Can hypermetabolic multinodular thyroid goiter with normal thyroid function tests be caused by Keytruda (pembrolizumab) infusion?

Pembrolizumab Can Cause Hypermetabolic Multinodular Thyroid Goiter as an Immune-Related Adverse Event

Yes, the hypermetabolic multinodular thyroid goiter with normal thyroid function tests observed on PET/CT one day after pembrolizumab infusion is very likely due to Keytruda (pembrolizumab)-induced thyroiditis. This represents a known immune-related adverse event (irAE) associated with immune checkpoint inhibitor therapy.

Immune-Related Thyroid Dysfunction with Pembrolizumab

• Thyroid dysfunction is a common endocrine-related adverse event associated with pembrolizumab therapy, with both hypothyroidism and hyperthyroidism reported 1
• Thyroid disorders occur in approximately 5-10% of patients receiving anti-PD-1 therapy such as pembrolizumab 1
• Thyroiditis can manifest as transient thyrotoxicosis that may precede hypothyroidism, or as direct hypothyroidism 1
• The timing of your case (one day after infusion) is consistent with immune-related thyroiditis, which typically occurs within weeks to 3 months after initiation of immune checkpoint inhibitors 1

Diagnostic Considerations

• Increased FDG uptake on PET/CT (SUV 7.1) in your case is consistent with inflammatory thyroiditis caused by pembrolizumab 2
• Diffuse increased FDG uptake by the thyroid gland has been observed in patients with thyrotoxicosis who progress to hypothyroidism after pembrolizumab treatment 2
• Normal TSH (3.2) does not rule out pembrolizumab-induced thyroiditis, as thyroid function may be normal initially before developing dysfunction 1
• The absence of symptoms is common in early stages of immune-related thyroiditis 1

Management Approach

1. Continue monitoring thyroid function tests:

   • Your plan to monitor with serial thyroid function testing every 4-6 weeks during ongoing therapy is appropriate 1
   • Testing should include TSH and free T4 at minimum 1

2. Watch for development of symptoms:

   • Monitor for symptoms of both hyperthyroidism (tachycardia, heat intolerance, anxiety) and hypothyroidism (fatigue, cold intolerance, constipation) 1
   • Even with subclinical hypothyroidism, hormone replacement should be considered if fatigue or other symptoms develop 1

3. Treatment if thyroid dysfunction develops:

   • For hyperthyroidism: beta-blockers (propranolol or atenolol) for symptomatic management 1
   • For hypothyroidism: thyroid hormone replacement therapy, which is usually long-lasting 1
   • Pembrolizumab can generally be continued during management of thyroid dysfunction 1

Important Clinical Considerations

• Thyroid dysfunction from pembrolizumab is thought to be mediated by T cells rather than B cell autoimmunity 1
• Some patients may have undetected chronic inflammation of the thyroid (such as Hashimoto's thyroiditis) that predisposes them to thyroid destruction when taking pembrolizumab 3
• Thyroid autoantibody testing may be helpful, as anti-thyroid antibodies are detected in approximately 80% of patients who develop thyroid dysfunction requiring hormone replacement 1
• Pembrolizumab therapy can generally continue despite development of thyroid dysfunction, as it is usually manageable with appropriate medical therapy 1

Monitoring Algorithm

1. Continue pembrolizumab therapy while monitoring for thyroid dysfunction
2. Check thyroid function tests (TSH, free T4) every 4-6 weeks during therapy 1
3. If TSH becomes abnormal:
   • Low TSH with elevated FT4: Treat with beta-blockers for symptoms; consider carbimazole if anti-TSH receptor antibodies are positive 1
   • Elevated TSH with low FT4 or TSH >10 with normal FT4: Start thyroxine replacement 1
4. A falling TSH across two measurements with normal or lowered T4 may suggest pituitary dysfunction - monitor cortisol levels in this case 1

The transient nature of the thyroid uptake on PET/CT with normal thyroid function and no symptoms supports your assessment of immune-mediated thyroiditis rather than structural malignancy, and your monitoring plan is appropriate.