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Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Research Article

Immune Checkpoint Inhibitor-induced Thyroid Disorders: A Single Center Experience

Author(s): Armando Patrizio, Poupak Fallahi*, Alessandro Antonelli and Silvia Martina Ferrari

Volume 29, Issue 4, 2023

Published on: 03 February, 2023

Page: [295 - 299] Pages: 5

DOI: 10.2174/1381612828666220518151509

Price: $65

Abstract

Background: Immune checkpoint inhibitors (ICI) foster T lymphocytes to fight cancer, but they can also trigger immune-related adverse events (irAE) in various organs, including thyroid dysfunction that can manifest itself in terms of both hyperthyroidism and hypothyroidism or subclinical disease.

Objective: Based on previous observations, this study evaluated the impact of oncological immunotherapy on the development of thyroid dysfunction in a cohort of patients treated with ICI at our institution.

Methods: We collected 10 cases of thyroid irAE that emerged from 24 cancer patients treated with immunotherapy, belonging to a cohort of 120 patients who were sent to our clinic by the Oncology Department of our institution, between December 2016 and March 2020.

Results: From the analysis of the data, thyroid irAEs emerged after a median time of 9 weeks, and they occurred mainly in females. Regardless of the initial presentation (thyroiditis with thyrotoxicosis, hypothyroidism, or worsening of the previous subclinical hypothyroidism), later all patients developed persistent hypothyroidism which required hormone replacement therapy with levothyroxine. This finding was confirmed by a statistically significant increase in the median value of TSH (thyroid-stimulating hormone) between the pre-ICI treatment and subsequent phases and, for the first time, by a reduction in the median value of the thyroid volume estimated by neck ultrasound, a sign of destructive thyroiditis.

Conclusion: Our results confirm that patients undergoing immunotherapy should be monitored for potential thyroid dysfunction with biochemical assessments and changes in thyroid volume estimated by ultrasound could be helpful in the diagnostic work-up.

Keywords: Immunotherapy, checkpoint inhibitor, thyroid dysfunction, cancer, thyroiditis, ultrasound, irAE.

[1]
Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer 2012; 12(4): 252-64.
[http://dx.doi.org/10.1038/nrc3239] [PMID: 22437870]
[2]
Postow MA, Sidlow R, Hellmann MD. Immune-related adverse events associated with immune checkpoint blockade. N Engl J Med 2018; 378(2): 158-68.
[http://dx.doi.org/10.1056/NEJMra1703481] [PMID: 29320654]
[3]
Ferrari SM, Fallahi P, Elia G, et al. Autoimmune endocrine dysfunctions associated with cancer immunotherapies. Int J Mol Sci 2019; 20(10): 2560.
[http://dx.doi.org/10.3390/ijms20102560] [PMID: 31137683]
[4]
Ferrari SM, Fallahi P, Galetta F, Citi E, Benvenga S, Antonelli A. Thyroid disorders induced by checkpoint inhibitors. Rev Endocr Metab Disord 2018; 19(4): 325-33.
[http://dx.doi.org/10.1007/s11154-018-9463-2] [PMID: 30242549]
[5]
Elia G, Ferrari SM, Galdiero MR, et al. New insight in endocrine-related adverse events associated to immune checkpoint blockade. Best Pract Res Clin Endocrinol Metab 2020; 34(1): 101370.
[http://dx.doi.org/10.1016/j.beem.2019.101370] [PMID: 31983543]
[6]
Muir CA, Clifton-Bligh RJ, Long GV, et al. Thyroid immune-related adverse events following immune checkpoint inhibitor treatment. J Clin Endocrinol Metab 2021; 106(9): e3704-13.
[http://dx.doi.org/10.1210/clinem/dgab263] [PMID: 33878162]
[7]
Barroso-Sousa R, Barry WT, Garrido-Castro AC, et al. Incidence of endocrine dysfunction following the use of different immune checkpoint inhibitor regimens: A systematic review and etma-analysis. JAMA Oncol 2018; 4(2): 173-82.
[http://dx.doi.org/10.1001/jamaoncol.2017.3064] [PMID: 28973656]
[8]
Su Q, Zhang XC, Wang DY, et al. The risk of immune-related endocrine disorders associated with anti-PD-1 inhibitors therapy for solid tumors: A systematic review and meta-analysis. Int Immunopharmacol 2018; 59: 328-38.
[http://dx.doi.org/10.1016/j.intimp.2018.04.021] [PMID: 29679857]
[9]
Iyer PC, Cabanillas ME, Waguespack SG, et al. Immune-related thyroiditis with immune checkpoint inhibitors. Thyroid 2018; 28(10): 1243-51.
[http://dx.doi.org/10.1089/thy.2018.0116] [PMID: 30132401]
[10]
Muir CA, Menzies AM, Clifton-Bligh R, Tsang VHM. Thyroid toxicity following immune checkpoint inhibitor treatment in advanced cancer. Thyroid 2020; 30(10): 1458-69.
[http://dx.doi.org/10.1089/thy.2020.0032] [PMID: 32264785]
[11]
Basak EA, van der Meer JWM, Hurkmans DP, et al. Overt thyroid dysfuction and anti-thyroid antibodies predict response to anti-PD-1 immunetherapy in cancer patients. Thyroid 2020; 30(7): 966-73.
[http://dx.doi.org/10.1089/thy.2019.0726] [PMID: 32151195]
[12]
Brilli L, Danielli R, Campanile M, et al. Baseline serum TSH levels predict the absence of thyroid dysfunction in cancer patients treated with immunotherapy. J Endocrinol Invest 2021; 44(8): 1719-26.
[http://dx.doi.org/10.1007/s40618-020-01480-6] [PMID: 33367977]
[13]
De Filette J, Jansen Y, Schreuer M, et al. Incidence of thyroid-related adverse events in melanoma patients treated with pembrolizumab. J Clin Endocrinol Metab 2016; 101: 4431-9.
[14]
Delivanis DA, Gustafson MP, Bornschlegl S, et al. Pembrolizumab-induced thyroiditis: Comprehensive clinical review and insights into underlying involved mechanisms. J Clin Endocrinol Metab 2017; 102(8): 2770-80.
[http://dx.doi.org/10.1210/jc.2017-00448] [PMID: 28609832]
[15]
Kotwal A, Kottschade L, Ryder M. PD-L1 inhibitor-Induced thyroiditis is associated with better overall survival in cancer patients. Thyroid 2020; 30(2): 177-84.
[http://dx.doi.org/10.1089/thy.2019.0250] [PMID: 31813343]
[16]
Brancatella A, Lupi I, Montanelli L, et al. Management of thyrotoxicosis induced by PD1 or PD-L1 blockade. J Endocr Soc 2021; 5: bvab093.
[17]
Osorio JC, Ni A, Chaft JE, et al. Antibody-mediated thyroid dysfunction during T-cell checkpoint blockade in patients with non-small-cell lung cancer. Ann Oncol 2017; 28(3): 583-9.
[http://dx.doi.org/10.1093/annonc/mdw640] [PMID: 27998967]
[18]
Kobayashi T, Iwama S, Yasuda Y, et al. Patients with antithyroid antibodies are prone to develop destructive thyroiditis by nivolumab: A prospective study. J Endocr Soc 2018; 2(3): 241-51.
[http://dx.doi.org/10.1210/js.2017-00432] [PMID: 29600292]
[19]
Sakakida T, Ishikawa T, Uchino J, et al. Clinical features of immune-related thyroid dysfunction and its association with outcomes in patients with advanced malignancies treated by PD-1 blockade. Oncol Lett 2019; 18(2): 2140-7.
[http://dx.doi.org/10.3892/ol.2019.10466] [PMID: 31423288]
[20]
Kimbara S, Fujiwara Y, Iwama S, et al. Association of antithyroglobulin antibodies with the development of thyroid dysfunction induced by nivolumab. Cancer Sci 2018; 109(11): 3583-90.
[http://dx.doi.org/10.1111/cas.13800] [PMID: 30230649]

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