Replacement Dose for Overt Hypothyroidism induced by Programmed Cell Death Protein 1 Antibodies

Qian Zhang; Yao Zhang; Huijuan Zhu; Kuanzhi Liu; Pingping Lou; Peixuan Kong; Lei Su; Shuchang Wang

doi:10.2174/1871530323666230821102730

Replacement Dose for Overt Hypothyroidism induced by Programmed Cell Death Protein 1 Antibodies

Endocr Metab Immune Disord Drug Targets. 2023 Aug 21. doi: 10.2174/1871530323666230821102730. Online ahead of print.

Authors

Qian Zhang¹, Yao Zhang², Huijuan Zhu³, Kuanzhi Liu⁴, Pingping Lou⁴, Peixuan Kong⁴, Lei Su⁵, Shuchang Wang⁴

Affiliations

¹ Department of Medical Oncology, Affiliated Hospital of Hebei University, Hebei Key Laboratory of Cancer Radiotherapy and Chemotherapy, Baoding, Hebei 071000, China.
² Department of Endocrinology, Affiliated Hospital of Hebei University, Baoding, Hebei 071000, China.
³ Key Laboratory of Endocrinology of National Health and Family Planning Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
⁴ Department of Endocrinology, the 3rd Hospital of Hebei Medical University, Shijia Zhuang, Hebei 050051, China.
⁵ Department of Radiotherapy, Affiliated Hospital of Hebei University, Baoding, Hebei 071000, China.

PMID: 37605413
DOI: 10.2174/1871530323666230821102730

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