Risk Factors for Development of Subclinical Hypothyroidism during Valproic Acid Therapy

Abstract

To identify risk factors for subclinical hypothyroidism (SCH) (thyroid-stimulating hormone levels >5 mIU/mL) in patients receiving valproate (VPA) therapy. During a period of 2 years, consecutive patients with epilepsy receiving VPA and a control group of patients with diseases other than epilepsy attending a tertiary care neurology clinic were screened for SCH. The 2 groups were compared. The association between SCH and specific risk factors was investigated with bivariate and multivariate analyses. Thirty-six of 143 patients receiving VPA (25.2%, mean age +/- SD: 8.5 +/- 6.6 years) and none of the 35 control subjects had SCH (P < .001). Predictors of SCH were younger age (OR: 1.15, cutoff age 3.9 years); duration of treatment between 6 and 24 months versus <6 months (OR: 2.98) and >24 months (OR: 2.66); VPA polytherapy with enzyme-inducing agents (OR: 6.08), or polytherapy with non-enzyme-inducing agents (OR: 3.34) compared with VPA monotherapy. Most (88.2%) patients with duration of therapy >2 years were older than 3.9 years. Risk factors for SCH were young age, co-medication with antiepileptic drugs, and duration of therapy between 6 and 24 months. Screening patients with these risk factors may be warranted.