{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T22:10:56Z","timestamp":1794003056682,"version":"4.8.0"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,1,27]],"date-time":"2023-01-27T00:00:00Z","timestamp":1674777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>The authors aimed to investigate the clinical characteristics of antithyroid drug-induced aplastic anemia cases over the past 30 years.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The data of patients with antithyroid drug-induced aplastic anemia were retrieved from PubMed and Wanfang Medical Network databases from 1992 to August 2022. The clinical characteristics, such as age distribution, gender tendency, common symptoms, blood cell count, bone marrow features, treatment strategy, and prognosis, were analyzed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 17 cases (male:female = 1:16) had been retrieved. Patients\u2019 age ranged from 16 to 74 years (median 50 years). Among them, 82.3% (14\/17) of the patients were administered methimazole (MMI), and 78.6% of them had MMI \u226530 mg\/day. In addition, 88.2% (15\/17) of the patients had sore throat and fever, and 47.1% (8\/17) of the patients had hemorrhagic symptoms. Aplastic anemia occurred within 6 months after initiation of the antithyroid therapy in 94.1% of the patients. Agranulocytosis (94.1%) was the most common and earliest blood cell change, and 47.1% of the patients experienced progressive platelet decline during the treatment process. The treatments include timely withdrawal of antithyroid drugs, broad-spectrum antibiotics, granulocyte colony-stimulating factor (G-CSF)\/granulocyte-macrophage colony-stimulating factor (GM-CSF), glucocorticoids and other immunosuppressive agents, and supportive treatments such as erythrocyte transfusion and platelet transfusion. Moreover, 70.6% of the patients had complete or near-complete remission within 8 days to 6 weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Aplastic anemia is a rare and serious adverse reaction of antithyroid drugs, which is more common in women. It usually occurs during early treatment with high-dose antithyroid drugs. Most patients have a good prognosis after timely drug ceasing and appropriate treatment.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2023.1064723","type":"journal-article","created":{"date-parts":[[2023,1,27]],"date-time":"2023-01-27T05:35:58Z","timestamp":1674797758000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Clinical characteristics of antithyroid drug-induced aplastic anemia cases over the past 30 years"],"prefix":"10.3389","volume":"14","author":[{"given":"Ying","family":"Cheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin-Yu","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Ren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen-Fu","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,1,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2011-2221","article-title":"Antithyroid drug-induced hematopoietic damage: A retrospective cohort study of agranulocytosis and pancytopenia involving 50,385 patients with graves\u2019 disease","volume":"97","author":"Watanabe","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.cn311282-20220624-00404","article-title":"Guidelines for diagnosis and management of hyperthyroidism and other causes of thyrotoxicosis","volume":"38","year":"2022","journal-title":"Chin J Endocrinol Metab"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-2569","article-title":"Analysis of 754 cases of antithyroid drug-induced agranulocytosis over 30 years in Japan","volume":"98","author":"Nakamura","year":"2013","journal-title":"J Clin Endocrinol Metab"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1097\/00000441-199103000-00008","article-title":"Case report: Aplastic anemia associated with antithyroid drugs","volume":"301","author":"Biswas","year":"1991","journal-title":"Am J Med Sci"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1988.tb04240.x","article-title":"Carbimazole-induced immune haemolytic anaemia: Role of drug-red blood cell complexes for immunization","volume":"68","author":"Salama","year":"1988","journal-title":"Br J Haematol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.13989","article-title":"Associations of HLA genotypes with antithyroid drug-induced agranulocytosis: A systematic review and meta-analysis of pharmacogenomics studies","volume":"85","author":"Chen","year":"2019","journal-title":"Br J Clin Pharmacol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra042972","article-title":"Antithyroid drugs","volume":"352","author":"Cooper","year":"2005","journal-title":"New Engl J Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/cen.14313","article-title":"Neutropenia in patients with hyperthyroidism: Systematic review and meta-analysis","volume":"94","author":"Scappaticcio","year":"2021","journal-title":"Clin Endocrinol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/s0378-4274(0100539-2","article-title":"Extrathyroidal actions of antithyroid thionamides","volume":"128","author":"Bandyopadhyay","year":"2002","journal-title":"Toxicol Lett"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1413485","article-title":"Aplastic anemia","volume":"379","author":"Young","year":"2018","journal-title":"New Engl J Med"},{"key":"B11","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1053\/j.seminhematol.2021.12.002","article-title":"Aplastic anemia: Pathophysiology","volume":"59","author":"Giudice","year":"2022","journal-title":"Semin In Hematol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1002\/ccr3.3860","article-title":"Fatal temozolomide induced aplastic anemia in a female with glioblastoma multiforme: A case report and literature review","volume":"9","author":"Ata","year":"2021","journal-title":"Clin Case Rep"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1177\/10781552211052030","article-title":"Aplastic anemia secondary to tyrosine kinase inhibitor therapy in a patient with chronic myeloid leukemia","volume":"28","author":"Kassar","year":"2022","journal-title":"J Oncol Pharm Pract"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.9734\/jpri\/2022\/v34i24a35933","article-title":"Antimicrobial therapy: an important risk for acquired aplastic anemia","volume":"15","author":"Syed","year":"2022","journal-title":"J Pharm Res Int"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1177\/0961203313504636","article-title":"Aplastic anemia secondary to azathioprine in systemic lupus erythematosus: report of a case with normal thiopurine s-methyltransferase enzyme activity and review of the literature","volume":"22","author":"Yeter","year":"2013","journal-title":"Lupus"},{"key":"B16","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1007\/BF02943616","article-title":"Fatal aplastic anaemia following prolonged diclofenac use in an elderly patient","volume":"158","author":"Eustace","year":"1989","journal-title":"Irish J Med Sci"},{"key":"B17","article-title":"A prospective study of the incidence of agranulocytosis and aplastic anemia associated with the oral use of metamizole sodium in Poland","volume":"10","author":"Maj","year":"2004","journal-title":"Med Sci Monitor"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.25259\/ijms_23_2019","article-title":"Phenytoin-induced aplastic anemia in generalized tonic clonic seizures patient: A case report","volume":"71","author":"Bindu","year":"2020","journal-title":"Indian J Med Sci"},{"key":"B19","article-title":"Acquired aplastic anemia secondary to perphenazine","volume":"6","author":"Oyewumi","year":"1999","journal-title":"Can J Clin Pharmacol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3760\/cma.j.issn.0253-2727.2017.01.001","article-title":"Chinese Expert consensus on the diagnosis and treatment of aplastic anemia (2017","volume":"38","year":"2017","journal-title":"Chin J Hematol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1159\/000204742","article-title":"Treatment of methimazole-induced severe aplastic anemia with recombinant human granulocytemonocyte colony-stimulating factor and glucocorticosteroids","volume":"87","author":"L\u00f3pez-Karpovitch","year":"1992","journal-title":"Acta Haematol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1177\/106002809603000622","article-title":"Methimazole-induced aplastic anemia","volume":"30","author":"Bishara","year":"1996","journal-title":"Ann Pharmacother"},{"key":"B23","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1089\/thy.1997.7.67","article-title":"Methimazole-induced severe aplastic anemia: Unsuccessful treatment with recombinant human granulocyte-monocyte colony-stimulating factor","volume":"7","author":"Escobar-Morreale","year":"1997","journal-title":"Thyroid"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1089\/thy.1998.8.791","article-title":"Methimazole-induced aplastic anemia in third exposure: Successful treatment with recombinant human granulocyte colony-stimulating factor","volume":"8","author":"Mezquita","year":"1998","journal-title":"Thyroid"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.1127","article-title":"Massive plasmocytosis due to methimazole-induced bone marrow toxicity","volume":"67","author":"Breier","year":"2001","journal-title":"Am J Hematol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1089\/105072504773297911","article-title":"Methimazole-induced aplastic anemia caused by hypocellular bone marrow with plasmacytosis","volume":"14","author":"Yamamoto","year":"2004","journal-title":"Thyroid"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1007\/BF03349180","article-title":"Successful treatment of methimazole-induced severe aplastic anemia with recombinant human granulocyte colony-stimulation factor and high-dosage steroids","volume":"29","author":"Jakucs","year":"2006","journal-title":"J Endocrinol Invest"},{"key":"B28","doi-asserted-by":"publisher","first-page":"665","DOI":"10.3969\/j.issn.1006-5725.2008.04.111","article-title":"A case of acute severe aplastic anemia caused by tabazol","volume":"24","author":"Zhang","year":"2008","journal-title":"J Pract Med"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2008.0097","article-title":"Antithyroid drug-induced aplastic anemia","volume":"18","author":"Thomas","year":"2008","journal-title":"Thyroid"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3969\/j.issn.1008-5734.2008.01.009","article-title":"Death from aplastic anemia and thyroid crisis due to inappropriate treatment with methimazole","volume":"10","author":"Hang","year":"2008","journal-title":"Adverse Drug Reactions J"},{"key":"B31","first-page":"43","article-title":"Methimazole overdose induced severe aplastic anemia complicated with hypothyroidism: Case report","author":"Yang","year":"2015","journal-title":"J Baotou Med Coll"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.4183\/aeb.2009.465","article-title":"Aplastic anemia during antithyroid drugs in hyperthyroidism. case report","volume":"4","author":"Gaman","year":"2008","journal-title":"Acta Endocrinolog-Bucharest"},{"key":"B33","doi-asserted-by":"publisher","first-page":"353","DOI":"10.3969\/j.issn.1001-9057.2016.05.026","article-title":"A case of severe aplastic anemia caused by methimazole","volume":"33","author":"Gu","year":"2016","journal-title":"J Clin Internal Med"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1177\/1078155217752079","article-title":"Aplastic anemia secondary to propylthiouracil: A rare and life-threatening adverse effect","volume":"25","author":"Shaikh","year":"2019","journal-title":"J Oncol Pharm Pract"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.13286\/j.1001-5213.2020.15.20","article-title":"A case of methimazole induced aplastic anemia with sepsis","volume":"40","author":"Liu","year":"2020","journal-title":"Chin J Hosp Pharm"},{"key":"B36","doi-asserted-by":"crossref","DOI":"10.1001\/archinte.1967.00300040071012","article-title":"Bone marrow aplasia following propylthiouracil therapy : Report of a case with complete recovery","volume":"120","author":"Martelo","year":"1967","journal-title":"Arch Internal Med"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1097\/SMJ.0b013e318172fcb8","article-title":"A very rare cause of aplastic anemia: Graves disease","volume":"101","author":"Aydin","year":"2008","journal-title":"South Med J"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.issn.0578-1426.2019.05.015","article-title":"Advances of pathogenesis and genetic abnormalities in acquired aplastic anemia","volume":"58","author":"Sun","year":"2019","journal-title":"Chin J Internal Med"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1159\/000206873","article-title":"Transient methimazole-induced bone marrow aplasia: in vitro evidence for a humoral mechanism of bone marrow suppression","volume":"69","author":"Moreb","year":"1983","journal-title":"Acta Haematol"},{"key":"B40","doi-asserted-by":"publisher","first-page":"129","DOI":"10.3969\/j.issn.1006-0979.2013.19.121","article-title":"Methimazole induced pancytopenia treated with high-dose glucocorticoids: Case report","author":"Li","year":"2013","journal-title":"Nei Mongol J Traditional Chin Med"},{"key":"B41","article-title":"Methimazole-induced aplastic anemia","volume":"90","author":"Mechelli","year":"1999","journal-title":"Recenti Progressi In Medicina"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1007\/s40618-017-0626-x","article-title":"Emphasis on the early diagnosis of antithyroid drug-induced agranulocytosis: Retrospective analysis over 16 years at one Chinese center","volume":"40","author":"He","year":"2017","journal-title":"J Endocrinol Invest"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2015.0439","article-title":"Characteristics of antithyroid drug-induced agranulocytosis in patients with hyperthyroidism: A retrospective analysis of 114 cases in a single institution in China involving 9690 patients referred for radioiodine treatment over 15 years","volume":"26","author":"Yang","year":"2016","journal-title":"Thyroid"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.4158\/EP-2019-0221","article-title":"Side effects of PTU and MMI in the treatment of hyperthyroidism: A systematic review and meta-analysis","volume":"26","author":"Yu","year":"2020","journal-title":"Endocr Pract"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.1.4981.1456","article-title":"Fatal marrow aplasia after treatment with carbimazole","volume":"1","author":"Burrell","year":"1956","journal-title":"Br Med J"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.1.4858.364","article-title":"Fatal case of marrow aplasia after treatment-with carbimazole; the effect of ACTH","volume":"1","author":"Richardson","year":"1954","journal-title":"Br Med J"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.issn.0376-2491.2020.04.016","article-title":"Aplastic anemia and bone marrow steatosis","volume":"100","author":"Cheng","year":"2020","journal-title":"Natl Med J China"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020007592","article-title":"Diversity, localization, and (pathophysiology of mature lymphocyte populations in the bone marrow","volume":"137","author":"Sch\u00fcrch","year":"2021","journal-title":"Blood"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2020.0715","article-title":"Abnormal liver blood tests in patients with hyperthyroidism: systematic review and meta-analysis","volume":"31","author":"Lorenzo","year":"2021","journal-title":"Thyroid"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2006.16.403","article-title":"Pancytopenia in untreated patients with graves\u2019 disease","volume":"16","author":"Lima","year":"2006","journal-title":"Thyroid"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.14661\/2014.877-882","article-title":"A report of three cases of untreated graves\u2019 disease associated with pancytopenia in Malaysia","volume":"6","author":"Rafhati","year":"2014","journal-title":"Electron phys"},{"key":"B52","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1007\/s42000-020-00227-5","article-title":"Graves\u2019 hyperthyroidism-related pancytopenia: a case report with literature review","volume":"20","author":"Scappaticcio","year":"2021","journal-title":"Hormones"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.20640","article-title":"Remission of aplastic anemia induced by treatment for graves disease in a pediatric patient","volume":"49","author":"Das","year":"2007","journal-title":"Pediatr Blood Cancer"},{"key":"B54","doi-asserted-by":"publisher","first-page":"213","DOI":"10.3969\/j.issn.1004-2806.2003.05.021","article-title":"Radioiodine treatment of 2 cases with aplastic anemia caused by hyperthyroidism","volume":"16","author":"Ye","year":"2003","journal-title":"J Clin Hematol"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2023.1064723\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,27]],"date-time":"2023-01-27T05:36:16Z","timestamp":1674797776000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2023.1064723\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,1,27]]},"references-count":54,"alternative-id":["10.3389\/fendo.2023.1064723"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2023.1064723","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,1,27]]},"article-number":"1064723"}}