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Best Practice & Research. Clinical... Mar 2023Graves' disease (GD) is a heterogeneous autoimmune disease affecting with varying degrees of severity the thyroid gland, orbital tissues and skin. The pathogenesis of GD... (Review)
Review
Graves' disease (GD) is a heterogeneous autoimmune disease affecting with varying degrees of severity the thyroid gland, orbital tissues and skin. The pathogenesis of GD involves a complex interplay between multiple genetic, environmental and endogenous factors. Although the genetic predisposition to GD is well established, the significance of genotype-phenotype correlations and the role of epigenetic modifications in the disease pathogenesis remains largely unknown. In this review, we provide an up-to-date overview of genotype-phenotype correlations and summarize possible clinical implications of genetic and epigenetic markers in GD patients. We will specifically discuss the association of genetic markers and epigenetic modifications with age of GD onset, severity of Graves' hyperthyroidism and the development of clinically evident Graves' orbitopathy.
Topics: Humans; Graves Ophthalmopathy; Graves Disease; Genetic Association Studies; Genetic Predisposition to Disease
PubMed: 36828713
DOI: 10.1016/j.beem.2023.101745 -
Frontiers in Endocrinology 2020Graves' Orbitopathy (GO) is an autoimmune orbital disorder usually presenting as a sequala of autoimmune thyroid disease. The presence of GO is associated with increased... (Review)
Review
Graves' Orbitopathy (GO) is an autoimmune orbital disorder usually presenting as a sequala of autoimmune thyroid disease. The presence of GO is associated with increased psychological burden and, in severe cases may cause blindness. While most patients with GO present with bilateral disease, asymmetric or unilateral GO may affect a significant proportion of patients diagnosed with GO. Older age, male sex, active and severe disease correlate with asymmetric disease. However, the exact mechanisms causing asymmetry remain elusive. Herein, we review the literature on asymmetric GO and highlight its differences compared with bilateral GO.
Topics: Age Factors; Animals; Graves Disease; Graves Ophthalmopathy; Humans; Sex Factors
PubMed: 33391188
DOI: 10.3389/fendo.2020.611845 -
Journal of Neuro-ophthalmology : the... Sep 2016We describe 2 unique cases of visual symptoms occurring during mastication in patients with lateral orbital wall defects. A 57-year-old man reported intermittent double...
We describe 2 unique cases of visual symptoms occurring during mastication in patients with lateral orbital wall defects. A 57-year-old man reported intermittent double vision and oscillopsia after a right fronto-temporal-orbito-zygomatic craniotomy with osteotomy of the lesser wing of the sphenoid for a complex invasive pituitary adenoma. Proptosis of the right globe was present only during mastication. Computed tomography (CT) revealed a bony defect in the right lateral orbital wall. A 48-year-old man presented with transient diplopia and scotoma in the right eye elicited by chewing. CT and magnetic resonance imaging demonstrated a bilobed lesion connecting the temporal fossa to the orbit through a defect in the right lateral orbital wall. The regional neuroanatomy and pathophysiology as pertaining to these cases are discussed.
Topics: Craniotomy; Diplopia; Exophthalmos; Humans; Magnetic Resonance Imaging; Male; Mastication; Middle Aged; Orbit; Postoperative Complications; Sphenoid Bone; Tomography, X-Ray Computed
PubMed: 26919071
DOI: 10.1097/WNO.0000000000000354 -
The Journal of Clinical Endocrinology... Dec 2023Early inflammatory thyroid eye disease (TED) can lead to symptomatic chronic disease, including disabling proptosis. Teprotumumab, an insulin-like growth factor-1... (Randomized Controlled Trial)
Randomized Controlled Trial
CONTEXT
Early inflammatory thyroid eye disease (TED) can lead to symptomatic chronic disease, including disabling proptosis. Teprotumumab, an insulin-like growth factor-1 receptor (IGF-1R) inhibitor, previously demonstrated efficacy in acute, high-inflammation TED trials.
OBJECTIVE
We present data from the first placebo-controlled trial with teprotumumab in chronic/low disease activity TED.
METHODS
This randomized double-masked, placebo-controlled trial, conducted at 11 US centers, enrolled adult participants with TED duration of 2 to 10 years, Clinical Activity Score (CAS) ≤ 1 or no additional inflammation or progression in proptosis/diplopia for ≥1 year, proptosis ≥3 mm from before TED and/or from normal, euthyroid/mildly hypo/hyperthyroid, no prior teprotumumab, and no steroids within 3 weeks of baseline. Patients received (2:1) intravenous teprotumumab or placebo once every 3 weeks (total 8 infusions). The primary endpoint was proptosis (mm) improvement at Week 24. Adverse events (AEs) were assessed.
RESULTS
A total of 62 (42 teprotumumab and 20 placebo) patients were randomized. At Week 24, least squares mean (SE) proptosis improvement was greater with teprotumumab (-2.41 [0.228]) than with placebo (-0.92 [0.323]), difference -1.48 (95% CI -2.28, -0.69; P = .0004). Proportions of patients with AEs were similar between groups. Hyperglycemia was reported in 6 (15%) vs 2 (10%) and hearing impairment in 9 (22%) vs 2 (10%) with teprotumumab and placebo, respectively. AEs led to discontinuation in 1 teprotumumab (left ear conductive hearing loss with congenital anomaly) and 1 placebo patient (infusion-related). There were no deaths.
CONCLUSION
Teprotumumab significantly improved proptosis vs placebo in longstanding/low inflammation TED, demonstrating efficacy regardless of disease duration/activity. The safety profile was comparable to that previously reported.
Topics: Adult; Humans; Antibodies, Monoclonal, Humanized; Exophthalmos; Graves Ophthalmopathy; Inflammation; Protein Kinase Inhibitors; Double-Blind Method
PubMed: 37925673
DOI: 10.1210/clinem/dgad637 -
BMJ Case Reports Dec 2019
Topics: Adult; Conservative Treatment; Exophthalmos; Humans; Magnetic Resonance Imaging; Male; Orbital Diseases; Varicose Veins
PubMed: 31818898
DOI: 10.1136/bcr-2019-232887 -
CMAJ : Canadian Medical Association... Apr 2019
Topics: Amphotericin B; Antifungal Agents; Blindness; Brain Diseases; Debridement; Exophthalmos; Eye Diseases; Fatal Outcome; Female; Humans; Magnetic Resonance Imaging; Maxillary Sinusitis; Middle Aged; Mucormycosis; Optic Neuritis
PubMed: 31015350
DOI: 10.1503/cmaj.181210 -
Frontiers in Endocrinology 2023Graves' disease (GD) is caused by an autoimmune formation of autoantibodies and autoreactive T-cells against the thyroid stimulating hormone receptor (TSHR). The... (Review)
Review
Graves' disease (GD) is caused by an autoimmune formation of autoantibodies and autoreactive T-cells against the thyroid stimulating hormone receptor (TSHR). The autoimmune reaction does not only lead to overstimulation of the thyroid gland, but very often also to an immune reaction against antigens within the orbital tissue leading to thyroid eye disease, which is characterized by activation of orbital fibroblasts, orbital generation of adipocytes and myofibroblasts and increased hyaluronan production in the orbit. Thyroid eye disease is the most common extra-thyroidal manifestation of the autoimmune Graves' disease. Several studies indicate an important role of sphingolipids, in particular the acid sphingomyelinase/ceramide system and sphingosine 1-phosphate in thyroid eye disease. Here, we discuss how the biophysical properties of sphingolipids contribute to cell signaling, in particular in the context of thyroid eye disease. We further review the role of the acid sphingomyelinase/ceramide system in autoimmune diseases and its function in T lymphocytes to provide some novel hypotheses for the pathogenesis of thyroid eye disease and potentially allowing the development of novel treatments.
Topics: Humans; Graves Ophthalmopathy; Sphingomyelin Phosphodiesterase; Sphingolipids; Graves Disease; Autoimmune Diseases; Ceramides
PubMed: 37082124
DOI: 10.3389/fendo.2023.1170884 -
The Israel Medical Association Journal... Mar 2017
Review
Topics: Female; Graves Ophthalmopathy; Humans; Male; Severity of Illness Index
PubMed: 28457100
DOI: No ID Found -
Acta Otorhinolaryngologica Italica :... Apr 2021
Review
Topics: Decompression, Surgical; Graves Ophthalmopathy; Humans; Orbit; Retrospective Studies
PubMed: 34060524
DOI: 10.14639/0392-100X-suppl.1-41-2021-09 -
Missouri Medicine 2022Thyroid eye disease (TED) is an immune mediated infiltration and inflammation of the orbital and periorbital soft tissues leading to facial disfigurement. Classically...
Thyroid eye disease (TED) is an immune mediated infiltration and inflammation of the orbital and periorbital soft tissues leading to facial disfigurement. Classically broken into two "phases," active inflammatory and quiescent, disease modifying therapy and surgical intervention are used to improve a number of clinical aspects of TED. Many medical modalities have been utilized to halt the inflammatory phase of the disease including steroids, orbital radiation, and targeted steroid-sparing chemotherapy. Teprotumumab is currently the only Federal Drug Administration approved therapy for the treatment of TED. Significant improvements in proptosis, diplopia and quality of life are noted following its 24-week course of therapy.
Topics: Antibodies, Monoclonal, Humanized; Diplopia; Graves Ophthalmopathy; Humans; Quality of Life
PubMed: 36033157
DOI: No ID Found