Graves’ disease: a new era of pathophysiology-guided therapeutics

Graves' disease (GD) is an autoimmune entity that had an unchanged treatment paradigm for more than half a century with radioactive iodine, antithyroid drugs (ATD), and surgery representing the mainstay of therapy, with variation in their use over time and geographic location. Hypothyroidism has been an accepted trade-off in many cases. though recently there are increased concerns about altered quality of life in these patients. Fortunately, the last decade has seen an intense pursuit of GD's immunological mechanisms and a recalibration of classic treatment modalities focusing on thyroid preservation, as reflected in the preference for ATD as primary therapy, including its use in long-term protocols. The immune targets currently explored aim to address this gap by intervening in the TRAb lifecycle: minimizing production (e.g., B-cell targeting), enhancing clearance (e.g., FcRn inhibitors), or neutralizing its target - the TSHR (e.g., receptor blockade). While these approaches are going through the necessary clinical trials evaluation, we are starting to see the potential for technology and artificial intelligence to make an impact on how we identify, treat and monitor patients with GD. The combination of these approaches will likely lead to a significant individualization of GD management that will take us from the goal of normalization of thyroid levels to that of inducing long-term remission and prevention of the associated autoimmune phenomena that GD is associated with. While time is needed for these aspects to mature, the future looks bright for our GD patients and maybe soon these lessons will open new doors for our patients with Hashimoto's thyroiditis as well.