DUOXA2 Variants as an Underrecognized Cause of Diffuse Goiter: A Euthyroid Adult Case Responsive to Levothyroxine.

Hydrogen peroxide (H2O2) is an essential substrate for thyroid peroxidase (TPO) and plays a key role in iodine oxidation, organification, and coupling reactions that generate thyroid hormones. Dual oxidase 2 (DUOX2) and its maturation factor dual oxidase maturation factor 2 (DUOXA2) are critical for H2O2 production in thyroid follicular cells. Although DUOXA2 variants typically present with congenital hypothyroidism, phenotypic variability has been reported. We present an adult woman with a diffuse thyroid goiter and normal thyroid function who was found to have compound heterozygous DUOXA2 variants (p.Tyr138 ∗/p.Tyr246 ∗). Despite the patient being euthyroid, levothyroxine (LT4) administration led to a reduction in thyroid size. This case highlights that DUOXA2 variants may be present in euthyroid adults with thyroid goiter and that LT4 therapy can lead to a reduction in thyroid volume. Long-term follow-up may clarify the natural history and therapeutic response in euthyroid adults with DUOXA2 variants.