From the Guidelines
Pembrolizumab can affect TSH levels, with approximately 5-10% of patients developing thyroid dysfunction, most commonly hypothyroidism, as reported in the Keynote-001 study 1. The incidence of thyroid dysfunction requiring thyroid hormone replacement was 21% in patients treated with pembrolizumab, with 80% of these patients having detectable anti-thyroid antibodies 1.
- The mechanism of thyroid dysfunction is thought to be mediated by T cells and not by B cell autoimmunity 1.
- Regular monitoring of thyroid function tests, including TSH, free T4, and sometimes T3, is recommended before starting treatment and periodically throughout therapy, usually every 6-12 weeks.
- If thyroid dysfunction develops, it can often be managed with appropriate thyroid medication, such as levothyroxine for hypothyroidism, while continuing pembrolizumab treatment 1.
- Most thyroid dysfunction from pembrolizumab is permanent and requires ongoing management, even after discontinuation of the immunotherapy. The reported thyroid dysfunction rate with anti-PD-1 therapy, such as pembrolizumab, varies from 5% to 10%, irrespective of tumor type 1.
- Thyroid dysfunction is most common upon treatment with anti-PD-1/PD-L1 or combination of anti-CTLA4 and agents blocking the PD-1/PD-L1 axis 1.
- With combination immunotherapy, the frequency of thyroid disorders increases to 20% 1.
From the Research
Pembrolizumab and Thyroid Function
Pembrolizumab, an anti-programmed cell death 1 (PD-1) receptor monoclonal antibody, has been associated with thyroid dysfunction, including changes in thyroid-stimulating hormone (TSH) levels.
- Studies have shown that thyroid dysfunction is a common adverse event in patients treated with pembrolizumab, with hypothyroidism and thyrotoxicosis being the most frequent presentations 2, 3.
- The mechanism of thyroid destruction appears to be independent of thyroid autoantibodies and may involve T cell, natural killer (NK) cell, and/or monocyte-mediated pathways 3.
- Pembrolizumab-induced thyroiditis has been reported, with symptoms including thyrotoxicosis, hypothyroidism, and painless thyroiditis 4, 5.
Incidence of Thyroid Dysfunction
The incidence of thyroid dysfunction in patients treated with pembrolizumab varies, but it is estimated to occur in around 14% of patients 3.
- A study of 99 patients with advanced melanoma found that 18 adverse events of thyroid dysfunction were observed in 17 patients, with thyrotoxicosis occurring in 12 patients and isolated hypothyroidism in six patients 2.
- Another study of 93 patients with advanced cancer found that 13 (14%) thyroid immune-related adverse events were observed, with thyroiditis occurring in seven patients and new onset of hypothyroidism in three patients 3.
Management of Thyroid Dysfunction
Thyroid dysfunction induced by pembrolizumab can often be managed by the treating oncologist, but in more severe cases, an endocrinological evaluation and prompt therapy may be needed 5.
- Levothyroxine therapy may be required in patients with hypothyroidism, and thyroid function tests should be monitored regularly in patients treated with pembrolizumab 2, 3.
- In cases of severe thyrotoxicosis, total thyroidectomy may be necessary, as reported in a case study of a patient with refractory thyrotoxicosis despite maximal medical therapy 4.