Immune Checkpoint Inhibitors-Related Thyroid Dysfunction: Epidemiology, Clinical Presentation, Possible Pathogenesis, and Management

Front Endocrinol (Lausanne). 2021 Jun 10:12:649863. doi: 10.3389/fendo.2021.649863. eCollection 2021.

Abstract

Immune checkpoint inhibitors (ICIs) are a group of drugs employed in the treatment of various types of malignant tumors and improve the therapeutic effect. ICIs blocks negative co-stimulatory molecules, such as programmed cell death gene-1 (PD-1) and its ligand (PD-L1) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), reactivating the recognition and killing effect of the immune system on tumors. However, the reactivation of the immune system can also lead to the death of normal organs, tissues, and cells, eventually leading to immune-related adverse events (IRAEs). IRAEs involve various organs and tissues and also cause thyroid dysfunction. This article reviews the epidemiology, clinical manifestations, possible pathogenesis, and management of ICIs-related thyroid dysfunction.

Keywords: clinical manifestations; epidemiology; immune checkpoint inhibitors; immune-related adverse events; management; pathogenesis; thyroid dysfunction.

Publication types

  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Aged
  • Aged, 80 and over
  • B7-H1 Antigen / metabolism
  • CTLA-4 Antigen / metabolism
  • Disease Progression
  • Female
  • Genetic Predisposition to Disease
  • HLA Antigens / biosynthesis
  • Homeostasis
  • Humans
  • Immune Checkpoint Inhibitors / adverse effects
  • Immune Checkpoint Inhibitors / metabolism*
  • Immune System
  • Immunotherapy / methods
  • Ligands
  • Male
  • Middle Aged
  • Programmed Cell Death 1 Receptor / metabolism
  • T-Lymphocytes / cytology
  • Thyroid Diseases / diagnosis*
  • Thyroid Diseases / epidemiology
  • Thyroid Diseases / immunology*
  • Thyroid Diseases / therapy*
  • Thyroid Gland / physiopathology

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • HLA Antigens
  • Immune Checkpoint Inhibitors
  • Ligands
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor