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Endocrine side effects of cancer immunotherapy
Priscilla Cukier1, Fernando C Santini2, Mariana Scaranti2
1Department of EndocrinologyInstituto do Cancer do Estado de São Paulo, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Abstract:
Immune checkpoint inhibitors have recently become a cornerstone for the treatment of different advanced cancers. These drugs, represented mainly by monoclonal antibodies anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4), anti-programmed cell death protein-1 (PD-1) and anti-PD-1 ligand molecules (PD-L1 and L2), have the ability to reactivate the immune system against tumor cells, but can also trigger a myriad of autoimmune side effects, termed immune-related adverse events (irAEs). In particular, there are a number of endocrine-related irAEs. Current data from clinical trials show increased incidence of hypophysitis with CTLA4 inhibition and thyroid dysfunction with PD-(L)1 blockade. In addition, a few cases of type 1 diabetes mellitus and primary adrenal insufficiency have been reported. We discuss the incidence, clinical manifestations, diagnosis and management of immune-related endocrinopathies in this highly complex context of oncological patients in need of immunotherapies.
Insights
Immune checkpoint inhibitors for cancer can cause autoimmune side effects called immune-related adverse events (irAEs). This review focuses on endocrine irAEs, including hypophysitis and thyroid dysfunction, in cancer patients.
Area of Science:
- Oncology
- Immunology
- Endocrinology
Background:
- Immune checkpoint inhibitors (ICIs) are crucial in advanced cancer treatment.
- ICIs, including anti-CTLA-4 and anti-PD-(L)1 antibodies, reactivate anti-tumor immunity.
- However, ICIs can induce immune-related adverse events (irAEs), particularly endocrinopathies.
Purpose of the Study:
- To review the incidence, clinical features, diagnosis, and management of endocrine irAEs.
- To provide insights into managing these side effects in cancer patients undergoing immunotherapy.
Main Methods:
- Literature review of clinical trials and case reports.
- Analysis of data on endocrine irAEs associated with CTLA-4 and PD-(L)1 inhibitors.
Main Results:
- Increased incidence of hypophysitis with CTLA-4 inhibition.
- Thyroid dysfunction is common with PD-(L)1 blockade.
- Rare cases of type 1 diabetes mellitus and primary adrenal insufficiency have been reported.
Conclusions:
- Endocrine irAEs are significant side effects of ICIs.
- Prompt diagnosis and management are essential for optimal patient outcomes.
- Understanding these events is critical for oncologists and endocrinologists managing patients on immunotherapy.
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