Long‐Term Treatment of Children with Epilepsy with Valproate or Carbamazepine May Cause Subclinical Hypothyroidism

Abstract

Summary:Purpose: 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 (TJ, thyroxine (TJ, free thyroxine (FT,), thyroxine-binding globulin (TBC), 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 mIUL in our study) and <6 mIU/L; 11, TSH between 6 and 12 mIUL; and 111, TSH >I2 mIU/L.Results: In all treated groups, mean T, and f14 levels were lower than in the control group, whereas the CBZ-and VPAtreated children additionally showed reduced mean T, and TBC levels and increased mean TSH levels. In the group receiving CBZ, 8.2% had TSH values higher than the normalrange 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.

Brief Communication: NO EFFECT OF LONG-TERM VALPROATE THERAPY ON THYROID AND PARATHYROID FUNCTIONS IN CHILDREN

“…Several studies have been performed to observe the effect of VPA on thyroid and parathyroid functions; the results, however, have been controversial. Normal and abnormal levels of thyroid and parathyroid hormones (PH) have been reported in epileptic patients (Bentsen, Gram, & Veje 1983;Conran et al, 1985;Eiris-Punal et al, 1999;Isojarvi et al, 2001;Pena Grinan et al, 1991;Tanaka et al, 1987;Verrotti et al, 2001). In this study, we studied serum thyroid and PH levels in children with epilepsy who had been receiving long-term VPA therapy in order to determine whether there was any effect of VPA therapy on these hormones.…”

“…Eiris-Punal et al (1999) recorded that mean T4, FT4, triiodothyronine (T3), and thyroid binding globulin levels were lower, and that mean TSH levels were higher in VPA-treated children than those of the control group. From these findings, they suggested that VPA might induce subclinical hypothyroidism (Eiris-Punal et al, 1999). Similarly, Bentsen et al (1983) noted that VPA caused a decrease in T4, FT4, and T3.…”

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

“…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.…”

The effects of oxcarbazepine treatment on vitamin B12 and folate levels, thyroid functions, sex hormones, and bone mineral density in epileptic patients

“…Cramer and Jones reported that fT4 levels were low in patients taking CBZ [23]. Eiris-Punal et al have reported low T4 and high TSH levels in patients taking CBZ and that subclinical hypothyroidism could develop in these patients [24]. Caksen et al reported that, although statistically not significant, long-term CBZ treatment caused a decrease in serum total and free T4 levels and that T4 levels returned to normal once the treatment was discontinued [25].…”