An Update on Immune Checkpoint Inhibitor-related Hypophysitis

I mmune checkpoint inhibitors (ICIs) are a novel form of immunotherapy increasingly used in the treatment of various cancers.These agents are monoclonal antibodies that target specific glycoproteins (cytotoxic T-lymphocyte-associated protein 4 [CTLA-4], programmed cell death protein 1 [PD-1]) on T cells or ligands (programmed death-ligand 1 [PD-L1]) on antigen producing cells.Blockade of CTLA-4 and PD-1 (or its ligand PD-L1) by ICIs results in T-cell activation and tumor cell death.Initially used in adults, ICI use is now also expanding into the pediatric population.While ICIs have proven to be effective in the treatment of certain cancers, they also cause immune-mediated endocrinopathies.Immune-mediated hypophysitis is often unrecognized and can range from isolated pituitary hormone deficiency to, rarely, panhypopituitarism.Severe cases can cause pituitary gland enlargement that can result in visual disturbances due to compression on the optic chiasm, and potentially death from adrenal crisis.Treatment of hypophysitis depends on the severity of illness and ranges from initiation of hormone replacement, discontinuation of ICIs, and administration of high glucocorticoid doses if mass-effect symptoms are present.Clinicians must be aware of ICI-related hypophysitis in order to promptly recognize and effectively treat this condition.Screening for endocrine dysfunction should continue even after completion of immunotherapy.In this review, we provide an update on the mechanism, incidence, clinical manifestations, and recommendations on diagnosis and treatment of ICI-related hypophysitis, specifically focusing on the use and dosing regimens of glucocorticoids in different clinical scenarios.