Endocrine Abstracts

Background

Pembolizumab is a highly specific, monoclonal antibody directed against the programmed cell death receptor, PD-1 and its ligand PD-L1. It is licenced as an immunotherapy for use in locally advanced or metastatic urothelial cell carcinoma, amongst other malignancies. Whilst rare, endocrinopathies, including thyroid dysfunction, are recognised side effects of immunotherapy such as Pembroluzimab. However, hyperthyroidism is much less common than hypothyroidism. When hyperthyroidism is present, it usually precedes a hypothyroid phase, which was not evident in this case.

Case Presentation

A 68-year old female who had recently received her first cycle of Pembrolizumab for locally advanced transitional cell carcinoma of the bladder presented with diarrhoea, vomiting and weight loss. The patient was clinically hyperthyroid, with tachycardia and goitre present. This was confirmed biochemically with a laboratory thyroid panel: Thyroid Stimulating Hormone (TSH) was 0.04 mU/l (reference range 0.27–4.5 mU/l), free T4 35.3 pmol/l (reference range 11–23 pmol/l) and free T3 6.42 mol/l (reference range 3.1–6.8 pmol/l). Thyroid ultrasound revealed benign nodules within both right and left lobes. The patient’s diarrhoea progressed to grade 3 and was managed with steroids. Radiologically there was no evidence of colitis. A euthyroid state was achieved with carbimazole. She made a full recovery and was able to continue with the second cycle of Pembrolizumab as planned.

Conclusion

This case demonstrates an unusual presentation of immunotherapy related thyrotoxicosis in a patient on Pembrolizumab, requiring anti-thyroid therapy. It is important for physicians to be aware of immunotherapy-related endocrinopathies as they can present similarly to other oncological emergencies – in this patient, sepsis or colitis were also suspected. European Society of Medical Oncology (ESMO) recommends regular monitoring of thyroid function tests during immunotherapy. Steroids can be used to relieve symptoms.