PubMed · 16985411
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Peter J Dolman, Jack Rootman. VISA Classification for Graves orbitopathy.. https://doi.org/10.1097/01.iop.0000235499.34867.85
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PURPOSE: To review current concepts regarding the pathogenesis of Graves ophthalmopathy (GO). We have presented this information in the context of potential target sites for novel disease therapies. DESIGN: Review of recent literature. METHODS: Synthesis of recent literature. RESULTS: Enlargement of the extraocular muscle bodies and expansion of the orbital fatty connective tissues is apparent in patients with GO. These changes result from abnormal hyaluronic acid accumulation and edema within these tissues and expanded volume of the orbital adipose tissues. Recent studies have suggested that the increase in orbital fat volume is caused by stimulation of adipogenesis within these tissues. The orbital fibroblast appears to be the major target cell of the autoimmune process in GO. A subset of these cells is capable of producing hyaluronic acid and differentiating into mature adipocytes, given appropriate stimulation. In addition, orbital fibroblasts from patients with GO have been shown to display immunoregulatory molecules and to express both thyrotropin receptors (TSHRs) and insulin-like growth factor 1 receptors (IGF-1Rs). Increased TSHR expression in the GO orbit appears to be the result of stimulated adipocyte differentiation. The activation of IGF-1R on orbital fibroblasts by immunoglobulins from GO patients results in increased production of both hyaluronic acid and molecules that stimulate the infiltration of activated T cells into areas of inflammation. CONCLUSIONS: Potential targets for novel therapeutic agents to be used in GO include blocking T-cell costimulation, depleting B cells, inhibiting cytokine action, targeting the IGF-1R or the TSHR, and preventing connective tissue remodeling.
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The importance of patient-reported outcomes such as health-related quality of life (HRQL) in clinical research is increasingly acknowledged. In order to yield valid results, the measurement properties of HRQL questionnaires must be thoroughly investigated. One aspect of such a validation process is the demonstration of content validity, i.e. that the questionnaire covers all relevant aspects. We review studies reporting on consequences of thyroid disorders and present the frequency of identified aspects, both overall HRQL issues and classical thyroid symptoms, in order to evaluate which issues are relevant for patients with thyroid diseases. Furthermore, existing questionnaires for thyroid patients are reviewed. A systematic search was performed in the Medline, Cinahl and Psycinfo databases and the reference lists of the relevant articles were hand-searched. Seventy-five relevant studies were identified. According to these studies, patients with untreated thyroid disease suffer from a wide range of symptoms and have major impairment in most areas of HRQL. Furthermore, the studies indicate that impairments in HRQL are also frequent in the long term. Six HRQL questionnaires for thyroid patients were identified. Generally, data supporting the validity of these questionnaires were sparse. According to the available literature, the quality of life of thyroid patients is substantially impaired over a wide range of aspects of HRQL in the untreated phase and continues to be so in many patients also in the long term. Studies systematically exploring the relative importance of these various aspects to thyroid patients are lacking, as is a comprehensive, validated thyroid-specific HRQL questionnaire.