Endocrine Abstracts

Background
Propylthiouracil treatment of Graves' disease has been postulated to provoke anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, particularly myeloperoxidase (MPO)-ANCA, however it is unclear whether the abnormal immune environment of autoimmine thyroid disease influences the development of ANCA.
Methods
The occurrence of ANCA and the relationship to thionamide treatment was investigated in 407 patients' with Graves' disease, 200 with Hashimoto's thyroiditis and 649 normal euthyroid subjects. ANCA was measured by indirect immunofluorescence (IIF) and ELISA for proteinase 3 and myeloperoxidase-ANCA. Immunoglobulin from one patient who developed propylthiouracil-associated vasculitis was isolated during acute disease and remission. The functional relevance of the antibody was investigated by its ability to induce a respiratory burst from neutrophils using the reduction of ferricytochrome C.
Results
The prevalence of ANCA, as measured by IIF, was increased in Graves' disease (19.9%) compared with controls (4.6%), p<0.001. The prevalence of MPO-ANCA was also increased in Graves' disease (p=0.019), measured by ELISA. ANCA positivity was not increased in patients with Hashimotos's thyroiditis. ANCA prevalence was more strongly associated with propylthiouracil treatment than carbimazole (p=0.0265). Furthermore, one patient developed active vasculitis while receiving propylthiouracil. The MPO-ANCA produced appeared to be involved in pathogenesis of disease as immuoglobulin isolated during acute disease induced greater neutrophil activation with increased superoxide production than remission immuoglobulin (acute 7.4 ± 1.1nmoles/105 cells; remission 1.6 ± 0.54nmoles/105 cells p=0.001).
Conclusion
This study revealed a high prevalence of ANCA in patients with Graves' disease treated with thionamide therapy and suggests that the altered immune environment associated with autoimmune thyroid disease is not sufficient to develop ANCA but treatment with thionamide acts as a second hit promoting ANCA development. Persistent ANCA may be an important risk for development of systemic vasculitis in patients with Graves disease, treated particularly with propylthiouracil.