Case: A 65-year-old man was commenced on immune-checkpoint inhibitor (ICI), pembrolizumab, for metastatic melanoma. He had a background of longstanding atrial fibrillation, well-controlled with sotalol 80mg twice daily. Baseline bloods demonstrated euthyroidism. Following his third cycle, he became thyrotoxic with TSH 0.01mIU/L(0.4-4.05), fT4 46pmol/L(8.5-27), fT3 16pmol/L(4.3-8.1). Thyroid stimulating immunoglobulin and thyroid peroxidase antibodies were negative. Initially asymptomatic, he deteriorated over the next fortnight, requiring intensive care admission for rapid atrial fibrillation complicated by cardiogenic shock, fluid overload and rate-related cardiomyopathy. His TSH was suppressed <0.01mIU/L and fT4 reached a maximum of 61.2pmol/L, fT3 18.3pmoll/L. He was managed with intravenous propranolol and diuresis. Prednisone 1mg/kg daily was commenced. His symptoms improved over the next 5 days and he was discharged with metoprolol 50mg twice daily and an 8-week tapering course of prednisone. Normalisation of fT4 and fT3 occurred after 4 weeks, and TSH after 8 weeks. Pembrolizumab has been withheld indefinitely.
Discussion: Thyroid dysfunction is the most common ICI-related endocrinopathy and prevalence of this is likely to increase with increasing prescription of ICIs. The thyrotoxic phase of destructive thyroiditis is transient and often mild or subclinical, lasting approximately 6 weeks[1]. Management for mild cases is supportive with beta blockade, however, the evidence is sparse for severe cases. Immunosuppressive agents have not demonstrated significant benefits. There is no role for thionamides. Corticosteroids can be considered for severe cases with added benefit of reducing T4 to T3 conversion; though doses prescribed in the literature are varied[2]. Our patient was commenced on high dose prednisone, though it is unclear how much benefit was derived as euthyroidism resulted in subsequent weeks, which is in keeping with the known transient nature of thyrotoxicosis. Further prospective randomised studies are required to determine the efficacy and role of glucocorticoids in managing severe cases of ICI-related thyroid dysfunction.