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The side effects of immune checkpoint inhibitor therapy on the endocrine system

Itivrita Goyal1, Manu Raj Pandey2, Rajeev Sharma3

  • 1Department of Endocrinology, Diabetes & Metabolism, State University of New York at Buffalo, Buffalo, NY, USA.

The Indian Journal of Medical Research
|April 18, 2022
PubMed

Insights

Immune checkpoint inhibitors (ICIs) can cause endocrine adverse events, varying by drug type. Prompt recognition and hormone replacement therapy are crucial for managing these immune-related adverse events (IrAEs) and allowing continued cancer treatment.

Area of Science:

  • Oncology
  • Endocrinology
  • Immunology

Background:

  • Immune checkpoint inhibitors (ICIs) are novel cancer therapies targeting malignancies like melanoma and lung cancer.
  • Endocrine immune-related adverse events (IrAEs) are common side effects of ICIs, with varying incidence based on drug class.
  • Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) inhibitors are linked to hypophysitis, while programmed cell death (PD)-1/ligand (PD-L) inhibitors are associated with thyroid disease.

Purpose of the Study:

  • To review endocrine endocrinopathies associated with ICIs.
  • To describe mechanisms, clinical presentation, assessment, and management of ICI-induced endocrinopathies.
  • To emphasize the importance of vigilance for endocrine IrAEs in patients receiving ICIs.

Main Methods:

  • Literature review of immune-related adverse events (IrAEs) affecting the endocrine system.
  • Analysis of mechanisms, clinical manifestations, and management strategies for endocrine toxicities.
  • Discussion of pre-existing autoimmune conditions and their exacerbation by ICI therapy.

Main Results:

  • Endocrine IrAEs can stem from hypersensitivity reactions and autoantibody development.
  • Pre-existing autoimmune endocrine diseases may worsen with ICI treatment.
  • Most endocrinopathies are manageable with hormone replacement, but pituitary-adrenal axis involvement requires urgent attention.

Conclusions:

  • Timely hormone replacement therapy enables continuation of ICI treatment for most endocrine IrAEs.
  • Severe endocrine toxicity (grade 3/4) may necessitate temporary ICI discontinuation and hormonal therapy.
  • Endocrinologists and internists must maintain high awareness for endocrine IrAEs during ICI therapy.
Keywords:
Adrenal insufficiencyautoimmune diabetesautoimmune endocrinopathycorticosteroidshormone replacementhypophysitishypothyroidismimmune checkpoint inhibitors

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