ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 63 PL6 | DOI: 10.1530/endoabs.63.63.PL6

Graves Orbitopathy

Professor George Kahaly


Graves’ orbitopathy (GO) is a rare complex auto-immune disorder which causes substantial morbidity. It can result in orbital disfigurement, double vision and even visual loss. Consequently it has a substantial negative effect on quality of life, mental health and socioeconomic status. The vast majority of patients have Graves’ disease (GD), an inflammatory auto-immune condition which is characterized by thyrotropin receptor auto-antibodies (TSHR-Ab). Ocular inflammation at baseline, smoking, TSHR-Ab titre and duration of thyroid dysfunction being the four key risk factors for developing GO in GD. Most of the signs and symptoms of GO can be explained by the expansion of the orbital contents. The orbital fibroblast is the target of a spectrum of autoimmune responses which collectively promote proliferation, excess adipogenesis (formation of new fat cells by differentiation of preadipocytes) and over-production of extra-cellular matrix (ECM). The ECM comprises glycosaminoglycans such as chondroitin sulphate and hyaluronic acid, which is not sulphated but is able to absorb up to 1000 times its weight in water. Steroids are the mainstay of treatment in GO. While this may be a non-specific effect of reducing inflammation and depleting leucocytes, a direct action on the adipocytes including the inhibition of “browning” processes in orbital fat cells is discussed. Other strategies such as radiotherapy have had their role in combination therapy called into question. Recurrence may occur once steroids are withdrawn. Furthermore, in most cases, normal orbital anatomy is not restored, and skilled rehabilitative surgery is required to reduce disfigurement, double vision and occasionally, to preserve vision. In the last decade, the pathophysiology of GO has also been revised with identification of new potential therapeutic targets. Recent clinical trials have shown that considerable benefit may be derived from the addition of anti-proliferative agents (e.g. mycophenolate sodium) in preventing deterioration after steroid cessation. In addition, targeted biologic therapies have shown promise, including teprotumumab (anti-IGFR) which appears to substantially reduce proptosis, rituximab (anti-CD20) which reduces inflammation and tocilizumab (anti-IL6) which potentially benefits both of these parameters. This review therefore outlines the optimal management of GO and summarises the recent research developments in this area.

Article tools

My recent searches

No recent searches.

My recently viewed abstracts

Graves Orbitopathy (<1 min ago)