Autoimmune Thyroid Disease Research Articles

The relationship between the gut microbiota and thyroid disorders.

Disorders of the thyroid gland are common, more prevalent in women than in men, and range from inflammatory to neoplastic lesions. Autoimmune thyroid diseases (AITD) affect 2-5% of the population, while thyroid cancer is the most frequent endocrine malignancy. Treatment for AITD is still restricted to management rather than prevention or cure. Progress has been made in identifying genetic variants that predispose to AITD and thyroid cancer, but the increasing prevalence of all thyroid disorders indicates that factors other than genes are involved. The gut microbiota, which begins to develop before birth, is highly sensitive to diet and the environment, providing a potential mechanism for non-communicable diseases to become communicable. Its functions extend beyond maintenance of gut integrity: the gut microbiota regulates the immune system, contributes to thyroid hormone metabolism and can generate or catabolize carcinogens, all of which are relevant to AITD and thyroid cancer. Observational and interventional studies in animal models support a role for the gut microbiota in AITD, which has been confirmed in some reports from human cohorts, although considerable geographic variation is apparent. Reports of a role for the microbiota in thyroid cancer are more limited, but evidence supports a relationship between gut dysbiosis and thyroid cancer.

Technetium-99m (99mTc) and Iodine-123 (123I) in comparison with thyroid ultrasonography in the differential diagnosis of Saudi patients with Graves, disease

In thyroid autoimmune diseases diagnosis, there is growing evidence that thyroid ultrasonography (US) can be helpful without accurate differentiation of Graves’ disease GD from other autoimmune diseases. Using histopathological findings as a reference standard, this study aimed to determine the diagnostic accuracy of 99mTc and 123I in comparison with US for the differential diagnosis of GD in Saudi patients. Results demonstrated that thyroid scintigraphy using 99mTc (sensitivity = 96.1 vs. 23.5%) and 123I (sensitivity = 83.33 vs. 25%) was superior to US in detection of GD in Saudi patients. All GD patients detected by US were detected by both 99mTc and 123I scans, whereas, 99mTc (37/39) and 123I (14/18) scans detected many patients from GD cases that US failed to detect. This superiority was found regardless of gender and age particularly in 99mTc scan. In the same group of patients, both 99mTc and 123I scans had the same sensitivity (80%) (P = 0.151). In conclusion, the conducting study findings proved that 99mTc and 123I thyroid scintigraphy scans could be used in the differential diagnosis of GD from other thyroiditis disorders with a higher degree of diagnostic accuracy.

Thyroid disfunction and obesity - what comes first? A complex relationship between hypothyroidism and weight gain

Introduction: Obesity and mild thyroid failure are common diseases, and the complex relationship between thyroid function and excess weight gain is still being researched. This study analyzes and summarizes the current scientific reports on the intricate correlation between thyroid dysfunction and obesity. Material and methods: We have gathered the available materials and scientific reports, analyzing and summarizing them in a single study. Aim of study: We aimed to summarize the studies conducted so far by analyzing the available scientific reports to answer the question of ‘what comes first’ and to understand the correlation between thyroid dysfunction and excessive weight gain. Discussion: Thyroid dysfunction in the form of hypothyroidism is associated with metabolic abnormalities, which may play a crucial role in the development of metabolic syndrome. On the other hand, excess level of leptin associated with excess adipose tissue is a potential cause of disruptions in the hypothalamic-pituitary-thyroid axis, manifested as elevated TSH levels. Therefore, it is worth considering certain aspects regarding the inclusion of hormone replacement therapy in obese patients presenting laboratory features of subclinical hypothyroidism. Conclusion. Obesity-induced thyroid dysfunction is typically reversible with weight loss and hormone replacement therapy should be considered for obese patients with subclinical hypothyroidism only if thyroid antibodies are present to confirm an autoimmune thyroid disorder.

Analysis of T follicular and T peripheral helper lymphocytes in autoimmune thyroid disease

PurposePeripheral helper T (Tph) cells have an important role in the induction of humoral immune responses and autoantibody production. Accordingly, it is feasible that this lymphocyte subset has a relevant role in the pathogenesis of autoimmune thyroid diseases (AITD). In this study we aim to analyze the levels and function of Tph cells in blood samples from patients with AITD.MethodsWe performed an observational study with cases and controls. Blood samples were obtained from nineteen patients with Hashimoto’s thyroiditis (HT), twenty-four with Graves’ disease (GD), and fifteen healthy controls. In addition, the levels of follicular T helper (Tfh) cells and Tph cells, the release of interleukin-21 (IL-21) by these lymphocytes and the number of plasmablasts were analyzed by multi-parametric flow cytometry analyses.ResultsIncreased percentages of Tfh and Tph lymphocytes were detected in patients with HT and GD. Furthermore, an enhanced synthesis of the cytokine IL-21 by these cells was observed. Accordingly, we detected significant higher percentages of plasmablasts in patients with GD, and these values tended to be also higher in HT patients. Moreover, significant positive associations were observed between the levels of Tfh or Tph and the number of plasmablast or anti-TSHR Ab titers in patients with AITD.ConclusionOur data suggest that Tph lymphocytes may have a relevant role in the pathogenesis of AITD.

Increased frequency of microalbuminuria in patients with type 3 autoimmune polyglandular syndrome (APS) compared to isolated autoimmune type 1 diabetes mellitus: A real-life study

Aim of the studyThe primary aim of the study was to evaluate the differences in metabolic control and chronic microvascular complications in patients with type 3 autoimmune polyglandular syndrome (APS3), compared to type 1 diabetes mellitus (T1DM) alone. Secondary aims were to evaluate the age of autoimmune thyroid disease (AIT) onset and the effects of levothyroxine treatment on metabolic control in patients with APS3. Material and methodsWe retrospectively reviewed 276 patients with T1DM alone and 214 patients with APS3 and evaluated clinical and metabolic parameters and microvascular complications. ResultsPatients with T1DM showed a longer duration of diabetes (p = 0.001) and lower age of diabetes onset (p = 0.020) compared to patients with APS3. Female gender (p = 0.001) and microalbuminuria (p = 0.006) were significantly more frequent in patients with APS3 compared to T1DM. In addition, patients with APS3 showed higher AIT onset frequency in the 16–30 quartile age-range. Furthermore, APS3 patients treated with levothyroxine showed significantly better HbA1c values than non-treated patients (p = 0.001). ConclusionsWe found that patients with APS3 showed positive microalbuminuria, earlier than T1DM. Patients with APS3 showed higher frequency of AIT age of onset in the 16–30 age-range and those treated with levothyroxine had better metabolic control, than untreated ones.

STAT3 single-nucleotide variants in autoimmune thyroid disease in the Pakhtun population of Khyber Pakhtunkhwa, Pakistan

The current study was conducted to assess the relationship between the STAT3 gene variants rs744166 and rs2293152 and autoimmune thyroid disorder in the Pakhtun population of the province, of Khyber Pakhtunkhwa, Pakistan. Blood was collected from 100 healthy individuals and 400 thyroid-disordered patients. Of these, one hundred were diagnosed with Hashimoto's thyroiditis (HT), while 32 were confirmed as Grave's disease (GD) patients. T3, T4, and TSH serum levels were checked to diagnose thyroid disorders. The blood was analyzed for anti-thyroid peroxidase antibodies (Anti-TPOAb) (AESKULISA- ATPO - elisa kit), (Germany), and thyroid stimulating hormone receptor antibodies (TSHRAb), TSHR Ab elisa kit (Diametra Italy), respectively. PCR was used to amplify the targeted STAT3 gene polymorphisms from rs744166 (301 bp) and rs2293152 (365 bp) sequences and then digested by specific restriction endonucleases (AluI) and AciI respectively. The disease displayed a female predominance. The genotype TC and CC of rs744166 showed a significant relationship with Grave's disease (p = 0.002, OR = 0.28, 95 % CI = 0.11–0.77) in patients. The C allele contributed significantly to the disease in GD patients. The SNP rs2293152 significantly differed between GD patients and control (p = 0.032, OR = 0.29, 95 % CI = 0.09–0.86). Similarly, the G and C alleles showed a significant (p = 0.02) difference between GD patients and the control. No significant association was found for both SNPs in Hashimoto's thyroiditis disease. It is concluded that the STAT3 gene (rs744166 and rs2293152) was found to have a potential role in autoimmunity in GD patients. Still, it needs further studies with larger sample sizes in the Pakhtun population to understand this relationship.

Comorbidity of Autoimmune Thyroid Disease and Psychiatric Disorders: A Cross-Sectional Study from Southern India.

Background and Aims: Autoimmune thyroid disease (AITD) is associated with a multitude ofneuropsychiatric symptoms and cognitive impairment. Though it is one of the most common cause ofacquired primary hypothyroidism, there is a dearth of literature regarding the psychiatricpresentations of thyroid autoimmunity in southern India. Objectives: To study the psychiatriccomorbidities in patients with AITD and determine the relationship between thyroid peroxidaseantibody level with severity of psychiatric illness and cognitive impairment. Materialsand Methods: This cross-sectional study of one year duration was conducted in department of Psychiatry ofatertiary-care hospital in Kerala. Subjects with AITD andnew onset behavioural symptoms wereselected, diagnosis was made based on DSM 5 diagnostic criteria, illness severity was assessed usingHAM-A, HAM-D, BPRS rating scales and severity of cognitive impairment was assessed usingMoCA scale. Statistical analysis was done using percentage, mean , SD andSpearmann’s correlationcoefficient. Results: Out of 60 subjects, 82%were women and 52%had a family history of thyroiddysfunction. The most common psychiatric diagnosis were Major Depressive Disorder, Panic disorderand Schizophreniform disorderwith moderate to severe illness and mild cognitive impairment. Significant positive correlation between thyroid peroxidase antibody level and severity of depressiveand anxiety disorder was found. Conclusion: The common psychiatric comorbities, its severity andcognitive impairment in AITD and its relation with thyroid peroxidase antibody level could bedescribed. A holistic teamwork comprising of endocrinologists and psychiatrists can help in earlydetection and management of these issues. Keywords: anxiety, autoimmunity, cognition, depression, psychosis, thyroid

Vitamin D: An Essential Nutrient in the Dual Relationship between Autoimmune Thyroid Diseases and Celiac Disease-A Comprehensive Review.

Autoimmune thyroid diseases (AITD) are among the most frequent autoimmune disorders, with a multifactorial etiology in which both genetic and environmental determinants are probably involved. Celiac disease (CeD) also represents a public concern, given its increasing prevalence due to the recent improvement of screening programs, leading to the detection of silent subtypes. The two conditions may be closely associated due to common risk factors, including genetic setting, changes in the composition and diversity of the gut microbiota, and deficiency of nutrients like vitamin D. This comprehensive review discussed the current evidence on the pivotal role of vitamin D in modulating both gut microbiota dysbiosis and immune system dysfunction, shedding light on the possible relevance of an adequate intake of this nutrient in the primary prevention of AITD and CeD. While future technology-based strategies for proper vitamin D supplementation could be attractive in the context of personalized medicine, several issues remain to be defined, including standardized assays for vitamin D determination, timely recommendations on vitamin D intake for immune system functioning, and longitudinal studies and randomized controlled trials to definitely establish a causal relationship between serum vitamin D levels and the onset of AITD and CeD.

Positive baseline thyroid autoantibodies as a predictive biomarker for thyroid immune-related adverse events: A systematic review and meta-analysis.

e24124 Background: Thyroid dysfunction is one of the most common immune-related adverse events (irAE) by immune checkpoint inhibitors (ICI). Given the known relationship between antithyroid autoantibodies (ATA), including antithyroid peroxidase (TPO Ab) and anti-thyroglobulin (Tg Ab), and autoimmune thyroid disease, they could also play a role as a predictive biomarker for thyroid irAE (T-irAE). We performed this meta-analysis to evaluate the association of positive baseline thyroid autoantibodies and T-irAE. Methods: Eligible studies were screened using Ovid Medline and Embase databases with search terms related to ATA and thyroid irAE. Studies must be case-control or cohort studies with patients who received ICI and report the numbers of patients who have thyroid dysfunction and do not have thyroid dysfunction by the pre-ICI treatment statuses of ATA, TPO Ab, or Tg Ab. The pooled odds ratio (OR) and the associated 95% confidence interval (95% CI) were calculated using the Mantel-Haenszel method. Subgroup analysis by types of ICI (anti-PD1, anti-PD-L1, or combination treatment) and study region were also performed. The presence of publication bias was assessed by direct visualization of funnel plots. Results: After two rounds of screening, 19 case-control and five retrospective cohort studies were included in the meta-analysis. Patients who had positive baseline ATA had increased odds of developing T-irAE, hypothyroidism, and hyperthyroidism (pooled OR 10.95, 95% CI 6.65-18.02, I2= 38%; 6.82, 95% CI 2.99-15.56, I2= 27%; and 7.59, 95% CI 2.51-22.96, I2= 42%; respectively). Positive pre-treatment TPO Ab and Tg Ab were also independently associated with higher odds of hypothyroidism (pooled OR 5.01, 95% CI 2.87-8.75, I2= 4%, and 18.73, 95% CI 9.04-38.80, I2= 0%, respectively) and hyperthyroidism (pooled OR 2.94, 95% CI 1.57-5.52, I2= 25%, and 8.36, 95% CI 1.18-59.31, I2= 82%, respectively). The associations did not significantly differ between the types of ICI utilized and the study region. Visualization of funnel plots did not reveal a presence of publication bias. Conclusions: Pre-ICI treatment statuses of ATA, TPO Ab, and Tg Ab are associated with both hypothyroidism and hyperthyroidism. Thyroid autoantibodies as a baseline predictive tool can be helpful for early detection of T-irAE in patients who receive ICI therapy.

Impact of Thyroid Autoimmunity on the Clinical and Biochemical Characteristics of Type 1 Diabetes Mellitus Patients.

Type 1 diabetes mellitus (T1DM) is frequently associated with other autoimmune disorders that are characterized by the presence of organ-specific autoantibodies. Autoimmune thyroid disease (AIT) is the most frequent autoimmune disorder associated with T1DM. Thyroid peroxidase antibodies (TPOAb) serve as a marker for diagnosing AIT. Prior research indicates that thyroid dysfunction can negatively impact linear growth and glycemic control in subjects with T1DM. The present study was done to determine the impact of thyroid autoimmunity on the clinical and biochemical characteristics of patients with newly diagnosed T1DM. In this single-center, hospital-based, observational cross-sectional study, we enrolled 70 patients with newly diagnosed T1DM ≤18 years of age. Type 1 diabetes mellitus was diagnosed based on the acute onset of osmotic symptoms with or without diabetic ketoacidosis (DKA), severe hyperglycemia (blood glucose >13.9 mmol/l (>250 mg/dl)), and insulin requirement from the onset of diabetes. Secondary diabetes, pancreatic diabetes (Type 3c), and maturity-onset diabetes of the young (MODY) were excluded. Participants were screened for AIT disease using TPOAb testing. Based on the presence or absence of TPOAb, the participants were categorized into two groups: Group A comprised individuals with T1DM who tested positive for TPOAb, while Group B consisted of those who tested negative for TPOAb. Out of 70 patients, 41.4% were girls and 58.6% were boys, with a mean age of 9.8±4.4 years. The prevalence of TPOAb among the cohort was 18.6%. A significant majority of patients (71.4%), presented with DKA. Group A showed significantly lower mean height standard deviation scores (SDS) compared to Group B (-0.3±0.6 vs. -0.8±0.5, p = 0.004), but no differences in weight SDS or BMI SDS. Hemoglobin A1C (HbA1c) levels, C-peptide levels, and frequency of DKA did not differ between groups. Group A had higher mean thyroid-stimulating hormone (TSH) levels (4.8±3.7 µU/ml vs. 2.6±1.5 µU/ml, p = 0.001) and a greater proportion of patients with TSH levels above the upper limit of normal compared to Group B (38.4% vs. 7.1%, p = 0.008). Additionally, Group A exhibited a higher frequency of glutamic acid decarboxylase antibody (GADA) positivity compared to Group B (46.1% vs. 17.5%, p = 0.04). Patients positive for TPOAb exhibited significantly lower height SDS compared to TPOAb-negative patients. Additionally, T1DM patients with TPOAb positivity showed an increased frequency of GADA compared to those without TPOAb. However, no significant differences were found in HbA1c levels, C-peptide levels, or hematological parameters between TPOAb-positive and TPOAb-negative patients. These findings emphasize the impact of TPOAb on growth parameters in T1DM and advocate for routine screening of TPOAb in all T1DM patients, starting at the time of diabetes diagnosis.

Hypothyroidism in Older Adults: A Narrative Review

The prevalence of hypothyroidism increases along with aging, resulting in one of the most common comorbidities among patients over 75 years. The leading causes of hypothyroidism in older adults are iatrogenic, Hashimoto's thyroiditis, and medications. The narrative review aimed to discuss the clinical characteristics of hypothyroidism in older adults and the impact of hormonal replacement therapy on survival rates. Thyroid function declines over time due to physiological changes in the thyroid stimulating hormone signaling, iodine absorption and metabolism, thyroid hormone metabolism, and activity at peripheral sites. A serum TSH value over the upper limit of the normal reference range is not necessarily attributable to hypothyroidism. However, an appropriate diagnostic work-up is required to rule out true hypothyroidism and discriminate the etiology (i.e., thyroid autoimmune diseases, iodine deficiency, drug-induced hypothyroidism). Levothyroxine treatment should be considered in cases of overt hypothyroidism. A complete risk-to-benefit assessment, particularly considering the overall health status, life expectancy, cognitive function, mood, and cardiovascular and neurological background, should be considered before treating subclinical hypothyroidism with more potential benefits in patients under 75 years old. Levothyroxine formulations facilitating hormone absorption and increasing compliance to long-term treatment should be preferred. TSH target should usually be set over 3 mIU/ml. Defining optimal diagnostic approaches and targeted therapeutic strategies should be considered in the personalized management of aged patients with hypothyroidism.

New-onset autoimmune thyroid disease following COVID-19.

New-onset autoimmune thyroid disease following COVID-19.

The causal relationship between vitiligo and autoimmune thyroid diseases: A bidirectional two-sample Mendelian randomization analysis.

Vitiligo is an acquired autoimmune depigmented disorder characterized by the presence of white and well-defined patches on the skin, mucous membrane, or both. It is associated with a significant disease burden and has a profoundly impacts patients' quality of life. Autoimmune thyroid diseases (AITDs) result from an autoimmune system dysregulation, leading to an erroneous immune attack on the thyroid gland. Previous observational and epidemiological studies have suggested the association between vitiligo and AITDs. However, the bidirectional cause-effect relationship between vitiligo and AITDs has not been formally assessed. Two-sample bidirectional Mendelian randomization (MR) analysis was conducted to explore potential causal relationships between genetically increased risk of vitiligo and AITDs, using summary statistics from genome-wide association studies in European populations. Causal effects were primarily estimated using the inverse variance weighted method, and additional quality control was performed using the MR-Egger, weighted median, simple mode, and weight mode methods. Sensitivity analysis was conducted to assess the robustness of the results. The forward MR analysis showed a positive causal relationship between vitiligo and autoimmune thyroiditis (AIT), autoimmune hyperthyroidism (AIH), and Graves' disease (GD). The odds ratio (OR) were 1.17 (95% CI, 1.01-1.35; p=0.04), 1.12 (95% CI, 1.03-1.22; p=0.01), and 1.13 (95% CI, 1.06-1.20; p<0.01), respectively. In the reverse MR analysis, a positive causal relationship was found between AIT and vitiligo, with an OR of 1.10 (95% CI, 1.01-1.35; p=0.04). However, no causal relationship was observed between AIH (p=0.10) or GD (p=0.61) and vitiligo. Sensitivity analysis revealed no evidence of horizontal pleiotropy or heterogeneity. The genetic-level investigation provides evidence of a genetic causal association between susceptibility to vitiligo and an increased risk of AITDs. Additionally, the results demonstrate a genetic causal association between susceptibility to AIT and an increased risk of vitiligo, while not indicating a similar association with susceptibility to AIH or GD.

A silent cause of shock: autoimmune polyglandular syndromes

Addison’s disease is a rare, autoimmune condition leading to the destruction of the adrenal gland. Autoimmune conditions are known to commonly co-occur. When Addison’s disease presents in the setting of autoimmune thyroid disease and/or type 1 diabetes, this condition is termed autoimmune polyendocrine syndrome type II, a rare endocrinopathy found in roughly 1.4-4.5 per 100,000 individuals. Here, we describe a clinical case presenting with hypotension refractory to fluid resuscitation and electrolyte derangements later diagnosed as autoimmune polyendocrine syndrome type II.

Toenail and blood selenium mediated regulation of thyroid dysfunction through immune cells: a mediation Mendelian randomization analysis.

Specific nutrients found in food, such as minerals, antioxidants, and macronutrients, have a significant impact on immune function and human health. However, there is currently limited research exploring the relationship between specific nutrients, immune system function, and thyroid dysfunction commonly observed in autoimmune thyroid diseases, which manifest predominantly as hyperthyroidism or hypothyroidism. Therefore, the objective of this study was to investigate the connections between dietary traits and thyroid dysfunction, as well as the potential mediating role of immune cells, using Mendelian randomization (MR) analysis. The two-step MR analysis used single-nucleotide polymorphisms as instruments, with a threshold of p < 5e-08 for nutrients and thyroid dysfunction, and p < 5e-06 for immune cells. Data from different GWAS databases and UK Biobank were combined to analyze 8 antioxidants and 7 minerals, while the data for 4 macronutrients came from a cohort of 235,000 individuals of European. The outcome data (hypothyroidism, N = 3340; hyperthyroidism, N = 1840; free thyroxin [FT4], N = 49,269; thyroid-stimulating hormone [TSH], N = 54,288) were source from the ThyroidOmics consortium. Immune trait data, including 731 immune phenotypes, were collected from the GWAS catalog. The results revealed that nutrient changes, such as lycopene, toenail and blood selenium, and α-tocopherol, impacted the immune system. Immune cells also affected thyroid function, with cDC cells promoting hypothyroidism and median fluorescence intensity (MFI) phenotypes correlating strongly with FT4 levels. Toenail and blood selenium reduce the relative cell counts (RCC) phenotypes of immune cells (CD62L- plasmacytoid DC %DC and transitional B cells %Lymphocyte), thereby diminishing its promoting effect on hypothyroidis. Furthermore, toenail and blood selenium mainly impacted phenotypes in three types of T cells (CD25 + ⁣ + CD8br, CD3 on CD45RA- CD4+, and CD45RA on Terminally Differentiated CD8br), reinforcing the negative regulation of FT4 levels. The role of immune cells as mediators in the relationship between nutrients and thyroid dysfunction highlights their potential as diagnostic or therapeutic markers. Toenail and blood selenium levels can indirectly impact hypothyroidism by influencing the RCC levels of two types of immune cells, and can indirectly affect FT4 levels by influencing three types of T cells.

Dissecting causal relationships between primary biliary cholangitis and extrahepatic autoimmune diseases based on Mendelian randomization

As an autoimmune disease, up to 73% of patients with primary biliary cholangitis (PBC) have a combination of extrahepatic autoimmune diseases (EHAIDs); however, the causal relationship between PBC and EHAIDs is unclear. The genome-wide association analyses provided 14 GWAS data for PBC and EHAIDs, and bidirectional, two-sample MR analyses were performed to examine the relationship between PBC and EHAIDs. The analysis using MR provides a strong and meaningful estimation of the bidirectional correlation between PBC and 7 EHAIDs: rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, autoimmune hypothyroidism, inflammatory bowel disease and ulcerative colitis of its types. In addition, PBC increases the risk of autoimmune thyroid diseases such as autoimmune hyperthyroidism and Graves' disease, as well as multiple sclerosis and psoriasis. Additionally, PBC is identified as a risk factor for Crohn's disease and Celiac disease. Based on genetic evidence, there may be connections between PBC and specific EHAIDs: not all coexisting EHAIDs induce PBC, and vice versa. This underscores the significance of prioritizing PBC in clinical practice. Additionally, if any liver function abnormalities are observed during treatment or with EHAIDs, it is crucial to consider the possibility of comorbid PBC.

Enzyme-linked immunosorbent assay of 3 Screen Islet Cell Autoantibody in patients with autoimmune thyroid disease.

In recent years, the emergence of multiplex technology that can simultaneously measure multiple anti-islet autoantibodies has become particularly valuable for the staging and early diagnosis of immune-mediated type 1 diabetes (T1D). While it has been established that 20%-30% of T1D patients suffer from autoimmune thyroid disease (AITD), there is limited available data regarding the presence of anti-islet autoantibodies in AITD patients. Among commercially available anti-islet autoantibodies, glutamic acid decarboxylase 65 autoantibodies (GADAs) are often the first marker measured in general clinical practice. To investigate the frequency of anti-islet autoantibodies in AITD patients. Our study involved four hundred ninety-five AITD patients, categorized into three distinct groups: AITD with T1D (n = 18), AITD with phenotypic type 2 diabetes (T2D) (n = 81), and AITD without diabetes (n = 396), and the enzyme-linked immunosorbent assay (ELISA) was employed to determine the frequencies of 3 Screen Islet Cell Autoantibody (3 Screen ICA), GADA, insulinoma-associated antigen-2 autoantibodies (IA-2As), and zinc transporter 8 autoantibodies (ZnT8As) within these groups. The frequency of 3 Screen ICA in AITD patients with T1D, T2D, and those without diabetes were 88.9%, 6.2%, and 5.1%, respectively, with no significant difference seen between the latter two groups. Notably, the frequency of 3 Screen ICA was 11.1% higher in AITD patients with T1D, 1.3% higher in AITD patients with T2D, and 1.1% higher in AITD patients without diabetes compared to GADA, respectively. Furthermore, 12.5%, 20.0%, and 20.0% of the 3 Screen ICA-positive patients were negative for GADA. Additionally, 1.3% of the AITD patients who tested negative for 3 Screen ICA in both the AITD with T2D and non-diabetic AITD groups were found to be positive for individual autoantibodies. Among the 3 Screen ICA-positive patients, there was a significantly higher proportion of individuals with multiple autoantibodies in AITD patients with T1D compared to those without diabetes (37.5% vs 5.0%, P < 0.05). However, this proportion was similar to that in AITD patients with T2D (20.0%). Nevertheless, there was no significant difference in 3 Screen ICA titers between AITD patients with T1D and those without diabetes (436.8 ± 66.4 vs 308.1 ± 66.4 index). Additionally, no significant difference in 3 Screen ICA titers was observed between Graves' disease and Hashimoto's thyroiditis in any of the groups. Our findings reveal that some AITD patients without diabetes exhibit 3 Screen ICA titers comparable to those in AITD patients with T1D. Thus, 3 Screen ICA outperforms GADA in identifying latent anti-islet autoantibody-positive individuals among AITD patients.

The interlink between thyroid autoimmunity and type 1 diabetes and the impact on male and female fertility.

The aim of this review is to discuss the several interconnections between thyroid autoimmunity and type 1 diabetes in terms of epidemiology, immunoserology, genetic predisposition, and pathogenic mechanisms. We will also analyze the impact of these conditions on both male and female fertility. A literature search was carried out using the MEDLINE/PubMed, Scopus, Google Scholar, ResearchGate, and Clinical Trials Registry databases with a combination of keywords. It was found that the prevalence of thyroid autoantibodies in individuals with type 1 diabetes (T1DM) varied in different countries and ethnic groups from 7 to 35% in both sexes. There are several types of autoantibodies responsible for the immunoserological presentation of autoimmune thyroid diseases (AITDs) which can be either stimulating or inhibiting, which results in AITD being in the plus phase (thyrotoxicosis) or the minus phase (hypothyroidism). Different types of immune cells such as T cells, B cells, natural killer (NK) cells, antigen presenting cells (APCs), and other innate immune cells participate in the damage of the beta cells of the islets of Langerhans, which inevitably leads to T1D. Multiple genetic and environmental factors found in variable combinations are involved in the pathogenesis of AITD and T1D. In conclusion, although it is now well-known that both diabetes and thyroid diseases can affect fertility, only a few data are available on possible effects of autoimmune conditions. Recent findings nevertheless point to the importance of screening patients with immunologic infertility for AITDs and T1D, and vice versa.

Promising Role of Alkaloids in the Prevention and Treatment of Thyroid Cancer and Autoimmune Thyroid Disease: A Comprehensive Review of the Current Evidence.

Thyroid cancer (TC) and thyroid autoimmune disorders (AITD) are among the most common diseases in the general population, with higher incidence in women. Chronic inflammation and autoimmunity play a pivotal role in carcinogenesis. Some studies, indeed, have pointed out the presence of AITD as a risk factor for TC, although this issue remains controversial. Prevention of autoimmune disease and cancer is the ultimate goal for clinicians and scientists, but it is not always feasible. Thus, new treatments, that overcome the current barriers to prevention and treatment of TC and AITD are needed. Alkaloids are secondary plant metabolites endowed with several biological activities including anticancer and immunomodulatory properties. In this perspective, alkaloids may represent a promising source of prophylactic and therapeutic agents for TC and AITD. This review encompasses the current published literature on alkaloids effects on TC and AITD, with a specific focus on the pathways involved in TC and AITD development and progression.

Investigating the Bidirectional Association of Rheumatoid Arthritis and Thyroid Function: A Methodologic Assessment of Mendelian Randomization.

Rheumatoid arthritis (RA) and thyroid dysfunction are frequently observed in the same patient. However, whether they co-occur or exhibit a causal relationship remains uncertain. We aimed to systematically investigate the causal relationship between RA and thyroid function using a large sample and advanced methods. Bidirectional two-sample Mendelian randomization (MR) analysis was performed based on RA and six thyroid function trait data sets from the European population. The robustness of the results was demonstrated using multiple MR methods and a series of sensitivity analyses. Multivariable MR using Bayesian model averaging (MR-BMA) was performed to adjust for possible competing risk factors. A sensitivity data set, which included data from patients with seropositive RA and controls, was used to repeat the analyses. Furthermore, enrichment analysis was employed to discover the underlying mechanism between RA and thyroid functions. A significantly positive causal effect was identified for RA on autoimmune thyroid disease (AITD) as well as for AITD on RA (P < 0.001). Further sensitivity analyses showed consistent causal estimates from a variety of MR methods. After removing the outliers, MR-BMA results showed that RA and AITD were independent risk factors in their bidirectional causality, even in the presence of other competing risk factors (adjusted P < 0.05). Enrichment analysis showed immune cell activation and immune response play crucial roles in them. Our results illustrate the significant bidirectional causal effect of RA and AITD, which holds even in multiple competing risk factors. Clinical screening for thyroid dysfunction in patients with RA deserves further attention, and vice versa.