Induction of Painless Thyroiditis in Patients Receiving Programmed Death 1 Receptor Immunotherapy for Metastatic Malignancies
Abstract
CONTEXT: Immunotherapies against immune checkpoints that inhibit T cell activation [cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed cell death 1 (PD-1)] are emerging and promising treatments for several metastatic malignancies. However, the precise adverse effects of these therapies on thyroid gland function have not been well described. CASE DESCRIPTION: We report on 10 cases of painless thyroiditis syndrome (PTS) from a novel etiology, following immunotherapy with anti-PD-1 monoclonal antibodies (mAb) during treatment for metastatic malignancies. Six patients presented with transient thyrotoxicosis in which thyrotropin binding inhibitory immunoglobulins (TBII) were absent for all, whereas four patients had evidence of positive antithyroid antibodies. All thyrotoxic patients required temporary beta-blocker therapy and had spontaneous resolution of thyrotoxicosis with subsequent hypothyroidism. Four patients presented with hypothyroidism without a detected preceding thyrotoxic phase, occurring 6-8 weeks after initial drug exposure. All of these patients had positive antithyroid antibodies and required thyroid hormone replacement therapy for a minimum of 6 months. CONCLUSIONS: Patients receiving anti-PD-1 mAb therapy should be monitored for signs and symptoms of PTS which may require supportive treatment with beta-blockers or thyroid hormone replacement. The anti-PD-1 mAb is a novel exogenous cause of PTS and provides new insight into the possible perturbations of the immune network that may modulate the development of endogenous PTS, including cases of sporadic and postpartum thyroiditis.
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In the literature, female gender is described as a risk factor for ICPi-induced thyroid dysfunction, although this is less pronounced than in spontaneous forms and is not described in all studies.
“In the literature, female gender is described as being a risk factor for ICPi-induced TD, although this is less pronounced than in spontaneous forms [7,46,47] and it is not described in all studies [11,48].”
From Graves’ Disease during Immune Checkpoint Inhibitor Therapy (A Case Series and Literature Review) (2021) · cites this paper as [47]
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- Authors
- Orlov, S., Salari, F., Kashat, L., & Walfish, P. G.
- Affiliations
- Mount Sinai Hospital (CA)
- Corresponding author
- Walfish, Paul G.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2015-05
- Volume
- 100
- Issue
- 5
- Pages
- 1738-1741
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2110773108
- Cited by
- 134
- References
- 12
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 6 · 2023: 9 · 2022: 12 · 2021: 11 · 2020: 11 · 2019: 25 · 2018: 23 · 2017: 21 · 2016: 10 · 2015: 1
- FWCI
- 15.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Abbott Laboratories
- American Thyroid Association
- University of Toronto
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- painless thyroiditis, anti-PD-1 monoclonal antibody, immune checkpoint inhibitors, metastatic cancer, thyrotoxicosis, hypothyroidism, thyroid autoantibodies, thyrotropin-binding inhibitory immunoglobulin, beta-blocker therapy, thyroid hormone replacement, drug-induced thyroid dysfunction
- MeSH terms
- Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Carcinoma, Non-Small-Cell Lung, Female, Humans, Immunotherapy, Lung Neoplasms, Male, Melanoma, Middle Aged, Neoplasm Metastasis, Skin Neoplasms, Thyroiditis, Thyrotoxicosis, Programmed Cell Death 1 Receptor
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