Radioactive Iodine Treatment of Graves' Disease: Predictors of Time Interval Greater than 90 Days for Treatment Success.

Objective: Radioactive iodine (RAI) is often used for treating Graves' disease. We study predictors for a time interval greater than 90 days between RAI treatment and success. Methods: This was a retrospective study of 106 patients with Graves' disease seen at a public hospital in suburban New York City. Predictor variables were from demographics, prior treatment history, iodine 131 RAI treatment, and thyroid function prior to RAI treatment. Results: There were 62.3% that had a time interval greater than 90 days between RAI treatment and success. Only the thyroid function prior to RAI treatment variable of free thyroxine (FT4) had statistically significantly increased odds for time interval greater than 90 days between RAI treatment and success (OR:1.28, 95% CI:1.02, 1.61, p = 0.03). Demographics, prior treatment history, and iodine 131 RAI treatment variables were not significantly associated with time interval greater than 90 days between RAI treatment and success. Conclusion: Thyroid function measured by FT4 was significantly associated with time interval greater than 90 days between RAI treatment and success. We suggest that the thyroid function variable of FT4 levels at initial diagnosis is most helpful for understanding the prognosis and success rate for using RAI treatment in patients with Graves' disease.

Autoimmune diseases refractory to corticosteroids and immunosuppressants.

Corticosteroids and immunosuppressive drugs can alleviate the symptoms of most autoimmune diseases and induce remission by restraining the autoimmune attack and limiting the damage to the target tissues. However, four autoimmune non-degenerative diseases-adult advanced type 1 diabetes mellitus, Hashimoto's thyroiditis, Graves' disease, and advanced primary biliary cholangitis-are refractory to these drugs. This article suggests that the refractoriness of certain autoimmune diseases is due to near-total loss of secreting cells coupled with the extremely low regenerative capacity of the affected tissues. The near-complete destruction of cells responsible for secreting insulin, thyroid hormones, or biliary HCO3 - diminishes the protective effects of immunosuppressants against further damage. The slow regeneration rate of these cells hinders tissue recovery, even after drug-induced immune suppression, thus preventing remission. Although the liver can fully regenerate after injury, severe primary biliary cholangitis may impair this ability, preventing liver recovery. Consequently, these four autoimmune diseases are resistant to immunosuppressive drugs and corticosteroids. In contrast, early stages of type 1 diabetes and early primary biliary cholangitis, where damage to secreting cells is partial, may benefit from immunosuppressant treatment. In contrast to these four diseases, chronic degenerative autoimmune conditions like multiple sclerosis may respond positively to corticosteroid use despite the limited regenerative potential of the affected tissue (the central nervous system). The opposite is true for acute autoimmune conditions like Guillain-Barré syndrome.

Pediatric Graves' Disease: Surgical Interventions in a Single Institution - A Comprehensive Case Series.

Introduction: Graves' disease (GD) is the most common cause of hyperthyroidism in children and adolescents. Data regarding pediatric GD in Indonesia are limited and pose challenges to diagnosing and treating the patients. In many aspects the clinical presentation of GD in children and adolescents resembles that of the adult population. There are three treatments for pediatric GD: anti-thyroid drugs, radioiodine ablation, and thyroidectomy. Although surgery is gaining acceptance as the definitive first-line treatment for children with GD, several studies examining pediatric populations have shown high complication rates. This study aims to describe a series of pediatric GD cases from a tertiary care center over an eight-year period. Presentation of Cases: Retrospective data of five patients with hyperthyroidism diagnosed with GD between 2014 and 2022 were reviewed. Clinical presentation, diagnosis, therapies, and short-term postoperative outcomes of GD were analyzed. All five GD patients presented with neck lumps. Low TSH levels and elevated FT4 levels were found in all patients preoperatively. Total thyroidectomy was performed in all patients, while one patient had lymphadenectomy concurrently. Histopathologic examination confirmed a diagnosis of GD in all patients. All patients in this study experienced postoperative complications such as hoarseness, while only three patients had hypocalcemia as a complication. Discussion: Total thyroidectomy in pediatric patients remains challenging. The euthyroid condition in patient prior to surgery is recommended to avoid the risk of thyroid storm during surgery, but a few studies have revealed that there is no difference in outcomes for hyperthyroid individuals. Close postoperative surveillance for complications of total thyroidectomy is necessary. Conclusions: Results of this study showed that pediatric GD patients had the same symptoms of hyperthyroidism as adults with all patients complained of neck lumps. Total thyroidectomy is the definitive therapy for GD in pediatrics as well as in adults. The minority of patients will experience transient and benign morbidities, with hoarseness of the voice being the most common transient postoperative morbidity. In performing total thyroidectomy, meticulous surgery and good anatomical recognition are required to avoid postoperative complications. So that, follow-up of post-total thyroidectomy in pediatric GD patients needs to be done.

Causal effects of post-traumatic stress disorder on autoimmune thyroid disease: insights from mendelian randomization.

Objective: The relationship between post-traumatic stress disorder (PTSD) and autoimmune thyroid disease (AITD) needs further evaluation. This study employs Mendelian randomization (MR) to investigate the causal correlations of PTSD with autoimmune thyroiditis (AIT) and Graves' disease (GD). Methods: Datasets for PTSD, AIT, and GD were obtained from FinnGen. The exposure-outcome causal relationship was assessed using inverse variance weighted, MR-Egger, and weighted median. Horizontal pleiotropy was evaluated through the MR-Egger intercept, heterogeneity was examined using Cochran's Q test, and robustness was assessed via leave-one-out sensitivity analysis. Results: MR analysis indicated no significant causal relationship between PTSD and AIT (OR 0.920, 95% CI 0.832 to 1.017, p = 0.103), but a potential increase in the risk of GD associated with PTSD (OR 1.056, 95% CI 1.008 to 1.105, p = 0.021). MR-Egger intercept showed no horizontal pleiotropy (p > 0.05), and Cochran's Q showed no heterogeneity (p > 0.05). Sensitivity analysis suggested the MR results were robust. Conclusions: Evidence of an MR association between genetic liability to PTSD and an increased risk of GD were provided, but no evidence of association between PTSD and AIT. The findings indicate that individuals with PTSD may have an increased likelihood of developing GD, underscoring the importance of further research to comprehend the intricate interplay between PTSD and thyroid disorders.

RARE ASSOCIATION BETWEEN HASHITOXICOSIS, BASEDOW DISEASE AND PAPILLARY THYROID CARCINOMA.

We present the case of a 32 yeas old male, diagnosed 7 years ago with Graves disease, with numerous recidives which needed anti-thyroid medication, with poor response (hypo to hyper-thyroid status, with high variations of TSH and FT4) whom after a period of remission (8 months, no treatment) came in for a polymorphic symptomatology sugestive for hyperthyroidism. The hyperthyroid state was confirmed he had high TRAb (31 UI/ml vs. <1.75 UI/ml) - on his last check in the detection rate of TRAb was under 0.3 UI/ml. The thyroid ultrasound revels on the left lobe a small mass of 0.8/0.8 cm, with EU-TIRADS score of 4, that was newly diagnosed. Postoperative histopathology revealed papillary microcarcinoma developed on Hashitoxicosis- pT1aN0, of 1 mm in the middle of left thyroid lobe. The particularity of this case consists in a long evolution of Graves disease with numerous relapses, the appearance of a thyroid nodule after 7 years in which they identified a papillary microcacinoma associated with Hashimoto thyroiditis and also the postoperative recovery that was slowed by the parathyreoprive tetany.

The gut microbiota and its role in Graves' Disease: a systematic review and meta-analysis.

Emerging research indicates the potential involvement of gut bacteria in the etiology of Graves' Disease (GD). However, the evidence regarding this matter is still conflicting. The primary objective of this investigation was to examine the correlation between gut microbiota and GD. A comprehensive search was conducted of the Cochrane Library, Scopus, Europe PMC, and Medline databases up until August 1, 2023, utilizing a combination of relevant keywords. This review incorporates literature that examined the composition of gut microbiota in patients with GD. We employed random-effect models to analyze the standardized mean difference (SMD) and present the outcomes together with their corresponding 95% confidence intervals (CIs). A total of ten studies were incorporated. The results of our meta-analysis indicated that patients with GD have a reduced alpha diversity of gut microbiota as evidence by a significant reduction of Chao1 (std. mean difference -0.58; 95% CI -0.90, -0.26, p=0.0004; I2 =61%), ACE (std. mean difference -0.64; 95% CI -1.09, -0.18, p=0.006; I2 =77%), and Shannon index (std. mean difference -0.71; 95% CI -1.25, -0.17, p=0.01; I2 =90%) when compared with healthy controls. At the phylum level, the abundance of Firmicutes was reduced in GD patients, while that of Bacteroidetes was increased. This study suggests a notable decrease in the richness and variety of gut microbiota among people diagnosed with GD in comparison with healthy controls.

Exploring the Association Between Hidradenitis Suppurativa and Hyperthyroidism.

PURPOSE: Hidradenitis suppurativa (HS) is an inflammatory disease affecting the pilosebaceous skin units and is linked to several autoimmune conditions. An area of exploration includes the connection between hyperthyroidism and HS. This study aims to investigate and establish the relationship between HS and hyperthyroidism. METHODS: The relationship between hyperthyroidism and HS was evaluated using data from the National Institute of Health (NIH) All of Us Researcher Program. A cross-sectional study was performed to assess the prevalence of HS in individuals with and without a history of hyperthyroidism matched by age ranges and health surveys. Relative risk and significance were determined by using standard statistical methods. RESULTS: A total of 407,333 patients were matched by health surveys and age ranges in the control and experimental groups. Among patients with a history of hyperthyroidism, the prevalence of HS was 1.40% compared to 0.38% in the control group. This difference was statistically significant (p < 0.0001 with an OR = 3.717, 95% CI 3.038-4.548). CONCLUSION: This study demonstrates a statistically significant correlation between hyperthyroidism and increased prevalence of HS. These results justify the need for further research regarding hyperthyroidism's role in HS and the potential screening tools and lifestyle management techniques that may be prevalent for both conditions.

[Survey of the management of moderate to severe active Graves' orbitopathy at 28 metropolitan centers of excellence in France]. / État des lieux de la prise en charge de l'orbitopathie dysthyroidïenne modérée à sévère active en France à partir de 28 centres experts métropolitains.

INTRODUCTION: This study investigates the management of Graves'orbitopathy (GO) in France, at 26 university medical centers (CHU) as well as the Rothschild Foundation and the Quinze-Vingts national eye hospital in Paris. METHODS: The 28 metropolitan university medical centers were contacted by telephone or e-mail. The authors devised a 5-item questionnaire that explored the scheduling of multidisciplinary meetings, the existence or lack of a dedicated Graves' consultation service, the place of hospitalization, and first- and second-line treatments. RESULTS: Eighty-nine percent of hospital departments had a dedicated service for patients with GO, with 36% organizing multidisciplinary meetings. Intravenous corticosteroid therapy is still used as first-line treatment, while mycophenolate is used much less (14.3%), despite the new EUGOGO (European Group on Graves' orbitopathy) 2021 recommendations. For second-line treatment, tocilizumab is most commonly used (64%). Teprotumumab is available in France only on a compassionate basis, and its use is limited (18%). CONCLUSION: This study highlights the variability in practices and the importance of a multidisciplinary approach, while calling for national standardization of practices. Despite disparities in the application of recommendations, the emergence of second-line treatments such as tocilizumab and teprotumumab indicates a steady evolution in therapeutic options, although obstacles in terms of accessibility and cost remain.

The association between methimazole tapering and intractable Graves' disease in children.

BACKGROUND: The aim of this study was to find predictive factors for intractable Graves' disease (GD). METHODS: Ninety-three GD patients who visited two pediatric endocrinology clinics from March 2009 to August 2019 were involved in this study. Data were collected on the methimazole (MZ) dosages prescribed from their first visits to their fifth visits. The amount of tapered dosage was presented as a "tapering velocity" (dosage difference (mg/m2)/follow-up interval (months)). The relationship between the tapering velocity and the remission rate of GD was analyzed. Remission of GD was defined as having a total period of MZ treatment less than 5 years with no relapse after MZ withdrawal for at least more than a year. RESULTS: Of 93 patients diagnosed with GD, 26 patients (28.0%) were classified as the "remission group" and 67 (72.0%) were classified as the "intractable group." The frequency of goiter was significantly higher in the intractable group (p = 0.031). Multivariate logistic analysis revealed that the tapering velocity change from the first to the fifth visit significantly influenced the risk of intractable GD: odds ratio (OR) = 0.598, 95% confidence interval (CI) 0.413-0.865, p = 0.006. An accompanying goiter at the time of diagnosis (OR = 4.706 95% CI 1.315-16.847, p = 0.017) and thyroid stimulation hormone receptor antibody titer (OR = 1.032 95% CI 1.002-1.062, p = 0.034) were also found to be independent factors associated with intractable progress in GD. CONCLUSION: Difficulty in tapering the MZ dosage in the first 4 months of treatment was an independent predicting factor for intractable GD.

Long-term outcome of Graves' orbitopathy following treatment with sirolimus.

OBJECTIVES: Sirolimus was found to be associated with a better outcome of Graves' orbitopathy (GO) at 24 weeks compared to methylprednisolone. We conducted a retrospective study to investigate its efficacy and safety over a longer period. METHODS: Data from 40 consecutive patients with moderate-to-severe, active GO, 20 treated with sirolimus and 20 with methylprednisolone, were collected. PRIMARY OUTCOME: overall outcome (composite evaluation) of GO at 48 weeks. SECONDARY OUTCOMES: (1) GO outcome at 24 weeks, and, at 24 and 48 weeks: (2) outcome of single eye features; (3) quality of life (GO-QoL); (4) TSH-receptor antibodies; (5) GO relapse at 48 weeks; (6) adverse events. RESULTS: The overall GO outcome at 48 weeks did not differ between the two groups (responders: 55% vs 55%). At 24 weeks, prevalence of responders was greater in sirolimus group (65% vs 25%; P = 0.01). A reduction ≥ 1 point in clinical activity score (CAS) was more frequent in sirolimus patients at 24 (85% vs 40%; P = 0.005) and 48 weeks (75% vs 60%; P = 0.03). The proportion of GO-QoL responders (appearance subscale) at 24 weeks was greater in sirolimus group (62.5% vs 26.3%; P = 0.03). No difference was observed for the remaining outcome measures. CONCLUSIONS: Treatment with sirolimus is followed by a greater overall response of GO compared with methylprednisolone at 24 weeks, but not at 48 weeks, when only CAS is affected. A more prolonged period of treatment may be required for a better outcome to be observed over a longer period.

Utility of ultra-portable ultrasound devices for the risk-stratification of thyroid dysfunctions in an emergency setting.

PURPOSE: We previously showed that the rapid TSH (rTSH) screening is able to detect a high prevalence of thyroid diseases in patients presenting to the Emergency department (ED), with a 7% prevalence of undiagnosed thyroid dysfunctions. The purpose of the present study is to implement our diagnostic flow-chart for thyroid dysfunctions in the ED with a rapid point-of-care thyroid ultrasound (rPOCUS). METHODS: rPOCUS was performed by an app-based mobile ultrasound device (Lumify® by Philips Healthcare) in patients with suppressed rTSH undergoing urgent procedures requiring iodinate contrast media. RESULTS: Our results suggest that rPOCUS is cost- and time-effective for the management of patients with a newly diagnosed hyperthyroidism requiring urgent iodinated contrast media or amiodarone administration. Moreover, this handled US scanner avoided rTSH measurement in patients found to have a normal thyroid gland, and detected some incidental findings (nodules, heterogeneous echotexture), which would lead to further diagnostic investigations. CONCLUSION: We demonstrate, for the first time, that rPOCUS greatly improves the management of patients attending the ED, including the prompt characterization and correct treatment of hyperthyroidism, and the prevention of iodine-induced thyrotoxicosis.

The Effects of Anti-thyroid Drugs on Lipoproteins and Insulin Resistance in Graves' Disease: A Randomized Clinical Trial.

Objective: Graves' disease (GD) is characterized by thyroid overactivity. Anti-thyroid drugs (ATDs), such as propylthiouracil (PTU) and methimazole (MMI), are commonly used for GD treatment, and studies have suggested a link between these drugs and elevated lipoprotein levels. However, data on their effects on lipoproteins, insulin resistance, or low-density lipoprotein receptor (LDL-R) levels are lacking, both in Indonesia and in other countries. This study investigated changes in lipoproteins, LDL-R, and insulin resistance markers with ATD treatment. Methods: This study is a secondary analysis of a randomized clinical trial entitled "The Differential Effects of Propylthiouracil and Methimazole as Graves' Disease Treatment on Vascular Atherosclerosis Markers" conducted in Jakarta, Indonesia. Thirty-seven newly diagnosed GD patients received MMI or PTU for 3 months. Results: After 3 months of ATD treatment, LDL-R levels significantly decreased compared to baseline (197 vs. 144 ng/mL, p<0.001), while most lipoproteins, including TC, LDL-C, HDL-C, non-HDL-C, the cholesterol ratio, and the LDL-C/HDL-C ratio, increased. Unexpectedly, neither the PTU nor MMI groups showed an increased dyslipidemia prevalence. Although body mass index increased significantly and fasting plasma glucose decreased slightly, no significant post-treatment change in insulin resistance was observed. The study received ethical approval from the Ethics Committee of the Faculty of Medicine, Universitas Indonesia (ref KET-784/UN.2.F1/ETIK/PPM.00.02/2019) and was registered on clinicaltrials.gov (NCT05118542). Conclusion: ATD treatment for GD led to a significant increase in total cholesterol, LDL-cholesterol, and high-density lipoprotein-cholesterol levels, along with a reduction in LDL-R levels. Both PTU and MMI showed similar effects. These findings provide valuable insights into the effects of ATDs on lipoproteins and insulin resistance in GD patients. Trial Registration: ClinicalTrials.gov Identifier: NCT05118542.

Emergency Endoscopic Endonasal Optic Nerve Decompression for Graves' Orbitopathy.

Graves' orbitopathy (GO) is a rare autoimmune disease that affects patients in their fourth to sixth decade, resulting in retro-orbital inflammation and hypertrophy of extraocular muscles and orbital fat. It is the most common disease affecting the orbit globally, and treatment options vary depending on the severity and activity status of the affection, ranging from local measures such as lubricating eye drops and patching, glucocorticoid eye drops, mydriatics, nonsteroid anti-inflammatory medications to systemic glucocorticoids, and emergency orbital decompression surgery. Immunotherapy and orbital radiation may as well be used as a treatment option even though their efficiency remains controversial. This paper presents the cases of two patients with GO who underwent endoscopic endonasal decompressive surgery. These patients' medical records, including symptoms and duration, clinical examination, imaging results, preoperative preparation, surgery steps, and postoperative course and outcomes, were collected from various specialties, including ophthalmologists and endocrinologists. We highlight the importance of a multidisciplinary approach to managing GO and its complications, with endoscopic endonasal techniques emerging as a minimally invasive and effective way to treat compressive optic nerve forms of the disease. However, the timing of decompression remains crucial, and early intervention is recommended to avoid sight-threatening ophthalmopathy when medical therapies are ineffective.

A combined transcriptomics and proteomics approach reveals S100A4 as a potential biomarker for Graves' orbitopathy.

Background: There are no reliable biomarkers to identify Graves' disease patients who will develop severe Graves' orbitopathy (GO). We hypothesize that integrating various omics platforms can enhance our understanding of disease mechanisms and uncover potential biomarkers. This study aimed to (1) elucidate the differential gene expression profile of orbital fibroblasts in GO during early adipogenesis to better understand disease mechanisms and (2) compare tear protein profiles from our earlier study and the transcriptome profiles of orbital fibroblasts (OFs) to identify possible biomarkers of the disease. Methods: OFs were grown from orbital adipose tissue obtained from nine GO patients (three for discovery and six for validation experiments). Total RNA was extracted from OFs on day 0 as the baseline for each sample and from differentiated OFs on days 4 and 8. Protein-protein interaction (PPI) analysis and functional enrichment analysis were also carried out. The differentially expressed genes (DEGs) from the RNA sequencing experiments were then compared to the full tear proteome profile from the author's previous study, which examined the tear protein changes of GO patients based on fold change > 1.6 or < -1.6. FDR < 0.05 was applied within all datasets. Further validation of S100 calcium-binding protein A4 (S100A4) downregulation in GO was performed via quantitative real-time PCR (qPCR). Results: The whole transcriptomic analysis revealed 9 upregulated genes and 15 downregulated genes in common between the discovery and validation experiments. From the PPI network analysis, an interaction network containing six identified DEGs (ALDH2, MAP2K6, MT2A, SOCS3, S100A4, and THBD) was observed. The functional enrichment network analysis identified a set of genes related to oxysterol production. S100A4 was found to be consistently downregulated in both our transcriptome studies and the full-tear proteome profile from the author's previous study. Conclusion: Our study identified several DEGs and potential gene pathways in GO patients, which concurred with the results of other studies. Tear S100A4 may serve as a biomarker for the propensity to develop thyroid eye disease (TED) in patients with autoimmune thyroid disease (AITD) before clinical manifestation and should be confirmed in future studies.

Immune Checkpoints and Graves' Disease, Thyroid Eye Disease, and Orbital Myopathy: A Comprehensive Review.

Immune checkpoints (ICPs) are essential regulators of the immune system, ensuring a delicate balance between self-tolerance and autoimmune responses. ICP therapy is a rapidly growing cancer treatment strategy that inhibits the interaction between ICPs and their ligands. This biological interaction increases the ability of the immune system in combating cancer. However, in some cases, the use of these agents may lead to immune hyperactivity and, subsequently, autoimmune diseases. Graves' disease (GD), thyroid eye disease (TED), and orbital myopathy are complex autoimmune disorders characterized by the production of autoantibodies. The emergence of these treatment-related adverse events underscore the critical need for a deeper understanding of the immune-checkpoint axis in autoimmune diseases. In this review article, we provide a comprehensive survey of the biological mechanisms of ICPs that are most frequently targeted in cancer therapy, including CTLA-4, PD-1, PDL-1, and LAG3. Furthermore, we investigate the latest scientific findings on the adverse events associated with the inhibition of these ICPs. This paper will particularly focus on the potential risks these complications pose to ocular and orbital tissues, which are a concern in the context of cancer treatment.

Thyroid Eye Disease and Glaucoma: A Cross-Sectional Study Comparing Clinical Characteristics and Disease Severity.

Background and Objectives: This study investigates the relationship between thyroid eye disease (TED) and open-angle glaucoma (OAG), focusing on disease severity and clinical features. Materials and Methods: Conducted at the Timis County Emergency Clinical Hospital, the research included 106 patients, with 53 having both conditions and 53 having only OAG. Key metrics analyzed included intraocular pressure (IOP) using a Goldmann applanation tonometer, the retinal nerve fiber layer (RNFL) thickness, and optic nerve head (ONH) characteristics evaluated using optical coherence tomography (OCT). Results: Results indicated that patients with both TED and OAG experienced a 6.09% reduction in RNFL thickness and showed more rapid disease progression, with 48.35% having active TED. The mean IOP in TED patients was 27.5 ± 4.9 mmHg, which was similar to those with only OAG. Demographic factors, including age and gender, influenced the clinical course and disease severity. Conclusions: These findings underscore the importance of specialized monitoring and treatment strategies for patients with coexisting TED and OAG to prevent vision loss.

Changes in bone density and microarchitecture following treatment of Graves' disease and the effects of vitamin D supplementation. A randomized clinical trial.

Thyrotoxicosis leads to loss of bone mass. Vitamin D is important to bone health. In this randomized, placebo-controlled trial, we showed that bone restoration did not improve when adding vitamin D supplementation to standard care of Graves' disease thyrotoxicosis. Bone density and microarchitecture improved markedly with treatment of thyrotoxicosis. PURPOSE: Vitamin D is important to skeletal health and ensuring a replete vitamin D status is recommended. In thyrotoxicosis, bone turnover is increased and bone mass density (BMD) reduced. We examined whether vitamin D supplementation improves bone recovery in thyrotoxicosis caused by Graves' disease (GD). METHODS: Using a double-blinded design, hyperthyroid patients with GD were randomized to vitamin D3 70 µg/day (2800 IU) or similar placebo as add-on to antithyroid drugs (ATD). At baseline and 9 months, we measured BMD and bone architecture using DXA and high resolution peripheral quantitative computerized tomography. Bone turnover markers (BTM) were measured at 3 months also. Effect of vitamin D versus placebo and the response to ATD treatment were analyzed using linear mixed modelling. RESULTS: Eighty-six GD patients were included (age 41 ± 14 years, 86% females). Compared to placebo, vitamin D3 did not improve BMD or microarchitecture. In response to ATD, BMD increased in the hip by 2% (95%CI: 1-4%). Cortical porosity decreased in tibia (- 7% [95%CI: - 12 to - 2%]) and radius [- 14% [95%CI: - 24 to - 3%]), and trabecular thickness increased (tibia (5% [95%CI: 2 - 9%]) and radius (4% [95%CI: 1-7%]). Changes in BTM, but not thyroid hormones, were associated with changes in BMD by DXA and with changes in the cortical compartment. CONCLUSION: In newly diagnosed GD, 9 months of high dose vitamin D3 supplementation does not offer benefit by improving skeletal health. Treatment of thyrotoxicosis is associated with the recovery of BMD and microarchitecture. GOV IDENTIFIER: NCT02384668.

The Increased FCRL mRNA Expression in Patients with Graves' Disease Is Associated with Hyperthyroidism (But Not with Positive Thyroid Antibodies).

Background: Fc receptor-like (FCRL) genes play a role in the immune system by encoding proteins that function as receptors on the surface of immune cells. The clinical significance of FCRL gene expression in Graves' Disease (GD) and Graves' Orbitopathy (GO) remains unclear. We evaluated the expression of FCRL 2, 3, 4 mRNA in patients with GD and GO and its role in the development and activity of these diseases. Methods: Peripheral blood samples from patients with GD (n = 24) or GO (n = 49) hospitalized in the Department of Endocrinology and Metabolic Diseases, Medical University of Lodz, were collected. Expressions of FCRL2, FCRL3 and FCRL4 were measured by real-time PCR. Results: FCRL3 expression was higher in patients with GD compared to GO (1.375 vs. 0.673, p = 0.004) and, specifically, active GO (1.375 vs. 0.639, p = 0.005). Regarding FCRL4, mRNA expression was higher in GD compared to Control (3.078 vs. 0.916, p = 0.003), GO (3.078 vs. 1.178, p < 0.001), active GO (3.078 vs. 1.186, p = 0.002) and inactive GO (3.078 vs. 1.171, p = 0.008). In turn, FCRL4 mRNA expression was higher in patients with hyperthyroidism (subclinical + overt) than in euthyroid patients (2.509 vs. 0.995, p = 0.001 when the whole group of individuals was considered; 2.509 vs. 1.073, p = 0.004 when GO + GD was considered). Conclusions: The increased FCRL mRNA expression in patients with GD is associated with hyperthyroidism (but not with positive TSHRAbs), and our study is the first one to confirm this relationship.

Graves' Disease Associated With Pulmonary Hypertension and Cardiac Arrest.

Thyrotoxicosis has been associated with several cardiac conditions including atrial fibrillation, congestive heart failure due to left ventricular dysfunction, and cardiomyopathy. However, few cases of ventricular fibrillation as a complication of thyrotoxicosis have been reported. Our case described a 45-year-old male with a history of hypertension and Graves' disease, who presented with 1 week of left-sided chest pain associated with shortness of breath on exertion and occasional palpitations. His workup revealed acute diastolic congestive heart failure secondary to thyrotoxicosis, causing pulmonary hypertension, which led to ventricular fibrillation and cardiac arrest. After being treated with methimazole and metoprolol, the patient's symptoms improved. This case underscores the significance of assertive medical interventions alongside both invasive and non-invasive cardiac procedures. Addressing thyrotoxicosis and ventricular arrhythmia in hyperthyroid patients is crucial to prevent potentially life-threatening complications.

Therapeutic role of histone deacetylase inhibition in an in vitro model of Graves' orbitopathy.

Graves' orbitopathy (GO), a manifestation of Graves' disease, is characterized by orbital fibroblast­induced inflammation, leading to fibrosis or adipogenesis. Histone deacetylase (HDAC) serves a central role in autoimmune diseases and fibrosis. The present study investigated HDAC inhibition in orbital fibroblasts from patients with GO to evaluate its potential as a therapeutic agent. Primary cultured orbital fibroblasts were treated with an HDAC inhibitor, panobinostat, under the stimulation of IL­1ß, TGF­ß or adipogenic medium. Inflammatory cytokines, and fibrosis­ and adipogenesis­related proteins were analyzed using western blotting. The effects of panobinostat on HDAC mRNA expression were measured in GO orbital fibroblasts, and specific HDACs were inhibited using small interfering RNA transfection. Panobinostat significantly reduced the IL­1ß­induced production of inflammatory cytokines and TGF­ß­induced production of fibrosis­related proteins. It also suppressed adipocyte differentiation and adipogenic transcription factor production. Furthermore, it significantly attenuated HDAC7 mRNA expression in GO orbital fibroblasts. In addition, the silencing of HDAC7 led to anti­inflammatory and anti­fibrotic effects. In conclusion, by inhibiting HDAC7 gene expression, panobinostat may suppress the production of inflammatory cytokines, profibrotic proteins and adipogenesis in GO orbital fibroblasts. The present in vitro study suggested that HDAC7 could be a potential therapeutic target for inhibiting the inflammatory, adipogenic and fibrotic mechanisms of GO.