Thyroid dysfunction is one of the most frequently occurring immune-related side effects of pembrolizumab, affecting a significant proportion of patients over the course of treatment. The good news is that it is usually detectable early, manageable with straightforward treatment, and does not typically require stopping pembrolizumab.
Why pembrolizumab affects the thyroid
The thyroid gland expresses PD-L1 on its cells. When pembrolizumab removes the PD-1 inhibitory signal, the immune system can sometimes direct activity against thyroid cells alongside tumour cells. The resulting inflammation - immune-mediated thyroiditis - disrupts normal thyroid hormone production. Thyroid dysfunction during pembrolizumab treatment is therefore an immune-related adverse event (irAE), not a direct drug toxicity.
How it presents: hyperthyroidism followed by hypothyroidism
The typical sequence begins with a phase of thyroid inflammation that releases stored thyroid hormone into the bloodstream - causing transient hyperthyroidism. Symptoms include palpitations, feeling hot, tremor, and anxiety. This phase is often brief and may pass before it is detected. As the thyroid cells are damaged by immune activity, hormone production falls - leading to hypothyroidism. Symptoms include fatigue, feeling cold, weight gain, constipation, and brain fog.
Many patients never notice the hyperthyroid phase at all, as it is picked up on routine blood tests (elevated free T4, suppressed TSH) before causing symptoms. The hypothyroid phase is more often symptomatic.
Detection through monitoring
Thyroid function tests (TSH, free T4) are included in the routine blood monitoring schedule for pembrolizumab. Testing before each cycle or at regular intervals allows changes to be detected early - often before symptoms develop. When thyroid dysfunction is identified, the oncologist is notified and management is initiated.
Management
The hyperthyroid phase is usually managed conservatively - monitoring, and occasionally beta-blockers for symptom relief if palpitations are troublesome. The hypothyroid phase is treated with levothyroxine, a synthetic thyroid hormone replacement taken as a daily tablet. Most patients require levothyroxine for the duration of treatment and sometimes indefinitely afterwards. Pembrolizumab does not usually need to be stopped for thyroid dysfunction - it is one of the most manageable immunotherapy-related irAEs.
Questions about side effect monitoring?
Our monitoring programme includes thyroid function testing at every relevant interval. Start with the eligibility check - an oncologist reviews it within 24 hours.
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