Nivolumab Induced Thyroid Dysfunction: Unusual Clinical Presentation and Challenging Diagnosis
Open accessAbstract
In recent years, immune checkpoint inhibitors (ICIs) had a great impact in cancer therapy. ICIs display a peculiar toxicity profile, which is characterized by autoimmune-like manifestations against multiple organs, including endocrine glands. We hereby report the case history of two patients who experienced nivolumab-induced endocrine immuno-related adverse events (irAEs). Thyroid dysfunction in both patients presented with a low serum level of TSH. However, endocrine evaluation showed a completely different etiology and clinical evolution. The two patients' histories indicate that nivolumab can cause a large spectrum of thyroid and endocrine dysfunctions resulting in cumbersome diagnostic problems. In these peculiar patients the evaluation of endocrine experts is warranted.
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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 [39]
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Experimental — accuracy not yet measuredPD-L1 expression is elevated in pancreatic beta cells of older mice and in mice whose islets have immune infiltration.
“PD-L1 expression is increased in pancreatic beta cells of older mice and in mice with immune infiltration of their islets69,70”
From Endocrine toxicities of immune checkpoint inhibitors (2021) · cites this paper as [70]
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- Authors
- Iadarola, C., Croce, L., Quaquarini, E., Teragni, C., Pinto, S., Bernardo, A., Fonte, R., Marinò, M., Rotondi, M., & Chiovato, L.
- Affiliations
- University of Pavia (IT)
- University of Pisa (IT)
- Corresponding author
- Chiovato, Luca
- ORCID
- Venue
- Frontiers in Endocrinology
- Publisher
- Frontiers Media SA
- Published
- 2019-01-17
- Volume
- 9
- Pages
- 813-813
- ISSN
- 1664-2392 (ISSN-L)
- PMC
- PMC6345097
- OpenAlex
- W2909148617
- Cited by
- 33
- References
- 15
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 4 · 2022: 5 · 2021: 5 · 2020: 7 · 2019: 5
- FWCI
- 2.30
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Endocrinology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- nivolumab, immune checkpoint inhibitors, thyroid dysfunction, immune-related adverse events, hypothyroidism, thyroid-stimulating hormone, autoimmune thyroid disease, endocrine toxicity, cancer immunotherapy
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