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High Prevalence of Antineutrophil Cytoplasmic Antibody Positivity in Childhood Onset Graves’ Disease Treated with Propylthiouracil

Divisions of Endocrinology (H.S., S.M.) and Nephrology (M.Ha.), Chiba Children’s Hospital, Chiba 266-0007; Department of Pediatrics, Kochi Medical School (M.F.), Kochi 783-8505; Department of Pediatrics, Daini Hospital, School of Medicine, Tokyo Women’s Medical University (S.S.), Tokyo 116-0011; Department of Pediatrics, Ichihara Hospital, School of Medicine, Teikyo University (H.I.), Chiba 299-0111; and Department of Pediatrics, Matsudo Municipal Hospital (M.Ho.), Chiba 271-0064, Japan

Address correspondence and requests for reprints to: Hirokazu Sato, M.D., Division of Endocrinology, Chiba Children’s Hospital, 579-1 Heta-cho, Midori-ku, Chiba 266-0007, Japan.

Propylthiouracil (PTU)-induced antineutrophil cytoplasmic antibody (ANCA)-related vasculitis and nephritis were recently reported in about 30 patients with hyperthyroidism. The objective of this study was to clarify the prevalence of ANCA and the relationship between ANCA and thyroid antibodies in children with Graves’ disease.

Titers of myeloperoxidase (MPO)-ANCA in sera of 51 patients with childhood onset Graves’ disease (16 before treatment, 25 and 10 treated with PTU and methimazole, respectively) were measured by enzyme-linked immunosolvent assay. Antithyroglobulin antibodies (TGAbs) and antithyroperoxidase antibodies (TPOAbs) were also measured by RIA in 25 PTU-treated patients. No patients had clinical manifestations of vasculitis and nephritis. MPO-ANCA was positive in 6.7% of patients before treatment and in 64.0% of those treated with PTU and in none of those treated with methimazole. MPO-ANCA had a significantly positive correlation with TGAbs (P < 0.05) and no significant correlation with TPOAbs.

These findings show the high prevalence of the MPO-ANCA positivity in PTU-treated childhood onset Graves’ disease, suggesting that PTU may not be preferred as the first line for the treatment of children with Graves’ disease. The significant correlation between MPO-ANCA and TGAbs indicates that the severity of Graves’ disease may be a factor responsible for the MPO-ANCA positivity. The cross-reactivity between MPO-ANCA and TPOAbs may not play a role in the high prevalence of MPO-ANCA in the patients exposed to PTU.

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