From the Guidelines
Yes, Keytruda could be causing the patient's thyroid abnormalities, as immune checkpoint inhibitors like Keytruda are known to trigger immune-related adverse events, including thyroid dysfunction, as noted in the 2021 ASCO guideline update 1. The patient's pattern of elevated TSH of 4, normal free T4, and low free T3 suggests subclinical hypothyroidism that may be progressing to overt hypothyroidism.
- Key points to consider in the management of this patient include:
- Regular monitoring of thyroid function tests every 4-6 weeks, as recommended by the ASCO guideline update 1
- Consideration of thyroid hormone replacement with levothyroxine if the TSH rises further or if the patient becomes symptomatic
- The dose of levothyroxine is usually started at 1.6 mcg/kg/day and adjusted based on TSH levels measured every 4-6 weeks until stable
- It is essential to note that Keytruda therapy can generally be continued while treating the hypothyroidism, as stated in the ASCO guideline update 1.
- The patient's thyroid function should be closely monitored throughout immunotherapy treatment, as thyroid dysfunction can develop at any point during therapy or even after discontinuation.
- According to the ASCO guideline update 1, for patients with asymptomatic or mild symptoms (G1), Keytruda can be continued, and beta-blockers can be used for symptomatic relief, with close monitoring of thyroid function every 2-3 weeks after diagnosis.
From the Research
Thyroid Hormone Levels and Ketruda
- The patient's thyroid hormone levels show a TSH of 4, free T4 within normal limits, and low FT3, which could be indicative of a non-thyroidal illness syndrome (NTIS) or a side effect of Ketruda (pembrolizumab) treatment 2.
- Studies have shown that patients treated with pembrolizumab can experience thyroid immune-related adverse events (irAEs), including thyroiditis and hypothyroidism, which can lead to changes in thyroid hormone levels 2.
- The low FT3 level in this patient could be a marker of frailty or malnutrition, as seen in other studies where low FT3 levels were correlated with frailty and malnutrition in elderly patients 3, 4.
- The FT3/FT4 ratio has been shown to be strongly associated with insulin resistance in euthyroid and hypothyroid adults, which could be relevant to this patient's condition 5.
- However, it is essential to note that the relationship between thyroid hormone levels and Ketruda treatment is complex, and more research is needed to fully understand the underlying mechanisms 2.
Possible Causes of Low FT3
- Non-thyroidal illness syndrome (NTIS) or euthyroid sick syndrome, which can occur in patients with chronic illnesses or those undergoing treatment with immunotherapy agents like Ketruda 3, 2.
- Malnutrition or inflammation, which can lead to changes in thyroid hormone levels, including low FT3 3, 4.
- Side effects of Ketruda treatment, including thyroiditis or hypothyroidism, which can cause changes in thyroid hormone levels 2.
Clinical Implications
- The patient's low FT3 level and normal free T4 level may require monitoring and potential treatment to prevent or manage related conditions, such as insulin resistance or frailty 5, 4.
- Clinicians should be aware of the potential for thyroid irAEs in patients treated with Ketruda and monitor thyroid hormone levels accordingly 2.