Neuropsychological Alterations in Patients with Congenital Hypothyroidism Treated with Levothyroxine: Linked Factors and Thyroid Hormone Hyposensitivity

Eighty-five percent of the studies of patients with congenital hypothyroidism (CH) treated with Levothyroxine (L-T(4)) report neuropsychological sequelae throughout life. In neonates and infants, there is a deficit in sensorimotor skills (impaired balance). In preschool and elementary school children and adolescents, there are alterations in intellectual quotient (low scores), language (delayed phonological acquisition), memory (visual, verbal, visuospatial, visuoconstructive, autobiographical, and semantic), sensorimotor skills (impaired fine and gross motor control), and visuoconstructive–visuospatial domain (low scores in spatial location, block design, and object assembly). These neuropsychological domains are also affected in young adults, except for language (adequate verbal fluency) and visuoconstructive–visuospatial domain (no data). The onset and severity of neuropsychological sequelae in patients with treated CH depend on several factors: extrinsic, related to L-T(4) treatment and social aspects, and intrinsic, such as severity and etiology of CH, as well as structural and physiological changes in the brain. In this review, we hypothesized that thyroid hormone hyposensitivity (THH) could also contribute to neuropsychological alterations by reducing the effectiveness of L-T(4) treatment in the brain. Thus, further research could approach the THH hypothesis at basic and clinical levels to implement new endocrinological and neuropsychological therapies for CH patients.