ABSTRACT:We aim to determine long-term intellectual outcome of adolescents with early high-dose treated congenital hypothyroidism (CH). Sixty-three prospectively followed children with CH were assessed at age of 14 y with the Wechsler Intelligence Scale for Children-Revised and compared with 175 healthy controls. Median age at onset of treatment was 9 d (range 5-18 d) and median starting dose of levothyroxine (L-T4) was 14.7 g/kg/d (range 9.9 -23.6 g/kg/d). Full-scale intelligence quotient (IQ) was significantly lower than in controls after adjustment for socioeconomic status (SES) and gender (101.7 versus 111.4; p Ͻ 0.0001). Children with athyreosis had a lower performance IQ than those with dysgenesis (adjusted difference 7.6 IQ scores, p Ͻ 0.05). Lower initial thyroxine (T4) levels correlated with poorer IQ (r ϭ 0.27, p ϭ 0.04). Lower SES was associated with poorer IQ, in particular in children with CH (interaction, p ϭ 0.03). Treatment during childhood was not related to IQ at age 14 y. Adolescents with CH manifest IQ deficits when compared with their peers despite early high-dose treatment and optimal substitution therapy throughout childhood. Those adolescents with athyreosis and lower SES are at particular risk for adverse outcome. Therefore, early detection of intellectual deficits is mandatory in children with CH. (Pediatr Res 65: 242-248, 2009)