Thyroid Function in Girls with Epilepsy with Carbamazepine, Oxcarbazepine, or Valproate Monotherapy and after Withdrawal of Medication

Abstract

Summary:Purpose: Antiepileptic drugs may affect the serum thyroid hormone concentrations. The aim of this study was to evaluate thyroid function in 78 girls taking carbamazepine (CBZ), oxcarbazepine (OXC), or valproate (VPA) monotherapy for epilepsy and after withdrawal of the treatment.Methods: Forty-one girls taking VPA, 19 taking CBZ, and 18 taking OXC for epilepsy, as well as 54 healthy age-matched controls, aged 8 to 18 years, participated in the study. All the girls were examined clinically, and their pubertal stage was assessed. Blood samples were obtained for thyroid hormone and antibody assays. These examinations were repeated after a mean followup of 5.8 years to assess thyroid function, and 64 (82%) of 78 patients and 42 (78%) of 54 controls agreed to participate in the second evaluation.Results: In the first evaluation, the mean serum thyroid hormone concentrations were lower in the girls taking CBZ [thyroxine (T 4 ), 70.2; SD, 10.9 nM; and free thyroxine (FT 4 ), 11.5; SD, 1.8 pM] or OXC (T 4 , 74.9; SD, 16.4 nM; and FT 4 , 11.3; SD, 1.8 pM) than in the control girls (T 4 , 96.6; SD, 15.1 nM, and FT 4 , 14.4; SD, 1.5 pM; p < 0.001, all comparisons). However, thyrotropin (TSH) concentrations were normal in the girls taking CBZ or OXC. Sixty-three% of the girls taking CBZ and 67% of the girls taking OXC had serum T 4 and/or FT 4 levels below the lower limit of the reference range. The VPA-treated girls with epilepsy had normal serum T 4 and FT 4 concentrations, but slightly increased TSH levels (3.3; SD, 1.5 mU/L; p < 0.01) compared with the control girls (2.5; SD, 1.0 mU/L). Normal serum hormone concentrations were restored in the patients who discontinued the medication.Conclusions: Both CBZ and OXC reduce serum thyroid hormone concentrations in girls with epilepsy. Conversely, VPA is associated with normal serum thyroid hormone and increased thyrotropin levels. However, our results suggest that the changes in serum thyroid hormone and thyrotropin levels are reversible after withdrawal of the medication. Key Words: Epilepsy-Children-Thyroid functionCarbamazepine-Oxcarbazepine-Valproate.It is well known that the traditionally used antiepileptic drugs (AEDs) may affect thyroid function (1-5). The effects of AEDs on thyroid function in children with epilepsy have been investigated less extensively, however. Moreover, no data exist on thyroid function in children treated with oxcarbazepine (OXC).Carbamazepine (CBZ) is the most widely used first-line AED in partial-onset epilepsy of both adults and children (6). OXC is the 10-keto analogue of CBZ and has anticonvulsant efficacy comparable to that of CBZ in partial seizures with or without generalization (7). Despite this, CBZ and OXC have different metabolic pathways in the liver: CBZ is oxidized and OXC is metabolized mainly by reduction to its active metabolite, 10,11-dihydro-10-hydroxy-carbamazepine.CBZ therapy has certain effects on thyroid function: it decreases the serum thyroid hormone levels, but allows the serum thyrotropin (TSH) concentrations ...

Thyroid hormones in children with epilepsy during long-term administration of carbamazepine and valproate

“…These data are in agreement with previous papers that found normal thyroid hormone levels (19,20,25,(28)(29)(30). By contrast, other studies (11,31) found normal thyroid hormone levels while TSH levels were increased. In a recent study, 36 out of 143 patients had TSHO5 m IU/l (index of subclinical hypothyroidism) during VPA treatment: 10 out of these patients also had low fT 4 levels; 9 out of these 36 patients had clinical symptoms of hypothyroidism but they are considered to have subclinical hypothyroidism because of high TSH values (32).…”

“…These results suggest that the changes in serum fT 4 levels are reversible. Our experience of 5 patients who have withdrawn CBZ-therapy is in agreement with previous reports (27,11).…”

“…Different thyroid dysfunctions have been reported in epileptic patients receiving VPA. In particular, reports on the effect of VPA on the thyroid hormones balance are conflicting, and both low and unchanged serum thyroxine (T 4 ) and free thyroxine (fT 4 ) levels have been found in patients receiving VPA monotherapy, never associated with overt thyroid dysfunction (9)(10)(11)(12)(13)(14): these studies showed normal mean TSH serum levels while other studies documented high TSH levels in patients receiving VPA therapy (10)(11)(12). However, the majority of studies have been performed in adult patients receiving these drugs, often in association with other AEDs.…”

A comparative study of thyroid status of patients on phenytoin, carbamazepine and valproate monotherapy

“…28,29 Valproate on the other side showed no significant change in the serum T3, T4 and TSH concentration, this results were in consistent with the other studies reported earlier in contrast other studies found normal thyroid hormone levels while TSH levels were increased. [30][31][32][33][34] This may be due to CBZ and Phenytoin induces hepatic microsomal enzymes markedly in dose-dependent fashion whereas VAL has no significant effect.…”

Efeitos endócrinos e metabólicos das drogas antiepilépticas

“…Há poucos dados disponíveis na literatura sobre potenciais interações do topiramato, gabapentina, felbamato, pregabalina e zonisamida sobre a produção, liberação e metabolismo dos hormônios tireoideanos (43). Em dois estudos clínicos, o uso de carbamazepina e oxcarbazepina associou-se à redução nos níveis de hormônios tireoideanos, que foram reversíveis com a suspensão das medicações (45,46). Há relatos em crianças de elevação do TSH (sem alterações nos níveis de T3 e T4) com uso crônico de valproato, mas esse quadro também é revertido com a supressão da droga (47,48).…”