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Extraocular Muscle Enlargement and Thyroid Eye Disease-like Orbital Inflammation Associated with Immune Checkpoint Inhibitor Therapy in Cancer Patients
Abstract
PURPOSE: To describe thyroid eye disease (TED)-like orbital inflammatory syndrome in 3 cancer patients treated with immune checkpoint inhibitors. METHODS: All consecutive patients treated by the senior author who were receiving immune checkpoint inhibitors and developed TED-like orbital inflammation were included. RESULTS: Three cancer patients treated with immune checkpoint inhibitors developed orbital inflammation. The first patient was treated with a combination of a cytotoxic T-lymphocyte antigen-4 inhibitor and a programmed cell death protein 1 inhibitor and developed TED-like orbital inflammation with normal thyroid function and antibody levels. The second patient had a previous diagnosis of Graves disease without TED, and developed TED soon after initiating treatment with a programmed cell death protein 1 inhibitor. The third patient developed acute hyperthyroidism with symptomatic TED following treatment with an investigational cytotoxic T-lymphocyte antigen-4 inhibitor agent. All 3 patients were managed with either systemic steroids or observation, with resolution of their symptoms and without the need to halt immune checkpoint inhibitor treatment for their cancer. DISCUSSION AND CONCLUSIONS: TED-like orbital inflammation may occur as a side effect of immune checkpoint inhibitor therapy with anti-cytotoxic T-lymphocyte antigen-4 or anti-PD-1 inhibitors. To the best of their knowledge, this is the first reported case of TED as a result of programmed cell death protein 1 inhibitor monotherapy. All 3 patients were treated with systemic steroids and responded quickly while continuing treatment with immune checkpoint inhibitors for their cancer. With increasing use of this class of drugs, clinicians should be familiar with the clinical manifestations and treatments for this adverse reaction.
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“To the best of our knowledge, there is only one reported case of pre-existing Graves’ hyperthyroidism before ICPi treatment [42].”
From Graves’ Disease during Immune Checkpoint Inhibitor Therapy (A Case Series and Literature Review) (2021) · cites this paper as [42]
In the citing paper
“This patient had a history of GD one year before immunotherapy; he commenced Nivolumab in a euthyroid state but experienced a recurrence of thyrotoxicosis with GO that evolved to hypothyroidism, despite persistent positive TRAbs.”
From Graves’ Disease during Immune Checkpoint Inhibitor Therapy (A Case Series and Literature Review) (2021) · cites this paper as [42]
In the citing paper
“The only case with an association of induced hyperthyroidism and orbitopathy was reported by Sagiv et al. and was treated with glucocorticoids, and hyperthyroidism resolved spontaneously [42].”
From Graves’ Disease during Immune Checkpoint Inhibitor Therapy (A Case Series and Literature Review) (2021) · cites this paper as [42]
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Metadata
- Authors
- Sagiv, O., Kandl, T. J., Thakar, S. D., Thuro, B. A., Busaidy, N. L., Cabanillas, M., Jimenez, C., Dadu, R., Graham, P. H., Debnam, J. M., & Esmaeli, B.
- Affiliations
- Orbital Oncology and Ophthalmic Plastic Surgery, Department of Plastic Surgery
- Department of Endocrine Neoplasia and Hormonal Disorders, Division of Internal Medicine
- Department of Surgical Oncology
- The University of Texas MD Anderson Cancer Center (US)
- Corresponding author
- Sagiv, Oded
- Kandl, Thomas J.
- Thakar, Sudip D.
- Thuro, Bradley A.
- Esmaeli, Bita
- ORCID
- Venue
- Ophthalmic Plastic & Reconstructive Surgery
- Published
- 2019-01
- Volume
- 35
- Issue
- 1
- Pages
- 50-52
- ISSN
- 0740-9303 (ISSN-L)
- OpenAlex
- W2808870673
- Cited by
- 71
- References
- 10
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 18 · 2023: 6 · 2022: 11 · 2021: 7 · 2020: 8 · 2019: 4
- FWCI
- 3.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Ophthalmic Plastic and Reconstructive Surgery (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Ophthalmology › Ophthalmology and Eye Disorders
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Ophthalmology › Ocular Oncology and Treatments
- Keywords
- Graves' ophthalmopathy, orbital inflammation, immune checkpoint inhibitors, CTLA-4 inhibitors, PD-1 inhibitors, Graves' disease, hyperthyroidism, extraocular muscle enlargement, adverse drug reactions, corticosteroid therapy, cancer patients
- MeSH terms
- Antineoplastic Agents, Immunological, Adult, Aged, Humans, Male, Middle Aged, Neoplasms, Oculomotor Muscles, Tomography, X-Ray Computed, Radioimmunotherapy, Graves Ophthalmopathy, Programmed Cell Death 1 Receptor
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