Resistance to thyroid hormone alpha (RTHα) is a rare disorder that may present with clear hypothyroid features despite normal thyroid-stimulating hormone (TSH) and marginally low free thyroxine (FT4), leading to underrecognition. We report a 12-year-old with a de novo thyroid hormone receptor alpha ( THRA ) variant (c.802G>A, p.Asp268Asn), treated with levothyroxine from the age of 14 months, who showed improved energy, motor milestones, and school performance. This case highlights that children with disproportionate hypothyroid signs and subtle thyroid function test abnormalities warrant early assessment of free triiodothyronine (FT3), timely THRA genetic testing, and a monitored levothyroxine trial, which may benefit milder RTHα phenotypes.
Wong et al. (2026) studied this question.