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

Immune checkpoint inhibitor (ICI)-related hypothyroidism is mostly irreversible and prompt thyroid hormone replacement therapy is crucial, especially for patients undergoing neoadjuvant immunotherapy.

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.

Retrospective study.

Tertiary academic hospital.

A total of 109 patients with ICI-related hypothyroidism.

Rapid vs conventional titration strategy.

The time to achieve normal free thyroxine and TSH levels.

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.

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.