Endocrine Abstracts

Graves’ orbitopathy or thyroid eye disease (TED) represents the most common extra thyroidal manifestation of Graves’ disease. Smoking and radioactive iodine therapy are the most important modifiable risk factors. Thyrotropin receptor and insulin-like growth factor-1 receptor crosstalk, orbital inflammatory infiltration and activation of orbital fibroblasts lead to perpetuation of orbital inflammation and expansion of orbital tissues, and hence various adverse mechanical consequences. Patients suffer from significant disfigurement, disability and impaired qualify of life because of the pathological processes. Early referral to specialized multidisciplinary care allows prompt diagnosis and treatment, which improves patients’ outcome. Selenium is useful in mild disease, while intravenous glucocorticoids (IVGC) are the mainstay of treatment in active or sight threatening cases. Novel immunomodulatory treatment can potentially overcome limitations of current therapies. It is reasonable to recommend the combination of IVGC and mycophenolate as the new standard of care in active moderate-to-severe TED in view of its practicability and superior efficacy to conventional treatment. Other combinations of widely available and affordable therapies may also be beneficial in TED, e.g. IVGC + orbital radiotherapy. Biologics (e.g. teprotumumab, tocilizumab) appear highly promising both in treatment naïve or resistant cases, although long term efficacy and safety data is still pending. The roles of other existing targeted therapies in TED are also worth exploring (e.g. anti-IL17 agents for the IL-23/IL-17/Th17 axis, sirolimus for the mTOR pathway). Furthermore, several novel therapeutic agents can potentially treat Graves’ hyperthyroidism and associated TED simultaneously by targeting their shared immunological mechanisms (e.g. antigen-specific immunotherapy ATX-GD-59; anti-CD40 monoclonal antibody iscalimab; TSH-R antagonists). Nonetheless, all new treatments should be carefully examined in randomized controlled trials (versus placebo and/or standard of care), preferably with standardized primary and secondary outcomes, in order to draw sound conclusions on the efficacy of certain intervention and facilitate comparisons among different trials.