enter site Because of the close clinical relation between Graves' hyperthyroidism and GO, investigators have long hypothesized that both autoimmune conditions derive from a single systemic process and share the TSH receptor as a common autoantigen. Bahn continues: "Our laboratory is interested in unraveling the pathogenesis of GO because a better understanding of the disease will enable development of novel and improved forms of therapy for this debilitating condition.
The GO-affected orbit is characterized by edema, hyaluronic acid HA accumulation, and increased volume of adipose tissue and extraocular muscles. The adipose tissue enlargement is in part due to the development of new fat cells within the orbital tissues. The muscle enlargement is produced as hydrophilic HA, and edema collects within the connective tissues lying between the intact muscle fibers.
The increase in tissue volume within the bony orbit displaces the globe forward and hinders venous outflow. As a result, cytokines and other mediators of inflammation, produced by infiltrating mononuclear cells and resident macrophages, accumulate within the orbit and contribute to the local inflammatory process.
Bahn further reports: "We have shown that TSH receptor is highly expressed in GO orbital tissues and is found specifically on the resident fibroblasts. Higher levels of TSH receptor expression can be measured in orbital fibroblasts from GO patients than in fibroblasts from normal orbits or other parts of the body.
Although some orbital fibroblasts are adipocyte precursor cells that further increase TSH receptor expression as they differentiate into mature adipocytes, others are capable of producing HA in large quantities. These and other findings suggest that orbital fibroblasts are the target cells in GO and that stimulation of TSH receptor on these cells by circulating TRAbs may contribute to the tissue remodeling characteristic of the disease. To address this question, Dr.
Bahn says: "We treated GO fibroblasts with a high-affinity human stimulatory monoclonal antibody directed against TSH receptor termed M In doing so, it acts as a pro-adipogenic factor to increase expression of genes found in late stages of adipogenesis and promotes lipid accumulation within the cells. Jarusaitiene, D. Eckstein, A. Prummel, M. Archives of internal medicine , — Bartley, G. American journal of ophthalmology , — Abraham-Nordling, M. Incidence of hyperthyroidism in Sweden. Laurberg, P. Perros, P. Age and gender influence the severity of thyroid-associated ophthalmopathy: a study of patients attending a combined thyroid-eye clinic.
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The thyrotropin receptor autoantigen in Graves disease is the culprit as well as the victim. Wiesweg, B. Moshkelgosha, S. Berchner-Pfannschmidt, U. Schluter, A. Gortz, G. Holthoff, H. Flogel, U. Multimodal assessment of orbital immune cell infiltration and tissue remodeling during development of graves disease by 1 H 19 F MRI.
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Bonner, F. Multifunctional MR monitoring of the healing process after myocardial infarction. Ling, W. Assessment of glycosaminoglycan concentration in vivo by chemical exchange-dependent saturation transfer gagCEST. Misharin, A. Thyrotropin TSH receptor residue E in the extracellular leucine-rich repeat domain is critical for linking TSH binding to receptor activation. Download references. We gratefully acknowledge Drs. Conceived and designed experiments: U. Performed experiments: A. Analyzed the data: A. Wrote paper: U. Review and Editing: all authors.
Recent Developments in Graves' Ophthalmopathy offers an overview of the pathogenesis, assessment and management of patients with thyroid-associated eye. J Endocrinol Invest. Mar;27(3) Recent developments in Graves' ophthalmopathy imaging. Kahaly GJ(1). Author information: (1)Department of.
Correspondence to Utta Berchner-Pfannschmidt. Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Reprints and Permissions. Thyroid Autoimmunity By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.
Advanced search. Skip to main content. Subjects Autoimmunity Eye abnormalities Thyroid diseases. The Mann—Whitney test was used for differences between the two groups. Table 3.
Table 4. The concept of QoL includes physical, mental, and social aspects 1 , 8. Thus, it is easy to understand that patients with severe GO, particularly those with sight impairment, have low QoL scores. However, most patients in clinical practice present with mild to moderate forms of GO 2 , 4.
In chronic diseases, the general health-related QoL questionnaire includes several short and simple self-assessment questions and measures the most important aspects of QoL Studies using general questionnaires with GO patients demonstrate that they are disturbed and dissatisfied with their appearance Likewise, a Swedish study using patients with hyperthyroidism and GO treated with radioiodine or with antithyroid drugs showed similar results when the MOS-SF36 was used.
A specific vision test such as The National Eye Institute Visual Function Questionnaire was instituted to evaluate the impact of chronic eye disease. Patients with mild to severe GO indicated worse QoL, particularly when diplopia was present Our findings using the GO-QoL questionnaire agree with those obtained in other countries 27 , Furthermore, this study is one of the first to show that patients with mild to moderate forms of GO have very low QoL scores even after lengthy follow-up 7 years , suggesting they should receive special attention and psychological support.
Even with the size of our cohort and the strength of our results, the number of patients with diplopia was small, possibly because diplopia usually improves with treatment. However, the presence of diplopia as well as asymmetry and proptosis are factors that significantly impair QoL. Thus, greater changes in the eye resulted in poorer QoL. However, this work has limitations including a lack of controls and QoL evaluations prior to GD treatment. Furthermore, GO decreases QoL, and its effects remain even after a lengthy follow-up, suggesting that GO behaves as a chronic disease.
An important corollary from these data is that changes in vision and appearance lead to difficulties in daily visual functioning and a declining psychological state. With the aid of the GO-QoL questionnaire, patients requiring specific support might be identified. This study was carried out in accordance with the recommendations of Ethics Committee, with written informed consent from all subjects.
All subjects gave written informed consent in accordance with the Declaration of Helsinki. JA and RS created the charts and figures. LW and JR provided overall guidance and edited the manuscript. The final manuscript was read and approved by all authors. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
We thank Cleide A. Endocrine dilemma: management of Graves' orbitopathy. Eur J Endocrinol. What are the psychosocial outcomes of treatment for thyroid eye disease a systematic review. Dolman PJ. Evaluating graves' orbitopathy.
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