The Pathophysiology of Thyroid Eye Disease

  title={The Pathophysiology of Thyroid Eye Disease},
  author={Shannon J. C. Shan and Raymond S. Douglas},
  journal={Journal of Neuro-Ophthalmology},
Abstract: The pathophysiology of thyroid eye disease (TED) is complex and incompletely understood. Orbital fibroblasts (OFs) seem to be the key effector cells that are responsible for the characteristic soft tissue enlargement seen in TED. They express potentially pathogenic autoantigens, such as thyrotropin receptor and insulin-like growth factor-1 receptor. An intricate interplay between these autoantigens and the autoantibodies found in Graves disease may lead to the activation of OFs, which… 

Medical management of thyroid eye disease – A paradigm shift

  • S. Honavar
  • Medicine, Biology
    Indian journal of ophthalmology
  • 2020
The clinical course of TED is heterogenous with numerous permutations of severity and duration of inflammation and functional derangement.

Morphofunctional characteristics and immunological regulation of the orbital fibroblasts function in endocrine ophthalmopathy

The importance of the further study of the orbital fibroblasts characteristics in EOP and their intercellular interaction with various immune cells was noted, which may be able to uncover new pathogenetic mechanisms of this pathology.

Immunotherapy of thyroid Eye Disease

The pathophysiology of TED has been reported to identify new effective therapeutic agents and immunotherapies are on the top of the list as they have shown considerable benefit affecting the nature course of the disease and improve the quality of life of the patients.

Role of the T and B lymphocytes in pathogenesis of autoimmune thyroid diseases

This review will focus on the role of the T regulatory (Treg) and T helper (Th) (especially Th17) lymphocytes, and also of B lymphocytes in AITD pathogenesis.

The Role of the Immune Response in the Pathogenesis of Thyroid Eye Disease: A Reassessment

This is the first study to compare gene expression in TED to gene expression associated with other causes of exophthalmos, and juxtaposition shows that inflammatory markers are far less characteristic of TED relative to other orbital inflammatory diseases.

Lessons from mouse models of Graves’ disease

New immunomodulatory therapies have been assessed and also diseaseprevention by inducing tolerance using small cyclic peptides from the antigenic region of the extracellular subunit of the TSHR.

Pathogenic Mechanisms of Autoimmune Thyroid Disease

Antithyroglobulin antibody, anti-thyroperoxidase antibody, serum thyroid-stimulating hormone, and exacerbation of lymphocytic infiltration in the thyroid were all higher in these persons, indicating that iodine overconsumption could cause hypothyroidism and exacerbate the autoimmune response.

IgG4 as a Biomarker in Graves' Orbitopathy

Characteristic features of Graves' Disease with elevated IgG4 levels include lower echogenicity of the thyroid gland on ultrasound examination, peripheral blood eosinophilia, higher prevalence of orbitopathy, and better response to antithyroid drugs with a tendency to develop hypothyroidism when compared to patients with GD and normal levels of IgG 4.

A case report of thyroid-associated Orbitopathy with elevated TPO antibodies

Biological investigation was notable for high levels of anti-thyroid peroxidase antibodies (Anti-TPO) in an otherwise euthyroid patient with negative TRAb and minor ocular manifestations of HT are common; however, severe sight threatening ophtalmopathy in the absence of TRAb is rare.

TSH-Mediated TNFα Production in Human Fibrocytes Is Inhibited by Teprotumumab, an IGF-1R Antagonist

By modulating the proinflammatory properties of FCs such as TNFα production, TMB may be a promising therapeutic agent for GO.



Pathogenesis of Graves' ophthalmopathy: the role of autoantibodies.

  • T. KhooR. Bahn
  • Biology, Medicine
    Thyroid : official journal of the American Thyroid Association
  • 2007
Evidence from the laboratory suggests that monoclonal TSHr autoantibodies (TRAbs) are potent stimulators of adipogenesis in GO orbital cells, and it is possible that circulating TRAbs in Graves' patients both stimulate overproduction of thyroid hormones and increase orbital adipose tissue volume.

Unique attributes of orbital fibroblasts and global alterations in IGF-1 receptor signaling could explain thyroid-associated ophthalmopathy.

The laboratory group has focused over the last several years on defining the peculiarities of the human orbital fibroblasts as a strategy for shedding more light on the pathologies occurring in TAO, reasoned that unique properties of these cells might ultimately prove the basis for why the manifestations of Graves' disease occur in an anatomically selective manner.

Orbital fibroblast heterogeneity may determine the clinical presentation of thyroid-associated ophthalmopathy.

It is reported that fibroblasts derived from the connective/adipose tissue depot are distinct from those investing the extraocular muscles, and differences in the potential for differentiation may reside with phenotypic attributes downstream from this receptor/ adipogenic transcription factor.

Clinical review 157: Pathophysiology of Graves' ophthalmopathy: the cycle of disease.

  • R. Bahn
  • Medicine, Biology
    The Journal of clinical endocrinology and metabolism
  • 2003
The progression of Graves’ ophthalmopathy and PTD from initiation to subclinical disease to fully developed ocular and dermal manifestations appears to be a positive feedback cycle composed of mechanical, immunological, and cellular processes.

Increased generation of fibrocytes in thyroid-associated ophthalmopathy.

The findings suggest that fibrocytes may participate in the pathogenesis of TAO because they express relevant autoantigens such as IGF-I receptor and functional TSHR and differentially accumulate in orbital tissue in TAO.

Current perspective on the pathogenesis of Graves' disease and ophthalmopathy.

Recent studies related to the molecular mechanisms of the disease pathogenesis and the development of animal models for GD have led to a better understanding of the pathogenesis of GD and GO and have opened up potential new avenues for developing novel treatments.

Graves’ ophthalmopathy: State of the art and perspectives

Progress in the management of the ophthalmopathy has been very limited, and glucocorticoids, orbital radiotherapy and orbital decompression remain the mainstays in GO treatment, while novel treatments, such as somatostatin analogues, antioxidants, cytokine antagonists are currently under investigation.

Immunoglobulins from patients with Graves' disease induce hyaluronan synthesis in their orbital fibroblasts through the self-antigen, insulin-like growth factor-I receptor.

The observation that hyaluronan production is induced by GD-IgG in fibroblasts suggests that the IGF-I receptor and its activating antibodies may represent a key pathway through which important pathogenic events in thyroid-associated ophthalmopathy are mediated.

Increased expression of TSH receptor by fibrocytes in thyroid-associated ophthalmopathy leads to chemokine production.

Frequency of circulating TSHR(+) fibrocytes is markedly increased in patients with TAO, and they express proinflammatory chemokines in response to TSH.