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: A total of 109 patients with ICI-related hypothyroidism.

Interventions: Rapid vs conventional titration strategy.

Main outcome measures: The time to achieve normal free thyroxine and TSH levels.

Results: Patients with transient thyrotoxicosis followed by overt hypothyroidism 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% 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 free thyroxine and TSH levels compared to conventional titration strategy (hazard ratio, 4.44; 95% CI, 2.24-8.82; and hazard ratio, 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 thyrotoxicosis followed by overt hypothyroidism.

Conclusion: 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.