Checkpoint Inhibitors and Immune-Related Adverse Events: A Focus on Autoimmune Endocrinopathies

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy by enhancing antitumor immune responses, particularly in malignancies such as melanoma, non-small cell lung cancer, and renal cell carcinoma. Despite their clinical success, ICIs are frequently associated with immune-related adverse events (irAEs), including a wide range of autoimmune endocrinopathies. These endocrine irAEs can involve the thyroid gland (thyroiditis, hypothyroidism, hyperthyroidism), pituitary gland (hypophysitis), adrenal glands (primary or secondary adrenal insufficiency), and, more rarely, the parathyroid glands (autoimmune hypoparathyroidism). These conditions often necessitate long-term hormone replacement and may impact quality of life and cancer treatment continuity. The mechanisms underlying these endocrinopathies are believed to involve autoreactive T cells and autoantibody production, although exact pathways vary across different glands. Emerging studies have revealed elevated CD4+ T-cell responses to thyroid antigens in patients with ICI-induced thyroiditis and a broader presence of autoantibodies. Additionally, genetic factors and gut-immune interactions may modulate susceptibility to these disorders. As ICIs become increasingly used in earlier stages of cancer and among patients with fewer comorbidities, early identification and management of endocrine irAEs are essential. Regular monitoring of hormone levels and prompt endocrine evaluation can minimize complications. Furthermore, increased awareness among oncologists and endocrinologists is crucial for timely diagnosis and intervention. This review highlights the current understanding of ICI-associated autoimmune endocrinopathies, emphasizing their clinical presentation, pathophysiology, and management. Future research is needed to identify predictive biomarkers and develop personalized strategies to mitigate these adverse effects without compromising the anticancer efficacy of ICIs.