Endocrine immune-related adverse events following immune checkpoint inhibitor therapy: A narrative review

Abstract

Background: Immune checkpoint inhibitors (ICIs) have improved outcomes in melanoma, lung, renal, and other advanced cancers. However, by increasing T-cell activity against cancer cells, they can also cause endocrine immune-related adverse events (irAEs), including thyroid dysfunction, hypophysitis, adrenal insufficiency, and diabetes mellitus. Some endocrine irAEs, especially thyroiditis, have been associated with better tumour response and survival, suggesting that they may also reflect an active antitumour immune response.

Objectives: To describe the oncological context, incidence, drug-specific risk, and possible association between endocrine irAEs and survival in patients receiving ICI therapy for cancer.

Methods: We conducted a narrative review of eleven publications (2018–2026) identified through PubMed. These included two meta-analyses (including one of 69 randomised oncology trials with 42,886 patients), four real-world cancer cohorts from Turkey, China, and Saudi Arabia, one prospective single-centre study, an ASCO management guideline, an international Delphi consensus on diagnostic criteria, and clinical reviews on management.

Results: Endocrine irAEs were reported in patients with melanoma, non-small cell lung cancer, renal cell carcinoma, and other solid tumours. Thyroid dysfunction was the most common endocrine irAE among patients receiving anti-PD-1 therapy, occurring in up to 40% of patients. Hypophysitis was more common with ipilimumab-containing regimens, occurring in up to 5.6% with monotherapy and 6.4% with combination therapy. Patients who developed thyroid-related irAEs had higher objective response and clinical benefit rates than those without these events, and this finding was also reported in independent cancer cohorts. However, similar associations were not consistently seen with hypophysitis or adrenal insufficiency. Diabetes mellitus was uncommon (0.087–3.7%) but often presented with diabetic ketoacidosis. Once stabilised, ICI therapy generally did not need to be discontinued, as endocrinopathies controlled with hormone replacement can usually be managed without stopping cancer treatment. Pre-treatment thyroid autoantibodies also predicted the development of thyroid-related irAEs in two independent cancer cohorts.

Conclusions: Endocrine irAEs are important but generally manageable complications of cancer immunotherapy. Thyroid-related irAEs, in particular, may be associated with better tumour response and survival. Recognising the endocrine risks of different ICI regimens can help oncology teams manage these complications with appropriate hormone replacement while avoiding unnecessary interruption of effective cancer treatment.

[J Assoc Clin Endocrinol Diabetol Bangladesh, 2026;5(Suppl 1): S39]