Endocrine dysfunction is frequently reported in patients receiving ICIs (5%-20%), with an average onset time within 12 weeks from treatment initiation, and higher incidence in patients receiving combination therapy compared with monotherapy. The adverse effects of ICI therapy on the endocrine system vary significantly, from commonly occurring thyroid and pituitary disorders to relatively rare adrenal insufficiency and type 1 diabetes.
Diagnosis of endocrine irAEs is often delayed due to the subtle nature of signs and symptoms that often overlap with symptoms typically experienced by patients with advanced cancer, including vomiting, headache, nausea and fatigue. While mild fatigue is common in patients receiving ICI, severe fatigue can be an indicator of a more serious underlying endocrine dysfunction. Most endocrine-related irAEs are low grade and easily managed; however, when left untreated, they can lead to life-threatening conditions. Clinical assessment involves serum testing including hormonal evaluation and an endocrinology consultation to rule out an underlying medical condition. Hormonal therapy is essential for proper treatment of most endocrine disorders. Immunotherapy may be held and/or discontinued based on the type and grade of endocrine irAE.
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