Graves' Disease Research Articles

Occurrence of Newly Diagnosed Thyroid Cancer Is Not Increased After Radioactive Iodine Therapy for Graves' Disease.

The purpose was to investigate i) whether the occurrence of newly diagnosed thyroid cancer is increased after radioactive iodine therapy (RAIT) for Graves' disease (GD), and ii) whether thyroid cancer following RAIT has poor prognosis. i) A total of 13,874 eligible patients diagnosed with untreated GD were retrospectively analyzed. The incidence rates of newly developed thyroid cancer by each treatment method for GD was evaluated using the person-year method.ii) Among the 23,179 patients who underwent RAIT for GD, including those with recurrent GD or a history of prior treatment for GD, those who developed thyroid cancer after RAIT were analyzed. Logistic regression analysis was performed to investigate the risk factors for thyroid cancer. i) A total of 2,273 cases underwent RAIT, 287 underwent surgical treatment, and 11,314 were treated with medication only, and new-onset thyroid cancer was identified in eight patients in the RAIT group and 39 in the medication-only group. A total of 107,218 person-years were observed, but no significant difference was observed in the incidence rate of thyroid cancer with treatment for GD. ii) Of the 23,179 cases underwent RAIT, 17 developed thyroid cancer. Sixteen were diagnosed with papillary thyroid carcinoma (PTC), of which 15 were microcarcinomas. Logistic regression analysis did not identify any significant risk factors for thyroid cancer development. In this study, the incidence of new thyroid cancer cases did not increase following RAIT for GD. Most thyroid cancers that developed after RAIT were micro-PTCs, with no evidence suggesting a poor prognosis.

Management of Ophthalmopathy and Use of Selenium in Graves' Disease: A Survey of Physicians from the Middle East and Africa

Abstract Objectives We explored how physicians in the Middle East and Africa (MEA) assess and manage Graves' ophthalmopathy (GO) and ascertain their perceptions of selenium (Se) in thyroid disease. Methods Two online questionnaires were sent to a sample of physicians from the MEA region. Responses from 183 GO and 102 Se surveys were received and analyzed. Results In the GO survey, 68.6% thought multidisciplinary team (MDT) was very valuable, but fewer participated in MDT (19.0%) or referred patients to MDT (44.2%). Respondents advocated the assessment of visual fields by perimetry (65.9%), magnetic resonance imaging (52.9%), color vision (51.8%), and ultrasonography (14.1%). Autoimmune thyroid diseases (ATDs) were the most common choice (95.1%) for first-line therapy for coexisting hyperthyroidism. Glucocorticoids (GCs) were preferred as the first-line therapy by the majority of respondents; among them, 63.1% chose the intravenous route. The treatment strategy for GO with intravenous GC therapy remains debatable and surgical decompression (31.3%) and radiotherapy (13.1%) were recommended. When diabetes coexists, radiotherapy and orbital decompression are more favored over GCs. Regarding the Se survey, a minority (10.3%) used Se routinely for Graves' disease (GD). However, this increased to 29.1% when GO exists. However, about a quarter needed to be sure/did not know (23.9%) the evidence in GD without GO and 27.4% for GD with GO. In GD without GO on ATDs, 67.5% never recommend Se, whereas 32.5% recommend Se sometimes. Conversely, when GO occurs, 65.0% recommend Se in variable frequencies. Of these, Se is used as an alternative to watchful waiting in patients with mild ocular involvement (22.1%) and as an adjuvant to the established treatment in patients with moderate to severe ocular involvement (20.4%). The dose of 200 mcg/day was recommended by 42.5% of respondents. Conclusion Gaps exist in the physicians' knowledge and practices concerning diagnosis and management of GO. More focused education and training are needed in the MEA region.

Assessing the Causal Association Between COVID-19 and Graves Disease: Mendelian Randomization Study.

Graves disease (GD) is an autoimmune thyroid disorder characterized by hyperthyroidism and autoantibodies. The COVID-19 pandemic has raised questions about its potential relationship with autoimmune diseases like GD. This study aims to investigate the causal association between COVID-19 and GD through Mendelian randomization (MR) analysis and assess the impact of COVID-19 on GD. We conducted an MR study using extensive genome-wide association study data for GD and COVID-19 susceptibility and its severity. We used stringent single nucleotide polymorphism selection criteria and various MR methodologies, including inverse-variance weighting, MR-Egger, and weighted median analyses, to assess causal relationships. We also conducted tests for directional pleiotropy and heterogeneity, as well as sensitivity analyses. The MR analysis, based on the largest available dataset to date, did not provide evidence supporting a causal relationship between COVID-19 susceptibility (odds ratio [OR] 0.989, 95% CI 0.405-2.851; P=.93), COVID-19 hospitalization (OR 0.974, 95% CI 0.852-1.113; P=.70), COVID-19 severity (OR 0.979, 95% CI 0.890-1.077; P=.66), and GD. Tests for directional pleiotropy and heterogeneity, as well as sensitivity analyses, supported these findings. This comprehensive MR study does not provide sufficient evidence to support a causal relationship between COVID-19 and the onset or exacerbation of GD. These results contribute to a better understanding of the potential association between COVID-19 and autoimmune diseases, alleviating concerns about a surge in autoimmune thyroid diseases due to the pandemic. Further research is warranted to explore this complex relationship thoroughly.

Chimeric autoantibody receptor T cells specifically eliminate Graves’ Disease autoreactive B cells

IntroductionChimeric antigen receptor (CAR) T cells have recently become an important treatment for hematological cancers by efficiently eliminating B cells. B cell depleting CAR T cells are also in clinical trials for their use in treating severe autoimmune diseases and have shown promise in patients who have exhausted other treatment options; however, they do result in immunosuppression due to B cell depletion. Specifically eliminating the disease-causing B cells while leaving the healthy B cells untouched could address this limitation.MethodsA chimeric autoantibody receptor (CAAR) has an autoantigen as the binding domain of the CAR T cell and could allow for specific targeting of autoreactive B cell populations. In Graves’ Disease (GD), pathogenesis is centered around autoreactive B cells which are specific for thyroid stimulating hormone receptor (TSHR). By engineering epitopes of TSHR as the binding domain, our CAAR was able to bind to anti-TSHR antibodies and B cell receptors.ResultsThese TSHR CAAR T cells specifically eliminated anti-TSHR B cells, without exhibiting cytotoxicity against healthy B cells. We hypothesized that soluble autoantibodies and thyroid stimulating hormone (TSH) could bind to the CAAR, potentially causing overactivation or inhibition. When evaluated, we found that one construct was significantly impacted by soluble autoantibodies, while the other construct was uninhibited. Soluble TSH did not significantly affect either construct. The TSHR CAAR T cells were also effective at eliminating anti-TSHR B cells in the presence of plasma from various GD patients.DiscussionThus, TSHR CAAR T cells show promise in eliminating the disease-causing autoreactive B cells in GD without eliminating healthy cells. This treatment mechanism also has the potential to be used in other B cell-mediated autoimmune diseases.

Thyroid peroxidase antibodies and their role in predicting outcomes in Graves' disease treatment.

Graves´ disease (GD) is the predominant cause of hyperthyroidism. Treatment options include antithyroid drugs (ATD), surgery, and radioactive iodine ablation (RI). Although thyroid peroxidase antibodies (anti-TPO) are prevalent in patients with GD, their role in driving relapse or hypothyroidism after treatment in patients with GD remains unclear. This study aimed to determine if patients with anti-TPO at GD diagnosis are more likely to relapse after ATD or RI treatment, and if patients with anti-TPO are at increased risk of developing hypothyroidism post-ATD treatment. This was an observational, non-interventional retrospective registry study, which included 712 patients treated for GD at a single center in Sweden during 2002-2018. After therapy with ATD, there was no difference in relapse rate between patients with (37.0%) or without (38.4%) anti-TPO at GD diagnosis. Age <40 years was a risk factor for relapse after ATD (p<0.0001). Presence of anti-TPO at diagnosis was associated with reduced relapse rate after RI (13.9% vs. 24.6%; p=0.049). Development of hypothyroidism after discontinuation of ATD did not correlate with anti-TPO status at diagnosis (with anti-TPO: 17.3%; without anti-TPO: 20.8%). Increased risk of hypothyroidism was seen with ATD treatment for >2 years, p<0.05. Anti-TPO positivity at diagnosis of GD did not affect the relapse rate after ATD treatment but could be associated with a better long-term effect of RI. Anti-TPO did not increase the risk of hypothyroidism post-ATD therapy. Understanding risk factors of relapse or hypothyroidism can facilitate treatment choices and help physicians individualize management and follow-up strategies for patients with GD.

EXPRESS: Spexin as a Potential Biomarker for Autoimmune Inflammation in Graves’ Disease

Graves’ disease (GD) is an autoimmune thyroid disorder characterized by excessive thyroid hormone production driven by thyroid-stimulating hormone receptor antibodies (TRAb). This study aimed to investigate the relationship between serum spexin (SPX) levels, TRAb levels, thyroid ultrasound findings, and metabolic parameters in GD patients, while evaluating SPX as a potential biomarker for autoimmune inflammation. A prospective, single-center study included 45 GD patients and 45 healthy controls. Serum TSH, fT3, fT4, anti-thyroglobulin, anti-thyroid peroxidase, TRAb, and SPX levels were measured. Thyroid ultrasonography classified patients into mild, moderate, and high heterogeneity groups. SPX levels were significantly higher in GD patients compared to controls (p &lt; .001) and showed a strong positive correlation with TRAb levels (r = .579, p &lt; .001) and thyroid heterogeneity (p &lt; .001). Newly diagnosed patients (&lt;6 months) exhibited the highest SPX levels, which decreased with prolonged disease duration. Receiver Operating Characteristic (ROC) analysis identified a cutoff value of 105 pg/mL for SPX, yielding 60% sensitivity and 91.1% specificity (AUC: 0.765, p &lt; .001). SPX levels were also inversely correlated with disease duration and positively associated with inflammatory markers, suggesting its utility in monitoring disease activity and progression. These findings highlight SPX as a novel biomarker for assessing disease severity and autoimmune inflammation in GD. Incorporating SPX measurements into clinical practice may aid in early diagnosis, disease stratification, and therapeutic monitoring, ultimately improving personalized care for GD patients.

Immune-parenchymal multicellular niches are shared across distinct thyroid autoimmune diseases.

Thyroid hormone, produced in the thyroid gland, regulates metabolism, development, and cardiac function. The thyroid is susceptible to autoimmune attack by both cellular and humoral immunity exemplified by Hashimoto's thyroiditis (HT) and Graves' Disease (GD), respectively. In HT, immune-mediated destruction impairs thyroid hormone production, while in GD, stimulating autoantibodies promote over-production. Here, we generated a multi-modal atlas of 604,076 human thyroid and blood cells from HT, GD, and control patients. We found that, despite markedly different clinical presentations and distinct antigenic triggers, HT and GD exhibit convergent cellular dynamics resulting in a shared continuum of immune infiltration. Along this continuum, a key feature is a thyrocyte niche containing CD8 + T cells that may segregate pathogenic T cells from regions with preserved thyroid hormone production. These findings of a shared disease continuum characterized by spatially defined immune niches provide a new framework for understanding tissue homeostasis in human autoimmune disease.

Incidental Thyroid Cancer in Patients With Graves' Disease: Not as Rare as We Previously Believed.

Incidental Thyroid Cancer in Patients With Graves' Disease: Not as Rare as We Previously Believed.

High-dose versus low-dose block-and-replace treatment for a first episode of Graves' disease.

The optimal treatment with antithyroid drugs (ATDs) for a first episode of Graves' disease (GD) remains controversial. Retrospective, two academic centres study of newly diagnosed GD between 1990 and 2022, treated with ATD in block-and-replace (B+R) regimen for at least 12 months and followed up for at least 1 year after ATD discontinuation or until disease relapse. Sixty patients received high-dose B+R (HD) with fixed ATD dose maintained during the study, and 60 patients received low-dose B+R (LD) with lower ATD dose adjusted during the study. Baseline characteristics were similar in both groups. The point-prevalence of euthyroidism was not different between HD and LD (38 vs 47%, P = 0.460 at 6 months, 69 vs 82%, P = 0.194 at 12 months, 70 vs 78%, P = 0.370 at 18 months, respectively). At 18 months, 27% HD vs 38% LD (P = 0.242) had thyroid eye disease. There were no differences in the number or type of ATD-related adverse events (AE) (no AE 73 vs 78%, P = 0.707). LD received mean lower ATD dose (15.3 ± 4.2 vs 30.0 ± 0.0 mg/day, P < 0.001) and lower levothyroxine dose (72.6 ± 16.7 vs 100.6 ± 24.5 μg/day, P < 0.001). After a first course of ATD, 63% of HD patients and 60% of LD patients relapsed (P = 0.707) after a median time (interquartile range) of 11.0 (18) vs 7.0 (19) months (P = 0.109). We observed similar relapse rates in patients with a first episode of GD receiving up to 50% less ATD and 30% less levothyroxine dose than high-dose B+R regimen.

Exploring glucagon-like peptide-1 receptor agonists as potential disease-modifying agents in autoimmune diseases.

Exploring glucagon-like peptide-1 receptor agonists as potential disease-modifying agents in autoimmune diseases.

Graves’ disease in Children: A Case Report of Rare Occurrence

Graves’ disease (GD) is an autoimmune disorder that manifests as goiter, weight loss, heat intolerance, and palpitations. It is rare in preschool-aged children (&lt;5 years) and can lead to serious acute and long-term complications, including growth and development, if left undiagnosed. We present the case of a four-year-old Hindu Asian girl from a low socioeconomic background who presented with progressive thyroid enlargement and symptoms of excessive sweating, heat intolerance, weight loss, diarrhea, fatigue, and palpitations over six months. Examination revealed symmetrical goiter, signs of thyrotoxicosis, bilateral exophthalmos, and raised blood pressure. Laboratory investigations confirmed Graves’ disease with suppressed TSH, elevated T3 and free T4, and persistently high TSH receptor antibodies (TRAb &gt;40 IU/L). She was started on carbimazole and propranolol, resulting in clinical improvement; however, biochemical parameters, including TRAb levels, remain persistently elevated at eight months and suppressed TSH at 13 months, indicating a high risk of relapse. Long-term ATD therapy will be continued, with definitive treatment (RAI or thyroidectomy) considered if remission is not achieved after three years. This case underscores the challenges of managing Graves’ disease in young children and the need for prolonged monitoring and individualized treatment strategies. doi: https://doi.org/10.12669/pjms.41.4.10689 How to cite this: Butt AT, Ayaz Ur Rehman, Ramzan S, Arif M. Graves’ disease in Children: A Case Report of Rare Occurrence. Pak J Med Sci. 2025;41(4):1253-1256. doi: https://doi.org/10.12669/pjms.41.4.10689 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

In vivo and in vitro evidence for a protective role of autoantibodies against the insulin-like growth factor-1 receptor (IGF-1R) in Graves' orbitopathy.

The insulin-like growth factor-1 receptor (IGF-1R) plays a role in the pathogenesis of Graves' orbitopathy (GO). A possible protective role of autoantibodies against IGF-1R (IGF-1R-Abs) on GO has been suggested. We conducted a cross-sectional study to investigate IGF-1R-Abs in 147 consecutive Graves' disease (GD) patients, with (n = 92) or without (n = 55) GO (primary outcome), their relationship with GO features and their effect on cell proliferation in primary cultures of orbital fibroblasts. Serum IGF-1R-Abs levels were higher (29.3 ng/mL, IQR 17.4-36.6) in patients without GO than in those with GO (19.8 ng/mL, IQR 11.2-29.8; Mann Whitney U 1819, P = 0.00509). The prevalence of IGF-1R-Abs levels above the previously established cut-off value of 55 ng/mL did not differ statistically between the two groups, despite a trend towards a greater prevalence in patients without GO (9 vs 3.2%) (Fig. 1b). Within GO patients, serum IGF-1R-Abs did not correlate with proptosis, CAS, eyelid width and visual acuity, whereas there was an inverse correlation with diplopia, being IGF-1R-Abs lower in patients with the most severe degrees (Omega square = 0.0123, P = 0.035). Incubation of orbital fibroblasts from GO patients with IgGs purified from a pool of sera with IGF-1R-Abs > 55 ng/mL decreased cell proliferation in a dose-dependent manner (Omega square = 0.747; P < 0.0001). Serum autoantibodies against the IGF-1R are present in a minority of patients with GD and seem to exert a protective role on GO development and features.

Machine learning in lymphocyte and immune biomarker analysis for childhood thyroid diseases in China

ObjectiveThis study aims to characterize and analyze the expression of representative biomarkers like lymphocytes and immune subsets in children with thyroid disorders. It also intends to develop and evaluate a machine learning model to predict if patients have thyroid disorders based on their clinical characteristics, ultimately providing insights to enhance the clinical guidelines for the pathogenesis of childhood thyroid disorders.MethodThis cross-sectional study conducted in China examined diagnosed cases to describe the characteristics and expression of lymphocyte and immune subsets as predicted by the model. The study included two groups of children: 139 who were hospitalized in the Department of Endocrinology and a control group consisting of 283 children who underwent routine health checks at the Department of Children Healthcare. Cases were classified into three groups based on diagnoses: Graves’ disease (GD), Hashimoto’s thyroiditis (HT), and hypothyroidism. By employing 11 readily obtainable serum biochemical indicators within three days of admission, the median concentrations and percentages of subset measurements were analyzed. Additionally, nine machine learning (ML) algorithms were utilized to construct prediction models. Various evaluation metrics, including the area under the receiver operating characteristic curve (AUC), were employed to compare predictive performance.ResultsGD cases had increased levels of CD3-CD19 + and CD3 + CD4 + T lymphocytes, and a higher CD4+/CD8 + ratio. In both GD and HT, the levels of complement C3c, IgA, and IgG were higher than those in the control group. HT cases also had an increasing percentage of CD3-CD16 + 56 + T lymphocytes. Most immune markers increased in hypothyroidism, except for some T lymphocyte percentages and the CD4+/CD8 + ratio. To reduce age-related bias, propensity score matching was used, yielding consistent results. Among the nine machine learning models evaluated, logistic regression showed the best performance, being useful in clinical practice.ConclusionsSpecific lymphocytes with different biomarkers are positively correlated with autoimmune thyroid disease (AITD) in children. Complement proteins C3c and C4, along with IgG, IgA, IgM, and T/B cells, are significant in childhood thyroid diseases. Our best model can effectively distinguish these conditions, but to enhance accuracy, more detailed information such as clinical images might be needed.

The Relationship Between Inflammatory Parameters in Hemogram and Thyroid Stimulating Immunoglobulin (TSI) Levels at the Beginning and the 6th Month of Treatment in Graves' Disease

Abstract Objective: Thyroid stimulating immunoglobulin (TSI) is used in the differential diagnosis of thyrotoxicosis and disease recurrence and activity. However, the accessibility and the cost can limit the use of TSI. In our study, we investigated the existence of easily accessible markers that can be used instead of TSI in the diagnosis and follow-up of Graves' disease (GD). The aim was to evaluate the relationship between TSI levels and inflammatory markers such as neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), platelet-lymphocyte ratio (TLR), systemic immune inflammation (SII) index, pan-immune inflammation value (PIV) obtained from the complete blood count of the patients at the beginning and 6 months after anti-thyroid treatment. Materials and Methods: 162 patients diagnosed with Graves' disease were retrospectively investigated. According to the free T4 level, the patients were divided into 3 groups as mild, moderate, and severe disease. Thyroid function tests, hemogram parameters, and TSI values of the patients at the time of diagnosis and after 6 months of anti-thyroid treatment were compared. The correlation of the statistically significant parameters with TSI was studied separately for each group. Results: While there was a significant increase in hemoglobin (p=0.009), leukocyte (p=0.001), neutrophil (p=0.002), lymphocyte (p=0.002), eosinophil (p=0.033), basophil (p=0.001) and TSH (p=0.001) levels after treatment compared to the baseline, there was a significant decrease in monocyte (p=0.003), platelet (p=0.010), TLR (p=0.001), MLR (p=0.001), freeT3 (p=0.001), freeT4 (p=0.001) levels. The correlation of these statistically significant parameters with TSI was observed. When the baseline and 6th month post-treatment values were investigated in all patients; a weak positive correlation was detected between TSI and monocytes and MLR, and a weak positive correlation was detected with freeT3. A weak positive correlation was detected between TSI and RDW and freeT3 in the severe disease group. Conclusion: Although a reliable marker that can be used as an alternative to TSI in the follow-up of Graves' disease has not been available, monocyte level, MLR and RDW in patients with severe Graves’ disease may predict an activation in the follow-up of the disease.

Evaluation of tear and serum clusterin levels in thyroid ophthalmopathy patients.

To evaluate tear and serum clusterin levels in thyroid eye disease (TED) patients. The study included 21 patients with Graves disease with TED, 20 patients with Graves disease without TED, and 21 healthy control subjects matched for sex and age. Clusterin and lysozyme C levels of tear and serum were detected using enzyme-linked immunosorbent assays. In addition, free triiodothyronine, free thyroxine, thyroid stimulating hormone (TSH), and autoantibody (anti thyroid peroxidase, anti thyroglobulin and TSH receptor antibody) levels were measured in all groups. The mean concentrations of tear clusterin and lysozyme C levels were 15.99 ± 4.07ng/mL and 54.54 ± 27.58ng/mL in Graves patients with TED, 26,28 ± 15,98ng/mL and 50,13 ± 46,59ng/mL in Graves patients without TED, and 55,53 ± 45,99ng/mL and 44,86 ± 27,42ng/mL in control subjects, respectively. The mean concentrations of serum clusterin and lysozyme C levels were 23.15 ± 4.25ng/mL and 93.14 ± 51.38ng/mL in Graves patients with TED, and 26.73 ± 15.93ng/mL and 74.22 ± 55.73ng/mL in Graves patients without TED, and 27.47 ± 12.83ng/mL and 76.13 ± 65.24ng/mL in control subjects, respectively. The tear clusterin levels showed significant differences in Graves patients with and without TED than in the control group (p < 0.001). In Graves patients with TED group, tear clusterin levels were lower than in Graves patients without TED, however this difference was not statistically significant (p = 0.431). There was a statistically significant low-grade correlation between tear clusterin and clinical activity score, retraction, and Hertel measurements (range of r value: -0.299 and -0.279, and range of p values:0.024-0.034). The tear clusterin levels were decreased in Graves patients with and without TED. The results suggest that a local reduction in the amount of clusterin may play an important role in the pathogenesis of Graves disease and might be used as a local biomarker.

The causal effects between autoimmune thyroid disease and urticaria: evidence from a Mendelian randomization study.

Previous studies have suggested a comorbidity between autoimmune thyroid disease (AITD) and urticaria. However, the causal effects between AITD and urticaria remain unclear. This study employed genome-wide association study (GWAS) data to analyze the associations between AITD and urticaria through bidirectional Mendelian randomization (MR), meanwhile, examined the role of 731 immune traits as mediators between the two diseases through mediation analysis. The IVW results indicated that Graves' disease (GD) and Hashimoto's thyroiditis (HT) have a potential risk effect on urticaria, particularly increasing the risk of other and unspecified urticaria and idiopathic urticaria. Urticaria, mainly other and unspecified urticaria, dermatographic urticaria demonstrated a potential risk effect on HT. The mediation analysis revealed that GD likely increases the risk of other and unspecified urticaria by reducing CD4-CD8- Natural Killer T Absolute Counts, and reduces the levels of three types of T cells thereby increasing the risk of idiopathic urticaria. HT increased the risk of idiopathic urticaria through reducing the levels of two types of myeloid Dendritic Cells. The study revealed both GD and HT have causal associations with urticaria, particularly with other and unspecified urticaria and idiopathic urticaria. GD and HT may elevate the risk of spontaneous urticaria by regulating different immune traits.

Graves' Disease: Is It Time for Targeted Therapy? A Narrative Review.

Current therapies for Graves' disease (GD) primarily aim to manage hyperthyroidism through synthetic antithyroid drugs, radioiodine, or surgery. However, these approaches are often limited by their incomplete efficacy and the risk of inducing hypothyroidism. The latest advances in understanding the autoimmune mechanisms driving GD have paved the way for novel therapies targeting the thyrotropin receptor (TSH-R) or immune pathways. Overall, key targets include cluster of differentiation 20 (CD20), cluster of differentiation 40 (CD40), protein tyrosine phosphatase non-receptor type 22 (PTPN22), cytotoxic T lymphocyte antigen-4 (CTLA-4), B cell-activating factor (BAFF), and the Fc receptor-like protein 3 (FcRL3). Recent preclinical studies and clinical trials testing targeted therapies have shown promising results in terms of efficacy and safety. Here, we present a narrative review of the literature on emerging therapeutic approaches for GD that are currently under investigation.

Management of Thyroid Disorders during Pregnancy: A Survey of Physicians from the Middle East and North Africa

Abstract Objectives We explored the clinical practice of screening and managing hyperthyroidism and hypothyroidism during pregnancy in the Middle East and North Africa. Methods We used an online questionnaire based on clinical case scenarios to a regional physician database and invited those managing pregnant women with thyroid disease to respond. Results We analyzed 136 eligible responses. For a woman with newly diagnosed Graves' disease (GD) and wishing to conceive, 77.5% of the respondents would initiate antithyroid drugs (ATDs), while 20.3% would recommend definitive treatment with radioiodine or surgery. In the case of a relapsed GD before pregnancy, 84.3% preferred definitive treatment. For a woman with newly diagnosed GD during pregnancy, 39.4% will start propylthiouracil (PTU), 8.5% with methimazole/carbimazole, while 50.0% will start with PTU and then switch to methimazole after the first trimester. Respondents used several combinations of tests to monitor the dose of ATDs, and the thyroid test results they targeted were inconsistent, though nearly half of the respondents targeted achieving low serum thyroid-stimulating hormone (TSH) with free thyroxine (or total T4) in the upper end of the normal range. For a lactating woman with GD, 80.3% would give ATDs without stopping lactation. For the management of gestational thyrotoxicosis, 45.1% chose to follow-up, and 40.8% treated patients with PTU. Although the timing of TSH receptor antibody measurement in pregnant hyperthyroid patients was variable, 53% of respondents would check it at least once during pregnancy. The starting dose of L-thyroxine for a woman diagnosed with overt hypothyroidism in pregnancy, preconception management of euthyroid women with known thyroid autoimmunity, and approach related to ovarian hyperstimulation in women with thyroid peroxidase antibodies were widely variable. For women with known hypothyroidism, 34.6% of respondents would increase the L-thyroxine dose by 30 to 50% as soon as pregnancy is confirmed. Concerning screening, 42.7% of respondents perform universal evaluation and 70% recommend TSH &lt; 2.5 mUI/L in the first trimester and TSH &lt; 3 mUI/L in the second and third trimester as target results in known hypothyroid women. Conclusion Physicians' clinical practices regarding thyroid disorders in pregnant women vary. This highlights the need for focused training and quality assurance to achieve more consistent care.

Vaccine to Nano-Vaccine: Novel Technique to Treat Rheumatoid Arthritis.

Autoimmune diseases are a class of diseases wherein the immune system of the body targets itself through autoreactive T cells and autoantibodies. Autoimmune diseases are classified as organ-specific autoimmune diseases and systemic autoimmune diseases. Organ-specific autoimmune diseases such as primary biliary cirrhosis, Hashimoto's Thyroiditis (HT), Type 1 Diabetes mellitus (T1D), and Graves' Disease (GD) are characterized by a unique immune system response to autoantigens in a single organ. Systemic autoimmune diseases such as Systemic Lupus Erythematosus (SLE), Rheumatoid Arthritis (RA), and Sjogren syndrome are characterized by a systemic spread of autoantigens causing a multi-organ attack. In this review, we discuss rheumatoid arthritis, its prevalence in India, and its risk factors. We discuss the pharmacotherapies for RA that are currently available on the market. By identifying the disadvantages and side effects of the treatment, we mainly focus on how nanotechnology will be helpful in vaccine research and the advancement of anti-RA therapeutics from vaccines to nano-vaccines. In addition, the benefits of nano-vaccines are explored in future perspectives. In conclusion, nano-vaccines will be a novel technique for treating RA because they show possible outcomes from nanovaccine use.

K-Means Clustering Reveals Long-Term Thyrotropin Receptor Antibody Patterns in Graves' Disease: Insights from a 10-Year Study with Implications for Graves' Orbitopathy.

Background/Objectives: We aimed to explore long-term trajectories of thyroid-stimulating hormone receptor antibody (TRAb) in patients with Graves' disease (GD) and to identify key factors associated with TRAb normalization. We also investigated whether these trajectories correlate with Graves' orbitopathy (GO) comorbidity. Methods: We retrospectively reviewed 403 patients with GD who had an initial TRAb level ≥ 1.5 IU/L between 2010 and 2021, monitoring their TRAb levels for at least 3 years. K-means clustering was performed to categorize patients into distinct TRAb change patterns (A, B, C, D). We employed a Cox regression-based time-to-event model, expressing results as "Survival ratio" rather than the conventional Hazard ratio, to reflect the proportion of patients achieving TRAb normalization over time. Key variables included age, sex, initial TRAb, and GO comorbidity. Results: Four unique TRAb patterns emerged, differing primarily in baseline TRAb levels, duration of GD, and treatment approaches. Pattern A demonstrated the highest TRAb normalization rate (96%), whereas Patterns B (80%), C (29%), and D (13%) showed lower probabilities. Regrouping into A vs. BCD further emphasized the distinct normalization profile of Pattern A. A higher "Survival ratio" was observed in female patients and those with baseline TRAb < 6.14 IU/L. In contrast, patients whose TRAb levels were ≥6.14 IU/L frequently exhibited persistently elevated values over a decade. GO comorbidity did not significantly differ among the four patterns. Conclusions: K-means clustering revealed four unique TRAb change patterns in GD, with baseline TRAb (stratified by the median of 6.14 IU/L) and sex emerging as significant predictors of normalization. These findings highlight the importance of early TRAb monitoring and tailored therapeutic strategies, particularly for those with persistently elevated TRAb levels.