Valproate use and thyroid dysfunction in children with idiopathic epilepsy

Abstract

Background Long-term administration of valproic acid (VPA) has side effects, including thyroid dysfunction. Subclinical hypothyroidism (SCH) identified by elevated serum thyroid stimulating hormone (TSH) concentrations with normal thyroxine (T4) and triiodothyronine (T3), or normal free thyroxine (fT4) and free triiodothyronine (fT3) has been demonstrated in idiopathic epilepsy patients receiving VPA.
 Objective To evaluate for associations between age at initiation of VPA treatment and duration of treatment with thyroid dysfunction.
 Methods A cross-sectional study was conducted from October 2012 to May 2013 in Haji Adam Malik and Pirngadi Hospitals, Medan, North Sumatera. Subjects were children ranging from 0 and below 18 years who had been diagnosed with idiopathic epilepsy. Blood specimens were taken to evaluate serum T3, T4, and TSH levels in all subjects. Data were analyzed using bivariate and multivariate analyses.
 Results A total of 49 subjects were included in the study. Age of ≤ 4 years at initiation of VPA was found to be a significant risk factor for SCH in the bivariate analysis (OR 6.67; 95%CI 1.215 to 36.594, P=0.036). Three factors had P values <0.25 in the bivariate analysis and were subsequently analyzed by stepwise multivariate regression test: age at initiation of VPA, duration of treatment, and drug dosage. The VPA initiation at age <4 years had 6.67 times the risk of SCH than the age of >4 years (95%CI 1.215 to 36.594; P=0.029). Duration of treatment and VPA dosage were not significantly associated with SCH on multivariate analysis
 Conclusion Age ≤ 4 years old at the initiation of VPA is associated with thyroid dysfunction. However, no significant association was found between duration of treatment as well as drug dosage with thyroid dysfunction.