Department of Pediatric Endocrinology, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, via Olgettina 60, 20132 Milan, Italy.
J Endocrinol Invest. 2013 Apr;36(4):261-6. doi: 10.3275/8847. Epub 2013 Feb 12.
Hydrogen peroxide (H2O2) is a key element in thyroid hormone biosynthesis. It is the substrate used by thyroid peroxidase for oxidation and incorporation of iodine into thyroglobulin, a process known as organification. The main enzymes composing the H2O2-generating system are the dual oxidase 2 (DUOX2) and the recently described DUOX maturation factor 2 (DUOXA2). Defects in these reactions lead to reduced thyroid hormone synthesis and hypothyroidism, with consequent increased TSH secretion and goiter. Since the first report in 2002 of DUOX2 mutations causing congenital hypothryoidism (CH), to date 25 different mutations have been described. Affected patients show a positive perchlorate discharge test and high phenotypic variability, ranging from transient to permanent forms of CH. Up to now, only two cases of CH due to DUOXA2 defects have been published. They also suggest the existence of a great genotype-phenotype variability. The phenotypic expression is probably influenced by genetic background and environmental factors. DUOX and DUOXA constitute a redundant system in which DUOX1/DUOXA1 can at least partially replace the function of DUOX2/DUOXA2. Furthermore, increased nutritional iodide could ensure a better use of H2O2 provided by DUOX1.
过氧化氢 (H2O2) 是甲状腺激素生物合成的关键元素。它是甲状腺过氧化物酶用于氧化和将碘掺入甲状腺球蛋白的底物，这一过程被称为碘化。构成 H2O2 生成系统的主要酶是双氧化酶 2 (DUOX2) 和最近描述的 DUOX 成熟因子 2 (DUOXA2)。这些反应的缺陷导致甲状腺激素合成减少和甲状腺功能减退，从而导致 TSH 分泌增加和甲状腺肿。自 2002 年首次报道 DUOX2 突变导致先天性甲状腺功能减退症 (CH) 以来，迄今为止已描述了 25 种不同的突变。受影响的患者表现出阳性高氯酸盐排出试验和高度表型变异性，从短暂到永久性 CH 形式不等。到目前为止，仅发表了两例由于 DUOXA2 缺陷导致的 CH 病例。它们还表明存在很大的基因型-表型变异性。表型表达可能受遗传背景和环境因素的影响。DUOX 和 DUOXA 构成一个冗余系统，其中 DUOX1/DUOXA1 至少可以部分替代 DUOX2/DUOXA2 的功能。此外，增加营养碘可以确保更好地利用 DUOX1 提供的 H2O2。
