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The course and pathogenesis of Graves' disease and Graves' ophthalmopathy are interdependent, influencing each other's therapeutic choices. Multiple factors including geographic location, access to medical services, patient and physician preferences influence the management of these conditions. Graves' disease is classically managed with one of three treatment options - antithyroid drugs, radioactive iodine, and thyroidectomy. In recent years, there has been a shift towards antithyroid drugs, including long term therapy with these agents, given the advantage of avoiding hypothyroidism and the apparent safety of this approach. In addition, new therapies are (slowly) emerging, focusing on immunomodulation. Technological advances are opening doors to non-pharmaceutical interventions that aim to deal with both structural thyroid abnormalities as well as biochemical abnormalities of hyperthyroidism. Graves' ophthalmopathy management is guided by its activity and severity status, with treatment options including smoking cessation, control of hyperthyroidism, local eye measures, glucocorticoids, selenium, orbital radiotherapy, and surgery. In addition to these established treatment choices, new immunotherapy- based approaches are being tested. Some of them (tocilizumab and teprotumumab) are very promising but further evaluation is needed before we can establish their role in clinical care. Agents identified as beneficial in Graves' disease management will likely be tested in Graves' ophthalmopathy as well. In the coming years, our main clinical responsibility will be to find the proper balance between the benefits and potential risks of these incoming therapies, and to identify the subgroups of patients where this ratio is most likely to favor a safe and successful therapeutic outcome. [ABSTRACT FROM AUTHOR]

The medical treatment of Graves' orbitopathy (GO) is usually reserved to moderate to severe disease. Steroids have been widely employed and possess anti-inflammatory activity, but about 20-30% of patients are not responsive and about 20% present with disease recurrence. Immunosuppressive therapy alternative to corticosteroids may target the different antigens involved in pathogenic mechanisms of GO. Some have already been employed in clinical studies and showed interesting results, although the lack of randomized and controlled trials suggests caution for their use in clinical practice. Potential targets for therapy in GO are the TSH receptor and the IGF-1 receptor on the fibroblasts, inflammatory cytokines, B and T cells. Most promising results are obtained by interacting with the PIK3/mTORC1 signaling cascades for adipogenesis and the anti-IGF-1R with the monoclonal antibody teprotumumab. A recent open study has shown that tocilizumab, an anti-sIL-6R antibody, inactivates GO. Consistent reports on the efficacy of rituximab have recently been challenged by randomized controlled trials. Clinical practice will greatly benefit from the use of disease modifying agents in GO, as compared to steroids, currently standard treatment for GO. Among these, rituximab may be useful, especially in patients resistant to steroid or with contraindications to steroids. However, larger randomized controlled trials are needed for definitive data on the potential disease-modifying role of rituximab in GO. Direct targeting of the orbital fibroblast via immunosuppression or nonimmunosuppressive drugs is emerging as a promising alternative. [ABSTRACT FROM AUTHOR]