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Purpose: To determine the relationship between Graves ophthalmopathy (GO) and triglyceride glucose index (TGI) and to evaluate the predictive importance of this index in terms of GO activity., Methods: This retrospective study included 20 inactive GO patients, 20 active GO patients, and 20 healthy controls. TGI was calculated using fasting plasma triglyceride and fasting plasma glucose levels and values were compared between the groups. The receiver operating characteristics curve was used to calculate the optimal TGI cutoff value and the sensitivity and specificity of this value between active and inactive GO groups., Results: No significant difference was detected between the groups in terms of age and gender ( p = 0.561 and p = 0.762, respectively). TGI value was 8.49 (8.41, 8.67) in the control group, 8.76 (8.74, 8.87) in the inactive GO group, and 9.06 (8.87, 9.08) in the active GO group ( p < 0.001 for control group vs. inactive GO group; p < 0.001 for control group vs. active GO group; p = 0.001 for inactive GO group vs. active GO group). The optimal receiver operating characteristics cutoff value of TGI between active and inactive GO groups was 8.86 with 85% sensitivity and 75% specificity (area under curve: 0.837, p < 0.001, 95% confidence interval: 0.711-0.964)., Conclusion: TGI was higher in both inactive and active GO patients compared with controls. It also appears that TGI may be used as a predictive marker indicating GO activity. This cheap and easily accessible parameter may be beneficial in detecting the disease and monitoring its activity in clinical practice., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Purpose: Thyroid eye disease (TED) associated with diabetes mellitus (DM) presents unique challenges. DM is a risk factor for TED. Standard management of TED with glucocorticoids (GC), orbital radiation, or teprotumumab can cause adverse events in poor glycemic control. The authors reviewed the literature on the relationship between TED and DM and the management of co-existing diseases., Methods: The authors searched PubMed with keywords "thyroid eye disease," "diabetes mellitus," and similar terms from 2013 to 2022. The authors included relevant studies after screening the abstracts. Additional references to the selected studies were included where applicable. Data were extracted from the final articles according to the preplanned outline of the review., Results: The initial search yielded 279 abstracts. The final review included 93 articles. TED and DM interact at multiple levels-genetic, immunologic, cellular, nutritional, and metabolic. Both DM and thyroid dysfunction exacerbate the morbidity caused by the other. Metabolic factors also affect the inflammatory pathway for TED. Patients with DM develop TED with greater frequency and severity, necessitating interventions for vision salvage. Agents (GC, teprotumumab, or radiation) used for TED are often unsuitable for treatment with DM, especially if there is poor glycemic control or diabetic retinopathy. There were no studies on using steroid-sparing agents in TED with DM., Conclusion: TED and DM co-exist because of multiple intersections in the pathophysiology. Challenges in the treatment include increased TED severity and risk of hyperglycemia and retinopathy. Multidisciplinary teams best undertake treatment of TED with DM., Competing Interests: Dr Suryasnata Rath - Editor of the book titled “Surgery in Thyroid Eye Disease - A Conceptual Approach” published by Springer. No other authors have any conflicts of interest., (Copyright © 2023 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Purpose: Graves orbitopathy (GO) is the most common extrathyroidal manifestation of Graves disease. Although its pathogenesis is not fully elucidated, GO is commonly considered an autoimmune disease due to loss of self-tolerance against autoantigens shared by thyroid epithelial cells and orbital fibroblasts. High-dose intravenous glucocorticoids (ivGCs) are the most used treatment for moderate-to-severe, active GO, but the addition of other immunomodulating treatments can improve the efficacy of ivGCs. Among the various risk factors that can affect the occurrence of GO, cholesterol may be worthy of interest. Since 2015 the role of cholesterol and cholesterol-lowering medications has been investigated. The purpose of this review is to discuss this topic, thereby offering new therapeutic opportunities for patients with GO., Methods: We searched PubMed for studies published between January 1, 1980 and June 1, 2023, using the search terms "Graves orbitopathy," "thyroid eye disease," "Graves ophthalmopathy," "thyroid ophthalmopathy," "thyroid-associated ophthalmopathy," "endocrine ophthalmopathy," "cholesterol," "lipids," "statins," "low-density lipoprotein," "atorvastatin," and "cholesterol-lowering drugs." Only English-language articles were included., Results: A correlation between low-density lipoprotein cholesterol and the risk of GO development has been reported. Furthermore, low-density lipoprotein cholesterol has been proposed as a risk factor that can affect the course of GO and the response to ivGCs. The protective role of cholesterol-lowering medications in preventing GO has been also investigated. Statin treatment was found to have potential benefits in reducing the risk of GO in patients with Graves disease. Given these findings, measurement of low-density lipoprotein cholesterol and treatment of hypercholesterolemia in patients with moderate-to-severe, active GO may be considered before starting ivGCs administration. Recently, a randomized clinical trial aimed at investigating the effects of statins in GO suggested that the addition of oral atorvastatin to ivGCs improves the overall outcome of moderate-to-severe, active GO in hypercholesterolemic patients given ivGCs., Conclusions: Overall, statins seem to have a preventive and therapeutic role in moderate-to-severe active GO. Their efficacy can be related to cholesterol-lowering activity, pleiotropic actions, and interaction with methylprednisolone., Competing Interests: The authors have no financial or conflicts of interest to disclose., (Copyright © 2023 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Background and Aims: Due to the worldwide increasing prevalence of diabetes (DM), patients with both diabetes and Graves' disease (GD) have become more frequent. Sporadic reports indicate that Graves' orbitopathy (GO), a GD complication that affects orbital soft tissues, can be severe in DM patients. The relationship between these diseases is not well understood. This study aims at evaluating the association of GD and GO with autoimmune and non-autoimmune diabetes (DM) and to assess diabetic features that influence GD and GO prevalence and severity., Methods and Results: This retrospective study evaluated GD, GO and DM association in 1211 consecutive GD patients (447 with GO and 77 with DM). A case-control study was carried out to evaluate DM relationship with GO severity by comparing at 1:2 ratio GO patients with or without DM. A strong association was found between GD and T1DM (p = 0.01) but not T2DM. Instead, the presence of GO was strongly associated with T2DM (p = 0.01). Moreover, GO was more frequently severe in GD patients with T2DM (11/30 or 36.6%) than in those without T2DM (1/60 or 1.7%, p = 0.05). T2DM was the strongest risk factor for severe GO (OR = 34.1 vs. 4.4 p < 0.049 in cigarette smokers). DM duration, obesity and vascular complications, but not metabolic control were significant determinants of GO severity., Conclusions: GD is associated with T1DM but not with T2DM, probably because of the common autoimmune background. GO, in contrast, is more frequent and severe in T2DM, significantly associated with obesity, diabetes duration and diabetic vasculopathy but not metabolic control., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background and Objective: Both extraocular muscle (EOM) and orbital fat are involved in Graves' orbitopathy (GO) but their enlargement might occur with a different temporal pattern. Two GO subtypes have been described, one with predominant EOM enlargement and the other with prevalent fat tissue involvement. We longitudinally investigated the EOM in patients with GO and their relationship with clinical activity., Patients and Methods: By using commercial software with a segmentation technique, we calculated from computed tomography (CT) scan EOM coronal area (CA) and total orbit coronal area (TOA) in 23 control subjects and in 32 patients with GO. The latter were studied both at presentation and 18 months later. Superior, lateral, inferior, and medial EOM areas and TOA were selected by 3 different contiguous CT slices: A, B, and C, chosen at globe pole tangent and 2 and 4 mm backward. The Clinical Activity Score (CAS) was also measured., Results: Orbital EOM CA/TOA ratio (OM/TOA ratio) after 18 months decreased in most patients with GO, indicating that EOM area decrement contributed significantly to OM/TOA ratio reduction. Clinical Activity Score decrease was significantly correlated to the OM/TOA ratio decrease., Conclusions: An easy method to measure CA of EOM and orbit allowed us to observe that in most patients with GO the OM/TOA ratio decreases with time, suggesting that macroscopic EOM involvement occurs initially and resolves as the other clinical signs and symptoms of the disease resolve, as indicated by the significant OM/TOA ratio correlation with CAS.

Background: Percutaneous ethanol injection (PEI) is used to treat cystic or mixed benign thyroid nodules. This treatment can result in rare complications, and three cases of Graves' disease (GD) without Graves' ophthalmopathy (GO) have been reported after PEI treatment of toxic thyroid adenomas. Here we present a 55-year-old male patient who developed GD and severe GO after PEI treatment of a mixed cystic-solid, nontoxic thyroid nodule., Patient Findings: Six months after PEI, the nodule volume had decreased from 8.9 to 3.0 mL, but we observed severe hyperthyroidism with elevated serum free triiodothyronine, free thyroxine, and thyrotropin receptor antibody levels. We also observed ophthalmopathy with symmetrical orbit and soft tissue involvement (grade b/c) and a clinical activity score of 4/7. The diagnosis of GO was confirmed by bilateral corneal damage, increased intraocular pressure on upgaze, and inconstant diplopia. A computed tomography scan showed that the inferior, medial, and superior extraocular muscles were bilaterally enlarged, the perineural space at the orbital cone was slightly reduced and the ophthalmic vein was congested., Summary: A cause-effect relationship between PEI and GD/GO was likely in this patient because of the temporal sequence. Although the mechanism was unknown, we speculated that the thyroid tissue damage caused by PEI released a large amount of antigenic materials from follicular thyroid cells, including thyrotropin receptor protein, which triggered the autoimmune inflammatory response against the thyroid itself and the orbital soft tissues. The patient did not have any risk factors for either GD or GO., Conclusions: This observation raises the concern, therefore, that unpredictable and severe complications, such as GD and GO, may occur in a few patients treated with PEI.

Purpose: The aim of the study was to investigate whether diabetes mellitus (DM) is an independent risk factor in sight-threatening thyroid eye disease (ST-TED) and explore the interaction of DM with other known risk factors in TED., Methods: This was a retrospective cohort study and included 202 consecutive TED patients presenting between 2013 and 2019. Data collected included demography, history of smoking, thyroid dysmetabolism, and presence of DM, TED-duration, activity and severity, best-corrected visual acuity (BCVA), and follow-up. Primary outcome measure was development of ST-TED and secondary outcome measures included change in BCVA, activity, and bilateral ST-TED., Results: Mean age of the cohort was 52.14 + 9.14 years and 74 (36%) were male. DM was present in 49 (24%) and a positive history of smoking in 65 (32%) TED patients. Cox's proportional hazards showed the presence of DM (hazard ratio [HR] 2.22; P = 0.02) and a positive history of smoking (HR 3.62; P = 0.003) were significant risk factors for development of ST-TED and dysthyroid optic neuropathy (DON). Older age was a risk factor (HR 1.05; P = 0.02) for DON. DM increased the risk of developing bilateral ST-TED (OR 4.14; P = 0.004). Median follow-up was 4 months (range 0.1-96 months). A linear mixed model to predict longitudinal interaction between risk factors, found TED patients in DM group were likely to have worsening of visual function and a positive history of smoking accentuated this adverse outcome., Conclusion: DM and smoking are major independent risk factors predictive of ST-TED. Coexisting DM either singularly or in combination with smoking may predict worsening of visual function in TED patients., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 The American Society of Ophthalmic Plastic and Reconstructive Surgery, Inc.)

Purpose: Thyroid-associated ophthalmopathy (TAO) might lead to blindness and orbital deformity. The early diagnosis and treatment are conducive to control disease progression, but currently, there is no effective screening method. The present study aimed to introduce an artificial intelligence (AI) model for screening and testing the model with TAO patients under clinical conditions., Methods: A total of 1435 computed tomography (CT) scans were obtained from the hospital. These CT scans were preprocessed by resampling and extracting the region of interest. CT from 193 TAO patients and 715 healthy individuals were adopted for three-dimensional (3D)-ResNet model training, and 49 TAO patients and 178 healthy people were adopted for external verification. Data from 150 TAO patients and 150 healthy people were utilized for application tests under clinical conditions, including non-inferiority experiments and diagnostic tests, respectively., Results: In the external verification of the model, the area under the receiver operating characteristic (ROC) curve (AUC) was 0.919, indicating a satisfactory classification effect. The accuracy, sensitivity, and specificity were 0.87, 088, and 0.85, respectively. In non-inferiority experiments: the accuracy was 85.67% in the AI group and 84.33% in the resident group. The model passed both non-inferiority experiments (p = 0.001) and diagnostic test (the AI group sensitivity = 0.87 and specificity = 0.84%)., Conclusions: A promising orbital CT-based TAO screening AI model was established and passed application tests under clinical conditions. This may provide a new TAO screening tool with further validation.

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