Endocrine side effects induced by immune checkpoint inhibitors

Area of Science:

• Immunology
• Endocrinology
• Oncology

Background:

• Cancer immunotherapy utilizes immune checkpoint inhibitors (ICIs) like CTLA4 and PD-1 blockers to enhance anti-tumor responses.
• ICIs modulate T-cell signaling, but can disrupt immune self-tolerance, leading to immune-related adverse events (irAEs).
• irAEs commonly manifest as rash, colitis, hepatitis, and endocrinopathies.

Purpose of the Study:

• To review the spectrum of endocrine adverse events associated with cancer immune therapies.
• To highlight hypophysitis as a significant and potentially life-threatening side effect of CTLA4 blockade.

Main Methods:

• Literature search using keywords: "hypophysitis," "hypopituitarism," "thyroid," "adrenal insufficiency," "endocrine adverse events," and specific ICIs (ipilimumab, tremelimumab, PD-1, PD-1-L).

Main Results:

• Endocrine diseases associated with ipilimumab include hypophysitis (most common), thyroid dysfunction, and adrenal insufficiency.
• Hypophysitis represents a novel form of autoimmune pituitary disease, potentially life-threatening due to secondary hypoadrenalism.
• Endocrine dysfunction induced by ICIs is often irreversible, necessitating long-term hormone replacement therapy.

Conclusions:

• The prevalence and precise mechanisms of endocrine side effects from cancer immunotherapy remain unclear.
• Further research, including well-designed correlative studies, is needed to identify predictive factors for ICI-induced autoimmune toxicity.