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Objective Graves' disease (GD) is a major autoimmune thyroid disorder and is associated with non-thyroidal autoimmune disease (NTAD). We aimed to investigate the risk of NTAD in patients with GD compared with age- and sex-matched controls and to evaluate whether the risk differs between individuals with or without Graves' ophthalmopathy (GO). Methods This was a retrospective cohort study using data from the Korean National Health Claims database. We included 77 401 patients with GD (2310 with GO) and 77 401 age- and sex-matched controls. Risk of NTAD were compared between the entire cohort and within the GD cohort. Results During a mean follow-up period of 9 years, NTAD developed in 12 341 (16.1%) patients in the GD cohort. Risk for SLE [adjusted hazard ratio (aHR) 1.15, 95% CI 1.02–1.29], vitiligo (aHR 1.24, 95% CI 1.10–1.40) and alopecia areata (aHR 1.11, 95% CI 1.04–1.20) were higher in the GD cohort than in the control cohort. In the GD cohort, risk for SLE (aHR 1.60, 95% CI 1.11–2.33), SS (aHR 1.89, 95% CI 1.30–2.74) and AS (aHR 1.53, 95% CI 1.08–2.17) were higher in the GO group than in the non-GO group. Conclusion This study demonstrated an increased risk of SLE, vitiligo and alopecia areata in patients with GD. In the GD cohort, patients with GO had an increased risk of SLE, SS and AS. These findings suggest the importance of implementing a strategy for early detection of NTAD based on the presence of GO. [ABSTRACT FROM AUTHOR]

Thyroid eye disease (TED) is a poorly understood autoimmune condition affecting the retroorbital tissue. Tissue inflammation, expansion, and fibrosis can potentially lead to debilitating sequelae such as vision loss, painful eye movement, proptosis, and eyelid retraction. Current treatment modalities for TED include systemic glucocorticoids, thioamides, methimazole, teprotumumab, beta-blockers, and radioactive iodine; however, it has been reported that up to 10%–20% of TED patients relapse after treatment withdrawal and 20%–30% are unresponsive to mainstay therapy for reasons that have yet to be more clearly elucidated. In the past 4 years, vision researchers have harnessed high-throughput single-cell RNA sequencing to elucidate the diversity of cell types and molecular mechanisms driving the pathogenesis of TED at single-cell resolution. Such studies have provided unprecedented insight regarding novel biomarkers and therapeutic targets in TED. This timely review summarizes recent breakthroughs and emerging opportunities for using single-cell and single-nuclei transcriptomic data to characterize this highly complex disease state. We also provide an overview of current challenges and future applications of this technology to potentially improve patient quality of life and facilitate reversal of disease endpoints.

Thyroid eye disease (TED) is a poorly understood autoimmune condition affecting the retroorbital tissue. Tissue inflammation, expansion, and fibrosis can potentially lead to debilitating sequelae such as vision loss, painful eye movement, proptosis, and eyelid retraction. Current treatment modalities for TED include systemic glucocorticoids, thioamides, methimazole, teprotumumab, beta-blockers, and radioactive iodine; however, it has been reported that up to 10%–20% of TED patients relapse after treatment withdrawal and 20%–30% are unresponsive to mainstay therapy for reasons that have yet to be more clearly elucidated. In the past 4 years, vision researchers have harnessed high-throughput single-cell RNA sequencing to elucidate the diversity of cell types and molecular mechanisms driving the pathogenesis of TED at single-cell resolution. Such studies have provided unprecedented insight regarding novel biomarkers and therapeutic targets in TED. This timely review summarizes recent breakthroughs and emerging opportunities for using single-cell and single-nuclei transcriptomic data to characterize this highly complex disease state. We also provide an overview of current challenges and future applications of this technology to potentially improve patient quality of life and facilitate reversal of disease endpoints. [ABSTRACT FROM AUTHOR]

The article in "Frontiers in Endocrinology" discusses a study on the use of azathioprine (AZA) as an adjuvant therapy in severe Graves' disease (GD). The research found that AZA significantly improved remission rates and reduced relapse in patients with severe, refractory GD. The study included 270 participants and showed a higher remission rate in the AZA group compared to the control group. While the study provides valuable insights, limitations such as a small sample size and open-label design were noted, suggesting the need for further research to confirm these findings and refine treatment recommendations. [Extracted from the article]

Coronavirus disease 2019 (COVID-19) is caused due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Both immediate and long-term adverse effects arise out of this disease’s aftermath. It involves various organs, which include endocrine glands, nervous system, musculoskeletal system, and other organs. The long-term outcomes of the SARS-CoV-2 infection are influenced by preexisting comorbidities. Genetic, environmental, and immunological factors contribute to the development of various autoimmune diseases, which include Graves’ disease (GD). The growing mystery surrounding this virus is exacerbated by auto-inflammatory diseases, such as pediatric inflammatory multisystemic syndrome (PIMS) or multisystem inflammatory syndrome in children (MIS-C), which raises concerns about the nature of the virus’ connection to the autoimmune and auto-inflammatory sequelae. There is a need to understand the underlying mechanisms of developing GD in post-COVID-19 patients. There are limited data regarding the pathogenesis involved in post-COVID-19 GD. Our goal was to understand the various mechanisms involved in post-COVID-19 GD among patients with confirmed COVID-19 infection. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for 2020, a literature search of medical databases (PubMed, Cochrane Central Register of Controlled Trials, and Scopus) from February 2021 to February 2022 was performed by five authors. The keywords used were “Post COVID-19,” “Grave’s disease,” “Cytokine storm,” “Autoimmunity,” and “Molecular mimicry.” This review revealed three underlying mechanisms that resulted in post-COVID GD, which included cytokine storm, molecular mimicry, ACE2 receptor concentration, and cell-mediated immunity. The full spectrum of the effects of COVID-19 needs to be researched.

Small extracellular vesicles (sEVs) contain microRNAs (miRNAs) which have potential to act as disease-specific biomarkers. The current study uses an established method to maintain human thyroid tissue ex vivo on a tissue-on-chip device, allowing the collection, isolation and interrogation of the sEVs released directly from thyroid tissue. sEVs were analysed for differences in miRNA levels released from benign thyroid tissue, Graves' disease tissue and papillary thyroid cancer (PTC), using miRNA sequencing and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) to identify potential biomarkers of disease. Thyroid biopsies from patients with benign tissue (n = 5), Graves' disease (n = 5) and PTC (n = 5) were perfused with medium containing sEV-depleted serum for 6 days on the tissue-on-chip device. During incubation, the effluents were collected and ultracentrifuged to isolate sEVs; miRNA was extracted and sequenced (miRNASeq). Out of the 15 samples, 14 passed the quality control and miRNASeq analysis detected significantly higher expression of miR-375-3p, miR-7-5p, miR-382-5p and miR-127-3p in the sEVs isolated from Graves' tissue compared to those from benign tissue (false discovery rate; FDR p < 0.05). Similarly, miR-375-3p and miR-7-5p were also detected at a higher level in the Graves' tissue sEVs compared to the PTC tissue sEVs (FDR p < 0.05). No significant differences were observed between miRNA in sEVs from PTC vs. those from benign tissue. These results were supported by Quantitative Reverse Transcriptase Polymerase Chain Reaction (qRT-PCR). The novel findings demonstrate that the tissue-on-chip technology is a robust method for isolating sEVs directly from the tissue of interest, which has permitted the identification of four miRNAs, with which further investigation could be used as biomarkers or therapeutic targets within thyroid disease. [ABSTRACT FROM AUTHOR]

The aim of this systematic review was to examine the characteristics of Paleolithic diet (PD) interventions designed for adult patients with autoimmune thyroid disease (AITD) in order to determine if diet elements have the potential to successfully reduce thyroid antibodies (Ab) such as thyroglobulin (Tg), thyroid peroxidase (TPO), and thyroid stimulating hormone receptor (TSHR), and improve thyroid hormones (thyroxine (T4), triiodothyronine (T3) and thyroid stimulating hormone (TSH)) or resolve AITD pathogenesis. Randomized controlled trials (RCTs) with an adult population of 18 years and older, diagnosed with Hashimoto's thyroiditis (HT) or Graves' disease (GD) (Basedow's), who were placed on a diet of Paleolithic or ancestral nature, and achieved reduction of AITD Abs, improvement of thyroid hormones, and, or resolution of AITD were searched. Various electronic databases were used. Bias was assessed using critical appraisal tools from the Scottish Intercollegiate Guidelines Network (SIGN) and Joanna Briggs Institute (JBI). Studies were excluded according to exclusion criteria and results analyzed. One randomized controlled trial (RCT), a pilot study, and six case studies were found. In total, eight AITD studies focusing on Paleolithic or ancestral interventions were located. In highlight, females were the predominant gender. Case studies solely focused on AITD with protocols ranging from 8–60 weeks. All studies showed clinical improvements, one had significant improvement, two showed AITD resolution. After structured evaluation of nutritional interventions utilizing the PD on the effects of AITD, it was concluded foods of ancestral nature along with the addition of specific supplements, food components, exercise and mindfulness meditation, and exclusion of modern day foods have a considerable impact on thyroid Ab and hormones. The relevant studies suggest while this dietary protocol can be useful in clinical practice, larger-scale studies need to be conducted. There are currently no dietary interventions recommended for the treatment of autoimmune thyroid disease. The Paleo diet has been documented to improve AITD antibodies and thyroid hormones in both Hashimoto's thyroiditis and Graves' disease. The Paleo diet can provide a natural source of nutrients similar to supplemental nutrients that have shown positive results on AITD. The paleo diet provides specific macronutrient percentages that may be beneficial in reducing AITD antibodies, while improving thyroid hormones. Methylation supplementation may be useful in AITD cases. [ABSTRACT FROM AUTHOR]

Thyroid eye disease (TED) is characterized by progressive orbital inflammation. In severe cases, it can lead to dysthyroid optic neuropathy (DON), involving death of retinal ganglion cells and permanent vision loss. Imaging with optical coherence tomography (OCT) has enabled noninvasive examination of the structural impact of the disease, including of the retinal nerve fiber layer (RNFL), the ganglion cell layer (GCL), and the inner plexiform layer (IPL). In this study, we systematically review 20 studies (897 patients, 1430 eyes) to evaluate changes in retinal thickness in patients with TED, stratified by severity. Most studies found a decrease in thickness in peripapillary RNFL (pRNFL), non-pRNFL, combined RNFL/GCL/IPL, or combined GCL/IPL when comparing patients with DON to healthy controls or to patients without DON. However, results were equivocal regarding differences between non-DON TED patients and controls. In addition, several studies reported a postoperative decrease in pRNFL thickness after orbital decompression surgery. Future studies examining OCT changes of retinal thickness along with disease progression are needed to assess the potential of OCT in diagnosis and management of patients with TED.

Thyroid function tests are commonly requested on children and young people in primary and secondary care settings. These tests include markers of thyroid function including thyroid stimulating hormone (TSH) and free thyroxine (FT4) concentrations. This short article aims to equip the reader to interpret them correctly. Not all biochemical parameters outside the reference range will require therapeutic intervention and there are a number of potential associated pitfalls. For example, a set of thyroid function test results may not be a cause for concern in one setting but require immediate action in another clinical context. Understanding whether abnormal thyroid function is cause or consequence and gaining insight into the likely underlying natural history are components of good clinical care. Knowing when not to treat abnormal thyroid function can be as important as knowing when treatment is required. [ABSTRACT FROM AUTHOR]

This study aims to determine the readability and trustworthiness of English and Spanish hypo- and hyperthyroid-related online information. Google searches were conducted for four search terms: hypothyroidism, Hashimoto's Disease, hyperthyroidism, and Graves' Disease. For each search term, the first 10 websites were analyzed with a total of 40 websites analyzed. Readability formulas were used to determine English and Spanish readability. Trustworthiness was determined using HONcode status, JAMA Benchmark Criteria, and NLM Trustworthy Score. Overall readability largely exceeded recommended grade levels. Only 1 website (2.5%) presented information below the eighth-grade reading level based on overall Readability Consensus score, while 31 websites (77.5%) exceeded this threshold for all measures. The mean (SD) English readability grade level was 9.6 (3.44); the mean (SD) Spanish grade was 8.5 (4.58). No significant relationships were found between the JAMA Benchmark Criteria, NLM Trustworthy Score, HONcode status, and readability. 67.5% of websites analyzed (n = 27) were certified with the Health on the Net Foundation's code of conduct. Websites about common thyroid-related conditions have overall poor readability. The availability of resources for Spanish-speaking patients is also poor. Steps should be taken to ensure that online health-related materials are comprehensible. Physicians should recognize that patients may have few trustworthy and easy-to-understand sources to access information. The readability and trustworthiness of sources should be considered when providing patients suggested sources for further reading. It may be particularly helpful for physicians to utilize websites with favorable readability scores such as the American Thyroid Association website. [ABSTRACT FROM AUTHOR]

Abstract Background Graves’ disease is the most common cause of hyperthyroidism. It results in accelerated tissue metabolism with multi-organ involvement ranging from cardiovascular to neuropsychological function. This results in a negative impact on the quality of life (QOL) of the individual patient. We aim to evaluate the psychometric properties of ThyPRO, a Thyroid-related Patient Reported Outcome questionnaire, and validate its use in our multi-ethnic Asian patients with Graves’ hyperthyroidism. Methods Forty-seven consecutive Graves’ hyperthyroidism patients answered the ThyPRO questionnaire at baseline and at 4 months after treatment initiation. Data were recorded for thyroid related symptoms and signs, thyroid function tests and thyroid volume. We analyzed the internal consistency using Cronbach’s alpha, construct validity by evaluating relationship between clinical variables and ThyPRO scales, ceiling and floor effects, and responsiveness of ThyPRO to treatment based on Cohen’s effect size. Results Correlations between individual scale scores and free thyroxine concentrations were moderate and statistically significant: 0.21–0.64 (p 0.7 for all scales. ThyPRO was responsive to the changes in QOL after treatment (Effect Size: 0.20–0.77) in 9 of the 14 scales including the hyperthyroid symptoms and psychosocial scales (Tiredness, Cognitive complaints, Anxiety, Emotional susceptibility, Impact on Social, Daily and Sex life). Conclusion This study provides evidence that ThyPRO has satisfactory measurement properties in hyperthyroid Graves’ disease patients in Singapore population with the potential to complement clinical care.

Background: Graves' orbitopathy (GO) is an autoimmune-driven manifestation of Graves' disease (GD) where pathogenic autoantibodies to the thyrotropin receptor (TSHR) activate orbital fibroblasts/preadipocytes in the orbital tissue to induce inflammation and extracellular matrix deposition. Since there are significant limitations to study immunological and proinflammatory mediator expression in early and during disease progression in GO patients, we used our experimental mouse model to elucidate early pathogenic processes. Methods: We have developed a robust mouse model of GD/GO induced by electroporation immunization of plasmid encoding human TSHR A-subunit, comprising multiple injections over a course of 15 weeks to fully recapitulate the orbital pathology. In this study, we investigated kinetics of GO development in the model by serial analyses of immunological and cellular parameters during course of orbital inflammation. Results: Pathogenic anti-TSHR antibodies with thyroid-stimulating properties developed early after the second immunization step with concomitant induction of hyperthyroidism. Examination of orbital tissue showed an early wave of macrophage infiltration followed subsequently by CD3+ T cells into the orbital tissue. Examination of antigen-specific T cell activity using recombinant human A-subunit protein showed high CD8+ T cell proliferation during this early phase of disease onset, whereas effector CD4+ T cells and CD25+FOXP3+ regulatory T cells (Tregs) were downregulated. The early phase of disease was also characterized by abundant presence of proinflammatory cytokines interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α). Moreover, as the disease progressed, there was significant increase in browning of orbital fat tissue, which may be dependent on the proinflammatory milieu and/or the increased thyroid hormone levels during the established hyperthyroid status. Conclusions: This work revealed early infiltration of macrophages in the orbital region and induction of pathogenic anti-TSHR antibodies during disease onset in the model. This was followed subsequently by influx of CD8+ T cells specific for TSHR coupled with reduction in Tregs and substantial increase in brown adipose tissue. These new insights into the development of orbital inflammation in the model have implications for testing new therapeutic regimens by targeting macrophage function during early phases of orbital inflammation in the model. [ABSTRACT FROM AUTHOR]

Background: Adipogenesis, glycosaminoglycan hyaluronan (HA) production, inflammation, and fibrosis are the main pathogenic mechanisms responsible for Graves' orbitopathy (GO). We hypothesized that disulfiram (DSF), an aldehyde dehydrogenase (ALDH) inhibitor used to treat alcoholism, would have therapeutic effects on orbital fibroblasts (OFs) in GO. This study aimed at determining the therapeutic effects and underlying mechanisms of DSF on these parameters. Methods: Primary cultures of OFs from six GO patients and six control subjects were established. The OFs were allowed to differentiate into adipocytes and treated with various concentrations of DSF. Lipid accumulation within the cells was evaluated by Oil Red O staining. Real-time polymerase chain reaction (RT-PCR) and Western blotting were used to measure the expression of key adipogenic transcription factors, ALDH1A1, ALDH2, and mitogen-activated protein kinase (MAPK) signaling proteins. Apoptosis assays and reactive oxygen species levels were evaluated by flow cytometry. HA production was measured by using an enzyme-linked immunosorbent assay (ELISA) kit. The mRNA levels of proinflammatory molecules were measured by using RT-PCR after interleukin (IL)-1β stimulation with or without DSF. The mRNA expression of markers associated with fibrosis was examined by using RT-PCR after transforming growth factor (TGF)-β1 stimulation with or without DSF. The wound-healing assay was assessed by phase-contrast microscopy. Results: Under identical adipogenesis conditions, GO OFs effectively differentiated, while normal control (NC) OFs did not. DSF dose dependently suppressed lipid accumulation during adipogenesis in GO OFs. The expression of key adipogenic transcription factors, such as perilipin-1 (PLIN1), PPARγ (PPARG), FABP4, and c/EBPα (CEBPA), was downregulated. Further, DSF inhibited the phosphorylation of ERK by inhibiting ALDH1A1. In addition, DSF attenuated HA production and suppressed inflammatory molecule expression induced by IL-1β in GO OFs and NC OFs. The antifibrotic effects of DSF on TGF-β1 were also observed in GO OFs. Conclusions: In the current study, we provide evidence of the inhibitory effect of DSF on GO OFs adipogenesis, HA production, inflammation, and fibrosis in vitro. The results of this study are noteworthy and indicate the potential use of DSF as a therapeutic agent for the treatment of GO. [ABSTRACT FROM AUTHOR]

Background: Graves' disease accounts for ∼80% of all cases of hyperthyroidism and is associated with significant morbidity and decreased quality of life. Understanding the association of total thyroidectomy with patient-reported quality-of-life and thyroid-specific symptoms is critical to shared decision-making and high-quality care. We estimate the change in patient-reported outcomes (PROs) before and after surgery for patients with Graves' disease to inform the expectations of patients and their physicians. Methods: PROs using the MD Anderson Symptom Inventory (MDASI) validated questionnaire were collected prospectively from adult patients with Graves' disease from January 1, 2015, to November 20, 2020, on a longitudinal basis. Survey responses were categorized as before surgery (≤120 days), short term after surgery (<30 days; ST), and long term after surgery (≥30 days; LT). Negative binomial regression was used to estimate the association of select covariates with PROs. Results: Eighty-five patients with Graves' disease were included. The majority were female (83.5%); 47.1% were non-Hispanic white and 35.3% were non-Hispanic black. The median thyrotropin (TSH) value before surgery was 0.05, which increased to 0.82 in ST and 1.57 in LT. In bivariate analysis, the Total Symptom Burden Score, a composite of all patient-reported burden, significantly reduced shortly after surgery (before surgery mean of 56.88 vs. ST 39.60, p < 0.001), demonstrating improvement in PROs. Furthermore, both the Thyroid Symptoms Score, including patient-reported thermoregulation, palpitations, and dysphagia, and the Quality-of-Life Symptom Score improved in ST and LT (thyroid symptoms, before surgery 13.88 vs. ST 8.62 and LT 7.29; quality of life, before surgery 16.16 vs. ST 9.14 and LT 10.04, all p < 0.05). After multivariate adjustment, the patient-reported burden in the Thyroid Symptom Score and the Quality-of-Life Symptom Score exhibited reduction in ST (thyroid symptoms, rate ratio [RR] 0.55, confidence interval [CI]: 0.42–0.72; quality of life, RR 0.57, CI: 0.40–0.81) and LT (thyroid symptoms, RR 0.59, CI: 0.44–0.79; quality of Life, RR 0.43, CI: 0.28–0.65). Conclusions: Quality of life and thyroid-specific symptoms of Graves' patients improved significantly from their baseline before surgery to both shortly after and longer after surgery. This work can be used to guide clinicians and patients with Graves' disease on the expected outcomes following total thyroidectomy. [ABSTRACT FROM AUTHOR]

Background: Patients with Graves' disease are commonly treated with radioiodine. There remains controversy over whether the aim of treatment should be to achieve euthyroidism or hypothyroidism, and whether treatments should be administered with standard levels of radioactivity or personalized according to the radiation absorbed doses delivered to the thyroid. The aim of this review was to investigate whether a relationship exists between radiation absorbed dose and treatment outcome. Methods: A systematic review and meta-analysis of all reports published before February 13, 2020, were performed using PubMed, Web of Science, OVID MEDLINE, and Embase. Proportion of patients achieving nonhyperthyroid status was the primary outcome. Secondary outcomes were proportion of patients who were specifically euthyroid or hypothyroid. A random-effects meta-analysis of proportions was performed for primary and secondary outcomes, and the impact of the radiation absorbed dose on treatment outcome was assessed through meta-regression. The study is registered with PROSPERO (CRD42020175010). Results: A total of 1122 studies were identified of which 15, comprising 2303 Graves' disease patients, were eligible for the meta-analysis. A strong association was found between radiation absorbed dose and nonhyperthyroid and hypothyroid outcomes (odds ratio [OR] = 1.11 [95% confidence interval {CI} 1.08–1.14] and OR = 1.09 [CI 1.06–1.12] per 10 Gy increase). Higher rates of euthyroid outcome were found for radiation absorbed doses within the range 120–180 Gy when compared with outside this range (n = 1172, OR = 2.50 [CI 1.17–5.35], p = 0.018). A maximum euthyroid response of 38% was identified at a radiation absorbed dose of 128 Gy. Conclusions: The presented radiation absorbed dose–response relationships can facilitate personalized treatment planning for radioiodine treatment of patients with Graves' disease. Further studies are required to determine how patient-specific covariates can inform personalized treatments. [ABSTRACT FROM AUTHOR]

Background Acute pericarditis as a sign of mediastinal mass is rare and aetiological diagnosis can be challenging without adequate imaging. Case summary An 18-year-old woman came to our attention describing acute sharp chest pain radiated to the left arm, exacerbated with supine positioning and attenuated while sitting or leaning forward. The electrocardiogram showed diffuse ST elevation and PR depression, with sinus tachycardia. Cardiac biomarkers and D-dimer were negative; echocardiography showed no abnormalities and the absence of pericardial effusion. Her blood work revealed no sign of inflammation or bacterial infection (PCR and procalcitonin were normal); thyroid-stimulating hormone plasma levels were suppressed, showing decompensated thyrotoxicosis. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Epstein–Barr virus, human immunodeficiency virus, hepatitis C virus, Enterovirus, Parvovirus B19, and Adenovirus tests were normal. Her past medical history was silent, apart from Grave's disease on treatment with methimazole. Chest computed tomography (CT) was performed and showed the presence of slightly increased density pericardial effusion, with a maximum thickness of 15 mm in the upper mediastinum. Finally, cardiac magnetic resonance (MR) identified a mass of 73 × 51 mm located in the upper mediastinum. The mass was subsequently biopsed with video-assisted thoracoscopic surgery and the histological analysis showed thymic hyperplasia. Discussion This case shows the importance of an adequate clinical suspicion of thymic hyperplasia in the context of acute pericarditis symptoms and known Graves' disease. In this case, a negative chest CT finding may not be sufficient to rule out the diagnosis and cardiac MR imaging is necessary. [ABSTRACT FROM AUTHOR]

Background: The autoimmune/inflammatory syndrome induced by adjuvants (ASIA) comprises four entities, including the postvaccination phenomenon, which appears after being exposed to adjuvants in vaccines that increase the immune response. There is limited information about autoimmune endocrine diseases and ASIA after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. Patient's Findings: Two female health care workers received a SARS-CoV-2 vaccine, and three days later developed clinical manifestations of thyroid hyperactivity, with increased thyroid hormone levels on thyroid function tests, suppressed thyroid-stimulating hormone, and elevated antithyroid antibodies. Summary: Vaccines have been shown to trigger an immune response that leads to a broad spectrum of autoimmune diseases, including autoimmune thyroid disease. Our patients met the diagnostic criteria for ASIA; they were exposed to an adjuvant (vaccine), and they developed clinical manifestations of thyroid hyperfunction within a few days, with the appearance of antithyroid antibodies, despite being healthy before vaccination. Conclusion: Graves' disease can occur after SARS-CoV-2 vaccination. [ABSTRACT FROM AUTHOR]

Background: The prognosis of Graves' disease (GD) is reportedly related to sex, age, and genetic factors, although there is no consensus. The objective of this study was to investigate the relationship between severity and prognosis of GD and sex or age. Methods: Subjects were patients newly diagnosed with GD between January 2005 and June 2019, and medical records were retrospectively reviewed. Patients diagnosed between January 2009 and December 2010 and followed up for at least 12 months were enrolled. Patients were divided into nine age-stratified groups. Remission was defined as maintenance of a euthyroid state for more than one year after withdrawal of antithyroid drugs (ATDs). Results: Participants comprised 21,633 patients (3954 males, 17,679 females). Initial free triiodothyronine (fT3) and free thyroxine (fT4) levels significantly decreased with increasing age, including after sex stratification. fT4 was significantly higher in males than females aged 20–39 years. In 2191 patients treated with ATDs alone, median durations until remission were 37.7 and 30.6 months in males and females, respectively. Remission and recurrence were observed in 1391 patients (204 males, 1187 females) and 262 patients (37 males, 225 females), respectively. By Kaplan–Meier analyses, males required a significantly longer time to achieve remission than females (p < 0.0001), although there were no significant age-related differences (p = 0.08). Cox proportional hazard modeling showed a 41% higher hazard ratio (HR) for remission in females than males (adjusted HRs [aHR] confidence interval [CI] = 1.41 [1.21–1.64]), and each additional 10 years of age had a 14% lower rate of recurrence (age [per 10-year increase], aHR [CI] = 0.86 [0.78–0.94]); no significant relationship between recurrence rate and sex was identified. Conclusions: Severity of hyperthyroidism in GD was significantly higher in males in their 20s and 30s, declining with advancing age in both sexes. Females were more likely to achieve remission than males, and younger patients had a higher risk of recurrence, although recurrence was unrelated to sex. [ABSTRACT FROM AUTHOR]

Background: Graves' disease is the most common cause of hyperthyroidism. It results in accelerated tissue metabolism with multi-organ involvement ranging from cardiovascular to neuropsychological function. This results in a negative impact on the quality of life (QOL) of the individual patient. We aim to evaluate the psychometric properties of ThyPRO, a Thyroid-related Patient Reported Outcome questionnaire, and validate its use in our multi-ethnic Asian patients with Graves' hyperthyroidism. Methods: Forty-seven consecutive Graves' hyperthyroidism patients answered the ThyPRO questionnaire at baseline and at 4 months after treatment initiation. Data were recorded for thyroid related symptoms and signs, thyroid function tests and thyroid volume. We analyzed the internal consistency using Cronbach's alpha, construct validity by evaluating relationship between clinical variables and ThyPRO scales, ceiling and floor effects, and responsiveness of ThyPRO to treatment based on Cohen's effect size. Results: Correlations between individual scale scores and free thyroxine concentrations were moderate and statistically significant: 0.21–0.64 (p < 0.05). There was high internal consistency between the items in this instrument, Cronbach's alpha > 0.7 for all scales. ThyPRO was responsive to the changes in QOL after treatment (Effect Size: 0.20–0.77) in 9 of the 14 scales including the hyperthyroid symptoms and psychosocial scales (Tiredness, Cognitive complaints, Anxiety, Emotional susceptibility, Impact on Social, Daily and Sex life). Conclusion: This study provides evidence that ThyPRO has satisfactory measurement properties in hyperthyroid Graves' disease patients in Singapore population with the potential to complement clinical care. [ABSTRACT FROM AUTHOR]

Graves' disease has a multitude of effects on the cardiovascular system. In the detection of subclinical left ventricular dysfunction, speckle-tracking echocardiography is more useful than conventional echocardiography. The aim of the present study was to compare the longitudinal global strain values and venous blood concentration of (tissue inhibitor of metalloproteinase-1) TIMP-1, a regulator of the extracellular matrix, among hyperthyroid patients with Graves' disease, euthyroid patients with Graves' disease and healthy control subjects. The study enrolled 40 hyperthyroid patients with newly diagnosed Graves' disease, 40 patients with Graves' disease who were euthyroid for at least 6 months and 40 control subjects with normal thyroid function. Participants underwent conventional echocardiography and speckle-tracking echocardiography to obtain segmental and global longitudinal strain values. In addition, the serum TIMP-1 value was assessed in the venous blood samples of the participants. The hyperthyroid Graves' patients showed greater serum TIMP-1 levels versus the control group and the euthyroid Graves' group. Compared to the control group, the TIMP-1 level was also significantly higher in the euthyroid Graves' group. Lower GLS (global longitudinal strain) average and GLS2C, GLS3C, GLS4C values were observed in both the hyperthyroid and euthyroid Graves' patients compared to the control group. The euthyroid Graves' patients and hyperthyroid Graves' patients had similar GLS values. The serum TIMP-1 level was negatively correlated with global strain values. Graves' disease coexists with impaired segmental and global longitudinal strain and increased TIMP-1 levels. This coexistence seems to be independent of serum thyroid hormone levels. [ABSTRACT FROM AUTHOR]

Background: Several studies have investigated the factors affecting the effects of radioactive iodine (131I) treatment (RAIT) in patients with Graves' disease. However, the influence of dietary or therapeutic iodine on the effect of RAIT has not been fully elucidated yet. The aim of this study was to investigate whether dietary or therapeutic iodine before RAIT influences the therapeutic effects of RAIT with a fixed-dose regimen and a short-term restriction of iodine intake in an iodine-sufficient area. Materials and Methods: We retrospectively analyzed 81 Japanese patients with Graves' disease treated with the following RAIT regimen: dietary iodine restriction for 7 days as well as discontinuation of antithyroid drugs (ATDs), potassium iodine (KI), or both for 5 days before RAIT. On the day of RAIT, we measured urinary iodine content to estimate daily iodine intake. After RAIT, we adjusted the dose of ATDs, KI, or both according to serum thyroid hormone levels every 1–2 months. Using the data from these patients, we investigated the effect of dietary and therapeutic iodine on the therapeutic effects of RAIT. The therapeutic effects at 1 year after RAIT were evaluated based on the necessity of ATDs, KI, or both. Results: Dietary iodine intake was weakly correlated with 131I uptake (RAIU), but the dose of therapeutic iodine was not correlated with RAIU. The therapeutic effects of RAIT were strongly negatively associated with estimated thyroid volume before RAIT. Neither dietary iodine intake nor therapeutic iodine before RAIT affected this association. Conclusion: This study did not find an association between short-term dietary or therapeutic iodine restriction before RAIT and the therapeutic effects of RAIT in an iodine-sufficient area. [ABSTRACT FROM AUTHOR]

Background: The overall changes of ocular motility in Graves' orbitopathy (GO) are not easily quantifiable with the methods currently available, especially in clinical studies. The aim of the present study was to calculate parameters that quantify the changes of ocular motility in GO in relation to the Gorman score for diplopia. Methods: We studied 100 GO patients (Group 1) and 100 controls (Group 2). We also included 30 patients treated with intravenous methylprednisolone (iv-MP), assessed at baseline and after 12 and 24 weeks (Group 3), and 66 patients submitted to squint surgery, assessed at baseline and after 12 weeks (Group 4). Ocular ductions were measured in four gaze directions by a perimeter arc and were used to calculate a total motility score (TMS) as the sum of ductions in each direction; a biocular TMS (b-TMS) as the sum of the TMS of two eyes; and an asymmetry ratio (AR) as the sum of the differences of the corresponding ductions between the two fellow eyes divided by the mean difference found in controls. Quality of life was accessed by a specific questionnaire (Graves' orbitopathy quality of life [GO-QoL] questionnaire). Results: TMS and b-TMS were lower, while AR was higher, in Group 1 compared with controls (p < 0.001). In Group 1, TMS and b-TMS were inversely correlated with the Gorman score (p < 0.001) and AR was higher in patients with constant diplopia compared with the others (p < 0.001). In Group 3, TMS and b-TMS increased after treatment in responders to iv-MP (p < 0.001). In Group 4, TMS and b-TMS improved in all patients after surgery (p < 0.01), while AR and GO-QoL score improved only in those without residual constant diplopia (p < 0.001). Conclusion: We describe a quantitative method to assess eye motility dysfunction in any stage of GO to be used as an outcome measure in clinical studies. [ABSTRACT FROM AUTHOR]

Background  The effects of hyperthyroidism on the heart are well documented, primarily consisting of supraventricular tachycardias, congestive heart failure, and dilated cardiomyopathy. Acute myopericarditis resulting from a hyperthyroid state is an uncommon but recognized association. Case summary  A 29-year-old man with a history of Graves' disease presented with chest pain and electrocardiogram changes suggestive of an infero-lateral ST-elevation myocardial infarction. However, emergent coronary angiography and bedside echocardiography were normal. Troponin-I was found to be >25 000 ng/L (normal value <57). Thyroid function tests showed a significantly raised free T4 and undetectable thyroid-stimulating hormone. Cardiovascular magnetic resonance (CMR) showed extensive myocardial oedema and late gadolinium enhancement (LGE) in keeping with acute myopericarditis, alongside an enlarged thyroid gland consistent with goitre. Propylthiouracil in combination with an angiotensin-converting enzyme inhibitor and beta-blocker were commenced and eventually definitive treatment with thyroidectomy was performed. Follow-up CMR at 6 months showed complete resolution of the prior noted oedema and a reduction in the location and extent of LGE with significant residual fibrosis. Discussion  Acute myopericarditis is a common diagnosis in young patients presenting with symptoms of chest pain with elevated troponin and is frequently related to a viral illness. Hyperthyroid states are also associated with acute myopericarditis and should be particularly considered in patients with a pre-existing thyroid condition or in those with symptoms suggestive of hyperthyroidism. Given the specific treatments required in a case of myopericarditis associated with hyperthyroidism, it is important to be aware of this association and consider screening where appropriate. [ABSTRACT FROM AUTHOR]

Background: Radioiodine (RAI) is a known risk factor for activation or de novo occurrence of Graves' orbitopathy (GO). Several studies demonstrated that GO can be prevented by glucocorticoids (GCs) in patients with pre-existing GO. We have previously shown that Graves' disease duration (GDd) <5 years is a risk factor for RAI-induced GO. We studied the effect of prophylaxis with either oral GCs (OGCs) or intravenous GCs (IVGCs) on GO activation in patients with GDd. Methods: In total, 99 hyperthyroid patients without GO or with pre-existing inactive GO with GDd <5 years were randomized to receive IVGCs (N = 49) or OGCs (N = 50) before RAI; 22 patients with GDd >5 did not receive steroids and were studied as controls. All patients underwent ophthalmological assessment before and 45, 90, 180 days and for a 5-year follow-up after RAI. Serum thyrotropin (TSH) receptor antibodies (TRAbs), thyroid hormones, and thyroid volume (TV) were also measured in response to RAI therapy and steroid prophylaxis. Results: No patient on prophylaxis developed GO after RAI. One woman of the control group, without steroid prophylaxis, and who had a marked elevation of her TSH, showed transient reactivation of GO, which spontaneously improved after restoring euthyroidism. On follow-up at 12 and 20 months after RAI, two patients developed overt optic neuropathy. A smaller TV was associated with a higher prevalence of RAI-induced hypothyroidism. Serum TRAbs increased significantly after RAI (p < 0.0001) but less in patients receiving steroids than in those without prophylaxis at 45 days (p < 0.01). Conclusions: The risk of RAI-induced GO can be prevented in all patients with GDd <5 years by steroids. Such treatment may not be necessary in patients with GDd >5 years. The blunting of TRAb elevation after RAI may be related to the prophylactic effect of steroids. [ABSTRACT FROM AUTHOR]

The article presents a randomized controlled crossover trial on the effectiveness of treating inactive Graves' orbitopathy using the prostaglandin F2-alpha analogue bimatoprost to reduce proptosis. It states participants were randomized between a placebo or receiving bimatoprost for three months and then underwent a two-month washout before switching to the opposite treatment. It discusses changes in exophthalmometry readings found no apparent improvement in proptosis.

Background: The thyrotropin receptor (TSHR) is the target for autoimmune thyroid stimulating antibodies (TSAb) triggering hyperthyroidism. Whereas elevated thyroid hormone synthesis by the thyroid in Graves' disease can be treated by antithyroid agents, for the pathogenic activation of TSHR in retro-orbital fibroblasts of the eye, leading to Graves' orbitopathy (GO), no causal TSHR directed therapy is available. Methods: Due to the therapeutic gap for severe GO, TSHR inhibitors were identified by high-throughput screening in Chinese hamster ovary cells expressing the TSHR. Stereo-selective synthesis of the screening hits led to the molecule S37, which contains seven chiral centers. Enantiomeric separation of the molecule S37 resulted in the enantiopure molecule S37a—a micro-molar antagonist of thyrotropin-induced cyclic adenosine monophosphate accumulation in HEK 293 cells expressing the TSHR. Results: The unique rigid bent shape of molecule S37a may mediate the observed high TSHR selectivity. Most importantly, the closely related follitropin and lutropin receptors were not affected by this compound. S37a not only inhibits the TSHR activation by thyrotropin itself but also activation by monoclonal TSAb M22 (human), KSAb1 (murine), and the allosteric small-molecule agonist C2. Disease-related ex vivo studies in HEK 293 cells expressing the TSHR showed that S37a also inhibits cyclic adenosine monophosphate formation by oligoclonal TSAb, which are highly enriched in GO patients' sera. Initial in vivo pharmacokinetic studies revealed no toxicity of S37a and a remarkable 53% oral bioavailability in mice. Conclusion: In summary, a novel highly selective inhibitor for the TSHR is presented, which has promising potential for further development for the treatment of GO. [ABSTRACT FROM AUTHOR]

Purpose: Surgical management of ophthalmic Graves’ disease traditionally involves, in order, orbital decompression, followed by strabismus surgery and eyelid surgery. Nunery et al. previously described two distinct sub-types of patients with ophthalmic Graves’ disease; Type I patients exhibit no restrictive myopathy (no diplopia) as opposed to Type II patients who do exhibit restrictive myopathy (diplopia) and are far more likely to develop new-onset worsening diplopia following medial wall and floor decompression. Strabismus surgery involving extra-ocular muscle recession has, in turn, been shown to potentially worsen proptosis. Our experience with Type II patients who have already undergone medial wall and floor decompression and strabismus surgery found, when additional decompression is necessary, deep lateral wall decompression (DLWD) appears to have a low rate of post-operative primary-gaze diplopia. Methods: A case series of four Type II ophthalmic Graves’ disease patients, all of whom had already undergone decompression and strabismus surgery, and went on to develop worsening proptosis or optic nerve compression necessitating further decompression thereafter. In all cases, patients were treated with DLWD. Institutional Review Board approval was granted by the University of Kansas. Results: None of the four patients treated with this approach developed recurrent primary-gaze diplopia or required strabismus surgery following DLWD. Conclusions: While we still prefer to perform medial wall and floor decompression as the initial treatment for ophthalmic Graves’ disease, for proptosis following consecutive strabismus surgery, DLWD appears to be effective with a low rate of recurrent primary-gaze diplopia. [ABSTRACT FROM AUTHOR]

Background: It was hypothesized that the biguanides metformin and phenformin, which are anti-hyperglycemic drugs used for diabetes mellitus, would have therapeutic effects in an in vitro model of Graves' orbitopathy (GO). Because adipogenesis, hyaluronan production, and inflammation are considered important in the pathogenesis of GO, this study aimed to determine the therapeutic effects and underlying mechanisms of biguanides on these parameters. Methods:In vitro experiments were performed using primary cultured orbital fibroblasts from patients with GO. Orbital preadipocyte fibroblasts were allowed to differentiate into adipocytes and were treated with various concentrations of metformin or phenformin. Oil Red O staining was performed to evaluate lipid accumulation within the cells. Western blot analysis was used to measure the expression of adipogenic transcription factors and the phosphorylation of AMP-activated protein kinase and mitogen-activated protein kinase signaling proteins. Hyaluronan production was measured using enzyme-linked immunosorbent assay, and mRNA levels of proinflammatory molecules were determined using real-time polymerase chain reaction after interleukin (IL)-1β stimulation with or without biguanide treatment. Results: Lipid accumulation during adipogenesis in GO orbital fibroblasts was dose-dependently suppressed by both metformin and phenformin. Adipocyte differentiation was attenuated, and the adipogenic transcription factors peroxisome proliferator-activated receptor γ and CCAAT-enhancer-binding proteins-α/β were downregulated. Furthermore, metformin and phenformin increased the phosphorylation of AMP-activated protein kinase and suppressed extracellular-regulated kinase activation. The IL-1β-induced hyaluronan production and mRNA expression of IL-6, cyclooxygenase-2, and intercellular adhesion molecule-1 were also significantly suppressed after metformin or phenformin co-treatment. Conclusions: The present study indicates that the biguanides metformin and phenformin exert an anti-adipogenic and inhibitory effect on hyaluronan production and expression of pro-inflammatory molecules in GO orbital fibroblasts, suggesting that they could potentially be used for the treatment of GO. [ABSTRACT FROM AUTHOR]

Background: Limited data suggest that treatment with statins is associated with a reduced risk of Graves' orbitopathy (GO) in patients with Graves' disease (GD), attributed to the anti-inflammatory rather than to the hypolipemic effects of these medications. The aim of the present study was to investigate whether there is an association between high cholesterol and GO. The primary outcome was the relation between GO and lowdensity lipoprotein (LDL)-cholesterol. The secondary outcomes were the relation between severity or activity (the clinical activity score [CAS]) of GO and LDL-cholesterol. Methods: A cross-sectional investigation was conducted in consecutive patients with GD who came under the authors' observation to undergo radioiodine treatment, a stratification aimed at forming two distinct groups of patients under the same conditions. A total of 250 patients were enrolled, 133 with and 117 without GO. Ophthalmological assessments and serum lipids measurements were performed. Results: In multivariate analyses with correction for the duration of hyperthyroidism, a variable that differed between patients with respect to the presence or absence of GO, a correlation between the presence of GO and both total (p = 0.01) and LDL-cholesterol (p = 0.02) was observed. In patients with hyperthyroidism lasting <44 months, total and LDL-cholesterol were higher (p = 0.01 and p = 0.008, respectively) among GO patients. In this subgroup, based on the presence/absence of GO, cutoff values were established for total (191 mg/dL) and LDL-cholesterol (118.4mg/dL), above which an increased risk of GO was observed (total cholesterol relative risk: 1.47; p = 0.03; LDL-cholesterol relative risk: 1.28; p = 0.03). GO severity and CAS did not correlate with serum lipids. However, CAS was found to be higher (p = 0.02) in patients with high total cholesterol. When the analysis was restricted to untreated GO patients, a correlation was found between CAS and both total (p = 0.04) and LDL-cholesterol (p = 0.03), after adjustment for GO duration. Conclusions: In patients with a short duration of hyperthyroidism, total and LDL-cholesterol correlate with the presence of GO, suggesting a role of cholesterol in the development of GO. Depending on GO duration, total and LDL-cholesterol correlate with GO activity, suggesting a role of cholesterol in the clinical expression of GO. [ABSTRACT FROM AUTHOR]

Purpose: The primary aim of this study is to isolate cytokines specific for active Graves’ orbitopathy (GO) in the tears of affected patients. The secondary aim is to identify other cytokines of interest and to look at the profile of their levels over time.Methods: This is a prospective pilot study conducted at the Singapore National Eye Centre. A total of 10 patients with active GO and 10 patients from each of 3 control groups were recruited. The 3 control groups were the following: age-matched normal female patients, patients with GO who were clinically inactive and patients with bilateral viral conjunctivitis. Tears from patients from the control groups were collected on a single visit. For patients with active GO, tears were collected on presentation, at 6 months, 12 months and 18 months.Results: Of all the cytokines examined, only IL-7 yielded a difference when the concentration in patients with active GO was compared with concentrations in all the control groups. This difference was most significant at the 18-month follow-up visit.Conclusions: Low concentrations of IL-7 in tears exhibit specificity for active GO in patients nearly 2 years from the clinical onset of activity. Although using IL-7 in tears as a biomarker for disease activity may be limited due to its late manifestation, targeting immune restitution using IL-7 may have disease modifying effects. [ABSTRACT FROM AUTHOR]

Background: There are currently no reliable biomarkers to predict relapse in Graves' disease (GD). In the present study, we investigated novel diagnostic biomarkers to predict the long-term remission of or relapse in GD. Methods: A DNA microarray analysis was performed to examine gene expression in the peripheral leukocytes of a frequently relapsing patient with GD and a patient in long-term remission after the discontinuation of antithyroid drugs (ATDs). Based on the DNA microarray analysis, we focused on Sialic acid-binding immunoglobulin-like lectin1 ( SIGLEC1) as a candidate novel biomarker to predict GD relapse. Three hundred and fifty-eight patients with GD in the thyroid clinics of four different hospitals in Japan were included in a cross-sectional study to establish whether SIGLEC1 mRNA levels distinguish GD relapse experience from long-term remission. An additional 55 patients with GD were enrolled in a prospective study to clarify whether SIGLEC1 mRNA levels at ATD discontinuation predict GD relapse. Results: SIGLEC1 mRNA levels were significantly higher in patients with GD relapse experience than in those in long-term remission. Based on the receiver operating characteristic analysis, we found that high SIGLEC1 mRNA levels (≥258.9 copies) significantly distinguished GD relapse experience from long-term remission ( p < 0.0001; sensitivity 66.7%, specificity 70.1%). In the prospective study, when the optimal cutoff value from the receiver operating characteristic curve analysis was applied to SIGLEC1 mRNA positivity at ATD discontinuation, SIGLEC1-positive patients (≥258.9 copies) showed a significantly higher cumulative risk of relapse than SIGLEC1-negative patients (<258.9 copies) ( p = 0.022, the log-rank test). Conclusions: SIGLEC1 mRNA levels have potential as a novel predictive biomarker for GD relapse. [ABSTRACT FROM AUTHOR]

Key Clinical Message Given the immune background, we hypothesize that active Grave's hyperthyroidism is a risk factor for an acute phase reaction associated with the use of bisphosphonates. We recommend that in patients with Graves' thyrotoxicosis and hypercalcemia, consider the risk of an acute phase reaction if planning to give bisphosphonate therapy. [ABSTRACT FROM AUTHOR]

Background: A recent clinical trial has shown a beneficial effect of the antioxidant agent selenium in Graves' orbitopathy (GO). In order to shed light on the cellular mechanisms on which selenium may act, this study investigated its effects in cultured orbital fibroblasts. Methods: Primary cultures of orbital fibroblasts from six GO patients and six control subjects were established. Cells were treated with H2O2 to induce oxidative stress, after pre-incubation with selenium-(methyl)selenocysteine (SeMCys). The following assays were performed: glutathione disulfide (GSSG), as a measure of oxidative stress, glutathione peroxidase (GPX) activity, cell proliferation, hyaluronic acid (HA), and pro-inflammatory cytokines. Results: H2O2 induced an increase in cell GSSG and fibroblast proliferation, which were reduced by SeMCys. Incubation of H2O2-treated cells with SeMCys was followed by an increase in glutathione peroxidase activity, one of the antioxidant enzymes into which selenium is incorporated. At the concentrations used (5 μM), H2O2 did not significantly affect HA release, but it was reduced by SeMCys. H2O2 determined an increase in endogenous cytokines involved in the response to oxidative stress and GO pathogenesis, namely tumor necrosis factor alpha, interleukin 1 beta, and interferon gamma. The increases in tumor necrosis factor alpha and interferon gamma were blocked by SeMCys. While the effects of SeMCys on oxidative stress and cytokines were similar in GO and control fibroblasts, they were exclusive to GO fibroblasts in terms of inhibiting proliferation and HA secretion. Conclusions: Selenium, in the form of SeMCys, abolishes some of the effects of oxidative stress in orbital fibroblasts, namely increased proliferation and secretion of pro-inflammatory cytokines. SeMCys reduces HA release in GO fibroblasts in a manner that seems at least in part independent from H2O2-induced oxidative stress. Some effects of SeMCys are specific for GO fibroblasts. These findings reveal some cellular mechanisms by which selenium may act in patients with GO. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to assess intraocular inflammation in patients with active and inactive Graves' ophthalmopathy (GO) using an aqueous laser flash meter and to assess its relationship with thyroid hormones, antibodies, and clinical activity score (CAS)., Methods: Forty patients (29 females and 11 males) were included in the study. The patients were divided into two groups according to CAS; patients with CAS <3 (inactive) were included in Group 1 and patients with CAS ≥3 (active) were included in Group 2. The laser flare meter was used to measure the flare of aqueous humor. Each patient's ocular findings, thyroid hormone, and antibody levels were also recorded., Results: The mean age of patients was 46.88±11.79 years in Group 1 and 44.50±12.59 years in Group 2 (p=0.555). The mean CAS was 0.88±0.65 in Group 1 and 3.57±0.85 in Group 2 (p<0.001). The mean aqueous flare was 6.5±2.2 ph/ms in Group 1 and 7.0±6.4 ph/ms in Group 2 (p=0.73). Hertel exophthalmometry, intraocular pressure (IOP), antithyroglobulin antibody, and thyroid stimulating hormone receptor antibody (TRAb) levels were similar in both groups (each p>0.05). There was no correlation between aqueous flare value and CAS, Hertel exophthalmometry, IOP, thyroid hormone, and antibody levels (each p>0.05). There was a significant correlation between CAS and antibody levels (each p<0.05)., Conclusion: Flare values that are not much above the normal range may be an indication that intraocular inflammation is not elevated in GO patients. This suggests that the damage to the blood-aqueous barrier in these patients is not severe enough to increase intraocular inflammation., Competing Interests: Conflict of Interest: None declared., (Copyright: © 2023 by Beyoglu Eye Training and Research Hospital.)

Background: C-reactive protein (CRP), which is a marker of inflammation, has not been widely studied in inflammatory thyroid disorders particularly in sub-acute thyroiditis (SAT). Aim: This study was aimed to find the significance of CRP level rise in patients with SAT and compare that to the rise in erythrocyte sedimentation rate (ESR), a gold standard laboratory parameter in establishing the diagnosis of SAT. Materials and Methods: Serum CRP levels were measured at initial presentation in 28 subjects with SAT(12 male, 16 female, age (Mean +SD) 37.96 ±8.5 years),and 19 patients with Graves′ disease (2 male, 17 female, age [Mean +SD] 36.8 ±16.5 years) as controls. Erythrocyte sedimentation rate (ESR) was measured in all 28 patients with SAT by Westergrens′ method. Either Tc 99 nucleotide thyroid scan or high resolution ultrasonography (HR-USG) was performed to differentiate SAT from Graves′ disease.Fine needle aspiration cytology (FNAC) of thyroid was performed selected patients. Results: Serum CRP level was high in 61% of SAT patients but in none of the Graves′patients. Mean (SEM) (90%CI) serum CRP level (mg/L) was also significantly higher (P

OBJECTIVES: To estimate oculometric parameters of Graves' ophthalmopathy in comparison to healthy eyes using digital photography and digital image analysis. INTRODUCTION: Graves' ophthalmopathy is the main cause of eye proptosis. Because these protrusions cause clinically perceived distortions in orbital architecture, digital photographs can be used to detect and quantify these changes. METHODS: We carried out a cross-sectional study comprising 12 healthy volunteers and 15 Graves' ophthalmopathy patients with the purpose of evaluating the use of simple, non-invasive digital photography to estimate oculometric parameters of Graves' ophthalmopathy and compare them with the parameters of unaffected eyes. Facial photographs of cases and controls were taken in a standardized manner. Oculometric parameters were compared between the groups and then correlated to proptometer measures. RESULTS: All estimated oculometric variables showed significant differences between the groups, in particular with regard to mediopupilar aperture, lateral height, distance from the iris edge to the lateral boundary of the palpebral fissure, and distance from the higher point of the iris to the lateral limit of the palpebral fissure. The product of medial aperture and horizontal palpebral fissure also revealed greater discrepancy between the groups. Proptometer measures showed significant linear correlation between the distance from the iris edge to the lateral boundary of the palpebral fissure and between the distance from the higher point of the iris to the lateral limit of palpebral fissure (p

Objective: Mental fatigue, depression, anxiety, and cognitive complaints are common in Graves' disease (GD). Our aims were to assess the relationship between these variables in patients with GD during both hyperthyroidism and a long stable euthyroidism., Methods: A prospective longitudinal case-control study where 65 premenopausal women diagnosed with GD and 65 matched controls were assessed twice with 15 months in between. The first visit for patients was in overt hyperthyroidism and the second after treatment., Results: During the hyperthyroid phase, mental fatigue, depression, and anxiety were significantly increased for GD patients compared to controls (all P < 0.001). Among GD patients, 89% reported mental fatigue and among controls 14%. No difference in cognitive tests was found. After 15 months, significant improvements for GD patients after treatment were found for the items of mental fatigue, depression, and anxiety (all P < 0.001), but these were unchanged in controls. GD patients reported residual mental fatigue (38%), 23% without depression, and 15% mental fatigue combined with depression. Self-reported cognitive complaints were pronounced while cognitive tests did not reveal any deficiencies., Conclusion: Mental fatigue and emotional distress are common in the hyperthyroid phase. These improve with treatment but are still more common in GD patients after 15 months of therapy than in controls. The residual mental fatigue is shown to be a phenomenon distinct from depression in this study. This indicates the importance of assessing mental fatigue in GD patients and underlines the need for rehabilitation and healthcare support as fatigue will have consequences for work ability.

Purpose: The traditional standard of care for Graves' ophthalmopathy (GO) is glucocorticoid therapy, which is associated with many long-term side effects. The aim of this systematic review and meta-analysis was to compare the traditional therapy to novel monoclonal antibodies (e.g. rituximab [RTX], teprotumumab, and tocilizumab [TCZ])., Methods: We searched the Medline, Embase, and Cochrane Central Register of Controlled Trials databases. We included randomized controlled trials (RCTs) that compared different monoclonal antibodies (e.g. RTX, teprotumumab, and TCZ) with glucocorticoids or placebo in patients with GO. We evaluated the clinical activity score (CAS), proptosis, subjective diplopia using the Gorman score, quality of life (QoT), adverse events, change in lid fissure, NOSPECS score, and TSH receptor antibody (TRAb) levels. The odds ratio (OR) was used to represent dichotomous outcomes. The continuous outcomes were represented as standardized mean difference (SMD). Data were pooled using the inverse variance weighting method. Risk of bias was assessed using the revised Cochrane risk-of-bias tool for randomized trials., Results: Six ( n = 571) RCTs were deemed eligible. The different monoclonal antibodies were significantly more efficacious than glucocorticoid/placebo in terms of reduction in CAS (SMD = -1.44, 95% confidence interval (CI): -1.91--0.97, P < 0.00001, I 2 = 74%), change in proptosis (SMD = -4.96, 95% CI: -8.02--1.89, P = 0.002, I 2 = 99%), QoL (SMD = 2.64, 95% CI: 0.50-4.79, P = 0.02, I 2 = 97%), and Gorman score for diplopia (OR = 3.42, 95% CI: 1.62-7.22, P = 0.001, I 2 = 8%). However, monoclonal antibodies have shown higher rates of adverse events (OR = 2.91, 95% CI: 1.12-7.56, P = 0.03, I 2 = 62%). No significant difference was found with respect to lid fissure, NOSPECS, and TRAb levels., Conclusion: This meta-analysis demonstrated that monoclonal antibodies were associated with more favorable clinical outcomes than standard steroid therapy or placebo, especially with regard to CAS, change in proptosis, diplopia, and QoL, with teprotumumab being superior. In addition, only minor safety concerns were identified with monoclonal antibodies though less worrisome than using traditional steroids., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Saudi Journal of Ophthalmology.)

Background: To determine the effects of previous overt hyperthyroidism due to Graves’ disease on BMD in euthyroid pre and post menopausal females. Methods: In this cross-sectional, non-interventional study,fifty patients with previous hyperthyroidism due to Graves’ disease (premenopausal:25, postmenopausal: 25) who remained euthyroid for at least 6 months prior to study were included and compared with fifty- matched respective controls. Free thyroxine (FT4), TSH, and BMD were measured. Comparison was made between two groups and also between patients and controls in each group. Results: Statistically significant (p