Objective  To analyze the characteristics of hypothyroidism caused by immune checkpoint inhibitors (ICIs) based on data from the U.S. FDA Adverse Event Reporting System (FAERS), focusing on the median onset time, clinical outcomes, reporting countries, and other relevant features of ICI-induced hypothyroidism.

Methods  Adverse event reports related to hypothyroidism associated with ICIs were extracted from the FAERS database covering the period from January 2004 to December 2024. The association between ICIs and hypothyroidism was evaluated using reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). Patterns in the onset of hypothyroidism were also analyzed.

Results  A total of 4,091 hypothyroidism reports identified ICIs as the suspected drug. Reports related to tremelimumab were excluded from signal analysis due to fewer than three cases. The classification of reported hypothyroidism cases was as follows: autoimmune hypothyroidism (76 cases), central hypothyroidism (29 cases), generalized thyroid hormone resistance (0 cases), goitrous hypothyroidism (3,354 cases), immune-mediated hypothyroidism (563 cases), myxedema (14 cases), myxedema coma (0 cases), postoperative hypothyroidism (2 cases), primary hypothyroidism (46 cases), thyroid atrophy (3 cases), and TSH deficiency (4 cases). The median time to onset of hypothyroidism induced by ICIs was 44 days, with a mean onset time of 85.61 days.

Conclusion  This study reveals the risk of hypothyroidism and its clinical features caused by different ICIs through analysis of the FAERS database. Pharmacists are advised to be more cautious in the treatment of hypothyroidism caused by ICIs and pharmaceutical monitoring to ensure the safety of patients' treatment.

1.U.S. Food and Drug Administration. FDA's Adverse Event Reporting System (FAERS)[EB/OL]. (2024-11-08) [2024-11-09]. https://www.fda.gov/drugs/surveillance/fdas-adverse-event-reporting-system-faers.

2.牛志成, 王雷, 汪治宇. 免疫检查点抑制剂相关不良反应的管理专家共识[J]. 河北医科大学学报, 2021, 42(3): 249-255. [Niu ZC, Wang L, Wang ZY. Expert consensus on management of immune checkpoint inhibitor-related adverse reactions[J]. Journal of Hebei Medical University, 2021, 42(3): 249-255.] DOI: 10.3969/j.issn.1007-3205.2021.03.001.

3.陈莉群. 免疫检查点抑制剂相关内分泌不良反应的临床特征及发生影响因素分析[D]. 杭州: 浙江大学, 2021. DOI: 10.27461/d.cnki.gzjdx.2021.003668.

4.Cardona Z, Sosman JA, Chandra S, et al. Endocrine side effects of immune checkpoint inhibitors[J]. Front Endocrinol (Lausanne), 2023, 14: 1157805. DOI: 10.1210/jc.2012-4075.

5.Kennedy OJ, Ali N, Lee R, et al. Thyroid dysfunction after immune checkpoint inhibitors in a single-centre UK pan-cancer cohort: a retrospective study[J]. Eur J Cancer, 2024, 202: 113949. DOI: 10.1016/j.ejca.2024.113949.

6.Vardarli I, Tan S, Brandenburg T, et al. Risk and incidence of endocrine immune-related adverse effects under checkpoint inhibitor mono- or combination therapy in solid tumors: a meta-analysis of randomized controlled trials[J]. J Clin Endocrinol Metab, 2024, 109(4): 1132-1144. DOI: 10.1210/clinem/dgad670.

7.Singh N, Hocking AM, Buckner JH. Immune-related adverse events after immune check point inhibitors: understanding the intersection with autoimmunity[J]. Immunol Rev, 2023, 318(1): 81-88. DOI: 10.1111/imr.13247.

8.Yamauchi I, Yabe D. Best practices in the management of thyroid dysfunction induced by immune checkpoint inhibitors[J]. Eur Thyroid J, 2025, 14(1): e240328. DOI: 10.1530/ETJ-24-0328.

9.Chen H, Yuhang D, And Shan Y. Post-marketing safety monitoring of tirzepatide: a pharmacovigilance study based on the FAERS database[J]. Expert Opin Drug Saf, 2025, 1-9. DOI: 10.1080/14740338.2025.2468860.

10.Lee H, Hodi FS, Giobbie-Hurder A, et al. Characterization of thyroid disorders in patients receiving immune checkpoint inhibition therapy[J]. Cancer Immunol Res, 2017, 5(12): 1133-1140. DOI: 10.1158/2326-6066.CIR-17-0208.

11.Paschou SA, Stefanaki K, Psaltopoulou T, et al. How we treat endocrine complications of immune checkpoint inhibitors[J]. ESMO Open, 2021, 6(1): 100011 . DOI: 10.1016/j.esmoop.2020.100011.

12.Ettleson MD, Raine A, Batistuzzo A, et al. Brain fog in hypothyroidism: understanding the patient's perspective[J]. Endocrine Practice, 2022, 28(3): 257-264. DOI: 10.1016/j.eprac.2021.12.003.

13.Kahaly GJ, Gottwald-Hostalek U. Use of levothyroxine in the management of hypothyroidism: a historical perspective[J]. Front Endocrinol (Lausanne), 2022, 13: 1054983. DOI: 10.3389/fendo.2022.1054983.

14.Panagiotou E, Ntouraki S, Vathiotis IA, et al. Endocrine immune-related adverse events are independent predictors of survival in patients with lung cancer[J]. 2024, 16(9): 1764. DOI: 10.3390/cancers16091764.

15.Mc Neil V, Lee SW. Advancing cancer treatment: a review of immune checkpoint inhibitors and combination strategies[J]. Cancers (Basel), 2025, 17(9): 1408. DOI: 10.3390/cancers17091408.