2022 Update on Clinical Management of Graves Disease and Thyroid Eye Disease

Hoang, Thanh D.; Stocker, Derek J.; Chou, Eva; Burch, Henry B.

doi:10.1016/j.ecl.2021.12.004

Cited by 50 publications

(37 citation statements)

References 87 publications

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“…Glucocorticoids (GCs) have long been used in the treatment of various ocular diseases due to their powerful anti-inflammatory, anti-edema, and anti-neoangiogenic properties (38)(39)(40). In patients with TAO, a GC is the main treatment option, and the European group for GD orbitopathy recommends intravenous GC therapy as the 1st-line option for patients with moderately severe active TAO (41,42). According to the prognostic model we constructed, we can predict the prognosis of TAO patients, and for patients with JAK1, HSP90AA1, PLA2G2A, FGF3, GPI and PDIA2 mutations, we can combine the clinical experience of drug use and the predicted targets to select therapeutic drugs.…”

Section: Discussionmentioning

confidence: 99%

Mechanisms of immune-related differentially expressed genes in thyroid-associated ophthalmopathy based on the GEO database

Gao¹,

Li²

2022

Ann Transl Med

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Background We performed a differential analysis, enrichment analysis, and immune-infiltration analysis of the thyroid-associated ophthalmopathy (TAO) gene using data from the Gene Expression Omnibus (GEO) database to provide a theoretical basis for understanding the immune-related mechanisms of TAO. Methods We searched the GEO database for “Graves disease” and selected the genes expressed in the lacrimal gland of thyroid-related eye disease patients as the test group and the genes expressed in the lacrimal gland of normal subjects as the control group. Immune-related differentially expressed genes (irDEGs), gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, protein-protein interaction, gene-gene interaction (GGI) network, pivotal gene identification, and immune-infiltration analyses were carried out, and finally, risk-prediction models were constructed. Results The GSE105149 and GSE58331 data sets contained 200 DEGs, of which 15 were immune-related. In relation to the GO biological processes (BPs), the main pathways included the interleukin (IL)-27-mediated signaling pathway, the IL-35-mediated signaling pathway, cytokine activity, T helper 17 cell differentiation, the phosphatidylinositol-3-kinase and protein kinase B signaling pathway, cytokine-cytokine receptor interaction, the Janus kinase and signal transducer and activator of transcription signaling pathway, and other KEGG pathways. Cluster of differentiation (CD)4 + T cells, monocytes, M0 macrophages, and Mast cells were significantly elevated in TAO, while M2 macrophages were significantly reduced. In the immune cell correlation analysis, CD4 + T cells and naïve B cells were significantly positively correlated with activated natural killer (NK) cells, and Mast cells were positively correlated with plasma cells and negatively correlated with M2 macrophages. Risk models for a total of 6 genes (i.e., Janus kinase 1, heat shock protein 90-α, phospholipase A 2 group IIA, fibroblast growth factor 3, glucose-6-phosphate isomerase, and protein disulfide isomerase family A, member 2), were constructed, and over 100 potential targeted therapeutic agents were obtained. Conclusions In TAO, various types of immune cells infiltrate to different degrees, and the immune response and inflammatory response are throughout the disease. Our constructed risk-prediction models provide a reference for predicting TAO.

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Section: Discussionmentioning

confidence: 99%

Mechanisms of immune-related differentially expressed genes in thyroid-associated ophthalmopathy based on the GEO database

Gao¹,

Li²

2022

Ann Transl Med

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“…Additionally, some subjects with HT may progress to GBD (or vice versa), and it is possible to identify individuals with simultaneous manifestations of both GBD and HT [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Molecular Mechanisms in Autoimmune Thyroid Disease

Vargas‐Uricoechea

2023

Cells

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The most common cause of acquired thyroid dysfunction is autoimmune thyroid disease, which is an organ-specific autoimmune disease with two presentation phenotypes: hyperthyroidism (Graves-Basedow disease) and hypothyroidism (Hashimoto’s thyroiditis). Hashimoto’s thyroiditis is distinguished by the presence of autoantibodies against thyroid peroxidase and thyroglobulin. Meanwhile, autoantibodies against the TSH receptor have been found in Graves-Basedow disease. Numerous susceptibility genes, as well as epigenetic and environmental factors, contribute to the pathogenesis of both diseases. This review summarizes the most common genetic, epigenetic, and environmental mechanisms involved in autoimmune thyroid disease.

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“…As for the treatment of GO, different strategies are recommended for different stages and severities, including orbital decompression surgery, orbital radiotherapy, and medications such as glucocorticoids, rituximab, tocilizumab, teplizumab, and teprotumumab [ 7 ]. However, traditional treatments have limitations, and more clinical trials are needed to evaluate the safety and efficacy of novel medications [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Prostaglandin F2α Regulates Adipogenesis by Modulating Extracellular Signal-Regulated Kinase Signaling in Graves’ Ophthalmopathy

Zhu

Wang

et al. 2023

IJMS

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Prostaglandin F2α (PGF2α), the first-line anti-glaucoma medication, can cause the deepening of the upper eyelid sulcus due to orbital lipoatrophy. However, the pathogenesis of Graves’ ophthalmopathy (GO) involves the excessive adipogenesis of the orbital tissues. The present study aimed to determine the therapeutic effects and underlying mechanisms of PGF2α on adipocyte differentiation. In this study primary cultures of orbital fibroblasts (OFs) from six patients with GO were established. Immunohistochemistry, immunofluorescence, and Western blotting (WB) were used to evaluated the expression of the F-prostanoid receptor (FPR) in the orbital adipose tissues and the OFs of GO patients. The OFs were induced to differentiate into adipocytes and treated with different incubation times and concentrations of PGF2α. The results of Oil red O staining showed that the number and size of the lipid droplets decreased with increasing concentrations of PGF2α and the reverse transcription-polymerase chain reaction (RT-PCR) and WB of the peroxisome proliferator-activated receptor γ (PPARγ) and fatty-acid-binding protein 4 (FABP4), both adipogenic markers, were significantly downregulated via PGF2α treatment. Additionally, we found the adipogenesis induction of OFs promoted ERK phosphorylation, whereas PGF2α further induced ERK phosphorylation. We used Ebopiprant (FPR antagonist) to interfere with PGF2α binding to the FPR and U0126, an Extracellular Signal-Regulated Kinase (ERK) inhibitor, to inhibit ERK phosphorylation. The results of Oil red O staining and expression of adipogenic markers showed that blocking the receptor binding or decreasing the phosphorylation state of the ERK both alleviate the inhibitory effect of PGF2a on the OFs adipogenesis. Overall, PGF2α mediated the inhibitory effect of the OFs adipogenesis through the hyperactivation of ERK phosphorylation via coupling with the FPR. Our study provides a further theoretical reference for the potential application of PGF2α in patients with GO.

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2022 Update on Clinical Management of Graves Disease and Thyroid Eye Disease

Cited by 50 publications

References 87 publications

Mechanisms of immune-related differentially expressed genes in thyroid-associated ophthalmopathy based on the GEO database

Mechanisms of immune-related differentially expressed genes in thyroid-associated ophthalmopathy based on the GEO database

Molecular Mechanisms in Autoimmune Thyroid Disease

Prostaglandin F2α Regulates Adipogenesis by Modulating Extracellular Signal-Regulated Kinase Signaling in Graves’ Ophthalmopathy

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