Immunotherapy with immune checkpoint inhibitors has become an effective treatment of many malignancies resistant to conventional chemotherapies. Immune checkpoints are molecules on the surface of immune cells involved in the regulation of the immune response and immune checkpoint inhibitors are monoclonal antibodies directed against certain immune checkpoints, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death 1 (PD-1) and its ligand (PD-L1), resulting in T-cell activation and antitumor activity. However, immune checkpoints also play a crucial role in maintaining immunological self-tolerance and preventing autoimmune disorders. Interfering with this mechanism can cause immune-related adverse events (irAEs) presenting as autoimmune disorders affecting numerous organs in the body. Endocrinopathies are among the most common irAEs associated with immune checkpoint inhibitors and most of them include thyroid dysfunction (typically associated with anti-PD-1 antibodies) and hypophysitis (typically associated with anti-CTLA-4 antibodies probably as a result of ectopic expression of CTLA-4 antigens on the cells of a human hypophysis). Insulin-deficient diabetes mellitus and primary adrenal insufficiency are rare endocrine toxicities associated with immune checkpoint inhibitors, but can be life-threatening if not promptly recognized and treated. Some endocrinopathies as thyrotoxicosis are transient, may resolve spontaneously and require only monitoring or symptom control but others, such as central adrenal insufficiency and primary hypothyroidism, are persistent and require proper life-long hormonal replacement. Combination of anti-CTLA-4 and anti-PD-1 treatment is usually associated with the highest incidence and severity of immune checkpoint inhibitors endocrinopathies. Given the increasing use of immune checkpoint inhibitors, cooperation between oncologists and endocrinologists is crucial in the management of patients with immunotherapy-induced endocrinopathies. Making an appropriate diagnosis and adequate hormonal relacement may improve the prognosis of oncological patients in whom immunotherapy-induced endocrinopathy have occurred.
18 - 21 May 2019
European Society of Endocrinology