Checkpoint Inhibitors have emerges as a major breakthrough in cancer therapy. Side effects are largely immune mediated, termed immune related adverse events. Whilst the majority of these respond to immunosuppressive treatment, most frequently glucocorticoids, endocrinopathies are amongst the more frequent adverse events, and usually lead to permanent hormone deficiency, requiring life long hormone replacement. There are differences in the pattern of endocrinopathy between different checkpoint inhibitors. The CTLA-4 inhibitor ipilimumab results in hypophysitis in up to 20% of individuals, usually resulting in multiple anterior pituitary deficiencies, whilst thyroid changes are often mild and sub-clinical. In contrast the PD-1 and PD-L1 inhibitors cause both a destructive thyroiditis with a transient thyrotoxic phase, often progressing to hypothyroidism, or de novo hypothyroidism. They are also associated less frequently with isolated ACTH deficiency and insulin requiring diabetes closely resembling type 1 diabetes. The non-specific symptoms of many endocrine disorders, coupled with the frequency of symptoms in patients with advanced cancer and other immune related adverse events means a high index of suspicion for the development of endocrine adverse events is required, aided by an understanding of the pattern of expected adverse events for each agent. Although initial management closely resembles that of more common endocrine dysfunction, the longer term outcomes and likelihood of recovery of hormone function are currently unknown. In addition, around a third of patients receiving checkpoint inhibitors require high dose steroids for management of non-endocrine toxicity, with a significant incidence of steroid induced hyperglycaemia and adrenal suppression, both of which may require the input of the endocrine team.
18 - 21 May 2019
European Society of Endocrinology