Changes in thyroid function tests induced by 2 month carbamazepine treatment in l-thyroxine-substituted hypothyroid children

Abstract

In five l-thyroxine-substituted hypothyroid children with partial epilepsy serum total thyroxine (T₄) and free T₄ (FT₄) significantly (P<0.01) decreased following 2 months of carbamazepine (CBZ) administration (20 mg/kg per BW per day) from mean (±SD) values of 12.7±1.1 μg/dl and 15.5±1.8 pg/ml to mean values of 7.5±2.3 and 10.1±1.7, respectively. In all but one patient important changes in both serum total and free triiodothyronine (T₃, FT₃) were not observed; consequently T₃∶T₄ and FT₃∶FT₄ ratios significantly (P<0.05) increased in the whole series. Three subjects had post-treatment serum TSH that rose to hypothyroid levels parallel to a T₄ decrease. The negligible thyroid hormone secretion and the unmodified T₃-uptake (T₃U) or T₄-binding globulin (TBG) exclude direct effects of CBZ on thyroid gland and on carrier serum proteins, respectively. The findings observed, instead, might be due to accelerated T₄ metabolic clearance together with augmented T₄ to T₃ conversion rate, as previously demonstrated for diphenylydantoin. The sharp reduction in T₄ and FT₃ concentrations is the peripheral display of this event, which is associated with a decompensation of the metabolic status, as indicated by serum TSH enhancement. In all cases a supplement of l-thyroxine by itself was able to restore euthyroid TSH serum concentrations, suggesting that hypothyroidism in patients with partial epilepsy to whom CBZ had been administered requires a higher l-T₄ substitutive regimen.