Cancer immunotherapy associated hypophysitis: Pathophysiology and management
Department of Zoology, Jhargram Raj College, West Bengal, India.
Review Article
World Journal of Advanced Research and Reviews, 2022, 15(02), 297–303
Publication history:
Received on 07 July 2022; revised on 10 August 2022; accepted on 12 August 2022
Abstract:
Immune checkpoints are small molecules produced by immune cells that play crucial role in maintaining homeostasis of immune system. Targeting the immune checkpoint molecule, specifically, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death 1 (PD1) with inhibitory monoclonal antibodies has been reported to have antitumor activity. The US Food and Drug Administration (FDA) has been recognized several immune checkpoint inhibitors (ICIs) for the treatment of several types of cancer, mainly two types of ICIs that target CTLA-4 and PD1, have been approved as immunotherapeutic agent for cancer treatment. Autoimmune side effects results from immune checkpoint blockade, termed as immune related adverse events (irAEs) are frequent and usually mild, can include multiple endocrinopathies. The unique characteristic of irAEs is their non-reversibility, with incidence and prevalence expected to be increased in the upcoming years. Immune-related hypophysitis (IRH) is one of the most frequently reported irAEs after thyroid dysfunction. Hypophysitis, specifically associated with anti-CTLA-4 therapy, primary adrenal insufficiency (PAI) and diabetes mellitus are rare irAEs but can be fatal if not diagnosed and treated in early stage. Combinatorial therapy using anti- CTLA-4 and anti-PD1 drug is associated with increasing prevalence of IRH. The exact mechanism behind the development of irAEs remain to be elucidated. Most ICI associated endocrinopathies are manifested within 8-12 weeks after the initiation of ICI therapy. Management of ICI associated hypophysitis requires withdrawal of the ICI therapy, initiation of steroids and finally initiation of hormone replacement therapy and usually includes long-term management and care for controlling the irreversible side effects. In this review, we try to summarize the current scenario regarding the epidemiology, mechanism pathophysiology and management procedure for IRH in cancer patients receiving immunotherapy.
Keywords:
Cancer immunotherapy; Immune-related adverse events; Hypophysitis; PD1; CTLA-4
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