title: Long-term treatment of children with epilepsy with valproate or carbamazepine may cause subclinical hypothyroidism.
abstract: OBJECTIVE
  The aim of the study was to evaluate serum thyroid hormone balance in children receiving long-term therapy with carbamazepine (CBZ), valproate (VPA), and phenobarbital (PB).
  
  
  METHODS
  We determined serum levels of triiodothyronine (T3), thyroxine (T4), free thyroxine (FT4), thyroxine-binding globulin (TBG), and thyroid-stimulating hormone (TSH) in 148 healthy children and 141 children with epilepsy who had been receiving CBZ (61 patients), VPA (51 patients), or PB (29 patients) for 12-161 months. In view of TSH values, three categories of subclinical hypothyroidism were considered: I, TSH greater than the control-group mean + 2 SD (4.37 mIU/L in our study) and <6 mIU/L; II, TSH between 6 and 12 mIU/L; and III, TSH >12 mIU/L.
  
  
  RESULTS
  In all treated groups, mean T4 and FT4 levels were lower than in the control group, whereas the CBZ- and VPA-treated children additionally showed reduced mean T3 and TBG levels and increased mean TSH levels. In the group receiving CBZ, 8.2% had TSH values higher than the normal-range maximum, by comparison with only 3.6% of healthy children. The increase in TSH levels was particularly marked in VPA-treated children, accounting for 26% of patients with subclinical hypothyroidism.
  
  
  CONCLUSIONS
  Our results, in contrast to previous reports, suggest that CBZ and particularly VPA may induce subclinical hypothyroidism. This suggests a need for careful monitoring of TSH levels in children receiving CBZ or VPA.
authors.affiliation: Departamento de Pediatría, Hospital General de Galicia, Santiago de Compostela, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Eirís-Puñal
authors.forename: M
authors.initials: M
authors.lastname: Del Río-Garma
authors.forename: M C
authors.initials: MC
authors.lastname: Del Río-Garma
authors.forename: S
authors.initials: S
authors.lastname: Lojo-Rocamonde
authors.forename: I
authors.initials: I
authors.lastname: Novo-Rodríguez
authors.forename: M
authors.initials: M
authors.lastname: Castro-Gago
mesh_terms: D000293:Adolescent; D000367:Age Factors; D002220:Carbamazepine / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000097:blood / Q000139:chemically induced*; D008297:Male; D010634:Phenobarbital / Q000009:adverse effects / Q000627:therapeutic use; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D013975:Thyroxine-Binding Proteins / Q000032:analysis; D014284:Triiodothyronine / Q000097:blood; D014635:Valproic Acid / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D013975:Thyroxine-Binding Proteins; D014284:Triiodothyronine; D002220:Carbamazepine; D014635:Valproic Acid; D013972:Thyrotropin; D013974:Thyroxine; D010634:Phenobarbital