Endocrine Abstracts

Immune checkpoint inhibitors have revolutionised the treatment of aggressive cancers by improving survival. However, immune-mediated endocrinopathies can occur and could be life-threatening if undiagnosed. Among hypophysitis, adrenalitis, thyroiditis and diabetes mellitus, thyroid dysfunction is the most common event. Among anti-PD-1/PD-L1 and anti-CTL4, the former carries a greater risk. Here, we present two cases of thyroiditis following the commencement of Pembrolizumab (ICPi) for carcinoma of breast. The first patient was a known case of hypothyroidism on levothyroxine and was euthyroid before starting Pembrolizumab (PD-1 inhibitors). Following 2 cycles, TFTs showed hyperthyroidism (TSH-0.01 mIU/l, FT4- 31.9 pmol/l). TSH receptor antibodies (0.31) and early morning cortisol levels were normal. TFTs were monitored regularly as she was at risk of hypothyroidism. She developed hypothyroidism within 3 weeks, was restarted on levothyroxine and the dose was titrated over the next few weeks. However, she required a higher dose of levothyroxine compared to her previous dose. Her thyroid function improved over 2 months and became normalised. She has completed her immunotherapy, and her thyroid functions were monitored 6-weekly. The second patient was euthyroid as well before starting immunotherapy. After receiving 3 cycles of pembrolizumab, she developed generalised body swelling. She had subclinical hyperthyroidism transiently which later progressed to severe hypothyroidism (TSH>100 mIU/l, FT4<1.3 pmol/l) and myxoedema. She was started on high dose levothyroxine, swelling improved and her FT4 has gradually increased. These cases reinforce the importance of monitoring thyroid function tests frequently (2 to 3 weekly) rather than 6 to 8 weekly during treatment with ICPis. Initial transient hyperthyroidism is often underreported and is followed by hypothyroidism which can be permanent and needs regular follow-up. Thyroxine should not be initiated without excluding adrenal insufficiency. Close monitoring for other endocrine organ dysfunctions such as hypoadrenalism, hypophysitis, and diabetes is also recommended.