Endocrine toxicity of cancer immunotherapy

Immune checkpoint inhibitors (ICPIs) based on the efficacious anti-tumour immune response become an integral part of a number of cancer therapies. However, their widespread use has been linked to an increase in adverse events affecting almost every organ system. Common ICPIs include cytotoxic T lymphocyte-associated protein 4 (CTLA-4) inhibitors, programmed death 1 (PD-1) inhibitors, and PD ligand 1 inhibitors. Among the ICPIs induced immune-related adverse events, endocrine events are particularly common. Thyroid gland is the most common endocrine organ affected by ICPIs, followed by the pituitary gland. Hypophysitis is specifically linked to anti-CTLA-4 therapy, while thyroid dysfunction is associated with anti-PD-1 therapy. Rare endocrine adverse effects such as diabetes mellitus and primary adrenal insufficiency can also occur with ICPI therapy and, if not promptly addressed, may be life-threatening. Combination therapy with anti-CTLA-4 and anti-PD-1 inhibitors results in the highest incidence of endocrinopathies. Although most ICPI-related endocrine dysfunction emerges within 12 weeks of starting the therapy, some may develop months to years later. While some endocrine issues may resolve spontaneously, central adrenal insufficiency and primary hypothyroidism tend to persist. Management of ICPI-induced endocrine dysfunction primarily involves hormone replacement and control of symptoms. This article aims to review the endocrine complications of ICPI therapy and offer guidance on screening and managing patients experiencing endocrine dysfunction in daily clinical practice.