irAE Thyroid — SCE Dermatology MCQ

Correct answer: B — Continue Nivolumab — thyroid dysfunction is a common immune-related adverse event managed with Levothyroxine replacement without requiring immunotherapy cessation in most cases

The correct answer is B: continue Nivolumab, since thyroid dysfunction is a common immune-related adverse event managed with levothyroxine replacement without requiring immunotherapy cessation in most cases. Immune-mediated thyroiditis causing biochemical hypothyroidism (raised TSH, low free T4) is a grade 1 to 2 endocrine toxicity, and per the Opdivo SmPC these grades do not mandate withholding or discontinuing the checkpoint inhibitor. Management is hormone replacement with levothyroxine, titrated to normalise TSH and free T4, alongside continued PD-1 blockade and ongoing thyroid function monitoring. Cessation is reserved for grade 3 to 4 or persistent grade 2 to 3 toxicity despite treatment, which does not apply here since the endocrinopathy is fully correctable with replacement therapy and the patient is not systemically unwell. This distinguishes endocrine irAEs from organ-threatening irAEs such as pneumonitis, colitis or hepatitis, where cessation and steroids are first-line. Why the other options are wrong: A, Increase Nivolumab dose: dose escalation is never recommended for nivolumab regardless of toxicity, and increasing dose would not address the thyroid failure or reduce further immune activation. C, Stop Nivolumab immediately: unnecessary cessation of effective adjuvant melanoma therapy for a manageable, non-life-threatening grade 1 to 2 toxicity risks losing oncological benefit without any advantage over continuing with replacement. D, Start systemic steroids: corticosteroids are reserved for higher-grade or organ-threatening irAEs (for example pneumonitis, colitis, hepatitis) and have no established role in isolated primary hypothyroidism, which responds to hormone replacement, not immunosuppression. E, Switch to Ipilimumab: ipilimumab (anti-CTLA-4) carries a higher, not lower, rate of immune-related endocrinopathy and other irAEs, so switching would increase risk rather than solve the current problem. Key point: Grade 1 to 2 immune-mediated hypothyroidism from checkpoint inhibitors is treated with levothyroxine replacement while continuing immunotherapy; cessation is reserved for severe or persistent higher-grade toxicity.

Reference: electronic Medicines Compendium (emc): OPDIVO 10 mg/ml concentrate for solution for infusion, Summary of Product Characteristics (SmPC), section 4.4 Special warnings and precautions for use, Immune-related adverse reactions (Bristol-Myers Squibb, current version), https://www.medicines.org.uk/emc/product/100807/smpc