Circular RNA circPHF16 enhances IL-17A expression and secretion by sequestering miR-378a-3p to activate the IL6ST axis in Graves' disease.

Interleukin-17A (IL-17A) plays a pivotal role in the pathogenesis of Graves' disease (GD), an autoimmune disorder affecting thyroid function, but the detailed regulatory mechanisms remain elusive. Circular RNAs (circRNAs) have emerged as key regulators of IL-17A expression and secretion in autoimmune diseases, yet their specific role in GD, especially within CD4 + T lymphocytes, are not well understood. In this study, a circRNA, circPHF16 (hsa_circ_0090364) was found to be highly expressed in the peripheral blood mononuclear cells and serum of GD patients. In vitro experiments in Jurkat T cells revealed that silencing of circPHF16 suppressed IL-17A expression and secretion, while overexpression of circPHF16 had the opposite effect. Furthermore, bioinformatics analysis demonstrated a circPHF16/miR-378a-3p/IL6ST pathway, in which circPHF16 regulates IL6ST expression, which, in turn, influences IL-17A expression and secretion by interacting with miR-378a-3p. In vivo studies in a mouse model of GD showed similar trends in molecular expression levels, consistent with competitive endogenous RNA interactions. Together the results of the study identify circPHF16 as a potential target in the development of new strategies for GD diagnosis and treatment, and thus, offer a theoretical foundation for clinical therapeutic approaches in GD.

A meta-analysis: elucidating diagnostic thresholds of peak systolic flow velocities in thyroid arteries for the discrimination of Graves' disease and destructive thyrotoxicosis.

Objective: This meta-analysis examines peak systolic velocities (PSVs) in thyroid arteries as potential biomarkers for thyroid disorders, which includes treated and untreated Graves' disease(GD) and destructive thyrotoxicosis(DT). Methods: A search across databases including PubMed, Google Scholar, Embase, and Web of Science identified studies assessing peak systolic flow velocity in the inferior thyroid artery (ITA-PSV) and superior thyroid artery (STA-PSV) diagnostic efficacy in GD and DT.And the search was restricted to publications in the English language.The analysis compared STA-PSV and ITA-PSV across patient groups, evaluating intra-group variances and synthesizing sensitivity and specificity data. Results: The analysis covered 18 studies with 1276 GD, 564 DT patients, and 544 controls. The difference of STA-PSV between GD group, DT group and normal group and the difference of ITA-PSV were analyzed in subgroups, and there was no statistical significance between subgroups when comparing any two groups. Normal subjects displayed intra-group ITA-PSV and STA-PSV differences with established cut-off values of 20.33 cm/s (95% CI, 17.48-23.18) for ITA-PSV and 25.61 cm/s (95% CI, 20.37-30.85) for STA-PSV. However, no significant intra-group differences were observed in the STA-PSV and ITA-PSV cut-off values among groups with GD or DT. The combined cut-off values for these patient groups and normal subjects were 68.63 cm/s (95% CI, 59.12-78.13), 32.08 cm/s (95% CI, 25.90-38.27), and 23.18 cm/s (95% CI, 20.09-26.28), respectively. The diagnostic odds ratio(DOR) for these values was 35.86 (95% CI, 18.21-70.60), and the area under the summary receiver operating characteristic (SROC) curve was 0.91, with a sensitivity estimate of 0.842 (95% CI, 0.772-0.866). Conclusion: PSVs in thyroid arteries are useful diagnostic tools in distinguishing DT from GD. A PSV above 68.63 cm/s significantly improves GD diagnosis with up to 91% efficacy. No notable differences were found between superior and inferior thyroid arteries in these conditions.

The Two-Year Results of Using Radiofrequency Ablation as a Novel Treatment for Persistent or Relapsed Graves' Disease: A Prospective Study.

Objectives: Graves' disease (GD) is the most common cause of hyperthyroidism. Antithyroid drugs (ATDs) are the first-line treatment, but when discontinued, >50% of patients experience relapses. Conventional definitive treatment options include surgery and radioiodine therapy (RAI), each with its own disadvantages. Radiofrequency ablation (RFA) achieved promising short-term remission rates in a previous pilot study. The current study reports our experience of using RFA to treat relapsed GD in the largest cohort of patients with a longer follow-up period. Methods: This single-arm prospective study recruited consecutive patients aged ≥18 with persistent/relapsed GD requiring ATD from two tertiary endocrine surgery centers. Those with compressive goiter, suspected thyroid malignancy, moderate-to-severe Graves' ophthalmopathy, preference for surgery/RAI, or pregnancy were excluded. Eligible patients received ultrasound-guided RFA to the entire bulk of the thyroid gland. ATDs were discontinued afterward, and thyroid function tests were monitored bimonthly. The primary outcome was the disease remission rate at 24 months follow-up after single-session RFA, defined as being biochemically euthyroid or hypothyroid without ATD. Secondary outcomes were complication rates. Results: Of the 100 patients considered, 30 (30.0%) patients were eligible and received RFA. Most were female patients (93.3%). The median total thyroid volume was 23 mL (15.9-34.5). All completed 24 months follow-up. After single-session RFA, disease remission rates were 60.0% at 12 months and 56.7% at 24 months. Among the 13 patients with relapse after RFA, 9 (69%) required a lower ATD dose than before RFA; 2 received surgery without complications. Total thyroid volume was the only significant factor associated with relapse after RFA (odds ratio 1.054, confidence interval 1.012-1.099, p = 0.012). At 24 months, RFA led to disease remission in 100% of the 9 patients with a total thyroid volume <20 mL and 35% of patients with a total thyroid volume ≥20 mL (p = 0.007). There was no vocal cord palsy, skin burn, hematoma, or thyroid storm after RFA. Conclusions: In a highly selected group of patients with relapsed GD and predominantly small thyroid glands, single-session RFA may achieve disease remission. Smaller total thyroid volume may be a favorable factor associated with disease remission after RFA. The results of this study need to be confirmed with a long-term clinical trial. Clinical Trial Registration: This study is registered at www.clinicaltrial.gov with identifier NCT06418919.

[Graves' orbitopathy as the cause of diplopia in old age-Differences between young and old]. / Endokrine Orbitopathie als Ursache einer Diplopie im Senium ­ Unterschiede zwischen Jung und Alt.

BACKGROUND: Endocrine orbitopathy (EO) is an autoimmune disease mostly associated with a disease of the thyroid gland, which leads to inflammation, adipogenesis and fibrosis. The severity of EO can vary greatly between individuals, which makes it difficult to exactly predict the natural course of the disease; however, this is important to be able to individually adapt the treatment. The aim of this study was to compare the clinical features, course, treatment and prognosis for patients with EO under 50 years old with older patients. The results of the study with a focus on motility are presented in this special issue. PATIENTS AND METHODS: The hospital records of a randomly selected sample of 1000 patients from the EO databank in Essen (GODE), which includes 4260 patients, were analyzed. The patients were divided into two groups: group 1 ≤50 years and group 2 >50 years. Only patients with complete data sets were included in the statistical analyses. RESULTS: Younger patients (n = 484) presented significantly more frequently with milder EO (53% vs. 33%, p < 0.0001), whereas older patients (n = 448) more frequently suffered from moderate or severe forms (44% vs. 64%, p < 0.0001). Older patients showed more severe strabismus, motility and clinical activity scores (5.9 vs. 2.3 prism diopters, PD/310° vs. 330°, both p < 0.0001, CAS 2.1 vs. 1.7, p = 0.001). Proptosis and the occurrence of optic nerve compression showed no significant differences between the groups (3% each). Multiple logistic regression showed that the necessity for a second eye muscle surgery was most strongly associated with a previous decompression (OR = 0.12, 95 % CI 0.1-0.2, p < 0.0001), followed by orbital irradiation and age. CONCLUSION: In summary, younger patients with EO presented with milder clinical features, such as a lower rate of restrictive motility disorders and weaker expression of signs of inflammation. Therefore, older patients needed steroids, irradiation, eyelid and eye muscle surgery more frequently; however, the risk of dysthyroid optic neuropathy and the necessity of a second eye surgery were not or only slightly associated with age.

Efficacy and safety of ultrasound-guided thermal ablation of graves' disease: a retrospective cohort study.

BACKGROUND: Ultrasound-guided thermal ablation (TA) has emerged as a robust therapeutic approach for treating solid tumors in multiple organs, including the thyroid. Yet, its efficacy and safety profile in the management of Graves' Disease (GD) remains to be definitively established. METHODS: A retrospective study was conducted on 50 GD patients treated with TA between October 2017 and December 2021. Key metrics like thyroid volume, volume reduction rate (VRR), thyroid hormones, and basal metabolic rate (BMR) were evaluated using paired Wilcoxon tests. RESULTS: The intervention of ultrasound-guided TA yielded a statistically significant diminution in total thyroid volume across all postoperative follow-up intervals-1, 3, 6, and 12 months-relative to pre-intervention baselines (p < 0.001). The median VRR observed at these time points were 17.5%, 26.5%, 34.4%, and 39.8%, respectively. Euthyroid status was corroborated in 96% of patients at the one-year follow-up milestone. Transient tachycardia and dysphonia were observed in three patients, while a solitary case of skin numbness was noted. Crucially, no instances of enduring injury to the recurrent laryngeal nerve (RLN) were documented. CONCLUSIONS: Our investigation substantiates ultrasound-guided TA as a pragmatic, well-tolerated, and safe therapeutic modality for GD. It effectively improves symptoms of hyperthyroidism, engenders a substantial reduction in thyroid volume, and restores thyroid hormone and BMR to physiological levels. Given its favorable safety profile, enhanced cosmetic outcomes, and minimally invasive nature, ultrasound-guided TA is a compelling alternative to thyroidectomy for GD patients.

Mechanism of Prunella vulgaris L. and luteolin in restoring Tfh/Tfr balance and alleviating oxidative stress in Graves' disease.

BACKGROUND: The pathophysiology of Graves' disease (GD) involves imbalances between follicular helper T (Tfh) and follicular regulatory T (Tfr) cells, as well as oxidative stress (OS). Prunella vulgaris L. (Xia Ku Cao, XKC) and its primary bioactive compound, luteolin, are recognized for their potential in treating GD. Yet, the mechanism accounting for the immune-modulatory and antioxidant effects of XKC remains elusive. PURPOSE: This study aims to evaluate the pharmacological effects and elucidate the underlying mechanism of XKC and luteolin in a GD mouse model induced by recombinant adenovirus of TSH receptor A subunit (Ad-hTSHR-289). METHODS: High-Performance Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry (HPLC-QTOF MS) was used to detect the constituents of XKC. The GD model was established through inducing female BALB/c mice with three intramuscular injections of Ad-TSHR-289. Thyroid function, autoantibody and OS parameters were measured by ELISA. Changes of Tfh cells and Tfr cells were detected by flow cytometry. RT-qPCR, Western Blotting, immunohistochemistry were used to explore the related molecular mechanisms. RESULTS: A total of 37 chemical components from XKC were identified by HPLC-QTOF MS, represented by flavonoids, steroids, terpenoids, and luteolin. XKC and luteolin reduced T4, TRAb levels and facilitated the recovery from thyroid damage in GD mice. Meanwhile, XKC and luteolin effectively alleviated OS by decreasing the levels of MDA, NOX2, 4-HNE, 8-OHdG, while increasing GSH level. Flow cytometry showed that XKC and luteolin restored the abnormal proportions of Tfh/Tfr and Tfh/Treg, and the mRNA levels of IL-21, Bcl-6 and Foxp3 in GD mice. In addition, XKC and luteolin inhibited PI3K, Akt, p-PI3K and p-Akt, but activated Nrf2 and HO-1. CONCLUSION: XKC and luteolin could inhibit the development of GD in vivo by rebalancing Tfh/Tfr cells and alleviating OS. This therapeutic mechanism may involve the Nrf2/HO-1 and PI3K/Akt signaling pathways. Luteolin is the main efficacy material basis of XKC in countering GD. For the first time, we revealed the mechanism of XKC and luteolin in the treatment of GD from the perspective of autoimmune and OS.

Exploring Post-treatment Weight Changes in Overweight and Obese Patients With Graves' Disease: A Retrospective Analysis.

INTRODUCTION: Graves' disease (GD) is associated with primary hyperthyroidism, leading to weight loss before treatment. During the treatment, weight gain is frequently observed, often surpassing the initial weight loss. This study aimed to analyze weight fluctuations in GD patients, focusing on the subset of overweight and obese (OAO) individuals, considering the significant metabolic implications and heightened cardiovascular risk of these weight changes. METHODS: A retrospective cohort study included 122 GD patients with biochemical primary hyperthyroidism and at least 12 months of clinical follow-up after treatment for analysis. The OAO cohort comprised individuals with a body mass index (BMI) ≥25 kg/m². Data on laboratory, demographic, and weight variables were collected longitudinally. RESULTS: During the hyperthyroidism state, 34.4% (n=42) of patients presented with weight loss, a phenomenon linked to lower serum thyroid-stimulating hormone levels at diagnosis (p=0.010) and an extended need for anti-thyroid drug treatment (p<0.001). Following treatment, around 60% (n=73) of individuals encountered weight gain, exhibiting a higher prevalence among women (p<0.001) and those undergoing definitive treatment modalities (p=0.024). Notably, 26.2% (n=32) experienced excessive weight gain, which was correlated with higher premorbid BMI and diminished weight loss induced by hyperthyroidism (p<0.001). Within the OAO cohort, 66.7% (n=26) observed an increase in weight post-treatment, and in 28.2% (n=11), excessive weight gain was reported. Weight gain and excessive weight gain were noted in patients with higher initial BMIs. CONCLUSIONS: This study highlights that post-treatment weight gain is common, emphasizing the need for careful weight management in GD. In OAO GD patients, the association between initial BMI and increased weight underscores potential cardiovascular risks, warranting vigilant monitoring and early intervention.

Visceral Fat Area and Subcutaneous Fat Area Increase in Hyperthyroidism Patients After Treatment-A Single-Group Repeated-Measures Trial.

Purpose: There is evidence that long-term vascular risk remains increased in patients with hyperthyroidism even after normalization of thyroid function, and the mechanisms that regulate this risk are unclear. The aim of this study was to assess how visceral fat area and subcutaneous fat area change after hyperthyroidism treatment, and to further explore the relationship between thyroid hormones, abdominal fat area (visceral fat area and subcutaneous fat area), and lipids. Patients and Methods: 50 patients with newly diagnosed Graves' disease were selected. Anthropometric parameters (weight, height, body mass index, waist circumference, neck circumference), laboratory parameters (thyroid hormones, lipid metabolism indices), abdominal fat area (visceral fat area and subcutaneous fat area), and drug dose were collected. Measurements were made at baseline, 6 and 12 months after treatment. We used linear mixed-effects models for analysis. Results: The results showed that the following indexes changed significantly at different time points: visceral fat area, subcutaneous fat area, free triiodothyronine, free thyroxine, thyroid stimulating hormone, total cholesterol, high-density lipoprotein, low-density lipoprotein, body weight, neck circumference, body mass index, waist circumference, and drug dose (All P<0.001). We found that free triiodothyronine and free thyroxine were significantly negatively associated with abdominal fat area (P<0.01). There was no significant correlation between drug dose and abdominal fat area (P>0.05). Total cholesterol and low-density lipoprotein were significantly positively associated with abdominal fat area (P<0.01). However, high-density lipoprotein (P=0.06) was not correlated with abdominal fat area. Moreover, the results showed a significant negative correlation between thyroid hormones and lipids (P<0.001). Conclusion: After anti-thyroid medicine treatment, patients had elevated visceral fat area and subcutaneous fat area and altered lipid profiles. These changes may be one of the reasons why metabolic and cardiovascular diseases remain increased after thyroid function is restored.

Fetal Hyperthyroidism Secondary to Maternal Basedow-Graves' Disease.

Fetal hyperthyroidism is a rare prenatal disease and can be life-threatening. The diagnosis is based on ultrasound in mothers with a history of Basedow-Graves' disease and elevation of thyrotropin receptor antibodies (TRAbs) levels. The treatment consists of antithyroid drugs. We present a mother with Basedow-Graves' disease, treated with radioactive iodine 16 years ago. She had an unplanned pregnancy at the age of 29 years, and an elevation of TRAbs (21 U/L) was found at the sixth week of pregnancy. At 22 weeks of gestation, fetal ultrasound displayed tachycardia, goiter, exophthalmos, and suspicion of craniosynostosis, hence methimazole was started. Concomitantly, suppressed maternal thyroid-stimulating hormone (TSH) was found. Her daughter was born at 33 + 6 weeks showing clinical and laboratory findings of hyperthyroidism. Consequently, treatment with methimazole was prescribed. Normal thyroid function was documented in the mother after giving birth. Clear explanation has not been found for the alteration of maternal TSH during pregnancy.

Association between serum vitamin D level and Graves' disease: a systematic review and meta-analysis.

OBJECTIVE: This meta-analysis aims to analyze the relationship between serum vitamin D (VD) levels and Graves' disease (GD). METHODS: We conducted a search for publications on VD and GD in the English language. Our search encompassed databases such as PubMed, Embase, Web of Science, and the Cochrane Library, covering publications available through August 2023. A meta-analysis was performed using Cochrane RevMan 5.4 software. The standardized mean difference (SMD) and 95% confidence interval (CI) were used for outcome calculation. We used R software to test for publication bias. RESULTS: Twelve studies were selected, comprising 937 (22.4%) cases with GD and 3254 (77.6%) controls. The overall meta-analysis revealed that patients with GD are significantly more likely to have low VD levels (SMD = - 0.66; 95% CI: -1.05, - 0.27; p = 0.001) than those in the control group. Egger's test results indicated no publication bias (p = 0.0791). These studies exhibited a high degree of heterogeneity (chi-square = 205.86, p < 0.00001; I2 = 95%). Subgroup analysis was conducted based on assay method, geographic location, and mean age of the case group to explore the heterogeneity sources. Assay methods and geographic locations were identified as potential heterogeneity sources. Based on the mean age, there were no statistically significant differences found in the subgroup analysis of the included studies. CONCLUSION: There is promising evidence that low serum VD levels may increase the risk of GD. Further rigorous and long-term trials are needed to explore the role of VD in the onset and treatment of GD.

Different Forms of Hypothyroidism in Infants with Maternal Graves' Disease: A Case Series.

Infants of mothers with Graves' disease (GD) may develop central hypothyroidism (CH) due to exposure of the foetal hypothalamic-pituitary-thyroid axis to higher-than-normal thyroid hormone concentrations, primary hypothyroidism (PH) due to transplacental passage of maternal thyroid stimulating hormone receptor antibody (TRAb), antithyroid drugs (ATD) or thyroid dysgenesis secondary to maternal uncontrolled hyperthyroidism. We describe two infants with PH and four infants with CH born to mothers with poorly controlled Graves' disease. All infants required levothyroxine and had normal developmental milestones. While national guideline consensus for high thyroid stimulating hormone (TSH) on neonatal screening is well-established, thyroid function tests (TFTs) should be serially monitored in infants with low TSH on screening, as not all mothers with Graves' disease are diagnosed antenatally.

Assessing the relationship between psoriasis and thyroid dysfunction through two sample MR analysis.

BACKGROUND: The association between psoriasis and hyperthyroidism/hypothyroidism remains inconclusive, with conflicting findings in prior studies. OBJECTIVES: This study employs Mendelian randomization methods to assess the potential relationship. METHODS: Given the inability to accurately observe the link between psoriasis and thyroid dysfunction, we prioritized utilizing known genetic variants to investigate the potential impacts of the disease.We analyzed data from genome-wide association studies (GWASs), FinnGen, and UK Biobank to extract information on psoriasis, hyperthyroidism, and hypothyroidism. Three MR approaches (MR Egger, weighted median, and inverse variance weighted) were used to scrutinize the causal link. RESULTS: Our analysis revealed no correlation between psoriasis and hyperthyroidism/hypothyroidism. However,  vulgar psoriasis and guttate psoriasis were associated with hypothyroidism/myxedema (IVW odds ratio (OR) = 1.00, 95% confidence interval (CI) = 1.00-1.00, P = 2.53E-03), and Graves' disease (IVW OR = 0.86, 95% CI = 0.72-1.01, P = 4.75E-02).In a subsequent analysis, we observed that hypothyroidism with mucinous edema showed no correlation with Graves' disease in the opposite(P = 9.33E-01). CONCLUSION: This MR analysis suggests no association between psoriasis and thyroid dysfunction, but highlights associations of vulgar/guttate psoriasis with hypothyroidism/myxedema and Graves' disease. In clinical practice, diagnosing guttate psoriasis requires vigilance for associated risks from hypothyroidism and Graves' disease. For patients with both vulgar psoriasis and hypothyroidism, careful monitoring for mucinous edema is crucial, as it may signal a hypothyroid crisis.

Long-Term Efficacy of Teprotumumab in Thyroid Eye Disease: Follow-Up Outcomes in Three Clinical Trials.

Introduction: Thyroid eye disease (TED) is an autoimmune process characterized by extraocular muscle and orbital fat remodeling/expansion resulting in swelling, pain, redness, proptosis, and diplopia. Teprotumumab, an insulin-like growth factor-I receptor inhibitor, demonstrated improvements in TED signs and symptoms in three adequately powered clinical trials of 24 weeks duration. Here we analyze the long-term maintenance of responses with teprotumumab from these trials. Methods: A total of 112 patients who received 7 or 8 infusions of teprotumumab in the Phase 2, Phase 3 (OPTIC study), and OPTIC Extension (OPTIC-X) studies were included in this analysis. Responses, including clinical activity score (CAS ≥2-point improvement), the European Group of Graves' Orbitopathy ophthalmic composite outcome, diplopia (≥1 Gorman grade improvement), proptosis (≥2 mm improvement), Overall (improvement in proptosis + CAS), and disease inactivation (CAS ≤1), were assessed and pooled from study baseline to week 24 (formal study) and up to week 72 (formal follow-up). Graves' Ophthalmopathy quality-of-life (GO-QoL) scores were also assessed. Outcomes included the percentages of observed patient responses from the study baseline. Additional alternative treatments for TED were assessed as a surrogate of persistent benefit from week 24 through week 120 (extended follow-up). Studies differed in the timing of follow-up visits, and data from some visits were unavailable. Results: At week 72, 52/57 (91.2%), 51/57 (89.5%), 35/48 (72.9%), 38/56 (67.9%), and 37/56 (66.1%) of patients were responders for CAS, composite outcome, diplopia, proptosis, and Overall response, respectively. The mean reduction in proptosis was 2.68 mm (SD 1.92, n = 56), mean GO-QoL improvement was 15.22 (SE 2.82, n = 56), and disease inactivation (CAS ≤1) was detected in 40/57 (70.2%). Over 99 weeks following teprotumumab therapy, 19/106 (17.9%) patients reported additional TED therapy during formal and extended follow-up. Conclusion: The long-term response to teprotumumab as observed 51 weeks after therapy was similar to week 24 results in the controlled clinical trials. Inflammatory and ophthalmic composite outcome improvements were seen in 90% of patients with nearly 70% reporting improvement in diplopia and proptosis. Further, 82% of patients in this analysis did not report additional TED treatment (including surgery) over 99 weeks following the final teprotumumab dose.

Unveiling Promising Modalities and Enhancing Patient Outcomes in Graves' Disease Treatment: A Systematic Review and Meta-Analysis.

Graves' disease (GD) is an autoimmune condition of the thyroid. The hyperthyroidism manifested by patients affected by this disease is caused by the production of autoantibodies against the thyroid-stimulating hormone (TSH, or thyrotropin) receptor (TSHR), which mimic the effects of the hormone on thyroid cells, thereby stimulating autonomic production of thyroxine and triiodothyronine. Deciding on a therapeutic approach to this condition presents intricate dilemmas for both clinicians and patients. Each of the three available treatment modalities is grounded in evidence-based medicine, affirming its efficacy. This systematic review and meta-analysis aimed to assess the effect of carbimazole (CBM), radioactive iodine (RAI), and surgery in treating GD and provide evidence-based recommendations for healthcare providers regarding the optimal management of the condition based on a comprehensive analysis of effectiveness, safety, patient satisfaction, and recovery outcomes. This systematic review and meta-analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We used the PubMed and Google Scholar databases to conduct a thorough web search for articles published between January 2019 and September 2023. The meta-analysis was carried out using Resource Manager (Revman) 5.4.1. The study found that propylthiouracil (PTU) or methimazole/carbimazole (MMI/CBM) treatment increases the risk of hyperlipidemia in patients with hyperthyroidism. Once in a euthyroid state, glucose tolerance increases; for children with GD, a computer model for customized dosing has been created. To sum up, CBM, surgery, and RAI are all useful treatment options for GD. Using steroids in conjunction with radiation therapy may help prevent Graves' ophthalmopathy (GO).

Associations between immune cell traits and autoimmune thyroid diseases: a bidirectional two-sample mendelian randomization study.

Autoimmune thyroid diseases (AITDs), mainly including Graves' disease (GD) and Hashimoto's thyroiditis (HT), are common autoimmune disorders characterized by abnormal immune responses targeting the thyroid gland. We conducted a bidirectional two-sample MR analysis using the largest dataset of peripheral immune cell phenotypes from Sardinia, and the AITD dataset from the 10th round of the FinnGen and the UK Biobank project. Instrumental variables (IVs) were rigorously selected based on the three assumptions of MR and analyzed using the Wald ratio, inverse-variance weighted (IVW), MR-Egger, and weighted median methods. Additionally, sensitivity analyses were performed using Cochrane's Q, the Egger intercept, the MR-PRESSO, and the leave-one-out (LOO) method to ensure the robustness of the results. The Steiger test was utilized to identify and exclude potential reverse causation. The results showed that 3, 3, and 11 immune cell phenotypes were significantly associated with the risk of AITD. In GD, the proportion of naive CD4-CD8- (DN) T cells in T cells and the proportion of terminally differentiated CD4+T cells in T cells showed the strongest inducing and protective effects, respectively. In HT, lymphocyte count and CD45 on CD4+T cells showed the strongest inducing and protective effects, respectively. In autoimmune hypothyroidism, CD127 CD8+T cell count and terminally differentiated DN T cell count exhibited the strongest inducing and protective effects, respectively. Through MR analysis, our study provides direct genetic evidence of the impact of immune cell traits on AITD risk and lays the groundwork for potential therapeutic and diagnostic target discovery.

Management of Graves' ophthalmopathy by radiotherapy: A literature review.

Orbital radiotherapy for Graves' ophthalmopathy is an example of non-oncological radiotherapy. First introduced in the 1930s, this treatment has become widely used since the 1980s with several studies showing proof of both effectiveness and safety: a decrease of soft tissue involvement in 70 to 80% of patients and an improvement of ocular mobility in 30 to 80% of patients. Nowadays, it's one of the second line treatment options recognized by the European Group on Graves' orbitopathy in the management of a moderate to severe and active disease after failure of glucocorticoids. In that setting, orbital radiotherapy should be combined with glucocorticoids. To our knowledge, there are no practical recommendations on how orbital radiotherapy should be planned and conducted for Graves' ophthalmopathy. Optimal dose is not defined however the most frequent regimen consists of 20Gy in ten fractions of 2Gy, though other options may yield better results. Lastly, the use of modern technique of radiotherapy such as intensity-modulated radiation therapy may allow a better sparing of organs at risk compared to three-dimensional radiotherapy using lateral opposing fields.

Profiling of carbonyl metabolic fingerprints in urine of Graves' disease patients based on atmospheric ionization mass spectrometry.

Graves' disease (GD) is considered among the organ autoimmune diseases and is somewhat linked to other autoimmune and secondary diseases. Commonly used detection methods rely on identifying characteristic clinical features and abnormal biochemical markers, but they have certain limitations and may be affected by patient medication. In this study, a desorption separation ionization (DSI) device coupled with a linear ion trap mass spectrometer is introduced for effective detection and screening of urine from GD patients. To enhance the sensitivity of MS analysis, derivatization reagent is utilized as a labeling method. The MS signal is used for metabolic profiling, through which differential metabolites and pathways are identified. Subsequently, processing the acquired spectra with a machine learning algorithm enables successful differentiation of GD patients and healthy individuals. This method is believed to provide versatile and powerful technical support for effective detection on the scene. Notably, this method offers the advantage of achieving early and rapid diagnosis of thyroid-related diseases.

Significant role of 1,25-dihydroxyvitamin D on serum calcium levels after total thyroidectomy: a prospective cohort study.

Introduction: Although active vitamin D (VD) has been used both preoperatively and postoperatively to prevent hypocalcemia risk in patients undergoing total thyroidectomy, the role of 1,25-dihydroxyvitamin D (1,25(OH)2D) has not been examined. This study comprehensively investigated the effects of 1,25(OH)2D on calcium (Ca) concentrations after total thyroidectomy. Methods: Serum Ca, parathyroid hormone (PTH), and 1,25(OH)2D levels were measured in 82 patients with thyroid disease before and after surgery. Results: Serum Ca, PTH, and 1,25(OH)2D levels decreased significantly on the morning of the first postoperative day. Notably, the decrease in 1,25(OH)2D concentration was significantly lower than that of PTH concentration (10.5 ± 33.4% vs. 52.1 ± 30.1%, p<0.0001), with 28% of patients showing increases in 1,25(OH)2D. The only factor predicting a postoperative 1,25(OH)2D decrease was a high preoperative 1,25(OH)2D concentration. Postoperative 1,25(OH)2D concentrations, as well as the magnitude and rate of decrease from preoperative levels, showed strong positive correlations with preoperative 1,25(OH)2D concentrations (p<0.0001 for all three variables) but not with PTH concentrations. These findings suggest that 1,25(OH)2D concentrations after thyroidectomy were more strongly dependent on preoperative concentrations than on the effect of PTH decrease and were relatively preserved, possibly preventing sudden severe postoperative hypocalcemia. A high 1,25(OH)2D level was the most important preoperative factor for hypocalcemia (<2 mmol/L; p<0.05) on the first postoperative day; however, only PTH decrease was statistically significant (p<0.001) when intraoperative factors were added. In the PTH >10 pg/mL group, the decrease in 1,25(OH)2D levels was significantly associated with postoperative hypocalcemia (p<0.05). Similarly, in the PTH levels >15 pg/mL group, a decrease in 1,25(OH)2D concentration was a significant factor, and the amount of PTH decrease was no longer significant. Conclusion: 1,25(OH)2D plays an important role in preventing sudden, severe hypocalcemia due to decreased PTH levels after total thyroidectomy, whereas high preoperative 1,25(OH)2D levels are a significant risk factor for postoperative hypocalcemia. Optimizing preoperative protocols to adjust Ca, PTH, and 1,25(OH)2D levels to improve the management of patients undergoing total thyroidectomy and to prevent extreme intraoperative PTH decreases may reduce the risk of hypocalcemia.

Methimazole Desensitization in a Patient Experiencing a Thionamide-induced Hypersensitivity Reaction.

Patients with newly diagnosed Graves disease often elect for treatment with the drug methimazole (MMI) over alternative therapies. However, MMI can commonly result in skin allergy that in severe cases can lead to discontinuation of therapy. We present a case of Graves thyrotoxicosis with a delayed hypersensitivity reaction while on MMI. The patient was successfully treated with a novel, individualized, 27-day desensitization protocol that resulted in tolerance of MMI with subsequent improvement in thyroid indices. Previous literature has offered various rapid desensitization protocols to MMI for immediate type hypersensitivity reactions. However, in nonimmediate, delayed hypersensitivity reactions, a slower desensitization protocol can be considered. As demonstrated in this case, desensitization to MMI is a reasonable alternative in patients who wish to avoid definitive therapy who develop an initial adverse reaction to MMI, as this can occur in up to 13% of treated cases.

Neurodevelopmental Follow-Up of Children Born to Mothers with Graves' Disease and Neonatal Hyperthyroidism.

INTRODUCTION: Neonatal hyperthyroidism, often caused by maternal Graves' disease (GD), carries potential neurodevelopmental risks for children. Excessive thyroid hormones during fetal development are linked to neurological issues like ADHD and epilepsy. However, the impact of transient neonatal hyperthyroidism is not well understood. METHODS: In a retrospective study at the Royal Children's Hospital in Melbourne, 21 neonates with hyperthyroidism from mothers with GD were examined. Of these, the parents of 10 children consented to participate; thus, questionnaires assessing executive functions, behavior, and social communication were completed. The outcomes were compared to those of control subjects recruited from the community using standardized tools (BRIEF, SDQ, SCQ). The results were analyzed against socio-demographic factors, maternal, and neonatal health. RESULTS: No significant demographic or clinical differences were found between study participants (n = 10) and non-participants (n = 11). Participants, compared to controls, showed similar family demographics but a higher proportion of control parents had university-level education (p = 0.003). Patients displayed more social (SCQ scores: 12.1 ± 2.5 vs. 6 ± 1.07, p = 0.008) and behavioral difficulties (SDQ scores: 10.2 ± 2.17 vs. 6.14 ± 1.03, p = 0.03), with increased executive function challenges (BRIEF scores indicating problem-solving and self-regulation difficulties). Significant effects of family living situation and partner education level on neurodevelopmental measures were noted, underscoring the influence of socio-demographic factors. CONCLUSIONS: These findings suggest neonatal hyperthyroidism might lead to subtle neurodevelopmental variations, with socio-economic elements and family dynamics possibly intensifying these effects. While most children did not show severe impairments, early detection and intervention are recommended. The research emphasizes the necessity for inclusive care approaches that consider socio-economic factors for children affected by neonatal hyperthyroidism.