Immune checkpoint inhibitors and endocrine side effects, a narrative review

ABSTRACT

Immune checkpoint inhibitors (ICPIs) are novel drugs in the field of oncology however carry the risk of immune-related dermatologic, gastrointestinal, and endocrine side effects which can be fatal. These new innovative immunoregulatory drugs have intertwined the fields of oncology and endocrinology. CTLA-4 and PD-1 are co-inhibitory receptors on T cells that turn the T cell ‘off’ when binding to receptors on APCs. Tumor cells can also carry receptors for CTLA- and PD-1. By rendering T cells inactive, tumor cells can evade immune attack. Antibodies that bind to CTLA-4 and PD-1 lead to T cell activation and destruction of both tumor and normal host cells. ICPIs have been used in a variety of malignancies including melanoma, kidney cancer, and non-small cell lung cancer. A unique underrecognized side effect of the autoimmune response is hypophysitis leading to central adrenal insufficiency which can be fatal. Additional immune-related adverse events (irAEs) include hypothyroidism, hyperthyroidism, diabetes, and hypoparathyroidism.

KEYWORDS:

• Immune checkpoint inhibitors
• CTLA-4 inhibitor
• PD-1 inhibitor
• ipilimumab
• nivolumab
• hypophysitis
• hypothyroidism
• hyperthyroidism
• adrenal insufficiency
• diabetes
• hypoparathyroidism

Article highlights

• Immune checkpoint inhibitors enhance the immune system response against tumor cells evading the immune system leading to tumor cell death.

• Immune checkpoint inhibitors include antibodies to CTLA-4 and PD-1.

• Activation of the immune response to receptors on tumor cells can also break tolerance to other ‘normal’ antigens, leading to immune attack on normal parts of the body.

• Immune-related adverse events include hypophysitis, hypothyroidism, hyperthyroidism, adrenal insufficiency, diabetes, and hypoparathyroidism.

• Providers should be vigilant of endocrine abnormalities in patients taking immune checkpoint inhibitors.

Declaration of interest

No potential conflict of interest was reported by the authors.

Disclosures

The contents of the paper and the opinions expressed within are those of the authors, and it was the decision of the authors to submit the manuscript for publication.

Review disclosure

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.