Thyroid disorders induced by immune checkpoint inhibitors

Abstract

Immune checkpoint inhibitors (ICIs) are a revolutionary class of drugs that powerfully contribute to cancer therapy by harnessing the immune system to fight malignancies. However, their successful use as anti-cancer drugs is accompanied by a wide spectrum of immune-related adverse effects (irAEs), including endocrinopathies. Among them, thyroid dysfunction stands out as one of the most common endocrinopathies induced by ICI therapy and surfaces as a prominent concern. Destructive thyroiditis is the pathophysiological basis shared by the most common patterns of thyrotoxicosis followed by hypothyroidism and isolated hypothyroidism. Diagnostic approach is guided by clinical manifestation, laboratory evaluation and imaging modalities. Treatment approaches range from the substitution of levothyroxine to the utilization of beta blockers, depending on the extent of thyroid dysfunction’s severity. While the medical community is dealing with the evolution and complexities of immunotherapy, recognizing and effectively managing ICI-induced thyroid dysfunction emerged as crucial for enhancing patient safety and achieving improved outcomes. The aim of this review is to navigate the significance of ICI-induced thyroid dysfunction unraveling the various patterns, underlying mechanisms, diagnostic approaches, and treatment strategies. It, also, highlights the impact of various factors such as cancer subtype, ICI dosage, age, and genetic susceptibility on the risk of experiencing dysfunction.

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“…Hypothyroidism is one of the most common endocrine diseases in ICIs therapy, usually occur within 3 weeks to 10 months after the start of ICIs treatment. Studies have indicated that the incidence of hypothyroidism when using PD-1 inhibitors alone ranges from 3.9% to 8.5%, while it increases to 10.2% to 16.4% with combination ICIs therapy ( 59 ). It is important to note that our patient did not experience any severe immune-related adverse reactions aside from hypothyroidism.…”