How to manage autoimmune hyperthyroidism (Graves' disease): from differential diagnosis to emerging immunological...

Graves' disease is an autoimmune disorder and represents the most prevalent cause of hyperthyroidism. Its pathogenesis involves a complex interplay of immunological mechanisms, with a central role attributed to stimulating autoantibodies directed against the thyroid-stimulating hormone receptor (TSHR) expressed on thyroid follicular cells. The differential diagnosis of hyperthyroidism is of paramount importance, including other causes of thyrotoxicosis such as autonomously functioning thyroid adenoma, toxic nodular goitre, various forms of inflammatory or destructive thyroiditis and factitious thyrotoxicosis. The cornerstone of initial therapy for Graves' disease is the administration of antithyroid drugs (ATDs), whereas radioiodine ablation and total thyroidectomy constitute important therapeutic options, primarily in cases of disease recurrence or when serious adverse events related to ATDs occur. During recent decades, prolonged low-dose ATD regimens have demonstrated comparable safety profiles whilst offering superior efficacy relative to the conventional 18-month treatment course. Emerging therapeutic approaches involve immunomodulatory strategies targeting B lymphocytes, IgG recycling pathways and TSHR itself. Furthermore, the induction of immune tolerance to TSHR represents a promising future direction. This review aims to provide a comprehensive overview of the differential diagnosis of thyrotoxicosis as well as current and evolving therapeutic strategies for the management of hyperthyroidism in Graves' disease.