Endocrine Abstracts

Graves’ disease is characterised by autoantibodies that stimulate the TSH receptor (TRAb) by engaging with its extracellular domain. Unlike most other autoimmune conditions, where prolonged tissue destruction or inflammation is required for the patient to present, hyperthyroidism may occur quickly after TRAb appear, meaning the autoimmune process may be evident at a much earlier stage. As neither antithyroid drugs, radioiodine or thyroidectomy are perfect options for long-term Graves’ disease management, novel therapies are being developed. The humoral immune system can be targeted in several ways, including by B lymphocyte depleting therapeutic antibodies, immunoglobulin recycling blockers and cytokine inhibitors (both IL6 and BAFF). TSH receptor may also be directly targeted by blocking TSH receptor antibodies such as K1-70 and potentially by direct small molecule inhibitors, although these have yet to be trialled in humans. Lastly, TRAb-capture molecules which may bind to TRAb using a TSHR-ECD bait in the circulation and target them for rapid clearance are being developed. Some of these approaches will translate into clinically available modalities of treatment over the next few years.