Optimal Levothyroxine Dosing Strategy for Immune Checkpoint Inhibitor-Related Hypothyroidism: A Retrospective Study

Abstract Context Immune checkpoint inhibitor (ICI)-related hypothyroidism is mostly irreversible and prompt thyroid hormone replacement therapy is crucial, especially for patients undergoing neoadjuvant immunotherapy. Objective This study aimed to propose a novel titration strategy for ICI-related hypothyroidism, evaluate levothyroxine (LT4) dose differences between hypothyroidism patterns, and develop a predictive equation for the optimal LT4 dose. Design Retrospective study. Setting Tertiary academic hospital. Patients 109 patients with ICI-related hypothyroidism. Interventions Rapid versus conventional titration strategy. Main outcome measures The time to achieve normal free thyroxine (FT4) and thyroid-stimulating hormone (TSH) levels. Results Patients with transient thyrotoxicosis followed by overt hypothyroidism (Toxic-OHypo) required higher LT4 doses to achieve a euthyroid state compared to isolated overt hypothyroidism, with a mean difference of 0.23 μg/kg/day (95% confidence interval [CI], 0.08-0.38). In patients with ICI-related overt hypothyroidism and no cardiac disease, who had elevated TSH levels within 4 weeks of the last documented low or normal TSH, a rapid titration strategy was implemented. This strategy significantly improved the cumulative incidence of achieving normal FT4 and TSH levels compared to conventional titration strategy (hazard ratio [HR], 4.44; 95% CI, 2.24-8.82; HR, 4.11; 95% CI, 2.18-7.73, respectively), with a comparable safety profile. Predicted LT4 dose at euthyroid state (µg/kg/day) = (-0.016×body weight) + (0.109×baseline TSH level) + 2.661 for patients with Toxic-OHypo. Conclusions LT4 requirements vary depending on the subtype of ICI-related hypothyroidism. The rapid titration strategy reduced the time to achieve a euthyroid state without a significant increase in adverse effects compared to conventional LT4 replacement therapy.