Genetic defects of hydrogen peroxide generation in the thyroid gland

G. Weber, S. Rabbiosi, I. Zamproni, L. Fugazzola

Research output: Contribution to journalArticlepeer-review


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 H2O 2-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 H 2O2 provided by DUOX1.

Original languageEnglish
Pages (from-to)261-266
Number of pages6
JournalJournal of Endocrinological Investigation
Issue number4
Publication statusPublished - Apr 2013


  • Congenital hypothyroidism
  • Dual oxidase (DUOX)
  • Dual oxidase maturation factor (DUOXA)
  • Genetics
  • Hydrogen peroxide.

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology


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