{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T09:27:08Z","timestamp":1787304428279,"version":"build-2736575974"},"reference-count":32,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T00:00:00Z","timestamp":1787270400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"abstract":"\n Agranulocytosis is a rare but serious side effect of antithyroid drugs (ATDs), defined by an absolute neutrophil count (ANC) below 500\/\u03bcL; some patients develop a more severe form with ANC below 100\/\u03bcL. We retrospectively compared the clinical, biochemical, and\n HLA\u2010B<\/jats:italic>\n allele profiles between the two presentations in 24 cases of ATD\u2010induced agranulocytosis. Based on nadir ANC, 15 participants with ANC\u2009<\u2009100\/\u03bcL formed the severe group and 9 with ANC 100\u2013500\/\u03bcL comprised the typical group. The severe group had a significantly longer neutrophil recovery time (5 [5\u20137] vs. 3 [2.5\u20133.5] days;\n P<\/jats:italic>\n \u2009=\u20090.003), higher median levels of total bilirubin (21.4 [13.3\u201330.4] vs. 7.1 [6.2\u201318.3] \u03bcmol\/L;\n P<\/jats:italic>\n \u2009=\u20090.003) and indirect bilirubin (9.9 [7.6\u201316.7] vs. 6.1 [3.6\u20139.8] \u03bcmol\/L;\n P<\/jats:italic>\n \u2009=\u20090.018), and fewer asymptomatic patients at presentation (0\/15 vs. 5\/9,\n P\u2009=<\/jats:italic>\n \u20090.003).\n HLA<\/jats:italic>\n typing confirmed that\n HLA\u2010B*38:02<\/jats:italic>\n was associated with severe ATD\u2010induced agranulocytosis (OR\u2009=\u200948.6; 95% CI\u2009=\u20092.3\u20131020.7;\n P<\/jats:italic>\n \u2009=\u20095.9\u2009\u00d7\u200910\n \u22124<\/jats:sup>\n ). Sensitivity analysis excluding the 2 PTU\u2010treated patients confirmed a robust and significant association (OR\u2009=\u200938.3; 95% CI\u2009=\u20091.8\u2013820.2;\n P\u2009=<\/jats:italic>\n \u20090.0039). No significant differences were observed in age, sex, drug type or dosage, or other biochemical parameters at agranulocytosis onset. Severe agranulocytosis accounted for 62.5% (15\/24) of cases, highlighting it as a common clinical phenotype of ATD\u2010induced agranulocytosis.\n HLA\u2010B*38:02<\/jats:italic>\n is associated with susceptibility to ATD\u2010induced severe agranulocytosis, an association predominantly driven by methimazole exposure.\n <\/jats:p>","DOI":"10.1002\/cpt.70444","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T08:58:21Z","timestamp":1787302701000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Characteristics of Severe and Typical Agranulocytosis Induced by Antithyroid Drugs"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4274-6006","authenticated-orcid":false,"given":"Leilei","family":"Mao","sequence":"first","affiliation":[{"name":"Department of Pharmacy Northern Jiangsu People's Hospital Yangzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0376-0204","authenticated-orcid":false,"given":"Ling","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Northern Jiangsu People's Hospital Affiliated to Yangzhou University Yangzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caiyun","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Northern Jiangsu People's Hospital Yangzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy Northern Jiangsu People's Hospital Yangzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenwen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Northern Jiangsu People's Hospital Affiliated to Yangzhou University Yangzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2426-7194","authenticated-orcid":false,"given":"Zilan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pathology Northern Jiangsu People's Hospital Yangzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0159-2952","authenticated-orcid":false,"given":"Yan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Northern Jiangsu People's Hospital Affiliated to Yangzhou University Yangzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"e_1_2_10_1_1","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1089\/thy.2015.0439","article-title":"Characteristics of antithyroid drug\u2013induced 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\u2009years","volume":"26","author":"Yang J.","year":"2016","journal-title":"Thyroid"},{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1097\/JCMA.0000000000000966","article-title":"Clinical characteristics of neutropenic patients under antithyroid drug: twelve\u2010year experience in a medical center","volume":"86","author":"Tseng C.\u2010H.","year":"2023","journal-title":"J. Chin. Med. Assoc."},{"key":"e_1_2_10_3_1","doi-asserted-by":"crossref","first-page":"4776","DOI":"10.1210\/jc.2013-2569","article-title":"Analysis of 754 cases of antithyroid drug\u2010induced agranulocytosis over 30\u2009years in Japan","volume":"98","author":"Nakamura H.","year":"2013","journal-title":"J. Clin. Endocrinol. Metabol."},{"key":"e_1_2_10_4_1","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1089\/thy.2013.0476","article-title":"Characteristics of agranulocytosis as an adverse effect of antithyroid drugs in the second or later course of treatment","volume":"24","author":"Kobayashi S.","year":"2014","journal-title":"Thyroid"},{"key":"e_1_2_10_5_1","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1007\/s40618-019-01054-1","article-title":"Safety of long\u2010term antithyroid drug treatment? A systematic review","volume":"42","author":"Azizi F.","year":"2019","journal-title":"J. Endocrinol. Invest."},{"key":"e_1_2_10_6_1","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1507\/endocrj.K05-068","article-title":"The relation of initial methimazole dose to the incidence of methimazole\u2010induced agranulocytosis in patients with graves' disease","volume":"54","author":"Tsuboi K.","year":"2007","journal-title":"Endocr. J."},{"key":"e_1_2_10_7_1","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1111\/fcp.12991","article-title":"Comparison of agranulocytosis and anti\u2010neutrophil cytoplasmic antibody\u2010associated vasculitis caused by two antithyroid drugs: a pharmacovigilance study using the WHO international database","volume":"38","author":"Han J.Y.","year":"2024","journal-title":"Fundamemntal Clin. Pharm."},{"key":"e_1_2_10_8_1","doi-asserted-by":"crossref","first-page":"1878","DOI":"10.1111\/bcp.13989","article-title":"Associations of HLA genotypes with antithyroid drug\u2010induced agranulocytosis: a systematic review and meta\u2010analysis of pharmacogenomics studies","volume":"85","author":"Chen W.","year":"2019","journal-title":"Br. J. Clin. Pharmacol."},{"key":"e_1_2_10_9_1","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1038\/s41397-020-00187-4","article-title":"HLA\u2010B*39:01:01 is a novel risk factor for antithyroid drug\u2010induced agranulocytosis in Japanese population","volume":"21","author":"Nakakura S.","year":"2021","journal-title":"Pharmacogenomics J."},{"key":"e_1_2_10_10_1","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s40268-017-0172-1","article-title":"Antithyroid drug\u2010induced agranulocytosis: state of the art on diagnosis and management","volume":"17","author":"Vicente N.","year":"2017","journal-title":"Drugs R D"},{"key":"e_1_2_10_11_1","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/S1726-4901(09)70402-2","article-title":"Antithyroid drug\u2010induced agranulocytosis","volume":"72","author":"Sun M.\u2010T.","year":"2009","journal-title":"J. Chin. Med. Assoc."},{"key":"e_1_2_10_12_1","first-page":"242","article-title":"Antithyroid drug\u2010induced agranulocytosis: report of 13 cases","volume":"30","author":"Huang C.\u2010H.","year":"2007","journal-title":"J. Chin Med. Assoc."},{"key":"e_1_2_10_13_1","doi-asserted-by":"crossref","first-page":"e56","DOI":"10.1093\/cid\/cir073","article-title":"Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America","volume":"52","author":"Freifeld A.G.","year":"2011","journal-title":"Clin. Infect. Dis."},{"key":"e_1_2_10_14_1","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1089\/thy.2016.0229","article-title":"2016 American Thyroid Association guidelines for diagnosis and Management of Hyperthyroidism and Other Causes of thyrotoxicosis","volume":"26","author":"Ross D.S.","year":"2016","journal-title":"Thyroid"},{"key":"e_1_2_10_15_1","first-page":"969","article-title":"Chinese guidelines for the clinical application of antibacterial drugs for agranulocytosis with fever (2020) [in Chinese]","volume":"41","author":"Chinese Society of Hematology, Chinese Medical Association, Chinese Medical Doctor Association, Hematology Branch","year":"2020","journal-title":"Chin. J. Hematol."},{"key":"e_1_2_10_16_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.clinme.2024.100235","article-title":"Approach to pancytopenia: from blood tests to the bedside","volume":"24","author":"Chew S.","year":"2024","journal-title":"Clin. Med."},{"key":"e_1_2_10_17_1","first-page":"15","article-title":"Severe neutropenia and agranulocytosis related to antithyroid drugs: a study of 30 cases managed in a single reference center","volume":"7","author":"Andr\u00e8s E.","year":"2020","journal-title":"Medicine"},{"key":"e_1_2_10_18_1","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1507\/endocrj.EJ12-0332","article-title":"The relationship between bone marrow characteristics and the clinical prognosis of antithyroid drug\u2010induced agranulocytosis","volume":"60","author":"Yang J.","year":"2013","journal-title":"Endocr. J."},{"key":"e_1_2_10_19_1","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1507\/endocrj.EJ24-0135","article-title":"Dose\u2010dependent incidence of agranulocytosis in patients treated with methimazole and propylthiouracil","volume":"71","author":"Yoshimura Noh J.","year":"2024","journal-title":"Endocr. J."},{"key":"e_1_2_10_20_1","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1089\/thy.2008.0364","article-title":"Methimazole\u2010induced agranulocytosis in patients with graves' disease is more frequent with an initial dose of 30 mg daily than with 15 mg daily","volume":"19","author":"Takata K.","year":"2009","journal-title":"Thyroid"},{"key":"e_1_2_10_21_1","doi-asserted-by":"crossref","first-page":"7633","DOI":"10.1038\/ncomms8633","article-title":"Genetic determinants of antithyroid drug\u2010induced agranulocytosis by human leukocyte antigen genotyping and genome\u2010wide association study","volume":"6","author":"Chen P.\u2010L.","year":"2015","journal-title":"Nat. Commun."},{"key":"e_1_2_10_22_1","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1002\/cpt.309","article-title":"HLA\u2010B*38:02:01 predicts carbimazole\/methimazole\u2010induced agranulocytosis","volume":"99","author":"Cheung C.","year":"2016","journal-title":"Clin. Pharmacol. Ther."},{"key":"e_1_2_10_23_1","doi-asserted-by":"crossref","first-page":"490","DOI":"10.7326\/0003-4819-124-5-199603010-00005","article-title":"Association between the DRB1*08032 histocompatibility antigen and methimazole\u2010induced agranulocytosis in Japanese patients with graves disease","volume":"124","author":"Tamai H.","year":"1996","journal-title":"Ann. Intern. Med."},{"key":"e_1_2_10_24_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2018\/7965346","article-title":"Association of HLA\u2010B * 38:02 with antithyroid drug\u2010induced agranulocytosis in Kinh Vietnamese patients","volume":"2018","author":"Thao M.P.","year":"2018","journal-title":"Int. J. Endocrinol."},{"key":"e_1_2_10_25_1","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/S2213-8587(16)00113-3","article-title":"Genetic variants associated with antithyroid drug\u2010induced agranulocytosis: a genome\u2010wide association study in a European population","volume":"4","author":"Hallberg P.","year":"2016","journal-title":"Lancet Diabetes Endocrinol."},{"key":"e_1_2_10_26_1","doi-asserted-by":"crossref","first-page":"11950","DOI":"10.1038\/s41598-017-12350-2","article-title":"Association of HLA\u2010B and HLA\u2010DRB1 polymorphisms with antithyroid drug\u2010induced agranulocytosis in a Han population from northern China","volume":"7","author":"He Y.","year":"2017","journal-title":"Sci. Rep."},{"key":"e_1_2_10_27_1","doi-asserted-by":"crossref","first-page":"D913","DOI":"10.1093\/nar\/gkq1128","article-title":"Allele frequency net: a database and online repository for immune gene frequencies in worldwide populations","volume":"39","author":"Gonzalez\u2010Galarza F.F.","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"e_1_2_10_28_1","doi-asserted-by":"crossref","first-page":"449","DOI":"10.4158\/EP09304.CR","article-title":"Antineutrophil cytoplasmic antibody\u2010positive Vasculitis in a patient with graves disease: cross\u2010reaction between propylthiouracil and methimazole","volume":"16","author":"Ahmed K.","year":"2010","journal-title":"Endocr. Pract."},{"key":"e_1_2_10_29_1","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0220754","article-title":"Informatics investigations into anti\u2010thyroid drug induced agranulocytosis associated with multiple HLA\u2010B alleles","volume":"15","author":"Ramsbottom K.A.","year":"2020","journal-title":"PLoS One"},{"key":"e_1_2_10_30_1","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1007\/s40618-017-0626-x","article-title":"Emphasis on the early diagnosis of antithyroid drug\u2010induced agranulocytosis: retrospective analysis over 16\u2009years at one Chinese center","volume":"40","author":"He Y.","year":"2017","journal-title":"J. Endocrinol. Invest."},{"key":"e_1_2_10_31_1","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1016\/j.eprac.2021.06.017","article-title":"Thionamide\u2010induced agranulocytosis: a retrospective analysis of 36 patients with hyperthyroidism","volume":"27","author":"Zhu D.","year":"2021","journal-title":"Endocr. Pract."},{"key":"e_1_2_10_32_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2016\/2157583","article-title":"Abnormalities of thyroid hormone metabolism during systemic illness: the low T3 syndrome in different clinical settings","volume":"2016","author":"Moura Neto A.","year":"2016","journal-title":"Int. J. Endocrinol."}],"container-title":["Clinical Pharmacology & Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.70444","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpt.70444","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.70444","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T08:58:25Z","timestamp":1787302705000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/cpt.70444"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,21]]},"references-count":32,"alternative-id":["10.1002\/cpt.70444"],"URL":"https:\/\/doi.org\/10.1002\/cpt.70444","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,21]]},"assertion":[{"value":"2026-04-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-31","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"cpt.70444"}}