lymphoid follicles. In the pituitary gland, there were increased numbers of large, basophilic cells throughout the adenohypophysis. Using a human electrochemiluminescence immunoassay (ECLIA), no autoantibodies against thyroglobulin, thyroid peroxidase, or thyroid-stimulating hormone receptor were detected.