Immune-Related Thyroid Dysfunction in Cancer Therapy

Immune checkpoint inhibitors have transformed oncology by harnessing the patient’s own immune system to target malignant cells. A recognised consequence of these therapies is immune-related thyroid dysfunction, which ranges from an initial thyrotoxic phase to permanent hypothyroidism. Incidence varies by agent and regimen, with combination approaches often carrying higher risk. Clinical patterns include transient destructive thyroiditis, often followed by a hypothyroid phase requiring lifelong hormone replacement. Emerging data link the development of thyroid irAEs with improved cancer outcomes, suggesting that autoimmunity against thyroid antigens may reflect a broader antitumour immune activation. Optimal management depends on early detection through regular monitoring of thyroid‐stimulating hormone and free thyroid hormones, timely initiation of levothyroxine when indicated, and interdisciplinary collaboration between oncologists and endocrinologists.

Research from Nature Portfolio

A recent investigation employed a polygenic risk score (PRS) derived from large‐scale genome‐wide association data to quantify predisposition to autoimmune hypothyroidism. When applied to patients receiving PD-L1 blockade, those with higher PRS exhibited a greater incidence of thyroid dysfunction and, notably in triple-negative breast cancer, experienced prolonged survival. This work illuminates how inherited genetic variation shapes both the likelihood of endocrine irAEs and the systemic antitumour response, underscoring the potential for genomic risk stratification to inform personalised monitoring and to anticipate therapeutic benefit.

Immune-Related Thyroid Dysfunction in Cancer Therapy publication trend

The graph below shows the total number of articles in immune-related thyroid dysfunction in cancer therapy across all publications each year (not limited to Nature Index journals).

Technical terms

Immune checkpoint inhibitors (ICIs): Monoclonal antibodies that block inhibitory receptors on T cells to enhance antitumour immunity.

Immune-related adverse events (irAEs): Autoimmune toxicities triggered by immune activation against non-malignant tissues.

Thyroiditis: Inflammation of the thyroid gland leading initially to hormone release and thyrotoxicosis.

Thyrotoxicosis: Clinical state of thyroid hormone excess causing metabolic acceleration and symptoms such as tachycardia.

Hypothyroidism: Deficiency of thyroid hormone characterised by fatigue, weight gain and elevated thyroid‐stimulating hormone.

Polygenic risk score (PRS): Aggregate measure of inherited susceptibility to a trait based on multiple genetic variants.

Tyrosine kinase inhibitors (TKIs): Small molecules targeting growth factor receptors, often combined with ICIs, with known thyroidal toxicity.

Antithyroid antibodies (ATAs): Autoantibodies against thyroid antigens that can predict risk of immune-related thyroid dysfunction.

References

1. Thyroid dysfunction in Chinese nasopharyngeal carcinoma after anti-PD-1 therapy and its association with treatment response. BMC Medicine (2023).
2. Clinical biomarkers for thyroid immune-related adverse events in patients with stage III and IV gastrointestinal tumors. Frontiers in Immunology (2024).
3. Combined use of tyrosine kinase inhibitors with PD-(L)1 blockade increased the risk of thyroid dysfunction in PD-(L)1 blockade: a prospective study. Cancer Immunology, Immunotherapy (2024).
4. Permanent hypothyroidism following immune checkpoint inhibitors induced thyroiditis may be associated with improved survival: results of an exploratory study. Frontiers in Endocrinology (2023).
5. Immune Related Adverse Events of the Thyroid – A Narrative Review. Frontiers in Endocrinology (2022).
6. Genetic variation associated with thyroid autoimmunity shapes the systemic immune response to PD-1 checkpoint blockade. Nature Communications (2021).