Low frequency of positive antithyroid antibodies is observed in patients with thyroid dysfunction related to immune check point inhibitors
Immune checkpoint inhibitors (ICI), such as programmed death-1 inhibitors (anti-PD1), have become a cornerstone for the treatment of different advanced cancers. These antibodies act as modulators of immune checkpoint proteins. However, ICI can lead to the breaking of immune self-tolerance, inducing autoimmune side effects (irAEs), including endocrinopathies. One of the most frequent endocrine irAE of anti-PD1 is thyroid dysfunction, but the exact mechanism of this disease still remains unknown.
Materials and methods
We conducted a descriptive retrospective study, analyzing 11 patients who received at least one dose of anti-PD1 (nivolumab or pembrolizumab) and presented thyroid irAEs. Data were collected between September 2015 and May 2018 in our hospital. The aim was to analyze the clinically relevant features of thyroid irAEs and the frequency of antithyroid antibodies (ATA) positivity observed on them.
Results and discussion
8 of the 11 patients were treated with nivolumab and the other three patients received pembrolizumab. Six patients presented silent thyroiditis with a thyrotoxicosis phase; three patients developed directly primary/subclinical hypothyroidism and two patients showed primary hyperthyroidism. Thyroid autoantibodies (anti-Thyroglobulin and anti-Thyroid Peroxidase) were assessed in all the 11 patients, and only in two of them (18%) a positive titer was displayed. Anti-TSH receptor antibodies (TRAbs) were examined in five patients, three with painless thyroiditis at the time of thyrotoxicosis and two with primary hyperthyroidism, and they all had undetectable levels.
In our sample of 11 Caucasian patients with thyroid dysfunction related with anti-PD1, we found low frequency of ATA positive titers, comparable to other recent reports in others ethnicities, which could suggest that silent thyroiditis due to pembrolizumab or nivolumab has a different pathogenesis from the classical autoimmune spontaneous thyroiditis. Further investigations are required to completely understand the immune mechanisms involved.
KeywordsImmune checkpoint inhibitors Endocrine adverse events Thyroid dysfunctions Cancer immunotherapy Thyroiditis Nivolumab
This article did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.
Compliance with ethical standards
Conflict of interest
The authors declare that there is no conflict of interest that could prejudice the impartiality of the article.
All procedures performed were in accordance with the ethical standards of the institution and with the 1964 Helsinki Declaration and its later amendments.
Informed consent is not required.
- 9.Guaraldi F, La Selva R, Samà MT et al (2018) Characterization and implications of thyroid dysfunction induced by immune checkpoint inhibitors in real-life clinical practice: a long-term prospective study from a referral institution. J Endocrinol Invest 41(5):549–556. https://doi.org/10.1007/s40618-017-0772-1 CrossRefPubMedGoogle Scholar