Thyroid dysfunction in patients undergoing Nivolumab cancer treatment: Case reports and review of literature

Abstract

Introduction: The recent development of anticancer treatments focused on disrupting the signaling pathways has arrived as a promising alternative for conditions previously untreatable. Nivolumab is a second-generation monoclonal antibody that works as a negative regulatory agonist of the programmed cell death protein 1 (PD-1) receptor expressed by B and T lymphocytes and natural killer cells, preventing the binding of PD-1 to its ligands programmed cell death ligand-1 (PD-L1) and programmed cell death ligand-2 (PD-L2), therefore protecting healthy tissues. As a result of an increased immune system activity, this may provide inflammatory side effects known as immune-related adverse events (IRAEs). Thyroid dysfunction (TD) is frequently observed in patients using Anti-PD-1. Case Report: Our case report refers to two patients of 67 and 75 years old, feminine and masculine genders, respectively, that developed Nivolumab-induced TD with transient hyperthyroidism and posterior evolution to hypothyroidism. Both were treated with Levothyroxine after thyrotoxicosis phase. Conclusion: Thyroid dysfunction has been a recurrent IRAE described in patients using Anti-PD-1 and it is usually a treatable condition. Our patients manifested a less common TD known as lymphocytic thyroiditis. Because there is an increased tendency of using immune checkpoint inhibitors, both cases highlight the importance of close monitoring to detect the development and progression of TD, avoiding preventable morbidity and allowing to maintain cancer therapy.