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Incidence of Thyroid-Related Adverse Events in Melanoma Patients Treated With Pembrolizumab
Open accessAbstract
Context: Immune checkpoint blockade is associated with endocrine-related adverse events.Thyroid dysfunction during pembrolizumab therapy, an anti-programmed cell death 1 (PD-1) receptor monoclonal antibody, remains to be fully characterized.Objective: To assess the incidence and characteristics of pembrolizumab-associated thyroid dysfunction.Design and Setting: Thyroid function was monitored prospectively in melanoma patients who initiated pembrolizumab within an expanded access program at a referral oncology center.18 Fluorodeoxyglucose uptake on positron emission tomography/computed tomography ( 18 FDG-PET/CT) was reviewed in cases compatible with inflammatory thyroiditis.Patients: Ninety-nine patients with advanced melanoma (age, 26.3-93.6 years; 63.6% females) who received at least one administration of pembrolizumab.Main Outcome Measures: Patient characteristics, thyroid function (TSH, free T 4 ), thyroid autoantibodies, and 18 FDG-PET/CT.Results: Eighteen adverse events of thyroid dysfunction were observed in 17 patients.Thyrotoxicosis occurred in 12 patients, of which nine evolved to hypothyroidism.Isolated hypothyroidism was present in six patients.Levothyroxine therapy was required in 10 of 15 hypothyroid patients.Thyroid autoantibodies were elevated during thyroid dysfunction in four of 10 cases.Diffuse increased 18 FDG uptake by the thyroid gland was observed in all seven thyrotoxic patients who progressed to hypothyroidism.Conclusions: Thyroid dysfunction is common in melanoma patients treated with pembrolizumab.Hypothyroidism and thyrotoxicosis related to inflammatory thyroiditis are the most frequent presentations.Serial measurements of thyroid function tests are indicated during anti-PD-1 monoclonal antibody therapy.Thyrotoxicosis compatible with inflammatory thyroiditis was associated with diffuse increased 18 FDG uptake by the thyroid gland.The prospective role of thyroid autoantibodies should be further investigated, together with the histopathological correlates.(
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“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 [19]
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“ICPi-induced thyrotoxicosis is generally due to destructive thyroiditis, with a first stage of hyperthyroidism which then resolves or evolves into secondary hypothyroidism (50–80%) [17,18,19].”
From Graves’ Disease during Immune Checkpoint Inhibitor Therapy (A Case Series and Literature Review) (2021) · cites this paper as [19]
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- [10]Delivanis D Merten MM Kottschade L Ryder M Immune therapies targeting the thyroid: new insights from a comprehensive review of pembrolizumab-induced thyroiditis cases at Mayo Clinic. Presented at 85th Annual Meeting of the American Thyroid Association: Lake Buena Vista, FL; October 20, 2015 Abstract 88.
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Pembrolizumab-Induced Thyroiditis
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Rubino, R., Marini, A., Roviello, G., Presotto, E. M., Desideri, I., Ciardetti, I., Brugia, M., Pimpinelli, N., Antonuzzo, L., Mini, E., et al. (2021) · Endocrine · doi:10.1007/s12020-021-02750-w · Cited by 37
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Yoo, W. S., Ku, E. J., Lee, E. K., & Ahn, H. Y. (2023) · Endocrinology and Metabolism · doi:10.3803/enm.2023.1785 · Cited by 35
Cooksley, T., Girotra, M., Ginex, P., Gordon, R. A., Anderson, R., Blidner, A. G., Choi, J. N., Dougan, M. L., Glezerman, I. G., Gupta, D., et al. (2020) · Supportive Care in Cancer · doi:10.1007/s00520-020-05709-1 · Cited by 34
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“Graves’ hyperthyroidism De Filette, 2016 [19] anti-PD-1 (Pembrolizumab) 2 mg/kg/na na na/na Yes No na na/na Positive (na) Negative na na na No Yes”
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Two distinct clinical patterns of checkpoint inhibitor-induced thyroid dysfunction
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Endocrinopathies with use of cancer immunotherapies
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Rapid Evolution of Thyroid Dysfunction in Patients Treated with Nivolumab
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Music, M., Iafolla, M. A. J., Soosaipillai, A. R., Batruch, I., Prassas, I., Pintilie, M., Hansen, A. R., Bedard, P. L., Lheureux, S., Spreafico, A., et al. (2020) · F1000Research · doi:10.12688/f1000research.22715.1 · Cited by 22
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Garon-Czmil, J., Petitpain, N., Rouby, F., Sassier, M., Babai, S., Yelehe‐Okouma, M., Weryha, G., Klein, M., & Gillet, P. (2018) · Fundamental and Clinical Pharmacology · doi:10.1111/fcp.12423 · Cited by 23
Miao, Y., Quan, W., Tang, X., Shi, W., Li, Q., Li, R. J., Wang, J., Gan, J., Dong, X., Liang, H., et al. (2024) · International Journal of Biological Sciences · doi:10.7150/ijbs.89376 · Cited by 23
Metadata
- Authors
- de Filette, J., Jansen, Y., Schreuer, M., Everaert, H., Velkeniers, B., Neyns, B., & Bravenboer, B.
- Affiliations
- Vrije Universiteit Brussel (BE)
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2016-11
- Volume
- 101
- Issue
- 11
- Pages
- 4431-4439
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC5095250
- OpenAlex
- W2512251660
- Cited by
- 244
- References
- 35
- Citations by year
- 2026: 14 · 2025: 15 · 2024: 24 · 2023: 26 · 2022: 35 · 2021: 22 · 2020: 33 · 2019: 29 · 2018: 23 · 2017: 22 · 2016: 1
- FWCI
- 13.41
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- VUBIR (Vrije Universiteit Brussel) (submittedVersion)
- Funders
- Amgen
- Bristol-Myers Squibb
- Vrije Universiteit Brussel
- Merck Sharp and Dohme
- 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
- pembrolizumab, melanoma, immune checkpoint blockade, thyroid dysfunction, thyrotoxicosis, hypothyroidism, thyroid autoantibodies, FDG PET/CT, levothyroxine, PD-1 inhibitors
- MeSH terms
- Positron Emission Tomography Computed Tomography, Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Female, Humans, Hypothyroidism, Male, Melanoma, Middle Aged, Thyroiditis, Thyrotoxicosis, Antibodies, Monoclonal, Humanized
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