Replacement Dose for Overt Hypothyroidism Induced by Programmed Cell Death Protein 1 Antibodies May Be Higher than Recommended.

Thyroid dysfunction occurred after approximately 3.0 ± 1.4 cycles of PD-1 therapy with a median onset time of 61.5 days.

• 18 patients with overt primary hypothyroidism induced by PD-1 antibodies were selected from 655 patients with different tumor types.
• Thyroid dysfunction occurred after approximately 3.0 ± 1.4 cycles of PD-1 therapy (1-6 stages).
• The median time of onset of thyroid dysfunction was 61.5 days.
• The median time of onset of hypothyroidism among all patients was 87.5 days (range 30-240 days).

Most patients with PD-1-induced hypothyroidism were asymptomatic, and onset of hypothyroidism was independent of age, sex, TPOAb, TgAb, and TSH.

• The majority of patients with hypothyroidism in group 1 were asymptomatic.
• The onset of hypothyroidism was independent of age, sex, TPOAb, TgAb, and TSH in group 1 (P>0.05).
• Retrospective analysis compared 18 PD-1-induced hypothyroidism patients (group 1) with 18 age- and sex-matched patients with naturally occurring overt primary hypothyroidism (group 2).

The average levothyroxine replacement dosage required for patients with PD-1-induced overt hypothyroidism was 1.8 ± 0.6 μg/kg/day.

• The average replacement dosage for patients in group 1 was 1.8 ± 0.6 μg/kg/d, with a range of 0.6-3.2 μg/kg/d.
• Multiple linear regression analysis showed that sex, age, TPOAb, TgAb, and TSH were not correlated with drug dosage.
• This dosage is described as potentially higher than currently recommended replacement doses for hypothyroidism.
• Current recommendations, consensus, or guidelines for replacement dosage for PD-1-induced hypothyroidism are described as not uniform.

Sex, age, TPOAb, TgAb, and TSH were not correlated with the levothyroxine replacement dosage required in PD-1-induced hypothyroidism.

• Multiple linear regression analysis was performed to assess predictors of replacement dosage.
• None of the tested variables—sex, age, TPOAb, TgAb, or TSH—were statistically correlated with the required drug dosage.
• This finding suggests that standard clinical parameters cannot be used to individualize dosing predictions in this patient population.