De novo clinical endocrine immune-related adverse events during immune checkpoint inhibitor therapy in adults with cancer (2000–2025) – a scoping review

Background: Immune checkpoint inhibitors (ICIs) have transformed cancer therapy but are frequently complicated by immune-related adverse events (irAEs). Endocrine irAEs are among the most common and clinically significant toxicities. Unlike many other irAEs, they often result in permanent endocrine organ failure requiring lifelong hormone replacement. Early recognition is essential to prevent life-threatening complications such as adrenal crisis or diabetic ketoacidosis.Objectives: To synthesise current evidence on de novo, clinically significant endocrine irAEs in adults receiving ICI therapy, with emphasis on presentation, diagnostic pathways, acute management, long-term outcomes, and implications for endocrine practice.Methods: A PRISMA-ScR-informed scoping review of English-language literature (2000–2025) was conducted using structured database discovery and citation chaining. Eligible evidence included systematic reviews, international guidelines, cohort studies, and phenotype-specific case aggregations restricted to endocrine irAEs requiring hormone replacement, insulin therapy, or urgent endocrine intervention.Results: Fourteen evidence sources were included. Thyroid dysfunction and hypophysitis accounted for most treatment-requiring endocrine irAEs, with clear regimen-specific patterns. Primary adrenal insufficiency and ICI-induced diabetes mellitus were uncommon but associated with substantial acute morbidity. Hypoparathyroidism was exceedingly rare and described predominantly in case-based literature. Management is phenotype-specific and largely centred on timely hormone replacement, as immunosuppression rarely reverses established endocrine failure.Conclusions: Endocrine irAEs represent a major and distinctive toxicity domain of ICI therapy. While most phenotypes are manageable with appropriate recognition and treatment, selected endocrinopathies carry high acute risk and long-term replacement needs. Structured diagnostic evaluation, careful hormone replacement sequencing, and longitudinal endocrine follow-up are essential as immunotherapy use expands.