Thyroid disorders induced by checkpoint inhibitors | JoVE Visualize

Area of Science:

Oncology
Immunology
Endocrinology

Background:

Immune checkpoint inhibitors (ICIs) like CTLA-4, PD-1, and PD-L1 antibodies are revolutionizing cancer treatment by enhancing anti-tumor immune responses.
However, ICIs can induce immune-related adverse events (irAEs), which are toxicities resulting from the overstimulated immune system.
Endocrine toxicities are a significant category of irAEs, potentially leading to serious health consequences.

Purpose of the Study:

To review the spectrum of immune-related endocrine toxicities associated with different classes of immune checkpoint inhibitors.
To highlight the specific endocrine organs affected and the frequency of these toxicities with different ICI agents.
To emphasize the importance of endocrinological evaluation and management for managing ICI-induced endocrinopathies.

Main Methods:

Review of approved immune checkpoint inhibitors: CTLA-4 monoclonal antibodies (e.g., ipilimumab), anti-PD-1 monoclonal antibodies (e.g., pembrolizumab, nivolumab), and anti-PD-L1 monoclonal antibodies (e.g., atezolizumab, avelumab, durvalumab).
Analysis of reported immune-related adverse events (irAEs), focusing on endocrine toxicities.
Correlation of specific ICI agents and combinations with particular endocrine irAEs.

Main Results:

Hypophysitis is the most common irAE associated with anti-CTLA-4 antibodies.
Thyroid abnormalities (hypothyroidism, thyrotoxicosis, thyroiditis) are more frequently linked to anti-PD-1 antibodies.
Combination therapy with anti-CTLA-4 and anti-PD-1 antibodies increases the risk of irAEs to approximately 30%.
Immune-related endocrine toxicities include thyroid dysfunction, hypophysitis, adrenal insufficiency, and type 1 diabetes mellitus, with 50% being irreversible.
Clinical presentation varies by the affected organ, and while oncologists can manage some cases, severe endocrinopathies necessitate specialist endocrinological care.

Conclusions:

Immune checkpoint inhibitors, while effective cancer therapies, carry a significant risk of immune-related endocrine toxicities.
Specific endocrine irAEs are associated with particular ICI classes, with hypophysitis and thyroid dysfunction being prominent examples.
Timely endocrinological consultation and management are essential for addressing severe or persistent ICI-induced endocrine disorders, improving patient outcomes.