A Case Report of Graves’ Disease Induced by the Anti-Human Programmed Cell Death-1 Monoclonal Antibody Pembrolizumab in a Bladder Cancer Patient
Open accessAbstract
Immune checkpoint inhibitors, such as anti-programmed cell death-1 (anti-PD-1), have been widely used in the treatment of malignancies. However, these drugs can cause immune-related adverse events resembling autoimmune diseases. There are some reports of Graves’ disease (GD) induced by anti-cytotoxic T-lymphocyte-associated antigen 4 antibodies, but reports which discussed GD induced by anti-PD-1 antibodies are very rare. We report the case of a 61-year-old man with bladder cancer who presented with severe diarrhea, fatigue, palpitation, body weight loss, and hyperthyroidism after the fifth treatment with the anti-PD-1 monoclonal antibody pembrolizumab. His thyroid function prior to pembrolizumab administration had been subclinical hyperthyroidism, despite a negative thyroid-stimulating hormone receptor antibody (TRAb) level. On admission, pembrolizumab administration was discontinued. Graves’ disease was diagnosed based on a positive TRAb test result and the ultrasonographic finding of increased blood flow in the superior thyroid artery. Based on colonoscopy findings, the cause of diarrhea was diagnosed as active colitis. His diarrhea was improved with prednisolone, and thyroid function was treated with potassium iodide and thiamazole. This case report of GD with positive TRAb induced by the anti-PD-1 antibody pembrolizumab may contribute to the understanding of the mechanism underlying the association between GD and autoimmune activation via PD-1.
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In the literature, only nine cases of ICPi-induced Graves' hyperthyroidism and seven cases of induced Graves' orbitopathy have been described, associated with anti-PD-1 or anti-CTLA-4 treatment or their combination, with only one patient presenting both thyrotoxicosis and orbitopathy.
“To the best of our knowledge at the time of writing, only nine cases of ICPi-induced Graves’ hyperthyroidism and seven cases of induced Graves’ orbitopathy have been described in the literature, associated with anti-PD-1 or anti-CTLA-4 treatment or their combination (Table 3), with only one patient presenting with both thyrotoxicosis and orbitopathy [19,29,30,31,35,36,37,38,39,40,41,42,43,44].”
From Graves’ Disease during Immune Checkpoint Inhibitor Therapy (A Case Series and Literature Review) (2021) · cites this paper as [38]
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- Authors
- Yajima, K., & Akise, Y.
- Affiliations
- Tachikawa Hospital (JP)
- Corresponding author
- Yajima, Ken
- ORCID
- Yajima, Ken
- Venue
- Case Reports in Endocrinology
- Publisher
- Wiley
- Published
- 2019-10-17
- Volume
- 2019
- Pages
- 1-5
- ISSN
- 2090-6501 (ISSN-L)
- 2090-651X
- PMC
- PMC6854234
- OpenAlex
- W2980516556
- Cited by
- 13
- References
- 11
- Citations by year
- 2025: 2 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 2
- FWCI
- 0.73
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Case Reports in Endocrinology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Neurology › Autoimmune Neurological Disorders and Treatments
- Keywords
- Graves' disease, pembrolizumab, anti-PD-1, immune checkpoint inhibitors, immune-related adverse events, bladder cancer, TSH receptor antibodies, subclinical hyperthyroidism, colitis, hyperthyroidism, PD-1
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