Decoding Checkpoint Inhibitor-induced Endocrinopathies

Immune checkpoint inhibitors predominantly monoclonal antibody inhibitors of CTLA-4 and PD-1/PD-L1, have dramatically changed the treatment landscape for people with cancer. Efficacy for the drugs is being demonstrated in an expanding number of malignancies, both as single agents and in combination with other immune-targeted or systemic therapies. A major limitation of checkpoint inhibitors is toxicity in the form of immune-related adverse events (irAEs), many of which affect endocrine organs. This includes but is not limited to the pituitary, thyroid, adrenal glands and pancreas, and results in acute inflammation of these organs and hormonal secretory disturbances. Sequelae include hypophysitis with single or multi-hormone deficiency, thyrotoxicosis with subsequent euthyroidism or hypothyroidism, adrenalitis with primary hypoadrenalism and checkpoint inhibitor-associated autoimmune diabetes mellitus.

This research topic aims to gain insight from experts across fields including immunology, endocrinology, oncology and microbiology, in order to synthesise a multi-disciplinary review, relevant to patient care and informing future research and clinical practice.

1. The epidemiology, clinical manifestations, diagnosis and management of specific endocrinopathies in patients with cancer treated with checkpoint inhibitors.
2. Contributing and predisposing factors to checkpoint inhibitor-induced endocrinopathies, including but not limited to pre-existing autoimmunity, genetic polymorphisms, and microbiome characteristics.
3. Immunological phenotypes of distinct checkpoint inhibitor-induced endocrinopathies.
4. Shared or distinct clinical and pathological features with known autoimmune or endocrine diseases
5. Relationship between endocrinopathy development with additional toxicity and patient outcomes.

Keywords: irAE, checkpoint inhibition, autoimmunity, endocrinopathies, hypophysitis, thyrotoxicosis, hypoadrenalism, diabetes mellitus, immunotherapy

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