title: Propylthiouracil and carbimazole associated-antineutrophil cytoplasmic antibodies (ANCA) in patients with Graves' disease.
abstract: OBJECTIVE
  Propylthiouracil treatment of Graves' disease has been postulated to provoke antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis. We aimed to investigate whether carbimazole therapy was also associated with increased risk of ANCA.
  
  
  METHODS
  The occurrence of ANCA and the relationship to thionamide treatment was investigated in a cross-sectional study in a consecutive series of 407 patients' with Graves' disease, 200 with Hashimoto's thyroiditis and 649 normal euthyroid subjects.
  
  
  METHODS
  ANCA was measured by indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assay (ELISA) for proteinase 3 and myeloperoxidase-ANCA.
  
  
  RESULTS
  The prevalence of ANCA, as measured by IIF, was increased in the Graves' disease cohort (19.9%) compared with euthyroid controls (4.6%; P < 0.001). The prevalence of MPO-ANCA (measured by ELISA) was also increased in Graves' disease (P = 0.019). ANCA prevalence was more strongly associated with propylthiouracil treatment than carbimazole (P = 0.0265), although risk of ANCA was also higher in Graves' patients treated with carbimazole than controls (RR 2.2, P < 0.0001). ANCA positivity was not increased in patients with Hashimoto's thyroiditis.
  
  
  CONCLUSIONS
  This study revealed a high prevalence of ANCA in treated patients with Graves' disease but not in those with Hashimoto's thyroiditis. Furthermore, within the Graves' disease population, ANCA development was associated with propylthiouracil usage to a greater extent than carbimazole. These findings suggest that the altered immune environment associated with autoimmune thyroid disease is not sufficient to develop ANCA but treatment with thionamides is important in promoting ANCA development.
authors.affiliation: Division of Medical Sciences, University of Birmingham, Edgbaston, Birmingham, UK. l.harper@bham.ac.uk
authors.forename: L
authors.initials: L
authors.lastname: Harper
authors.forename: L
authors.initials: L
authors.lastname: Chin
authors.forename: J
authors.initials: J
authors.lastname: Daykin
authors.forename: A
authors.initials: A
authors.lastname: Allahabadia
authors.forename: J
authors.initials: J
authors.lastname: Heward
authors.forename: S C
authors.initials: SC
authors.lastname: Gough
authors.forename: C O
authors.initials: CO
authors.lastname: Savage
authors.forename: J A
authors.initials: JA
authors.lastname: Franklyn
mesh_terms: D000328:Adult; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood*; D013956:Antithyroid Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002231:Carbimazole / Q000009:adverse effects* / Q000627:therapeutic use; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006111:Graves Disease / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011441:Propylthiouracil / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D013956:Antithyroid Agents; D011441:Propylthiouracil; D002231:Carbimazole