Long-term treatment of children with epilepsy with valproate or carbamazepine may cause subclinical hypothyroidism.
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.
Eirís-Puñal
J
J
Departamento de Pediatría, Hospital General de Galicia, Santiago de Compostela, Spain.
Del Río-Garma
M
M
Del Río-Garma
M C
MC
Lojo-Rocamonde
S
S
Novo-Rodríguez
I
I
Castro-Gago
M
M
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
D013975:Thyroxine-Binding Proteins; D014284:Triiodothyronine; D002220:Carbamazepine; D014635:Valproic Acid; D013972:Thyrotropin; D013974:Thyroxine; D010634:Phenobarbital