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Endocrine, Metabolic & Immune Disorders - Drug Targets

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ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

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Research Article

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

Author(s): Qian Zhang, Yao Zhang, Huijuan Zhu, Kuanzhi Liu, Pingping Lou, Peixuan Kong, Lei Su and Shuchang Wang*

Volume 24, Issue 10, 2024

Published on: 19 September, 2023

Page: [1169 - 1179] Pages: 11

DOI: 10.2174/1871530323666230821102730

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Abstract

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.

Keywords: Hypothyroidism, programmed cell death protein 1 antibodies, immune-related adverse events (irAEs), immune checkpoint inhibitors, thyroid irAEs, replacement dosage.

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