Immune checkpoint inhibitors and endocrine side effects, a narrative review

Postgrad Med. 2020 Mar;132(2):206-214. doi: 10.1080/00325481.2019.1709344. Epub 2020 Jan 10.

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

Publication types

  • Systematic Review

MeSH terms

  • Adrenal Gland Diseases / chemically induced
  • Antineoplastic Agents, Immunological / adverse effects*
  • Antineoplastic Agents, Immunological / immunology
  • Antineoplastic Agents, Immunological / pharmacology
  • CTLA-4 Antigen / antagonists & inhibitors*
  • CTLA-4 Antigen / immunology
  • Diabetes Mellitus, Type 1 / chemically induced
  • Endocrine System Diseases / chemically induced*
  • Endocrine System Diseases / physiopathology
  • Humans
  • Hypophysitis / chemically induced
  • Immunotherapy / adverse effects*
  • Immunotherapy / methods
  • Neoplasms / drug therapy
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Programmed Cell Death 1 Receptor / immunology
  • Severity of Illness Index
  • T-Lymphocytes / immunology
  • Thyroid Diseases / chemically induced

Substances

  • Antineoplastic Agents, Immunological
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Programmed Cell Death 1 Receptor