title: Antithyroid drug-induced hematopoietic damage: a retrospective cohort study of agranulocytosis and pancytopenia involving 50,385 patients with Graves' disease.
abstract: BACKGROUND
  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.
  
  
  METHODS
  This was a retrospective cohort study in Tokyo, Japan.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
authors: Ito Hospital, 4-3-6 Jingumae, Shibuya-ku, Tokyo 150-8308, Japan.
authors: Natsuko
authors: N
authors: Watanabe
authors: Hiroto
authors: H
authors: Narimatsu
authors: Jaeduk Yoshimura
authors: JY
authors: Noh
authors: Takuhiro
authors: T
authors: Yamaguchi
authors: Kazuhiko
authors: K
authors: Kobayashi
authors: Masahiro
authors: M
authors: Kami
authors: Yo
authors: Y
authors: Kunii
authors: Koji
authors: K
authors: Mukasa
authors: Kunihiko
authors: K
authors: Ito
authors: Koichi
authors: K
authors: Ito
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000380:Agranulocytosis / Q000139:chemically induced* / Q000453:epidemiology; D013956:Antithyroid Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D002648:Child; D015331:Cohort Studies; D005260:Female; D006111:Graves Disease / Q000188:drug therapy* / Q000453:epidemiology; D006410:Hematopoiesis / Q000187:drug effects*; D006801:Humans; D007564:Japan; D008297:Male; D008713:Methimazole / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D010198:Pancytopenia / Q000139:chemically induced* / Q000453:epidemiology; D011441:Propylthiouracil / Q000009:adverse effects / Q000627:therapeutic use; D012189:Retrospective Studies; D014041:Tokyo; D055815:Young Adult
chemical_list: D013956:Antithyroid Agents; D008713:Methimazole; D011441:Propylthiouracil