Outcomes and Management of Immune Checkpoint Inhibitor-Induced Hypothyroidism: A Retrospective Analysis

Background: Immune checkpoint inhibitors (ICIs) used in cancer treatment cause immune-related adverse effects (irAEs), including thyroiditis leading to hypothyroidism. The management and outcomes of this irAE are not well established. Objective: The purpose of this analysis is to describe the onset, management, and outcomes of patients experiencing hypothyroidism from ICI. Methods: A retrospective study was conducted of adults receiving ICI therapy at a community cancer center between January 1, 2017, and February 1, 2020. The primary endpoint was to describe onset (timing) of hypothyroidism (thyroid-stimulating hormone [TSH] > 10 mu IU/mL). Secondary outcomes included describing hypothyroidism symptoms and levothyroxine use, time to documented disease progression, and occurrence of additional adverse effects (AEs). Results: Of the 200 patients included in the study, 19% developed clinical hypothyroidism (TSH > 10 mu IU/mL, or required initiation of or dose increase in levothyroxine). Median time to TSH higher than 10 mu IU/mL was 13.3 weeks and symptoms of hypothyroidism occurred in 34% of patients developing clinical hypothyroidism. The median final daily levothyroxine dose was 88 mcg (0.88 mcg/kg). Time to disease progression was longer in those with clinical hypothyroidism (27.4 months vs. 6.8 months, respectively, P = .015). Additional AEs occurred in 68% of those developing hypothyroidism versus 49% without hypothyroidism (P = .029). Conclusion and Relevance: Patients with clinical hypothyroidism during ICI treatment may have improved cancer outcomes, but they also are more likely to develop other AEs. Patients requiring thyroid replacement therapy with levothyroxine may benefit from a starting dose between 50 and 100 mcg/day, approximately 0.88 mcg/kg/day.