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 . Endocrine toxicities are amongst the latest irAEs to present, usually after approximately 9 weeks .
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.
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:
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- Corsello SM, Barnabei A, Marchetti P et al. Endocrine side effects induced by immune checkpoint inhibitors. J Clin Endocrinol Metab 2013; 98(4): 1361–1375.
- Barroso-Sousa R, Barry WT, Garrido-Castro AC et al. Incidence of Endocrine Dysfunction Following the Use of Different Immune Checkpoint Inhibitor Regimens: A Systematic Review and Meta-analysis. JAMA Oncol 2018; 4(2): 173–182.
- Weber JS, Kähler KC, Hauschild A. Management of immune-related adverse events and kinetics of response with ipilimumab. J Clin Oncol 2012; 30(21): 2691–2697.
- yun DJ, Wolchok JD, Rosenberg LM, Girotra M. Cancer immunotherapy - immune checkpoint blockade and associated endocrinopathies. Nat Rev Endocrinol 2017; 13(4): 195–207.
- Ryder M, Callahan M, Postow MA. Endocrine-related adverse events following ipilimumab in patients with advanced melanoma: a comprehensive retrospective review from a single institution. Endocr Relat Cancer 2014; 21(2): 371–381.
- Spain L, Diem S, Larkin J. Management of toxicities of immune checkpoint inhibitors. Cancer Treat Rev 2016; 44: 51–60.
- Juszczak A, Gupta A, Karavitaki N et al. Ipilimumab: a novel immunomodulating therapy causing autoimmune hypophysitis: a case report and review. Eur J Endocrinol 2012; 167(1): 1–5.