Immunotherapy-induced endocrinopathies: assessment, management and monitoring

Abstract

Immunotherapy with checkpoint inhibitors has transformed the treatment of cancer, but frequently results in immune-mediated adverse events affecting multiple organs, amongst which endocrine adverse events are frequent. The patterns of endocrine adverse events differ between inhibitors of the CTLA-4 and PD-1/PD-L1 pathways, but most frequently involve the thyroid and pituitary with insulin deficient diabetes also emerging as an important adverse event. These frequently result in long-lasting hormone deficiency requiring replacement. This review explores the mechanism of action of checkpoint inhibitors and details the expected endocrine adverse events and typical presentations. The effect of high-dose glucocorticoids therapy to treat nonendocrine adverse events is also discussed.

Keywords: cancer; diabetes; endocrinopathy; glucocorticoids; hypophysitis; immunotherapy; thyroiditis.

Figure 1.

The immune checkpoints, such as the PD-1/PD-L1 or CTLA-4 pathways serve to drive autoreactive T cells towards anergy, preventing autoimmunity. Immune checkpoint inhibitors (ICIs) prevent this, enabling an immune-mediated response against a cancer (a). However, they also promote immune responses against self, in this case the thyroid (b) resulting in thyroiditis.