Immunotherapies such as IL-2 and interferon have long been used in the treatment of certain cancers and immune mediated conditions. It has also long been recognised that their use is associated with an increased risk of autoimmune thyroid disease. Recent advances in the use of checkpoint inhibitors, such as ipilimumab and PD-1 inhibitors, in the treatment of a number of common cancers, as well as treatments such as alemtuzumab in multiple sclerosis have dramatically increased the number of patients treated with these immune modulating drugs.
Thyroid dysfunction has emerged as a common adverse event of these therapies. For example, phase 3 trials of Nivolumab and Pembrolizumab in cancers such as melanoma and renal cell cancer report rates of thyroid dysfunction of around 10%. However, trials report on the basis of symptoms not laboratory abnormalities and real-world data suggests much higher rates of thyroid dysfunction when including all those with abnormal thyroid function tests (up to 50% in patients with melanoma with a combination of Ipilimumab and Nivolumab).
Hypothyroidism is the most common presentation, although many patients develop a thyroiditis with a thyrotoxic phase proceeding hypothyroidism. The thyrotoxicosis rarely requires specific management, although beta-blockers may be required for symptomatic relief, but the hypothyroidism appears to be permanent requiring thyroid hormone replacement. Interestingly the literature reports a rate of thyroid peroxidase antibody positivity of between 30 and 80%, lower than that seen in classic autoimmune hypothyroidism. A similar pattern and frequency of thyroid dysfunction is described with Alemtuzumab. There are also isolated case reports of Graves disease following immunotherapy.
There is now some evidence that patients who develop thyroid dysfunction may be more likely to have a tumour response, although it remains unclear whether this is a causal relationship or not.