Vitamin D3 attenuates autoimmune thyroiditis by regulating Th17/Treg cell differentiation via YAP/JAK1/STAT1 axis.

BACKGROUND: Autoimmune thyroiditis (AITD) is an organ-specific autoimmune disease. Substantial evidence suggests that Vitamin D (VitD) deficiency is closely associated with an increased risk of AITD. However, the effects of VitD3 on immune cells, especially Th17/Treg cell subsets, and the underlying molecular mechanism in AITD have not yet been investigated. METHODS: An experimental autoimmune thyroiditis (EAT) mouse model was established with a high-iodine diet. After 8 weeks, thyroid injury was assessed using hematoxylin and eosin (H&E) staining. ELISA was employed to measure serum levels of thyroxine (T3 and T4), thyroid autoimmune antibodies (Tg-Ab and TPO-Ab), and inflammatory cytokines. Flow cytometry and multiplex fluorescence immunohistochemical (mIHC) assays were used to analyze Th17/Treg cell subsets. The CCK-8 and flow cytometry assays were used to determine cell viability and apoptosis. RESULTS: Administration of VitD3 reduced thyroid follicle destruction, decreased lymphocyte infiltration, and lowered T3, T4, Tg-Ab, and TPO-Ab serum levels in EAT mice. VitD3 treatment also reduced the frequency of Th17 cells while promoting the Treg cell subset both in the thyroid tissue and in the splenocytes cultured in vitro. Furthermore, VitD3 administration suppressed the production of inflammatory cytokines in EAT mice. VitD3 was also found to regulate Treg cells' differentiation, viability, and apoptosis. Mechanistically, we discovered that VitD3 treatment upregulated YAP expression and activated the JAK/STAT pathway. Rescue assays confirmed that depletion of YAP counteracted the effects of VitD3 on Treg cell differentiation and function. CONCLUSION: Vitamin D3 attenuates AITD by modulating Th17/Treg cell balance via regulating the YAP/JAK1/STAT1 axis.

γδT Cells Induce the Inflammatory Response of Human Fibroblast-Like Synoviocytes Directly or by Stimulating B Cells to Activate IL-17/STAT3 Signaling Pathway.

INTRODUCTION: Rheumatoid arthritis (RA) combined with hashimoto thyroiditis (HT) is an important cause of various fatal comorbidities of RA. There is no precise conclusion about the cause of this disease. METHODS: Peripheral blood and synovial tissue were collected from healthy participants, patients with RA, and patients with both RA and HT. Immunofluorescence staining and Pearson correlation analysis were used to detect the levels of γδTCR and the correlation between IL-17 and p-STAT3, respectively. ELISA, chemiluminescence assays, qRT-PCR and Western blot were performed to detect the levels of IgG, IgM, IFN-γ, IL-1ß, TNF-α, Tg-Ab, Tpo-Ab, IL-17, IL-2, p-SATA3, and STAT3, respectively. RESULTS: There was increased proportion of γδT cells, IL-17, and p-STAT3 levels in RA and HT patients. IL-17 was positively correlated with p-STAT3. γδT cells significantly promoted the expression of IgG, Tg-Ab, Tpo-Ab, and IL-17. When γδT and human fibroblast-like synoviocytes (FLSs) were co-cultured, the levels of IL-2, IFN-γ, IL-1ß, TNF-α, and IL-17 were increased, and the IL-17/STAT3 signaling pathway was activated. When IL-17-silenced γδT cells and STAT3-silenced FLSs were co-cultured, the levels of IL-1ß and TNF-α in FLSs were significantly decreased. Furthermore, when STAT3-silenced FLSs were added to the co-culture medium of B cells and γδT cells, the levels of IL-1ß and TNF-α were also decreased significantly. CONCLUSION: γδT cells induced RA directly or by stimulating B cells to activate STAT3 through IL-17.

The Effect of a Casein and Gluten-Free Diet on the Epigenetic Characteristics of FoxP3 in Patients With Hashimoto's Thyroiditis.

Background Hashimoto's thyroiditis (HT) is an autoimmune thyroid disease characterized by inflammation and dysfunction of the thyroid gland, resulting in hypothyroidism, it results in impaired thyroid hormone generation and mimics hypothyroidism. The disease involves complex interactions among genetic, environmental, and epigenetic factors, particularly affecting the regulation of T regulatory (Treg) cells, including CD4 + foxp3 + T cells. Treg cells, defined as CD4 + T cells, rely on the expression of the foxp3 transcription factor, which is crucial for their development and differentiation. Disruptions in this regulation can lead to immune dysregulation and potential proinflammatory responses. The study focuses on investigating the impact of dietary patterns on the epigenetic changes in the foxp3 gene, a key player in the development of HT. The primary aim was to evaluate how eliminating gluten and casein proteins from dietary regimens may influence the methylation levels of the foxp3 gene, considering the potential link between these dietary components and the triggering of autoimmune diseases. Methods An epigenetic analysis of the foxp3 gene in HT patients who were strictly following a dietary plan compared with the control group. For the epigenetic study, a methylation analysis experiment was conducted.  Results Our findings revealed a notable reduction in foxp3 gene methylation levels among HT patients who adhered to a diet excluding casein and gluten. The control maintained normal dietary guidelines and showed no significant alterations in methylation levels. Discussion The laboratory values showed a decrease in methylation levels of the foxp3 gene, with statistical significance indicated as *p<0.005, **p<0.001, ***p<0.0001, suggesting a potential enhancement in its expression which could have profound implications for immune system regulation. Disruptions in the foxp3 pathway are crucial in the development of autoimmune disorders, where altered activity hinders the regulation of T cell (Treg) development, ultimately contributing to conditions like HT disease. These findings imply that nutritional interventions, especially for individuals with HT, could potentially be a strategy for mitigating autoimmunity through epigenetic mechanisms.

Association between Benign Paroxysmal Positional Vertigo and Thyroid Diseases: Systematic Review and Meta-Analysis.

Introduction Benign paroxysmal positional vertigo (BPPV) is the peripheral vestibular dysfunction that most affects people worldwide, but its etiopathogenesis is still not fully understood. Considering the etiological diversity, some studies highlight the association between BPPV and thyroid diseases. Objective To investigate the association between thyroid diseases and BPPV. Data Synthesis Systematic review and meta-analysis of epidemiological studies searched in the PubMed, Web of Science, Embase, Cochrane Library, and Scopus databases. Studies that were fully available and investigated the association between BPPV and thyroid diseases were selected. The articles that composed the meta-analysis were analyzed using the dichotomous model, the Mantel-Haenszel statistical test, odds ratio (OR), and a 95% confidence interval (CI). Of the 67 articles retrieved from the databases, 7 met the eligibility criteria of the systematic review, and 4 had data necessary to perform the meta-analysis. Qualitative analysis revealed that the studies were conducted in the European and Asian continents. The predominant methodological design was the case-control type, and thyroid dysfunctions, hypothyroidism, and Hashimoto thyroiditis occurred more frequently. The meta-analysis showed no association between hypothyroidism and BPPV; however, there was a statistically significant relationship between Hashimoto thyroiditis and BPPV. Conclusion The meta-analysis results suggest a possible association between BPPV and Hashimoto thyroiditis. Nevertheless, we emphasize the need for further studies to elucidate the evidence obtained.

Subacute Thyroiditis Following COVID-19: A Case of Diagnostic Challenge in the Absence of Neck Pain.

This case report presents a 77-year-old woman who developed subacute thyroiditis following COVID-19. The patient exhibited atypical symptoms, including fever, fatigue, anorexia, significant weight loss, headaches, and palpitations, without the typical neck pain or tenderness associated with thyroiditis. One week later, a follow-up examination showed mild enlargement and tenderness of the thyroid. Laboratory tests indicated elevated thyroid hormone levels and suppressed thyroid-stimulating hormone. Ultrasonography revealed diffuse thyroid enlargement with poor blood flow, consistent with subacute thyroiditis. Despite the absence of typical neck pain, the diagnosis was supported by clinical, laboratory, and imaging findings. This case suggests the importance of considering subacute thyroiditis as a potential secondary condition following COVID-19, even in the absence of typical symptoms. Clinicians should consider that and perform thorough evaluations in patients with recent COVID-19 exposure and nonspecific symptoms.

The Coexistence of Occult (Latent) Thyroid Cancer and Multinodular Goiter After Total Thyroidectomy: A Retrospective Study.

Introduction Multinodular goiter (MNG) is a common thyroid disorder characterized by the presence of multiple nodules within the thyroid gland. While most cases of MNG are benign, there is a risk of malignancy, particularly in nodules with certain features. The coexistence of occult (latent) thyroid cancer within MNG presents diagnostic and management challenges, underscoring the need for comprehensive investigation and treatment strategies. Objective The objective of this retrospective study is to investigate the prevalence of occult thyroid carcinoma in non-toxic MNG following total thyroidectomy. Materials and methods The study population consisted of 412 patients who underwent total thyroidectomy between 2004 and 2022 at the Second Surgical Department of the 424 General Military Hospital of Education in Thessaloniki. Data collection included patients' demographic characteristics, surgical indications for thyroidectomy, and histopathological examination findings. Initial data were available for all 412 patients, while sufficient information was present for 319 individuals, with a subset of 271 undergoing total thyroidectomy due to non-toxic MNG. Out of the aforementioned group, 253 cases were histologically confirmed as MNG. Subsequently, a statistical analysis was conducted concerning age, gender, the association of MNG with malignancy, and other thyroid disorders. Results Out of the total 412 thyroidectomies performed, 271 patients remained for statistical analysis and study. Among them, 253 patients had histologically confirmed MNG. Among the histological findings, 38 cases (14.02%) were identified with occult carcinoma within MNG. The predominant histological type was papillary thyroid carcinoma (PTC), comprising 93.3% of cases. Additionally, 18 patients (6.64%) were diagnosed with MNG, Hashimoto's thyroiditis (HT), and malignancy concurrently. Conclusions The coexistence of occult thyroid carcinoma within MNG underscores the importance of vigilant evaluation and management strategies in patients undergoing total thyroidectomy. These findings emphasize the need for comprehensive preoperative assessment and postoperative surveillance to detect and address occult thyroid cancer, thereby optimizing patient care and outcomes.

The role of severity and duration of inflammation and hematological parameters on the outcome of subacute thyroiditis.

Background: The role of severity and duration of inflammatory findings on the development of persistent hypothyroidism and anemia has not been clarified in subacute thyroiditis (SAT). Methods: Demographic data and laboratory parameters of patients with SAT were analyzed retrospectively. Results: Permanent hypothyroidism was observed in 28.1% of patients. Baseline elevated erythrocyte sedimentation rate as defined >74.5 mm/h was found to be associated with permanent hypothyroidism, but the duration of inflammation was not different between the recovered and hypothyroid patients. Baseline hemoglobin values improved without specific therapy in 3.5 months. Conclusion: The initial severity but not the duration of inflammation increases the risk for the development of permanent thyroid dysfunction, and anemia improves with the resolution of inflammation.

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Fetal thymus size in pregnant women with Hashimoto disease.

PURPOSE: This study compared fetal thymic-thoracic ratios and fetal thymus transverse diameter measurements in pregnant women with Hashimoto's thyroiditis (HT) and non-immune hypothyroidism. METHODS: The study included a total of 141 pregnant women in three groups: 41 with HT, 50 with non-immune hypothyroidism, and 50 healthy individuals. Fetal thymus transverse diameter and thymic-thoracic ratio were compared between these groups. RESULTS: The mean fetal thymic-thoracic ratio was greater in pregnant women with HT than in the healthy controls (p = 0.031). Mean fetal thymus transverse diameter showed no statistically significant difference between the groups. CONCLUSIONS: Maternal HT was associated with an increased fetal thymic-thoracic ratio. More comprehensive studies are needed on this subject.

Effects of calorie-restricted diet on health state and intestinal flora in Hashimoto's thyroiditis patients: Study protocol for a randomized controlled trial.

BACKGROUND AND OBJECTIVES: Hashimoto's thyroiditis (HT) is an autoimmune disease, characterized by abnormal elevation in thyroid peroxidase antibody and/or thyroglobulin antibody. In recent decades, HT disease has become more and more widespread. Patients always report multiple symptoms, even though their thyroid hormone levels are kept in normal ranges. However, no treatment exists to effectively reduce the levels of thyroid antibodies. Our study aims to determine whether calorie-restricted diet is helpful in improving health of HT patients. METHODS AND STUDY DESIGN: This is a 3-month randomized controlled trial. HT patients will be randomized into a calorie-restricted (CR) group or a calorie-unrestricted control group. All the participants will be instructed to consume a diet that includes a combination of 45-55% calories from carbohydrates, 20-30% from fats, and 15-25% from proteins, according to current Chinese Dietary Guidelines. Participants in CR group need to limit their calories intake equal to their basal energy expenditure, which means that their daily caloric intake will be limited by about 20-30%. RESULTS: The study population is planned to be 66 HT patients aged 18 to 65 years. The primary outcome is change of thyroid antibody levels from baseline. Secondary outcomes include the changes of non-hypothyroid symptoms scores, thyroid function indexes, morphology of thyroid, T lymphocyte subpopulations, inflammatory biomarkers and lipids from baseline to 12 weeks. CONCLUSIONS: This trial will have implications for nutrition treatment policy in regard to thyroid antibodies control, immune dysfunction and related non-hypothyroid symptoms improvement among HT patients.

Late-onset Schmidt's Syndrome Presenting with Severe Hyponatremia: A Case Report.

BACKGROUND: Schmidt's syndrome (SS) is a subtype of polyglandular autoimmune syndrome type-2 combining autoimmune thyroiditis (AIT) and autoimmune Addison's disease (aAD). It occurs most frequently in young adult females, and aAD is the most common initial manifestation [1]. We present a rare case of SS with late-onset aAD and severe hyponatremia as the first sign. CASE REPORT: A 73-year-old woman presented to the emergency department (ED) with a 10-day history of vomiting, diarrhea, and altered mental status. Her past medical history was remarkable for AIT and hypokinetic cardiomyopathy. Moreover, she had recently undergone a 2-week course of corticosteroid therapy for vertiginous symptoms, reporting subjective well-being. In ED, she appeared confused and hypotensive. Blood tests revealed a sodium level of 99 mEq/l with normal potassium. Initial treatment with saline infusions were started, followed by ex juvantibus intravenous hydrocortisone awaiting hormone results, which proved consistent with primary adrenal insufficiency (ACTH 1314 pg/ml, cortisol 4.72 ug/dL). Replacement therapy with both hydrocortisone and fludrocortisone was then implemented, with substantial clinical improvement and normalization of sodium levels. However, the patient later developed right heart failure and hypokalemia, which were likely caused by overreplacement and resolved after adjusting the treatment regimen. The final diagnosis of aAD was confirmed by positive adrenal autoantibodies. CONCLUSIONS: aAD should be suspected in each case of severe hyponatremia [2], especially in patients with AIT independent of age. Furthermore, caution is needed in managing high-dose glucocorticoids along with fludrocortisone in elderly patients with cardiac disease to limit the risk of excessive mineralocorticoid activity and heart failure [3].

Difficulties in the Diagnostics and Treatment of Hashimoto's Encephalopathy-A Systematic and Critical Review.

Hashimoto's encephalopathy (HE) has been a poorly understood disease. It has been described in all age group, yet, there is no specific HE marker. Additionally, the treatment data in the available studies are frequently divergent and contradictory. Therefore, the aim of our systematic and critical review is to evaluate the diagnosis and treatment of HE in view of the latest findings. The databases browsed comprised PubMed, Scopus, and Google Scholar as well as Cochrane Library, and the search strategy included controlled vocabulary and keywords. A total of 2443 manuscripts were found, published since the beginning of HE research until February 2024. In order to determine validity of the data collected from studies, bias assessment was performed using RoB 2 tool. Ultimately, six studies were included in our study. HE should be considered in the differential diagnosis in patients with psychiatric and neurological symptoms. According to our findings, negative thyroid peroxidase antibodies (anti-TPOs) may represent a valuable parameter in ruling out HE. Nonetheless, this result cannot be used to confirm HE. Furthermore, the proposed anti NH2-terminal-α-enolase (anti-NAE) is non-specific for HE. The effectiveness of glucocorticoid therapy is 60.94%, although relapse occurs in 31.67% of patients following the treatment. Our review emphasizes the significance of conducting further large-scale research and the need to take into account the potential genetic factor.

Serum autotaxin level: a promising diagnostic biomarker in differentiating Graves' disease and thyroiditis.

BACKGROUND: Recent studies have suggested that serum autotaxin (ATX) may be a promising diagnostic biomarker in differentiating between Graves' disease (GD) and thyroiditis, as well as serving as a monitoring biomarker for GD. This study will evaluate the use of serum ATX as a diagnostic biomarker in these conditions. METHODS: In this prospective interventional study, blood samples were collected from the patients who met both inclusion and exclusion criteria, and serum ATX levels were measured by using the MyBioSource human Autotaxin ELISA kit. RESULTS: A total of 32 patients were enrolled, of which 18.8% were newly diagnosed with GD, 21.9% were thyroiditis, and 59.3% were on treatment for GD. Serum autotaxin antigen was significantly higher in GD patients than in thyroiditis (603.3217 ± 444.24 v/s 214.74 ± 55.91, P = <.005). Serum ATX measurement successfully discriminated GD patients from thyroiditis (AUC = 0.952, 95%CI: 0.00-1.00) with an optimal cutoff value of ≥257.20 ng/L (sensitivity = 100 and specificity = 81.71). Monitoring the efficacy of serum ATX was analyzed and showed a significant difference. CONCLUSION: The serum ATX was higher in subjects with GD as compared to thyroiditis, and ATX levels were found to be decreased during the treatment period. In conclusion, serum ATX can be used as a diagnostic and monitoring biomarker in GD.

Celiac Disease and Autoimmune Diseases in a Pediatric Population in Morocco: A Cross-Sectional Study.

INTRODUCTION: Celiac disease (CD) is defined as an autoimmune disease (AD) caused by gluten ingestion in genetically sensitive individuals. Several publications have demonstrated the increased risk of AD in patients with CD, both adults and children, which requires systematic research. Our study aimed to determine the prevalence of AD in 60 patients diagnosed with CD and to highlight risk factors that may contribute to the emergence of AD. MATERIALS AND METHODS: We collected medical data from all CD patients under 16 years of age who also had AD. Our study was conducted in the Gastroenterology-Hepatology and Pediatric Nutrition Unit of the Pediatrics Department of the Mohamed VI Hospital and University Center in Oujda, Morocco, during a seven-year period between January 2017 and January 2024. RESULTS: We studied 60 patients with CD in our study. Eight patients (13%) had an associated AD. Their average age was eight years, with extremes varying between two and 15 years. AD was diagnosed before CD in six cases (75%), in parallel with CD in one patient (12.5%), while in only one case, it was diagnosed after CD (12.5%). All our patients had a single AD associated with CD. These ADs were mainly type 1 diabetes in seven cases and autoimmune thyroiditis in only one case. All our patients followed a gluten-free diet in addition to specific treatment for associated AD. Nevertheless, despite regular medical follow-up and targeted dietary advice for the management of CD and associated AD, three patients encountered difficulties in following the recommended diet. CONCLUSION: Younger patients with CD have an increased risk of hypothyroidism and insulin-dependent diabetes. These data necessitate improved surveillance to discover these illnesses as early as possible in order to optimize management and reduce related consequences.

Sonographic characteristics and clinical characteristics combined with nomogram for predicting the aggressiveness of papillary thyroid carcinoma coexisted with Hashimoto's thyroiditis.

OBJECTIVE: The association between Papillary Thyroid Carcinoma (PTC) and coexistent Hashimoto's Thyroiditis (HT) was controversial. The purpose of this study was to evaluate the presence of HT exerts any influence on the aggressiveness of PTC, and to establish a nomogram for predicting the possibility of aggressiveness in PTC. METHODS: 373 consecutive PTC patients with/without coexistent HT from January 2017 to December 2020 were retrospective reviewed. Patients' clinicopathologic and sonographic characteristics were collected for univariate and multivariate analyses. A nomogram was established based on the risk factors for aggressiveness in PTC. RESULTS: Male (p = 0.001), tumor size >1.0 cm (p = 0.046) and lymph node metastasis (p = 0.018) were negatively associated with PTC coexisted with HT, while it was significantly positively associated with the frequence of multifocality (p = 0.010). Univariate and multivariate analyses suggested that age ≥55 years (p = 0.000), male (p = 0.027), HT (p = 0.017), tumor size >1.0 cm (p = 0.015), multifocality (p = 0.041), distance to capsular ≤0 cm (p = 0.050) and blood flow (Grade I: p = 0.044) were independent risk factors for predicting the aggressiveness in PTC. A nomogram according to these predictors was further developed and validated. The receiver operating characteristic curve (AUC = 0.734 and 0.809 for training and validation cohorts, respectively) and decision curve analyses indicated that the nomogram model was clinically useful. The calibration curve revealed that the nomogram exhibited an excellent consistency. CONCLUSIONS: In this study, the coexistent HT might play a protective role in preventing the proliferation of PTC. Dispensable aggressive treatment may be reduced in PTC by pre-operative identification of sonographic and clinical characteristics and incorporating with the predicted nomogram model.

Thyroid dysfunction in Hashimoto's thyroiditis: a pilot study on the putative role of miR-29a and TGFß1.

PURPOSE: Hashimoto's thyroiditis (HT) is one of the most common causes of thyroid dysfunction in iodine sufficient worldwide areas, but its molecular mechanisms are not completely understood. To this regard, this study aimed to assess serum levels of miRNA-29a (miR-29a) and transforming growth factor beta 1 (TGFß1) in HT patients with different patterns of thyroid function. METHODS: A total of 29 HT patients, with a median age of 52 years (21-68) were included. Of these, 13 had normal thyroid function (Eu-HT); 8 had non-treated hypothyroidism (Hypo-HT); 8 had hypothyroidism on replacement therapy with LT4 (subst-HT). All patients had serum miR-29a assayed through qRT-PCR and serum TGFß1 assayed by ELISA. RESULTS: Serum miR-29a levels were significantly down-regulated in patients with Hypo-HT compared to Eu-HT patients (P < 0.01) and subst-HT patients (P < 0.05). A significant negative correlation was detected between serum miR-29a levels and TSH levels (r = -0.60, P < 0.01). Serum TGFß1 levels were significantly higher in Hypo-HT than both Eu-HT (P < 0.01) and subst-HT patients (P < 0.05). A negative correlation was observed between serum miR-29a and TGFß1 (r = -0.75, P < 0.01). CONCLUSIONS: In conclusion, Hypo-HT patients had lower levels of serum miR-29a and higher levels of TGFß1 in comparison with Eu-HT patients. Worthy of note, subst-HT patients showed restored serum miR-29a levels compared with Hypo-HT group, associated with lower serum TGFß1. These novel findings may suggest a possible impact of replacement therapy with levothyroxine on serum miR-29a levels in HT.

Evaluation of ovarian reserve in women with thyroid autoimmunity.

OBJECTIVE: To compare the ovarian reserve of women of reproductive age with and without thyroid autoimmunity (TAI). METHODS: We performed a retrospective analysis of medical records from an assisted reproduction clinic from February 2017 to December 2021. Women aged between18 and 47 years with data on antithyroperoxidase and antithyroglobulin (anti-Tg) antibodies and assessment of ovarian reserve by anti-müllerian hormone (AMH) and antral follicle count (AFC) were included. Among the 188 participants included, 63 were diagnosed with TAI, and 125 had both antibodies negative. AMH and AFC were compared between groups. Subanalysis based on age, types of antibodies, and thyroid function markers were performed. In addition, bivariate analysis and regression models were used. RESULTS: Overall, there was no difference in the median levels of AMH or AFC between the two groups. However, in the subgroup analysis by age, we observed a trend towards lower median levels of AMH in women over 39 years with TAI (0.9 ng/mL vs. 1.5 ng/mL, p=0.08). In a subanalysis according to antibodies, we found a significantly lower median AFC in the group with anti-Tg than in the group without this antibody (8.0 follicles vs. 11.5 follicles, p=0.036). We also found a significantly higher prevalence of anti-Tg in patients with low ovarian reserve compared to those with normal reserve (60.7% vs. 39.3%, p=0.038). CONCLUSIONS: The ovarian reserve of women with TAI appears to be insidiously compromised over the years, with a decreased ovarian reserve in women with anti-Tg.

Chronic Suppurative Thyroid Abscess: A Case Report.

Thyroid abscess is a rare occurrence and is characterized by an accumulation of pus within the thyroid gland. It most commonly forms as a sequela of acute suppurative thyroiditis, and it presents as a painful swelling of the anterior neck with fever. Patients may also develop referred ear pain and compressive symptoms such as difficulty breathing and swallowing as the abscess enlarges. On examination, the swelling is often associated with erythema, local rise of temperature, and tenderness. Laboratory investigations may reveal leukocytosis, elevated acute phase reactants, and an abnormal thyroid function test. Despite advancements in diagnostic modalities and treatment approaches, literature on thyroid abscesses remains limited. We present a unique case of a long-standing thyroid abscess resulting from chronic suppuration which did not exhibit any of the mentioned expected findings seen in other cases. This patient was euthyroid, and laboratory investigations showed no significant abnormality. It was successfully treated with total thyroidectomy and appropriate antibiotics.

Combined use of tyrosine kinase inhibitors with PD-(L)1 blockade increased the risk of thyroid dysfunction in PD-(L)1 blockade: a prospective study.

BACKGROUND: Anti-programmed cell death-1 (ligand-1) antibody [PD-(L)1-Ab] can cause destructive thyroiditis and/or hypothyroidism. In addition, tyrosine kinase inhibitors (TKIs) frequently induce hypothyroidism. The aim of this prospective study is to examine the incidence and clinical characteristics of thyroid dysfunction induced by combination therapy of a PD-(L)1-Ab and TKI [PD-(L)1-Ab/TKI]. METHODS: A total of 757 patients treated with PD-(L)1-Ab or PD-(L)1-Ab/TKI were evaluated for anti-thyroid antibodies (ATAs) at baseline and for thyroid function for 48 weeks after treatment initiation and then observed until the last visit. RESULTS: The cumulative incidences of destructive thyroiditis [4/23 (17.4%) vs. 45/734 (6.1%) patients, p < 0.001], isolated hypothyroidism [10/23 (43.5%) vs. 29/734 (4.0%) patients, p < 0.001], and all thyroid dysfunction [14/23 (60.9%) vs. 74/734 (10.1%) patients, p < 0.001] were significantly higher in the PD-(L)1-Ab/TKI group than PD-(L)1-Ab group, respectively. All patients positive for ATAs at baseline developed thyroid dysfunction after PD-(L)1-Ab/TKI treatment, a significantly higher incidence than that in those negative for ATAs at baseline [4/4 (100%) vs. 10/19 (52.6%) patients, p = 0.026]. CONCLUSIONS: The addition of TKIs increased the risk of thyroid dysfunction induced by PD-(L)1-Ab, with the risk being higher in patients positive for baseline ATAs.

Genetically predicted associations between circulating cytokines and autoimmune diseases: a bidirectional two-sample Mendelian randomization.

Objectives: Previous studies have indicated a correlation between cytokines and autoimmune diseases. yet the causality remains uncertain. Through Mendelian Randomization (MR) analysis, we aimed to investigate the causal relationships between genetically predicted levels of 91 cytokines and three autoimmune diseases: Multiple Sclerosis (MS), Systemic Lupus Erythematosus (SLE), and Hashimoto's Thyroiditis (HT). Methods: A bidirectional two-sample MR approach was utilized to assess the causal relationships between cytokines and MS, SLE, and HT. The datasets included 47,429 MS cases and 68,374 controls, 5,201 SLE cases and 9,066 controls, and 16,191 HT cases with 210,612 controls. Data on 91 cytokines comprised 14,824 participants. Causal analyses primarily employed inverse variance weighted, weighted median, and MR-Egger methods, with sensitivity analyses including heterogeneity and pleiotropy assessment. Results: Genetically predicted levels of IL-18 (OR = 0.706; 95% C.I. 0.538-0.925), ADA (OR = 0.808; 95% C.I. 0.673-0.970), and SCF (OR = 0.898; 95% C.I. 0.816-0.987) were associated with a decreased risk of MS. IL-4 (OR = 1.384; 95% C.I. 1.081-1.771), IL-7 (OR = 1.401; 95% C.I. 1.010-1.943), IL-10RA (OR = 1.266; 95% C.I. 1.004-1.596), CXCL5 (OR = 1.170; 95% C.I. 1.021-1.341), NTN (OR = 1.225; 95% C.I. 1.004-1.496), FGF23 (OR = 0.644; 95% C.I. 0.460-0.902), and MCP4 (OR = 0.665; 95% C.I. 0.476-0.929) were associated with SLE risk. CDCP1 (OR = 1.127; 95% C.I. 1.008-1.261), IL-33 (OR = 0.852; 95% C.I. 0.727-0.999), and TRAIL (OR = 0.884; 95% C.I. 0.799-0.979) were associated with HT risk. Bidirectional MR results suggest the involvement of CCL19, IL-13, SLAM, ARTN, Eotaxin, IL-22RA1, ADA, and MMP10 in the downstream development of these diseases. Conclusions: Our findings support causal relationships between certain cytokines and the risks of MS, SLE, and HT, identifying potential biomarkers for diagnosis and prevention. Additionally, several cytokines previously unexplored in these autoimmune disease contexts were discovered, laying new groundwork for the study of disease mechanisms and therapeutic potentials.

Assessment of Vitamin Concentrations in Patients with Hashimoto's Thyroiditis and Their Relationships with Thyroid Function, Biochemical Status, and Anthropometric Parameters-A Preliminary Study.

Hashimoto's thyroiditis (HT) is the leading cause of hypothyroidism, affecting mainly the female population. Many patients with HT have metabolic disorders and nutritional deficiencies. The aim of this study was to evaluate vitamin D, A, E, B2, and B6 concentrations, thyroid function, metabolic profile, and anthropometric parameters of patients with Hashimoto's thyroiditis. In 81 female patients with HT (study group), vitamin A and B2 concentrations were significantly lower than in 34 healthy women (control group). No differences were noted in vitamin D, E, and B6 concentrations between groups. Moreover, HT patients had similar anthropometric parameters, lipid profiles, and glucose and insulin concentrations compared to controls. This study showed some relationships between vitamin concentrations and anthropometric or biochemical profiles in HT patients. Among others, in the HT group, the concentration of vitamin D was positively correlated with the level of HDL and negatively correlated with BMI, total fat mass, and insulin level, which influence cardiovascular risk. The results indicate that patients with HT should be routinely tested for vitamin concentrations to prevent nutritional deficiencies. Further studies are also needed on the role of vitamins in the development and progression of HT and the presence of metabolic complications in this population.