Immune checkpoint inhibitor-related endocrinopathies: from immune crosstalk to predictive biomarkers and precision management.

Immune checkpoint inhibitors (ICIs) have significantly prolonged patient survival in cancer therapy; however, overactivated immune responses can lead to endocrine immune-related adverse events (irAEs), primarily manifesting as thyroid dysfunction, hypophysitis, adrenal insufficiency, and insulin-dependent diabetes mellitus. Some of these endocrine injuries are irreversible and lack early warning indicators. This narrative review summarizes current evidence regarding the mechanisms underlying ICI-induced endocrine toxicities, including immune checkpoint pathways, organ-specific autoimmune responses, host-related factors, predictive biomarkers, and emerging precision management strategies. It summarizes potential predictive biomarkers, including thyroid autoantibodies, cytokine profiles, and single-cell sequencing, and discusses emerging approaches, including imaging-based assessment, liquid biopsy, and multidimensional prediction models, while emphasizing their current limitations and the need for prospective validation. Finally, by integrating organ-specific mechanistic evidence, biomarker-based prediction, and risk-stratified monitoring, this review frames these advances within the concept of "proactive endocrine protection," emphasizing the transition from passive toxicity management toward earlier identification and individualized surveillance.