Endocrine Abstracts

Introduction: Development and progression of cancers is multifactorial encompassing several mechanisms that aid its proliferation. One of the hallmarks of cancer progression is inhibition of the immune system. Cancer cells can activate different immune checkpoint are pathways that harbour inhibitory or stimulatory mechanisms that enabled self-tolerance and assist with immune response. Through activation of immune checkpoint pathways cancers can suppress immune response against it. Monoclonal antibodies that target immune checkpoints have garnered immense interest in management of solid tumours. The mechanism of action immune checkpoint inhibitors is that they block inhibitory molecules on T-Cells. However, they also downregulate immunological tolerance to self-antigens, inducing immune related adverse events (IrAES). IrAES have been reported in several organs including the endocrine glands including the thyroid and pituitary glands. Here we present cases of two patients which developed hypothyroidism following immune checkpoint inhibitor therapy for their metastatic carcinoma.

Case presentations: Case-1. An 80-year-old gentleman with a background his of metastatic squamous cell carcinoma of the lung was given pembrolizumab(anti-PD-1) treatment. He subsequently developed transient hyperthyroidism (characterised by TSH -69.10 mU/l, FT4 -0.5 Pmol/l). Five months post therapy he became hypothyroid, (elevated TSH and low FT4). He was subsequently started on levothyroxine and became euthyroid.

Case-2. A 63-Year-old male with history of metastatic cancer of the colon was started on atezolizumab (anti-PD-L1). Post therapy the patient developed severe hypothyroidism characterised by myopathy and myosititis. Before immunotherapy the patient was euthyroid with normal levels of TSH and FT4. Subsequent blood test post treatment showed high levels of TSH >150 mU/l and FT4 6 Pmol/l. He was treated with high dose of levothyroxine to get him back to his baseline.

Discussion/Conclusion: Thyroid toxicity post immune checkpoint inhibitor therapy is being reported with increasing frequency, based on literature this complication irreversible with patients requiring continuous therapeutic management and follow up which can put increased pressure on patients, who are often under increased mental strain in dealing with their cancer treatment. Based on the case reported here we recommend baseline thyroid function test should be done at initiation of therapy, periodically after immunotherapy and during each cycle of infusion.