Approach to thyroid disorders associated with immune checkpoint inhibitors and tyrosine kinase inhibitors

Abstract

Immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) have revolutionised the therapeutic landscape for a range of malignancies. However, their use is frequently associated with immune‐related adverse events (irAEs), particularly affecting the endocrine system. Thyroid dysfunction is the most common endocrine irAE, often occurring without symptoms, making routine thyroid function monitoring critical for early detection. Hypothyroidism is the predominant manifestation, though hyperthyroidism and central hypothyroidism due to immune‐mediated hypophysitis are also observed. Subclinical hypothyroidism may be monitored in the absence of symptoms; however, early treatment with cautious levothyroxine initiation is advised in patients with pre‐existing cardiac disease. When central hypothyroidism is suspected, adrenal insufficiency must be excluded before starting thyroid hormone therapy, and glucocorticoid replacement should precede levothyroxine to avoid precipitating an adrenal crisis. In cases of hyperthyroidism, transient thyroiditis and Graves disease should be considered. Persistent hyperthyroidism warrants further evaluation with thyroid receptor antibodies or a radionuclide thyroid scan. Management of endocrine irAEs depends on the severity (toxicity grade). Immunotherapy may be continued in mild cases but should be withheld temporarily in moderate to severe presentations. A multidisciplinary approach, particularly involving oncologists and endocrinologists, is essential to ensure optimal care and improve long‐term outcomes for patients.