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21-06-2018 | Immunotherapy | Practical management guide | Article

A guide to the management of adverse events in patients receiving immunotherapy for cancer

6. Endocrine immune-related adverse events

What are endocrine irAEs?

Immunotherapy has been causatively associated with a number of endocrinopathies, including hypophysitis, hypopituitarism, adrenal insufficiency, and hypo-/hyperthyroidism. These endocrinopathies can be both life threatening and irreversible, and may require lifelong maintenance. Patients may present with nonspecific symptoms that may resemble other causes such as brain metastasis or underlying disease. Therefore, a high index of suspicion should be maintained. The most common clinical presentation includes headache and fatigue. Adrenal crisis is a medical emergency, and must be excluded.

Incidence and onset of endocrine toxicities in patients receiving immunotherapy

In a meta-analysis of 38 randomized clinical trials incorporating 7551 patients, endocrine toxicity was reported in around 10% of patients [2].  Endocrine toxicities are amongst the latest irAEs to present, usually after approximately 9 weeks [1].

Specific endocrinopathies:

Symptoms and management of endocrine toxicities

Often insidious in onset with vague and non-specific symptoms, imbalances in hormones should be monitored both during and upon completion of immune checkpoint inhibition treatment. Specific features, investigations and management strategies are listed below.

Management algorithm

Algorithms for managing immune-related endocrine toxicities have been published by the Clatterbridge Cancer Centre NHS foundation. These have been utilized and adapted by other cancer centers are user friendly and offer safe, concise and standardized management of immune-related endocrinopathies.

Click below for the Clatterbridge Cancer Centre NHS Foundation algorithm on managing:

Primary thyroid dysfunction

Hypophysitis

Adrenal dysfunction

˂ Back: Renal irAEs                                             Next: Rare irAEs​​​​​​​

Literature