Autoimmune Thyroid Disease Research Articles

Sex-Based Differences in Thyroid Plasma B Cell Infiltration: Implications for Autoimmune Disease Susceptibility.

Thyroid autoimmune diseases, such as Hashimoto's thyroiditis and Graves' disease, are significantly more prevalent in women than in men, suggesting underlying biological differences in immune system function and regulation between sexes. Plasma B cells are crucial in autoimmunity due to their role in producing antibodies targeting self-antigens, but their presence in the thyroids of women without clinical autoimmune diseases remains largely unexplored. This study investigates the infiltration of plasma B cells in female thyroids specifically excluding those with any clinical signs of autoimmune diseases. Using bulk RNA-seq analysis, we identified significant sex differences in gene expression profiles, particularly in genes associated with plasma B cells. Single-cell RNA-seq and spatial transcriptomic analyses further revealed that the CXCL13-CXCR5 signaling axis plays a pivotal role in recruiting and organizing plasma B cells within the thyroid tissue. These findings suggest that the inherent presence of plasma B cells in the female thyroid, driven by CXCL13, may contribute to the higher risk of developing autoimmune thyroid diseases in women. Our study provides new insights into the immune landscape of the thyroid and underscores the importance of understanding sex-specific differences in immune cell distribution and function.

Selenium and Graves’ Disease

Selenium, a trace element present in specific selenoproteins, is essential for thyroid hormone metabolism. Selenium is also an antioxidant with immunosuppressive properties and may help in managing thyroid autoimmune diseases, including Graves’ (GD) hyperthyroidism and Graves’ ophthalmopathy (GO). There were 320 clinical studies related to selenium and thyroid published in English and French between January 1, 2000, and June 1, 2023. Our focus was to identify studies reporting levels of serum selenium in patients with GD and studies that assessed the effect of selenium supplementation on outcomes of GD hyperthyroidism and GO. We also reviewed 20 systematic reviews and meta-analyses of randomized controlled trials that reported selenium levels in GD and the effects of supplementation on GD and GO outcomes. Our review showed that patients with GD had serum selenium levels lower than those of various control patients. In the short-term, a selenium supplement to antithyroid drugs showed benefit for GD hyperthyroidism in most studies, but long-term benefits and positive effects on remission rate were unclear. Some studies did not show benefit. The benefits may depend on baseline selenium deficiency. Two randomized controlled trials showed positive effects of supplementation for mild GO; however, studies about moderate and severe GO are still needed. There is evidence for benefit with short-term selenium supplementation for GD hyperthyroidism, but controlled studies are needed to assess long-term benefits, and benefits in selenium-sufficient areas.

Correlation of thyroid function and sensitivity to thyroid hormone with spinal bone mineral content, bone mineral density, and osteoporotic vertebral fracture: A cross-sectional study based on NHANES.

Previous studies have demonstrated that thyroid hormone plays an important role in normal bone development, bone metabolism, and establishment of peak bone mass. However, the correlation of thyroid status with bone mineral content (BMC), bone mineral density (BMD), and osteoporotic vertebral fracture (OVF) is rarely discussed. The current study probes into the potential association between thyroid status and spinal BMC, BMD, and OVF from a novel perspective of thyroid function (TF) and sensitivity to thyroid hormone based on the National Health and Nutrition Examination Survey database. A total of 1844 participants were included in this study. The association of thyroid status with outcome variables, like spinal BMC, BMD, and OVF, was analyzed using thyroid function indices and sensitivity to thyroid hormone indices as influence factors. The correlation of them were assessed using univariate and multivariable weighted linear regression, weighted logistic regression models, restricted cubic spline model, and subgroup analyses. The results of this study showed that the association of free triiodothyronine (FT3)/free thyroxine (FT4) with BMC remained negatively associated after adjustment for all covariates. Higher thyroid peroxidase antibody (TPOAb) was significantly associated with an increased risk of developing OVF in both unadjusted and adjusted models. In addition, the results of the restricted cubic spline model were consistent with the weighted multivariate regression analysis after adjustment. The results of this cross-sectional study showed that higher FT3/FT4 and TPOAb were associated with decreased spinal BMC and the increased risk of OVF, indicating a complex link between thyroid status and bone health. Therefore, patients with hyperthyroidism, hypothyroidism, autoimmune thyroid disease, or abnormal peripheral thyroid sensitivity, especially who with elevated TPOAb or FT3/FT4, should focus on the prevention of vertebral osteopenia, osteoporosis, and OVF.

Should we routinely assess ovarian reserve in girls and young women with autoimmune thyroid disease?

Should we routinely assess ovarian reserve in girls and young women with autoimmune thyroid disease?

Mechanisms of Amomum villosum essential oil in enhancing tilapia (Oreochromis niloticus) intestinal health

Amomum villosum is a member of the ginger family to treat gastrointestinal diseases in humans. Supplementing the diet of tilapia (Oreochromis niloticus) with essential oil (EOA) can enhance digestive and intestinal antioxidant capacity. We conducted a comparative experiment using tilapia to further understand the potential molecular response mechanism to dietary EOA. Fish were divided into four groups with different feeding doses of EOA: L (2 g/Kg) group, M (4 g/Kg) group, and H (8 g/Kg) group, along with a control group without EOA supplementation. The level of inflammatory factors (TNF-α, IL-1) declined significantly in the EOA group. Comparative transcriptome of the intestines revealed differentially expressed genes (DEGs) in each group, which further revealed that enriched terms were closely related to important pathways such as PI3K-Akt signaling, cell adhesion molecules, regulation of actin cytoskeleton, and autoimmune thyroid disease. These pathways play significant roles in regulating various cellular processes and immune responses of intestines. Intestine metabolomic analysis indicated that dietary EOA caused changes in metabolic processes, particularly in nucleotide metabolism, indicating the potential impact of EOA on these processes. To identify key factors regulating the molecular response to EOA supplementation, a weighted gene co-expression network analysis combined with transcriptome and differential metabolites to identify key genes and metabolites. Glycitein and genistein are substances related to the metabolism of soybean meal were identified. Hmgb2, Parp11, Bcoll is considered to be the key genes, and has the immune regulation function. This study provides new insights into the molecular basis underlying the protective effects of dietary EOA in tilapia. The results can benefit the aquaculture industry by developing dietary strategies to improve the health and welfare of tilapia in intensive farming.

Circulating Autoantibodies in Adults with Hashimoto’s Thyroiditis: New Insights from a Single-Center, Cross-Sectional Study

Background: Hashimoto’s thyroiditis (HT) is a common autoimmune thyroid disorder characterized by elevated anti-thyroid peroxidase (A-TPO) antibodies. HT frequently coexists with other autoimmune conditions, which are marked by organ-specific and non-organ-specific autoantibodies, reflecting a deregulated immune response. However, the burden and clinical significance of these circulating autoantibodies in adult patients with HT remains unclear. Methods: A cross-sectional study was conducted at the University Hospital “R. Dulbecco” in Catanzaro, Italy, from November 2023 to May 2024, involving 200 euthyroid adults. The study population comprised 100 A-TPO-positive HT patients and 100 A-TPO-negative controls, matched for age and sex. Laboratory assessments included thyroid function tests and detection of autoantibodies [e.g., antinuclear antibodies (ANA), anti-parietal cell antibodies (APCA), and anti-neutrophil cytoplasmic antibodies (ANCA)]. Cytokine profiles were also measured using sensitive chemiluminescent multi-array technology. Results: HT patients were predominantly female (77.0%) with a median age of 56 years. Compared to controls, HT patients had higher median thyroid stimulating hormone (TSH) levels (2.215 vs. 1.705 μIU/mL, p = 0.025). Circulating autoantibodies were more prevalent in the HT group, with higher rates of APCA positivity (16.3% vs. 4.1%, p = 0.008) and atypical ANCA positivity (27.3% vs. 10.2%, p = 0.003). This suggests an increased risk for autoimmune gastritis and systemic inflammation. Additionally, HT patients with positive atypical ANCA showed elevated inflammatory cytokines, particularly interleukin-1 alpha (IL-1α), in female patients (p = 0.035). Conclusions: HT is significantly associated with a higher prevalence of circulating autoantibodies, such as APCA and atypical ANCA, which may indicate a heightened risk for autoimmune gastritis and broader autoimmune involvement. Detecting these autoantibodies in HT patients could serve as markers for more severe autoimmune dysfunction. These findings emphasize the need for proactive screening, especially in older patients and those with elevated A-TPO levels. Further research is essential to better understand the clinical implications and develop targeted management strategies for these patients.

Associations vulvar lichen sclerosus with autoimmune thyroid diseases.

Vulvar lichen sclerosus (VLS) is defined as a chronic inflammatory skin disease that most often involves lesions on the mucous membranes of the vulva with a tendency to progress to the anal skin. The etiopathogenesis of VLS remains unknown and is likely multifactorial. Data emphasize the role of immunological factors - more than 25% of VLS cases coexist with autoimmune diseases. The purpose of the present study was to determine the correlation of the prevalence of anti-thyroid antibodies - IgG class antibodies against thyroid peroxidase and IgG class antibodies against thyroglobulin in women with vulvar lichen sclerosus, and the appropriateness of screening tests for autoimmune thyroid diseases in women with vulvar lichen sclerosus. Fifty women with vulvar lichen sclerosus were enrolled in the study. The control group consisted of 41 healthy women. A detailed medical history was taken with all patients, followed by laboratory determinations - anti-thyroid antibodies - IgG class antibodies against thyroid peroxidase and IgG class antibodies against thyroglobulin. Antibodies to thyroid peroxidase were present in 12% of the study group with vulvar lichen sclerosus and 4.88% of the control group, and this difference was not statistically significant (p = 0.41). Anti-thyroglobulin antibodies were detected in 4% of the patients with vulvar lichen sclerosus and 4.88% of the control group, and this difference was not statistically significant either (p = 0.76). The study did not confirm the association of VLS with autoimmune thyroid diseases. Undoubtedly, based on the data available in the literature, further studies are needed to determine the mechanisms behind the association between vulvar lichen sclerosus and autoimmune thyroid diseases.

A Real-Life Study in Patients Newly Diagnosed with Autoimmune Hashimoto’s Thyroiditis: Analysis of Asthenia as Admission Complaint

Background: Amid the large panel of autoimmune thyroid diseases, Hashimoto’s thyroiditis (HT) represents a major point across multidisciplinary daily practice. When it comes to the clinical picture, particularly in regard to asthenia (also described as “fatigue” or “decreased energy”), the differential diagnosis is challenging, and a meticulous anamnesis should be backed up by focused lab investigations. Our objective was to analyze the thyroid panel in newly diagnosed patients with HT in relationship with the presence of asthenia as an admission complaint. Methods: This was a retrospective, multi-centric, real-life study conducted in secondary endocrine units (university hospitals) from July 2022 to July 2023. The exclusion criteria were COVID-19 infection; an active malignancy, etc. Results: The cohort (N = 120) included an asthenia group (AS, 49.2%) and a non-AS group of a similar age (49.3 ± 14.7 vs. 47.1 ± 14.8 y, p = 0.426). Headache was more frequent in the AS group (35.6% vs. 18%, p = 0.03). Thyroid function and HT-related antibodies assays were similar between the groups and show no correlation with serum total cholesterol and triglycerides, respectively. TSH levels did not vary among the age sub-groups (p = 0.701). One third of the studied population was affected by hypothyroidism (TSH > 4.5 μIU/mL), being seen at a higher rate in the AS (39%) vs. non-AS group (23%). Total cholesterol positively correlated with the patients’ age (r = 0.180, p = 0.049) and triglycerides (N = 120; r = 0.324, p < 0.001), as found only in the non-AS group (r = 0.246, p = 0.006, respectively, r = 0.319, p < 0.001). Conclusions: The analysis of the AS vs. non-AS group pinpointed the fact that, in regard to daily practice, asthenia as an admission complaint seems less of an indicator of an underlying thyroid dysfunction or a higher level of serum antibodies against thyroid in patients without a full clinical picture of thyrotoxicosis or myxoedema.

The Absence of Thyroid-Stimulating Hormone Receptor Expression on Natural Killer T Cells: Implications for the Immune–Endocrine Interaction

The expression of thyroid-stimulating hormone receptor (TSHR) has been documented on various immune cells, including B lymphocytes, T lymphocytes, Natural Killer (NK) cells, monocytes, and dendritic cells (DCs). Natural Killer T (NKT) cells serve as a crucial link between innate and adaptive immunity, playing significant roles in immunological interactions and autoimmune diseases. The aim of the present study was to evaluate the presence of TSHR on NKT cells. Our research involved patients with thyroid disease, as well as healthy controls. Peripheral blood mononuclear cells (PBMCs) and, thereafter, NKT cells were isolated from 86 patients with benign nodular thyroid disease with and without autoimmune thyroid disease (AITD) (28 and 56 cases, respectively), and TSHR expression was analyzed using fluorescence-activated cell sorting (FACS). In order to confirm the results, the reverse-transcription polymerase chain reaction (RT-PCR) method was used in cells obtained from healthy individuals. Our findings obtained with application of the FACS method revealed that TSHR is not expressed on NKT cells in either AITD or non-AITD patients, though TSHR was detected in the total PBMC population (TSHR+ cells 2.77%). The absence of TSHR on NKT cells was further confirmed with RT-PCR in healthy individuals (p < 0.0001). These results questioned the previously suggested direct influence of NKT cells on AITD development.

Use of rituximab in the of immunoinflammatory rheumatic diseases combined with Graves' disease (autoimmune polyglandular syndrome in adults): case report and literature review

Rituximab (RTM) is a chimeric (murine and human) monoclonal antibody against B-lymphocytes (CD20). RTM is widely used in hematology for lymphoproliferative diseases and in rheumatology for rheumatoid arthritis, Sjögren's disease, some types of vasculitis and systemic connective tissue diseases. The administration of RTM is associated with a depletion of B-cells mediated by the regulation of apoptosis and cytotoxic effects via complement-dependent and antibody-dependent mechanisms. Considering the pathogenesis of autoimmune damage in Graves' disease (GD), an autoimmune thyroid disease associated with thyrotoxicosis, the use of RTM could be effective in this pathology. We present three patients with a combination of diffuse toxic goiter and rheumatic pathology treated with RTM; different outcomes of GD were observed.

STAT1 and STAT3 gain of function: clinically heterogenous immune regulatory disorders.

The identification of STAT1 gain-of-function (GOF) in 2011 and STAT3 GOF in 2014 has advanced our understanding of the host immunity along the JAK/STAT pathway and allowed targeted treatment approaches. We review the clinical features and pathogenesis of STAT1 and STAT3 GOF and how this has shaped new approaches to therapy. STAT1 GOF, initially described in patients with chronic mucocutaneous candidiasis (CMC) and autoimmune thyroid disease, is now recognized to cause early-onset multisystem autoimmunity and a range of infections. STAT3 GOF comprises mostly lymphoproliferation and autoimmunity but also with varying severity, including some with life threatening organ dysfunction. Treatment has evolved along with the understanding of the pathogenesis, with patients now receiving JAK inhibition to block upstream of the STAT defect with good response in autoimmunity and CMC in STAT1 GOF. Blockade of IL-6 signaling has also been used in STAT3 GOF. Hematopoietic cell transplantation had initial poor outcomes, but outcomes are now improving with focus on the control of inflammation pretransplant. Understanding the pathogenesis of STAT1 and STAT3 GOF has allowed great recent advancements in therapy, but many questions remain as to the best approach to therapy for each patient's clinical presentation as well as the durability of these therapies.

Advances in thyroid peroxidase (TPO) and thyroid stimulating hormone receptor (TSHR) biomarkers for autoimmune thyroid diseases

The development of immunological methods in the 1970s and 1980s led to the identification of thyroid peroxidase (TPO) and thyroid stimulating hormone receptor (TSHR) as key players in the onset of autoimmune thyroid diseases (AITD). TSHR is primarily associated with hyperthyroidism, while TPO is linked to hypothyroidism. Advances in understanding TPO and TSHR as biomarkers over recent decades have enhanced their clinical application. This review explores the molecular basis of TPO and TSHR as biomarkers, highlighting their importance in diagnosing AITD and their potential to guide effective therapeutic strategies. Additionally, it discusses the development of lateral flow assay (LFA) kits developed by the authors, which show promise as rapid and reliable diagnostic tools for AITD.

Vestibular Dysfunction in Euthyroid Children with Hashimoto's Thyroiditis.

A relationship exists between autoimmune thyroid disorders and vestibular dysfunction. This study aimed to analyze cervicalevoked myogenic potentials (cVEMP) and video head impulse test (vHIT) results between children with Hashimoto thyroiditis (HT) and healthy controls to determine vestibular end-organ problems. Thirty-six children with HT and 30 healthy subjects were recruited. The main inclusion criteria for the healthy group were the presence of normal thyroid function and no clinical history of vestibular problems. Each participant (both HT and healthy groups) was assessed using audiovestibular tests, cVEMP, and vHIT. There was no significant difference between the groups in terms of cVEMP (p1 and n1) latencies for both ears. There was no significant difference in cVEMP amplitudes (p1-n1 peak-to-peak) between the groups. There were statistically significant differences in the VOR gain of the right and left ears between the groups (P < .001, P < .001). When we considered lower cutoff value as 0.80 for VOR gain, 29 of 36 patients with HT (80.6%) had lower VOR gain scores. Only 1 of 30 healthy participants (3.3%) had a lower VOR gain score. This difference was statistically significant (P < .001). Subclinical vestibulopathy may occur in children with HT. The vHIT seems to be a valuable tool for identifying and screening preclinical vestibular pathologies in this patient group.

Role of immune cells in mediating the effect of gut microbiota on Hashimoto's thyroiditis: a 2-sample Mendelian randomization study.

Hashimoto's thyroiditis (HT) is one of the most commonly encountered types of autoimmune thyroid disorders (AITDs), influenced by environmental factors, genetics, and the immune system. Previous research has shown a correlation between gut microbiota and HT, as well as the involvement of immune cells in its onset and progression. We aimed to investigate whether immune cells act as intermediaries in the causal relationship between gut microbiota and HT. In this study, we conducted bidirectional two-sample Mendelian randomization (MR) analyses to explore the relationship between gut microbiota and HT using data from genome-wide association studies (GWAS) and the MiBioGen study. Subsequently, MR analyses were performed to investigate the interactions between 731 immune cells and gut microbiota. Additionally, an MR analysis was performed to examine the association between HT and these 731 immune cells, using a GWAS dataset that included 3,757 European subjects. This approach provided insights into the impact of 22 million genetic variants on 731 immune cell signatures. There was a causal relationship between the increase in the number of 15 gut microbiota and HT. We observed that the genus Akkermansia, family Alcaligenaceae, family Desulfovibrionaceae, family Verrucomicrobiaceae, class Verrucomicrobiae, order Verrucomicrobiales, phylum Verrucomicrobia, class Alphaproteobacteria, order Desulfovibrionales, genus Ruminococcus torques group, genus Butyrivibrio, and genus Coprococcus3 were negatively correlated with HT. In addition, the genus Intestinimonas, genus Turicibacter, and genus Anaerostipes were positively correlated with HT. We identified EM CD4 + T cells as a mediator between the gut microbiota and HT. In conclusion, we presented causal associations between the EM CD4 + T cell-mediated gut microbiota and HT, as inferred from the MR findings derived from extensive aggregated GWAS data. Our research offers guidance and direction for treating and preventing HT.

Unveiling the Role of Gut Microbiota and Metabolites in Autoimmune Thyroid Diseases: Emerging Perspectives.

Autoimmune thyroid diseases (AITDs) are among the most prevalent organ-specific autoimmune disorders, with thyroid hormones playing a pivotal role in the gastrointestinal system's structure and function. Emerging evidence suggests a link between AITDs and the gut microbiome, which is a diverse community of organisms that are essential for digestion, absorption, intestinal homeostasis, and immune defense. Recent studies using 16S rRNA and metagenomic sequencing of fecal samples from AITD patients have revealed a significant correlation between a gut microbiota imbalance and the severity of AITDs. Progress in animal models of autoimmune diseases has shown that intervention in the gut microbiota can significantly alter the disease severity. The gut microbiota influences T cell subgroup differentiation and modulates the pathological immune response to AITDs through mechanisms involving short-chain fatty acids (SCFAs), lipopolysaccharides (LPSs), and mucosal immunity. Conversely, thyroid hormones also influence gut function and microbiota composition. Thus, there is a bidirectional relationship between the thyroid and the gut ecosystem. This review explores the pathogenic mechanisms of the gut microbiota and its metabolites in AITDs, characterizes the gut microbiota in Graves' disease (GD) and Hashimoto's thyroiditis (HT), and examines the interactions between the gut microbiota, thyroid hormones, T cell differentiation, and trace elements. The review aims to enhance understanding of the gut microbiota-thyroid axis and proposes novel approaches to mitigate AITD severity through gut microbiota modulation.

Thyroid peroxidase antibodies were associated with prevalent carotid intima-media thickness in middle-age and older adults: the ELSA-Brasil cohort.

Understanding the relationship between antithyroperoxidase antibodies (TPOAb) and carotid intima-media thickness (cIMT) could provide insights into the mechanisms linking thyroid autoimmunity and cardiovascular disease. We aimed to explore the association of multiple categories of TPOAb with the increased cIMT at baseline and at follow-up in participants from the ELSA-Brasil Study. This prospective cohort study analyzed data from 9,264 participants (51.5 ± 8.9 years old, 55.9% women) without a history of cardiovascular disease. Fasting serum TPOAb levels were determined. Values of cIMT equal to or above one deviation standard of the sample's mean were classified as increased cIMT at baseline. The increased cIMT after the 8-year follow-up was calculated after excluding participants with increased cIMT at baseline. Multivariate analyses were done using binary logistic and Poisson regression models. The increased cIMT was prevalent in 14.3% of the participants at baseline and its development occurred in 16.8% participants during the cohort. After adjustment for all confounder variables, TPOAb detectability (OR = 1.84, 95%CI = 1.21-2.79), and low detectable (OR = 1.81, 95%CI = 1.18-2.75), high detectable (OR = 2.01, 95%CI = 1.29-3.11) and positive (OR = 1.70, 95%CI = 1.07-2.70) TPOAb were positively associated with increased cIMT at baseline. The associations of low and high detectable TPOAb and increased cIMT at baseline were consistent when excluding those with thyroid dysfunction. There was no statistically significant association between TPOAb levels and increased cIMT at follow-up (p > 0.05), neither for all sample nor for euthyroid individuals. Different levels of TPOAb, including its detectability, were associated with increased cIMT at baseline in the studied sample. We highlight that may be relevant to consider the levels of TPOAb detectability as possible marker of increased cardiovascular risk.

Evaluation of alpha Klotho and fibroblast growth factor-23 levels in Iraqi patients with Graves’ disease

Background &amp; Objective: Graves’ disease (GD) is an autoimmune condition that targets the thyroid gland, resulting in excessive stimulation and synthesis of thyroid hormones. Excessive synthesis of these hormones can lead to symptoms such as loss of body weight, accelerated heart rate, irritability, reduced tolerance to heat, and excessive perspiration. Alpha-Klotho (KL), a protein crucial for physiological processes, is also involved in GD. The defective immunological condition of GD patients may increase Klotho expression, and the enhanced expression of fibroblast growth factor-23 (FGF23) in GD may be linked to the disease pathophysiology. We investigated serum levels of KL and FGF23 in Iraqi patients with Graves’ disease, analyzing correlations with clinical status and evaluating their potential as biomarkers for disease activity. Methodology: We conducted this cross-sectional study at The National Diabetes Center, Mustansiriyah University, between December 2022 and April 2023. The study involved 103 patients diagnosed with GD, and 103 patients, aged 21-70 y, as a control group. Patients with multinodular goiter, single thyroid nodules, thyroiditis, pregnant women, and those on medications or oral contraceptives, were excluded. Result: clinical significance of FGF23 and Klotho (KL) levels in patients with Graves’ disease (GD) compared to a control group. Results indicate that the median of KL levels are significantly higher in GD patients (KL = 6.31) compared to the control group (KL = 2.40), with a highly significant difference (P &lt; 0.001). In contrast, differences in median of FGF23 levels between GD patients (149) and controls (86.05) were not statistically significant (P = 0.07). Furthermore, KL levels were significantly higher in hyperthyroid patients compared to other thyroid statuses (P = 0.023), while FGF23 levels did not significantly differ across thyroid statuses (P = 0.255). Additionally, the study found a strong correlation between TRAb levels and both KL (r = 0.291, P &lt; 0.001) and FGF23 (r = 0.211, P = 0.003), and between KL and FGF23 directly (r = 0.412, P &lt; 0.001). These findings suggest that while KL may be a significant biomarker in GD, FGF23 relevance appears limited in this context. Conclusion: In Graves’ Disease patients have significantly higher levels of KL and FGF23 compared to controls, suggesting a distinct pathophysiological role for these biomarkers in mineral homeostasis and thyroid hormone regulation. Abbreviations: AITD - Autoimmune thyroid diseases; KL - Alpha-Klotho; FGF23 - fibroblast growth factor-23; GD - Graves’ disease; HT - Hashimoto's thyroiditis; IGF-1R - Insulin-like Growth Factor-1 Receptor; Keywords: Autoimmune Thyroid Disorders, Hyperthyroidism, Graves’ disease, Alpha-Klotho Citation: Rashid MF, Alammar HAJ, Rahmah AM. Evaluation of alpha Klotho and fibroblast growth factor-23 levels in Iraqi patients with Graves’ disease. Anaesth. pain intensive care 2024;28(5):836−841. DOI: 10.35975/apic.v28i5.2567 Received: June 16, 2024; Reviewed: July 07, 2024; Accepted: July 18, 2024

Association between air pollutants, thyroid disorders, and thyroid hormone levels: a scoping review of epidemiological evidence.

Over the past two decades, the incidence of thyroid disorders has been steadily increasing. There is evidence to suggest that air pollution may be one of the etiological factors of thyroid diseases. This comprehensive review aimed to examine the evidence related to air pollutants and thyroid disorders and thyroid hormones levels from an epidemiological perspective. The scoping review adopted a systematic approach to search for, identify, and include peer-reviewed articles published in English. We performed a comprehensive search of three databases-PubMed, Embase, and Web of Science to identify relevant literature on the relationship between air pollution [particulate matter, nitrogen oxide, carbon monoxide (CO), ozone (O3), sulfur dioxide (SO2)] exposure and thyroid disorders, including hypothyroidism, congenital hypothyroidism (CH), thyroid nodules, thyroid cancer, autoimmune thyroid diseases, as well as thyroid hormone levels, such as thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4). Articles published until August 1, 2023, were included. A total of 3,373 studies were retrieved, and among them, 25 studies covering eight different air pollutants were relevant. The most frequently studied air pollutants in this review included fine particulate matter (with fine particulate matter (PM2.5), n=21; inhalable particles (PM10), n=10; PM10-2.5, n=1) and nitrogen oxides (with NO2, n=13; NOx, n=3). The thyroid disorders and thyroid hormone levels most commonly associated with evidence of air pollution exposure were hypothyroidism (n=7) and TSH (n=12). Despite variations in study designs and exposure assessments, the findings consistently highlight the substantial health risks that air pollution, particularly PM2.5, poses to thyroid health, especially among vulnerable populations. Given that our study was limited to epidemiological investigations and the increasing prevalence of toxic substances in the environment, there is an urgent need for further research to elucidate the mechanisms by which these pollutants disrupt thyroid function and contribute to the development of thyroid diseases.

8176 An Unusual Case of Thyroid Eye Disease (TED) Occurring in Autoimmune Hypothyroidism

Abstract Disclosure: K. Prasongdee: None. C.M. Tessier: None. Background: It is unusual for TED to present in patients with autoimmune thyroid disease who are euthyroid or hypothyroid. Clinician recognition of this rare presentation is important in ensuring proper treatment and improving patient outcomes. Clinical Case:Our patient is a 57-year-old female with a past medical history of COPD, hypothyroidism presenting with several months of blurry vision. She reports double vision when looking down, and eye pain at rest and with eye movement. She was diagnosed with hypothyroidism one year prior to presentation, and her TSH subsequently normalized after titration to levothyroxine of 112 mcg daily. She reported no history of head or neck radiation. No family history of thyroid disease. She smoked for 30 pack years but stopped 2 years prior. Physical exam showed eye lid swelling and redness, pain and diplopia on end-lateral gaze, no chemosis, no conjunctival injection, or inflammation of the caruncle, lids closed completely, proptosis with Hertel ophthalmometer measured 23 mm on the right eye and 22 mm in the left eye (normal range &amp;lt; 18 to 20 mm for Caucasians), thyroid not enlarged with no palpable nodules, no thyroid bruits. The initial Clinical Activity Score (CAS) was 4, which indicated active TED. A thyroid ultrasound showed Inhomogeneous echogenicity with increased vascularity consistent with autoimmune thyroiditis. An MRI of the orbits revealed diffuse extraocular muscle enhancement and enlargement with tendinous insertion sparing, increased T2 hyperintensity findings which favored thyroid eye disease. Further laboratory testing confirmed the presence of multiple thyroid autoantibodies: Thyrotropin binding inhibitory immunoglobulin 2.76 IU/L (normal range &amp;lt; 1.75 IU/L), Thyroid peroxidase antibody 1135 IU/mL (normal range &amp;lt;9 IU/mL), Thyroglobulin antibodies 157 IU/mL (normal range &amp;lt; 116 IU/mL), thyroid-stimulating immunoglobulin 447% (normal range &amp;lt;140 % Baseline). She was referred to ophthalmology for management of TED and was started on teprotumumab. Her CAS improved to 0 and her diplopia resolved. Her proptosis remained stable. This case illustrates an unusual clinical course in a patient who initially presented with autoimmune hypothyroidism, later developed Thyroid Eye Disease. A study by Kahaly GJ et al showed that in Hashimoto’s thyroiditis (HT), thyroid-stimulating autoantibodies are highly correlated with thyroid eye disease (TED) with positive thyroid-stimulating autoantibodies detected in 5.5% of the patients with HT and 68.2% in the patients with HT and TED. Even though it is less common, up to 6% of patients with HT may be affected by TED. Rare presentations such as this case emphasizes the need to be vigilant when evaluating eye symptoms in patients with autoimmune thyroid disease. Teprotumumab that showed improvement in patients with Grave’s and thyroid eye disease, was also successful in treating our patient symptoms. Presentation: 6/3/2024

8746 Primary Prevention and Early Intervention for Cardiovascular Disease in Polyglandular Autoimmune Syndrome Type 2

Abstract Disclosure: V.N. Flores-Robles: None. Y. Fuentes-Rosa: None. M. Sanchez-Cordero: None. D.A. Lopez: None. M. Carrero-Quinones: None. Introduction: Polyglandular autoimmune syndrome type 2 (PAS-2) is an autoimmune syndrome that is known for lymphocytic infiltration causing organ-specific damage. It can include primary adrenal insufficiency (Addison's disease), type 1 diabetes mellitus (T1DM), autoimmune thyroid disease-causing Grave’s disease, or hypothyroidism, and can be diagnosed when two out of these three pathologies are present. Carpenter syndrome, a type of PAS-2, is described as the triad of Addison's disease, autoimmune thyroid disease, and T1DM. Its initial manifestation can be associated with non-endocrine and endocrine disorders as in autoimmune thyroid disease, T1DM, primary hypogonadism, and diabetes insipidus. It is well documented that uncontrolled diabetes mellitus can accelerate the progression of cardiovascular disease of co-existing coronary artery disease, but documentation that Addison’s disease may accelerate the progression is scant with only ten cases documented. On the other hand, there are no documented cases of the presence of coronary artery disease in patients with PAS-2. Case report: This case involves a 66-year-old Hispanic male with a past medical history of hypertension, and PAS-2, presenting with Addison’s disease, type 1 diabetes mellitus, and hypothyroidism. The initial presentation at the hospital was that of a complete atrioventricular block that required pacemaker placement. Cardiology services were consulted as the patient also had a positive stress test and eventually cardiac catheterization was done as further workup. Cardiac catheterization showed obstruction of the left main coronary artery of 80% and left circumflex with mild disease, that required coronary artery bypass (CABG). A 2D ECHO was done for further evaluation of cardiac function and findings were pertinent for an ejection fraction of 65-70%, mild concentric hypertrophy of the left ventricular wall, and left ventricular diastolic function with impaired relaxation pattern. The patient underwent the CABG procedure without any complications. He has been followed up outpatient and remains without any symptoms or pertinent presentation. Early intervention in this patient with PAS-2 prevented any further cardiovascular complications. Conclusion: Patients with PAS-2 may have a predisposition to developing coronary artery disease due to concomitant endocrinopathies that independently increase the risk of cardiovascular disease. This promotes further investigation into the primary prevention of cardiovascular disease in patients presenting with PAS-2. Taking into consideration the increased risk and/or progression of cardiovascular disease in these patients, early intervention and evaluation by cardiology services should be suggested as it may decrease their morbidity or mortality. Presentation: 6/2/2024