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

Background: The present recommendations, consensus, or guidelines for the replacement dosage for hypothyroidism induced by programmed cell death protein 1 (PD-1) therapy are not uniform, and there are very few special clinical trials that have examined the replacement dosage for it.

Objectives: This article illustrates the clinical characteristics of hypothyroidism induced by PD-1 antibodies (Abs) and reports the recommended replacement dosage for hypothyroidism.

Methods: Eighteen patients with overt primary hypothyroidism induced by PD-1 Abs (group 1) were selected from 655 patients with different tumor types. Retrospective analysis was performed on patients in group 1 and 18 patients with natural courses of overt primary hypothyroidism who were age- and sex-matched with the patients in group 1 (group 2). The replacement dosages required for the patients in the two groups were compared.

Results: Thyroid dysfunction occurred in group 1 after approximately 3.0 ± 1.4 cycles of PD-1 therapy (1-6 stages), with a median time of 61.5 days. The median time of onset of hypothyroidism among all patients was 87.5 days (30-240 days). Most of the patients with hypothyroidism were asymptomatic, and the onset of hypothyroidism was independent of age, sex, TPOAb, TgAb and TSH in group 1 (P>0.05). The average replacement dosage for patients in group 1 was 1.8 ± 0.6 μg/kg/d (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.

Conclusion: It seemed that the average maintenance dosage of levothyroxine might need to be 1.8 μg/kg/day for patients with overt hypothyroidism induced by PD-1 Abs.