Expression of integrin α4ß1 and α4ß7 on B cells correlates with autoimmune responses in Graves' disease.

BACKGROUND: Integrins are upregulated on endothelial cells and T-lymphocytes in autoimmune thyroid disease (AITD), potentially contributing to immune response localization. The role of integrins on B-cells in AITD remains unclear. METHODS: Peripheral blood samples were collected from healthy controls (n = 56), patients with Graves' disease (GD) (n = 37) and Hashimoto's thyroiditis (HT) (n = 52). Ultrasound-guided fine-needle aspiration (FNA) of the thyroid was performed in patients with non-autoimmune thyroid disease (nAITD) (n = 19), GD (n = 11), and HT (n = 40). Integrins α4ß7, α4ß1, and αEß7 in B cells were measured by flow cytometry. Serum zonulin levels were quantified via ELISA. Associations of integrins on B cells with thyroid hormones, thyroid autoantibodies, AITD duration, and zonulin were analyzed. RESULTS: HT patients exhibited lower α4ß7 and higher α4ß1 expression on B cells compared to healthy controls and GD patients. While α4ß7 was predominant on circulating B cells, the dominant integrin expressed on intrathyroidal B cells varied with specific thyroid diseases. In GD patients, α4ß7 and α4ß1 expression on circulating B cells correlated positively and negatively with thyroid function and thyroid stimulating immunoglobulins (TSI) levels, respectively. Intrathyroidal α4ß1+ B cells positively correlated with TSH levels in HT patients. Additionally, serum zonulin was elevated in HT patients, and intrathyroidal α4ß7+ B cells and α4ß1+ B cells correlated negatively and positively with zonulin levels, respectively. Integrin αEß7 on B cells showed no significant association with AITD. CONCLUSION: Integrins expressed on B cells potentially play a role in the pathogenesis of AITD and might serve as immune biomarkers for the disease.

Thyrotoxic periodic paralysis complicated by carbimazole-associated myositis.

A male of East Asian background in his 30s presented to the emergency department with acute onset global muscle weakness, elevated creatine kinase, profound hypokalaemia and hyperthyroidism. A diagnosis of thyrotoxic periodic paralysis was made and the myopathy resolved promptly with potassium replacement. However, 3 months after being commenced on carbimazole for hyperthyroidism, the patient developed myalgias without weakness associated with an elevated creatine kinase. The myositis panel was negative, while a muscle biopsy showed nonspecific, mild myopathic changes with minimal lymphocytic inflammation. As a change in therapy from carbimazole to propylthiouracil resulted in prompt symptom improvement and normalisation of serum creatine kinase levels, a presumptive diagnosis of carbimazole-induced myositis was made. Genetic testing for hereditary skeletal muscle channelopathies did not identify any gene of interest.

Aquaporin4-IgG seropositivity significantly increases the risk of comorbid autoimmune diseases in NMOSD patients: population-based registry data.

BACKGROUND: The aim of our study was to estimate the frequency of autoimmune comorbidities, in NMOSD patients from the national Serbian NMOSD Registry. METHODS: Our study comprises 136 patients with NMOSD, diagnosed according to the NMOSD criteria 2015. At the time of the study, in the Registry were collected demographic and clinical data, including those related to the coexisting comorbidities and pathogenic autoantibodies. Not all patients were tested for all autoimmune antibodies. None of the seronegative aquaporin4-IgG (AQP4-IgG) NMOSD patients, included in the Registry, were positive for the myelin oligodendrocyte glycoprotein IgG. RESULTS: Among 136 NMOSD patients, 50 (36.8%) had at least one associated autoimmune disorder. AQP4-IgG was present in the sera from 106 patients (77.9%), the proportion of NMOSD patients with autoimmune comorbidities being significantly higher in the AQP4-IgG positive subgroup in comparison to the AQP4-IgG negative (p = 0.002). AQP4-IgG seropositive NMOSD patients had 5.2-fold higher risk of comorbid autoimmune diseases (OR = 5.2, 95% CI 1.4-18.5, p = 0.012). The most frequently reported diseases were autoimmune thyroid disease (15.4%), Sjogren's syndrome (11.0%), systemic lupus erythematosus (5.1%), myasthenia gravis (4.4%), and primary antiphospholipid antibody syndrome (2.9%). Antinuclear antibodies (ANAs) were frequently detected in the subgroup of NMOSD patients tested for this antibody (50/92; 54.3%). The higher frequency of ANAs and anti-extractable nuclear antigen autoantibodies, in the subgroups of AQP4-IgG-positive patients compared to the AQP4-IgG negative, tested for these antibodies, was statistically significant (p = 0.009, and p = 0.015, respectively). CONCLUSION: In conclusion, based on our results, in a defined cohort with European ethnical background, a wide spectrum of autoimmune diseases is frequently associated with AQP4-IgG seropositive NMOSD patients.

Causal relationship between insomnia and thyroid disease: A bidirectional Mendelian randomization study.

OBJECTIVE: Some correlations between thyroid disorders and insomnia have been found in previous studies; however, the causal relationship between them is unclear. The aim of this study was to investigate the causal relationship between insomnia and five thyroid disorders (hyperthyroidism, hypothyroidism, thyroiditis, thyroid nodules, and thyroid cancer). METHODS: We assessed the causal relationship between insomnia and thyroid disorders using inverse variance weighted, weighted median, and Mendelian randomization (MR)-Egger analyses in MR analyses and then used inverse MR analyses to assess the causal relationship between thyroid disorders and insomnia. RESULTS: MR analysis showed that insomnia did not increase the risk of hyperthyroidism, hypothyroidism, thyroiditis, thyroid nodules, and thyroid cancer. However, reverse MR analysis showed that thyroid cancer increased the risk of insomnia (OR = 1.01, 95%CI: 1.00-1.02, p = .01), and the other four thyroid disorders had no direct causal relationship with insomnia. Sensitivity analyses indicated that the results were robust and no pleiotropy or heterogeneity was detected. CONCLUSION: This study did not find evidence of a bidirectional causal relationship between genetically predicted insomnia and hyperthyroidism, hypothyroidism, thyroiditis, and thyroid nodules. However, we found that although insomnia does not increase the risk of thyroid cancer, thyroid cancer does increase the risk of insomnia.

Antithyroid Antibodies and Reproductive Parameters of Women with Hashimoto's Thyroiditis.

OBJECTIVES/INTRODUCTION: To evaluate the presence and concentration of antithyroid peroxidase (TPOAb) and antithyroglobulin (TGAb) antibodies at the onset of Hashimoto's Thyroiditis (HT) and their association with disease characteristics and reproductive parameters before and after diagnosis. METHODS: This is a cross-sectional study with 65 women with HT followed in an outpatient clinic. The data was collected by interviews and review of medical records. The variables were characteristics of the disease; TPOAb and TGAb measurements; pregnancies; live children; premature births; pregnancy losses and infertility. We used the chi-square or Fisher's exact tests, the Mann-Whitney test and the Spearman correlation. The significance level was set at 5%. RESULTS: The mean age at diagnosis was 38 (SD ± 11.1) years and the duration of the disease was 7.5 (SD ± 5.3) years; 46% of the women reported infertility periods. 59/65 (90.7%) women had TPOAb and 42 (64.6%) had TGAb antibodies. Comparison between the groups with and without TPOAb or TGAb showed no differences between all variables studied. We found positive correlations between TPOAb concentration and preterm births and thyroid volume; and TGAb concentration was positively correlated with age. CONCLUSION: The presence of autoantibodies did not influence reproductive parameters; TPOAb concentration was correlated with premature births and thyroid volume.

Type 1 diabetes, celiac disease, and autoimmune thyroiditis autoantibodies in population-based type 2 diabetes patients.

Aims: The study aims were to determine autoantibodies associated with type 1 diabetes (T1D), celiac disease (CD) and autoimmune thyroid disease (AITD) in individuals living with type 2 diabetes (T2D) compared to T1D and matched controls. Methods: Individuals with T1D and T2D were randomly identified in health-care registers. Blood was collected through home-capillary sampling and autoantibodies associated with either T1D against glutamic acid decarboxylase (GADA), insulin (IAA), insulinoma antigen-2 (IA-2A), and zinc transporter 8 (ZnT8A), CD against tissue transglutaminase (tTGA) or AITD against thyroid peroxidase (TPOA) were determined in an automated, multiplex Antibody Detection by Agglutination-PCR (ADAP) assay. Results: GADA were detected in 46 % (88/191) of T1D and increased to 6.2 % (23/372) in T2D compared to 2.6 % (7/259) of controls (p = 0.0367). tTGA was low (1.1-2.6 %) and not different in between the study cohorts, nonetheless, in T1D tTGA was associated to islet autoantibodies. TPOA was more frequent in T1D, 27.1 % (53/191), compared to either T2D, 14.8 % (55/372; p = 0.0002) or controls, 14.3 % (37/259) (p = 0.0004). Overall, TPOA was more frequent in GADA positive (34.8 %; 8/23) than negative (13.5 %; 47/349; p = 0.0053) T2D individuals. Conclusion: It's suggested that analyzing GADA and TPOA may refine the autoimmune landscape in individuals clinically classified as T2D.

Alemtuzumab-induced thyroid disease: A Danish cohort study.

OBJECTIVES: Alemtuzumab, a monoclonal antibody against the cluster of differentiation 52 (CD52) molecule, is used in the treatment of multiple sclerosis (MS). A side effect of the treatment is development of secondary autoimmune thyroid disease. The aim of this study was to evaluate the rate, type and course of thyroid disease in Danish patients with multiple sclerosis (MS) treated with alemtuzumab. METHODS: We conducted a retrospective cohort study of patients treated with a first series of alemtuzumab for MS in the Capital and Zealand regions of Denmark (population: 2.6 million) between 2014 and 2018 (n = 60 RESULTS: The duration of follow-up was median 81 months (range 54-105). Thyroid disease occurred in 47 % of the patients with the following distribution: Graves' disease (GD), thyrotropin (TSH) receptor antibody (TRAb) positive hyper- or hypothyroidism 35 %; multinodular goitre 5 %; silent thyroiditis, gestational transient thyrotoxicosis or unclassified hyperthyroidism 7 %. Of patients with GD, 14 % had an additional silent or postpartum thyroiditis before onset or after remission of GD. Unusual courses of GD occurred in 67 %, most commonly fluctuation from hypo- to hyperthyroidism or vice versa, mainly treated with antithyroid drug alone or thyroxine substitution regime but switched to concomitant block and replace treatment in 25 % and/or subsequent total thyroidectomy in less than 25 %. CONCLUSION: Data from the largest Danish MS center supports previous observations of unusual, long-lasting and unpredictable courses of alemtuzumab-induced GD. Thus, follow-up of these patients may require long lasting and more frequent biochemical measurements compared to other patients with GD. Also, concomitant block and replace treatment or definitive treatment, such as thyroidectomy, should be considered in a subgroup of patients.

Recent advances in liquid chromatography-tandem mass spectrometry for the detection of thyroid hormones and thyroglobulin in clinical samples: A review.

Thyroid hormones (THs), including triiodothyronine (T3), thyroxine (T4), and their metabolites, are essential for regulating development, growth, and energy metabolism. Thyroglobulin (Tg) produced by thyroid follicular cells acts as an essential substrate for TH synthesis. The combination of THs with Tg is a widely used serological laboratory test for thyroid function assessment. Early detection and timely intervention are significant for preventing and managing thyroid disease. In recent years, liquid chromatography-tandem mass spectrometry (LC-MS/MS) has emerged as a powerful tool for the precise detection of small molecular analytes and steroid hormones in clinical practice as a result of its high sensitivity and specificity. While LC-MS/MS has been increasingly used for detecting THs and Tg recently, its application in clinical practice is still in its early stages. Recent advances in the assessment of thyroid metabolism using LC-MS/MS in clinical samples published during 2004-2023 were reviewed, with a special focus on the use of this technique for quantifying molecules involved in thyroid diseases.

Mixed thyrotropin-secreting pituitary neuroendocrine tumor coexisting with Graves' disease: a case report.

Background: Thyrotropin (TSH)-secreting pituitary neuroendocrine tumors (PitNETs) are recognized as a rare disease. Mixed TSH PitNETs account for 20-25% of TSH PitNETs. This study aimed to report an extremely rare case of a mixed TSH PitNET coexisting with Graves' disease (GD) and also to review the literature. Case presentation: A 36-year-old male patient presented with elevated levels of free triiodothyronine (FT3), free thyroxine (FT4), and insulin-like growth factor 1 (IGF-1) but a non-suppressed thyroid-stimulating hormone (TSH) level. His anti-thyroglobulin antibody (TgAb), anti-thyroid peroxidase autoantibody (TPOAb), and thyrotropin receptor antibody (TRAb) tests were positive. Symptoms of palpitations, hyperhidrosis, heat intolerance, and irritability appeared 2 years before his admission. However, he showed neither any signs nor any symptoms of acromegaly. The contrast-enhanced pituitary magnetic resonance imaging (MRI) showed enlargement of the pituitary fossa, with an irregular abnormal signal mass. The patient underwent endoscopic pituitary tumor resection via a transsphenoidal approach. The postoperative pathology suggested a mixed pituitary adenoma. At 8 months after the surgery, the patient had a postoperative recurrence of hyperthyroidism, and methimazole (MMI) was then administered. The recurrence of the TSH PitNET was confirmed by the positron emission tomography-computed tomography (PET-CT), which was performed 11 months after the surgery, and treatment with lanreotide was initiated. Gradually, his levels of FT3, FT4, TSH, TPOAb, and TgAb became normal and the levels of TRAb and IGF-1 improved. Conclusion: When the circulating levels of both FT4 and FT3 were upregulated, non-suppressed TSH levels and positive thyroid antibodies were found. TSH PitNETs coexisting with GD should be carefully taken into account to avoid the potential risk of treatment-induced tumor progression.

Postoperative laryngeal granuloma in mediastinal goitre with gastro-oesophageal reflux disease.

Reported postoperative complications of mediastinal goitre include recurrent laryngeal nerve palsy, hypoparathyroidism and tracheomalacia. Voice and swallowing symptoms after thyroid surgery have been associated with laryngopharyngeal reflux, but it is unclear whether the retrograde flow of gastric contents into the oesophagus, larynx and pharynx worsens after thyroid surgery. We present the case of a man in his 40s with gastro-oesophageal reflux disease (GERD) who developed heartburn and laryngeal granuloma after total thyroidectomy for mediastinal goitre. Vonoprazan therapy effectively controlled these symptoms. Although the exact cause remains unclear, we suggest that changes in pressure dynamics after thyroidectomy may worsen the retrograde flow of gastric contents into the oesophagus, larynx and pharynx, contributing to GERD symptoms and laryngeal granuloma. This case highlights the need to consider the management of retrograde flow of gastric contents into the oesophagus, larynx and pharynx in the postoperative care of mediastinal goitre resections.

Efficacy of selenium supplementation for patients with Graves' hyperthyroidism during methimazole treatment: protocol for a systematic review and meta-analysis.

INTRODUCTION: The most common cause of hyperthyroidism, Graves' disease is a common organ-specific autoimmune disease. Selenium is an essential trace element of the human body that is mainly concentrated in the thyroid gland and is involved in the synthesis and metabolism of thyroid hormones. Most studies have shown that the level of selenium is closely related to the occurrence and development of thyroid diseases, and selenium supplementation can help improve thyroid function. This study aims to evaluate the efficacy of selenium supplementation for patients with Graves' hyperthyroidism during methimazole treatment. METHODS AND ANALYSIS: We will search the electronic databases including PubMed, Web of Science, Embase, the Cochrane Library, China National Knowledge Infrastructure, Wanfang Data and Chinese Biomedical Literature, and the time was deadline to December 2023. To evaluate the efficacy of methimazole combined with selenium supplementation in the treatment of Graves' hyperthyroidism, randomised controlled trials will be included. The Cochrane Collaboration's risk of bias tool will be used to assess the quality of all included studies, and the baseline data of all the studies are extracted by the authors. A random-effects model or a fixed-effects model is used to analyse the outcomes. The primary outcomes are the levels of selenium, triiodothyronine, free thyroxine and thyroid-stimulating hormone (TSH), whereas the secondary outcomes include TSH receptor antibody, thyroid peroxidase antibody and thyroglobulin antibody. ETHICS AND DISSEMINATION: Ethics approval is not required since no original data will be collected. The results of this study will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: CRD42023410999.

Autoimmune thyroid disease modifies the clinical expression of hand osteoarthritis in older people: a third National Health and nutrition examination survey study.

Introduction: The risk factors linked to hand osteoarthritis (OA) that contribute to its distinct symptoms and clinical presentation are not thoroughly understood. This study aimed to examine whether the autoimmune thyroid disease (AITD) autoantibodies, anti-thyroid peroxidase antibody (TPOAb), and anti-thyroglobulin antibody (TgAb), associate with hand OA and symptomatic hand OA in the Third National Health and Nutrition Examination Survey (NHANES III). Materials and methods: We included 2,429 persons from NHANES III ≥60 years of age. Data on hand OA or symptomatic hand OA were examined with respect to their associations with TPOAb and TgAb. Log-binomial and modified Poisson regression models were fit to examine the associations between the anti-thyroid autoantibodies and hand OA or symptomatic hand OA. Results: Higher levels of TPOAb were associated with a higher prevalence of symptomatic hand OA in the unadjusted (PR = 1.182, p = 0.024) and adjusted models after controlling for age, gender, and diabetes (PR = 1.174, p = 0.039). This association was no longer significant when positive TPOAb was considered a categorical variable with four levels and compared with negative TPOAb. TgAb showed a trend toward being positively associated with symptomatic hand OA (p < 0.10). When positive TgAb was considered a categorical variable with four levels and compared with negative TgAb, the highest quartile was associated with a higher prevalence of symptomatic hand OA than negative TgAb in the unadjusted (PR = 2.242, p = 0.008) and adjusted models (PR = 2.045, p = 0.038). There was no significant association between TPOAb or TgAb and hand OA. Conclusion: Higher levels of TPOAb may be associated with the presence of symptomatic hand OA in persons ≥60 years old. Persons ≥60 years old with the highest quartile levels of TgAb may be more likely to present with symptomatic hand OA.

Thyroid autoimmunity is associated with dietary fat consumption.

CONTEXT: Dietary factors are crucial in the onset and development of autoimmune thyroid disease (AITD), but the relationship between specific fatty acids and AITD remains unexplored. METHODS: We analyzed the US National Health and Nutrition Examination Survey (NHANES) 2007-2012 data on 3949 men and 3964 women aged 20 years and over with valid data on TPOAb, TgAb and details of fat intake, using multivariable regression models to examine the relationship of fat intake and specific fatty acid intake with thyroid autoimmunity. RESULTS: Of the 7913 participants, 7.5% had TgAb seropositivity and 11.9% had TPOAb seropositivity. The seropositivity of TgAb and TPOAb was more common in low-fat intake participants. In the overall population and men, fats were associated with thyroid autoimmunity before and after full adjustment for age, ethnicity, body mass index, smoking status and urine iodine concentration (total fat: OR=0.64, 95% CI 0.49 to 0.83; SFA: OR=0.65, 95% CI 0.51 to 0.84; MUFA: OR=0.65, 95% CI 0.50 to 0.85; PUFA: OR=0.76, 95% CI 0.57 to 0.995, after full adjustment in men). Some specific fatty acids followed a similar pattern. The association between fats and TgAb seropositivity was significant in the overall population and men. The association between fats and TPOAb seropositivity was only found in the overall population. CONCLUSION: We found a strong association between fat consumption and thyroid autoimmunity in the overall population and men from the nationally representative population-based survey. Fat and fatty acid consumption may be of benefit to individuals with thyroid autoimmunity.

Acute Pericarditis Triggered by Severe Thyrotoxicosis.

Acute pericarditis is a common inflammatory disorder with several causes including infection, malignancy, acute myocardial infarction, and autoimmune disease. Acute pericarditis can rarely present in the setting of thyrotoxicosis. A 65-year-old man with a past medical history of HIV, diastolic dysfunction, and prediabetes presented with positional chest pain, respiratory distress, and altered mentation. He was found down on the ground in a lethargic state and was last seen normally five days before the presentation. On presentation, he was tachycardic and tachypneic, requiring supplemental oxygenation with a nonrebreather mask to maintain adequate oxygen saturation. Initial electrocardiogram (EKG) demonstrated diffuse ST-elevations with early repolarization, consistent with acute pericarditis. Laboratory diagnostics revealed elevated lactic acid, leukocytosis, acute kidney injury, undetectable thyroid stimulating hormone, and elevations in T3, T4, C-reactive protein, brain natriuretic peptide, and creatinine kinase. Given the patient's complex presentation involving thyrotoxicosis and pericarditis, a multidisciplinary team discussion was pursued involving critical care, cardiology, and endocrinology. He was started on intravenous methylprednisolone (subsequently transitioned to prednisone), methimazole, and metoprolol. Colchicine was subsequently added for the management of pericarditis and prednisone was continued (given concomitant thyroid disease) with a plan for tapering them off, per cardiology and endocrinology recommendations. A transthoracic echocardiogram revealed a small pericardial effusion. Anticoagulation was not initiated given the potential risk of developing a hemorrhagic pericardial effusion. Thyroid ultrasound was nonsuggestive of Graves' disease. Thyrotoxicosis may present with a constellation of symptoms, including acute pericarditis. Timely recognition with EKG and echocardiography can aid in prompt management.

Refractory amiodarone-induced thyrotoxicosis requiring adjunctive cholestyramine treatment.

Amiodarone is an antiarrhythmic drug which may be associated with thyroid dysfunction. Type I amiodarone-induced thyrotoxicosis (AIT) is treated with thionamides and type II AIT is treated with glucocorticoids. Combined therapy is used in mixed or indeterminate forms. When medical treatment is unsuccessful, radioiodine ablation or thyroidectomy is considered. This report reviews a case of AIT refractory to conventional treatment. Despite high doses of methimazole and prednisone, the patient remained clinically and biochemically thyrotoxic. Cholestyramine, a bile salt sequestrant, was used as an off-label adjunctive treatment resulting in significant improvement and achievement of euthyroidism that may also be in part due to the expected natural timeline of recovery from AIT after several months. The patient subsequently trended towards hypothyroidism with symptomatic weight gain and cold intolerance for which he was initiated on levothyroxine.

Patterns, treatment outcome and associated factors of surgically treated thyroid disease at public hospitals in Eastern Ethiopia: a retrospective cross-sectional study.

BACKGROUND: Thyroid disease is a global health problem and the most common type of endocrine disorder next to diabetic mellitus, accounting for around 30-40% burden of the endocrine disorders. OBJECTIVE: The objective of the study was to assess patterns, treatment outcome and associated factors of surgically treated thyroid disease at Public Hospitals in Eastern Ethiopia. METHODS: The study was conducted among surgically treated patients for thyroid disorders using a retrospective cross-sectional study design by reviewing all patients' charts. A data abstraction sheet was used to collect relevant data, and the collected data was analyzed using SPSS version 26 software. Bi-variable and multivariable binary logistic regression was employed to assess the association between dependent and independent variables. RESULTS: The study was conducted on 200 patients' medical records who had complete information. Out of this, 84.5% were female and 66.5% of patients' age was between 20 and 40 years. Toxic goiter was the most common thyroid disease which accounted for 49.5%. Hemorrhage and Hypocalcemia were the most common complications after surgery. Anterior neck swelling of greater than 15 years [(AOR: 52.892 CI = 95% (6.087-459.5.68) (P-0.000)], Total/ near total thyroidectomy [(AOR: 20.139 CI = 95% (4.059-99.931) P-00.000] were significantly associated with complicated post-operative course, while female sex [(AOR: 0.124 CI = 95% (0.34-0.494) P- 0.003)] was associated with lower risk of developing post-operative complications. CONCLUSION: This study showed that 9.5% of operated patients with thyroid disease had complicated post-operative course. Long standing goiter and total/ near total thyroidectomy were significantly associated with complicated post-operative course.

The Effect of Vitamin D Supplementation on Thyroid Hormone Levels in Patients With Autoimmune Thyroid Disease: A Systematic Review.

Autoimmune thyroid diseases (AITDs) pose significant challenges in clinical practice, representing one of the most common endocrine abnormalities. Vitamin D deficiency has been linked as one of the contributing factors to the etiology of AITDs. This systematic review evaluates the effects of vitamin D supplementation on thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) levels in adults with AITDs. Using a PICO (population, intervention, comparison, and outcome) framework and adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, seven relevant studies were identified from an initial pool of 1,469 articles. The population comprised individuals with thyroid autoimmunity, as evidenced by at least one elevated positive thyroid autoimmune marker and intervention involved the supplementation of vitamin D, regardless of the dose or method of administration. All randomized clinical trials within the last 10 years, which fit the study criteria, were included. These studies showed varying results based on follow-up duration. Short-term studies (three months or less) demonstrated no significant changes in mean TSH, T3, or T4 levels compared to the control group with vitamin D supplementation. However, all of the long-term studies (greater than three months) indicated significant improvements compared to the control in mean TSH, T3, and T4 levels. Additionally, all long-term studies that compared TSH, T3, and T4 to baseline levels revealed significant changes by the trial's end. Despite these promising findings, the review highlights limitations, including small sample sizes, short study durations, and the need for further research to establish optimal dosing and treatment duration for vitamin D in AITD management. The overall findings suggest that vitamin D supplementation may play a part in thyroid hormone regulation in AITD, particularly with prolonged administration.

Effect of DNA methylation at the CTLA4 gene on the clinical status of autoimmune thyroid diseases.

The pathogenesis and manifestation of autoimmune thyroid diseases (AITDs), Graves' disease (GD), and Hashimoto's disease (HD) are associated with T cell activation. Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) plays a crucial role in the regulation of T cell activation. DNA methylation levels of eight CpG sites in the CTLA4 gene and expression levels of soluble CTLA-4 were examined. Methylation levels of +22 CpG and CT60 CpG-SNPs in patients with GD and HD with the CT60 GG genotype were lower than those in control subjects. Methylation levels of the-15 CpG sites were lower in patients with intractable GD than those in GD patients in remission. These results suggest that demethylation of +22 CpG and CT60 CpG-SNPs may be associated with susceptibility to GD and HD in subjects with the CTLA4 CT60 GG genotype, and that demethylation of -15 CpG may be associated with the intractability of GD.

Thyroid Diseases After Total Knee Replacement: A Multi-center, Propensity-score-matched Cohort Study.

BACKGROUND/AIM: Thyroid diseases are prevalent endocrine disorders that significantly affect overall health. Although the impact of pre-existing thyroid dysfunction on total knee replacement (TKR) outcomes has been studied, the potential for TKR to increase the risk of developing thyroid disorders remains unexplored. PATIENTS AND METHODS: We examined electronic medical records from a large U.S. research network in the TriNetX research network. The study focused on patients with osteoarthritis, comparing those who had total knee replacement surgery (TKR) between 2005 and 2018 to a non-TKR group who did not have the surgery. Propensity score matching was employed to control for critical confounders. The hazard ratios (HRs) for the risk of thyroid diseases in TKR patients versus non-TKR controls were assessed. RESULTS: Post-matching, the TKR cohort demonstrated a significantly higher risk of developing thyroid diseases compared to the non-TKR cohort (unadjusted HR=1.218, 95%CI=1.169-1.269). This elevated risk persisted after adjusting for confounders (adjusted HR=1.126, 95%CI=1.061-1.196). Stratification analysis indicated that female TKR patients and those aged ≥65 years were at higher risk of developing thyroid diseases than their respective control groups. CONCLUSION: This study suggests a potential link between TKR and an increased risk of thyroid diseases, particularly among older adults and females. Potential mechanisms include inflammatory processes, surgical stress, autoimmune responses, and pharmacological effects. Healthcare providers should be vigilant in monitoring and managing thyroid dysfunction in TKR patients. Further research is necessary to elucidate the underlying mechanisms and develop preventive strategies.

Meta-Analytical and Meta-Regression Evaluation of Subclinical Hyperthyroidism's Effect on Male Reproductive Health: Hormonal and Seminal Perspectives.

Subclinical hyperthyroidism (SCH) is a subtle thyroid dysfunction marked by decreased serum thyroid-stimulating hormone (TSH) levels while maintaining a normal thyroid hormone profile. Despite its mild nature, SCH can significantly impact various physiological functions, including male reproductive health. However, the effects of SCH on reproductive hormones and semen quality are less understood compared to overt thyroid disorders. This study employed extensive search methods across various databases from January 2000 to February 2024 to explore the relationship between SCH and Hormonal and Seminal Perspectives. Effect sizes, estimated using the standardized mean difference (SMD) and pooled with a Random-effect model, provided significant insights from 748 participants. Included studies adhered to the following criteria: Patients (male individuals with SCH), Intervention (assessment of reproductive hormones and semen quality), Comparison (SCH patients versus healthy controls), and Outcome (changes in reproductive factors). Significant alterations in reproductive hormones were observed in SCH patients, including reduced LH levels (SMD = - 0.20; p = 0.007), elevated FSH levels (SMD = 0.25; p = 0.002), and stable testosterone levels (SMD = - 0.05; p = 0.50). Regarding thyroid profile, SCH was associated with increased FT3 (SMD = 0.15; p < 0.001) and FT4 (SMD = 0.08; p = 0.002) levels, along with decreased TSH levels (SMD = - 2.00; p < 0.001). Adverse effects on semen quality were also observed. These findings underscore the need to incorporate thyroid health assessments in the evaluation of male infertility, recognizing the impact of minor thyroid hormone deviations on reproductive outcomes.