Sato H, Hattori M, Fujieda M, Sugihara S, Inomata H, Hoshi M, Miyamoto S
Divisions of Endocrinology, Chiba Children's Hospital, Japan.
J Clin Endocrinol Metab. 2000 Nov;85(11):4270-3. doi: 10.1210/jcem.85.11.7000.
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.
最近有报道称，约30例甲状腺功能亢进患者出现了丙硫氧嘧啶（PTU）诱发的抗中性粒细胞胞浆抗体（ANCA）相关血管炎和肾炎。本研究的目的是明确Graves病患儿中ANCA的患病率以及ANCA与甲状腺抗体之间的关系。采用酶联免疫吸附测定法检测了51例儿童期起病的Graves病患者（16例未治疗，25例和10例分别接受PTU和甲巯咪唑治疗）血清中的髓过氧化物酶（MPO）-ANCA滴度。还采用放射免疫分析法检测了25例接受PTU治疗患者的抗甲状腺球蛋白抗体（TGAbs）和抗甲状腺过氧化物酶抗体（TPOAbs）。所有患者均无血管炎和肾炎的临床表现。未治疗患者中MPO-ANCA阳性率为6.7%，PTU治疗患者中为64.0%，甲巯咪唑治疗患者中无一例阳性。MPO-ANCA与TGAbs呈显著正相关（P<0.05），与TPOAbs无显著相关性。这些结果表明，PTU治疗的儿童期起病的Graves病患者中MPO-ANCA阳性率较高，提示PTU可能不是治疗儿童Graves病的首选一线药物。MPO-ANCA与TGAbs之间的显著相关性表明，Graves病的严重程度可能是导致MPO-ANCA阳性的一个因素。MPO-ANCA与TPOAbs之间的交叉反应性可能在接触PTU患者中MPO-ANCA的高患病率中不起作用。
