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Antithyroid Drug-Induced Hematopoietic Damage: A Retrospective Cohort Study of Agranulocytosis and Pancytopenia Involving 50,385 Patients with Graves' Disease
Abstract
CONTEXT: Although antithyroid drug (ATD)-induced hematopoietic damage is a significant concern, it has not been comprehensively investigated. OBJECTIVE: Our objective was to describe the clinical features of ATD-induced hematopoietic damage. DESIGN AND SETTING: This was a retrospective cohort study in Tokyo, Japan. PATIENTS: Between January 1983 and December 2002, 50,385 patients at Ito Hospital were diagnosed with Graves' disease. We retrospectively reviewed their medical, pathological, and laboratory records between January 1983 and December 2010. MAIN OUTCOME: Incidence and clinical features of ATD-induced agranulocytosis and pancytopenia were evaluated. RESULTS: Of 55 patients with documented hematopoietic damage, 50 had agranulocytosis and 5 had pancytopenia. All of them received ATD, either methimazole (n = 51) or propylthiouracil (n = 4). Median intervals between initiation of ATD therapy and the onset of agranulocytosis and pancytopenia were 69 d (range, 11-233 d) and 41 d (range, 32-97 d), respectively. Either anemia or thrombocytopenia was also documented in seven of the 50 patients with agranulocytosis. Agranulocytosis was the first manifestation of hematopoietic damage in four of the five patents with pancytopenia. Hematopoietic damage recovered with supportive measures including granulocyte colony-stimulating factor (n = 37), steroids (n = 10), and other supportive measures (n = 8) in 54 patients, whereas the remaining patient died of complications from infection. This study failed to identify the risk factors for ATD-induced hematopoietic damage. CONCLUSIONS: This study showed that ATD cause hematopoietic changes, which are occasionally severe and potentially fatal. The pathogenesis of agranulocytosis and pancytopenia might overlap, and additional studies are warranted to clarify this and to establish an optimal treatment strategy.
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“Three recent reports of large numbers of ATD-treated patients who developed hematologic complications provide information on risk factors, treatment, and outcomes (127-129).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [127]
In the citing paper
“Two studies were from Japan and one was from Denmark.In both countries the majority of patients are treated with MMI, so data are more limited for PTU-associated agranulocytosis.”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [127]
In the citing paper
“No predictive risk factors for the development of agranulocytosis could be identified.”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [127]
In the citing paper
“In the first study, a retrospective cohort analysis of over 50,000 GD patients, 55 developed agranulocytosis, of whom five had pancytopenia, for an estimated cumulative incidence of 0.3% in 100 days (127), with a median interval to onset of 69 days.”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [127]
In the citing paper
“All 50 patients with agranulocytosis alone were successfully treated with granulocyte colony stimulating factor, steroids, or supportive care, but one of five patients with pancytopenia died.”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [127]
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Cites
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Self-citationHaematopoietic growth factor in antithyroid-drug-induced agranulocytosis
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Ross, D. S., Burch, H. B., Cooper, D. S., Greenlee, M. C., Laurberg, P., Maia, A. L., Rivkees, S. A., Samuels, M., Sosa, J. A., Stan, M. N., et al. (2016) · Thyroid® · doi:10.1089/thy.2016.0229 · Cited by 2,938
“3% in 100 days (127), with a median interval to onset of 69 days.”
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2018 European Thyroid Association Guideline for the Management of Graves’ Hyperthyroidism
Kahaly, G. J., Bartalena, L., Hegedüs, L., Leenhardt, L., Poppe, K. G., & Pearce, S. H. S. (2018) · European Thyroid Journal · doi:10.1159/000490384 · Cited by 1,025
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Metadata
- Authors
- Watanabe, N., Narimatsu, H., Noh, J. Y., Yamaguchi, T., Kobayashi, K., Kami, M., Kunii, Y., Mukasa, K., Ito, K., & Ito, K.
- Affiliations
- Ito Hospital (JP)
- Yamagata University (JP)
- Tohoku University (JP)
- JR Tokyo General Hospital (JP)
- Institute of Medical Science, The University of Tokyo (JP)
- Corresponding author
- Noh, Jaeduk Yoshimura
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2012-01
- Volume
- 97
- Issue
- 1
- Pages
- E49-E53
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2143907782
- Cited by
- 167
- References
- 19
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 11 · 2023: 12 · 2022: 15 · 2021: 12 · 2020: 21 · 2019: 8 · 2018: 11 · 2017: 14 · 2016: 11 · 2015: 9 · 2014: 10 · 2013: 9 · 2012: 4
- FWCI
- 4.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Blood disorders and treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Hematology › Hematological disorders and diagnostics
- Keywords
- antithyroid drugs, agranulocytosis, pancytopenia, hematopoietic damage, Graves' disease, methimazole, propylthiouracil, drug-induced neutropenia, granulocyte colony-stimulating factor, infectious complications, risk factors
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Agranulocytosis, Child, Female, Graves Disease, Hematopoiesis, Humans, Japan, Male, Methimazole, Middle Aged, Pancytopenia, Propylthiouracil, Retrospective Studies, Antithyroid Agents, Tokyo, Cohort Studies, Young Adult
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