Endocrine Abstracts

Thyroid dysfunction by Immune Checkpoint Inhibitors (ICPI) is a common Immune-Related Adverse Event (IRAE). Thyroid dysfunction is prevalent in cancer patients receiving pembrolizumab treatment (ICPI). Most prevalent clinical manifestations are reversible destructive thyroiditis and overt hypothyroidism. Pembrolizumab-induced thyroid IRAE’s have been reported to range from 3.2% to 10.1%.

Case report: This case reports a 64-year-old lady who treated for relapse of Grave’s thyrotoxicosis and developed overt hypothyroidism after commencing therapy with Pembrolizumab, for squamous cell carcinoma of the left lung. Initially thyrotoxicosis treated with carbimazole and Levothyroxine for 18 months, discontinued treatment in February 2020. She had relapse of Grave’s thyrotoxicosis in July 2020 and commenced carbimazole 20 mg twice daily. Routine TFT’s 6 weeks later showed TSH 1.6mU/l, Free T4 10.4 pmol/l. She remained biochemically euthyroid on carbimazole 15mg per day. She was diagnosed with squamous cell carcinoma of left lung in June 2022 and commenced on combination ICPI therapy in July 2022. 5 weeks post ICPI treatment: TSH 35mU/l, Free T4 4.3 pmol/l, TPO >600kIU/l, consistent with immune therapy induced thyroiditis. Carbimazole dose reduced to 5mg per day. Subsequent routine TFT with oncology team, carbimazole discontinued and commenced levothyroxine 50mg per day in view of being symptomatic of hypothyroidism. She remained biochemically euthyroid and Levothyroxine discontinued in January 2023. Her TFT in February 2023 showed TSH 53mU/l, Free T4 2.3 pmol/l. Levothyroxine recommenced 75mg per day, TSH showing downward trend; 6.5mU/l, Free T4 15.7 pmol/l. Combination ICPI therapy continues, alongside levothyroxine.

Conclusion: ICPI can convert pre-existing Graves’ disease to autoimmune hypothyroidism. When employing ICPI in patients with pre-existing autoimmune thyrotoxicosis, a multidisciplinary team approach is essential. Close biochemical monitoring and awareness of the risk of evolution toward hypothyroidism should be considered with ICPI treatments.