Risk factors for development of subclinical hypothyroidism during valproic acid therapy

J Pediatr. 2007 Aug;151(2):178-81. doi: 10.1016/j.jpeds.2007.02.046. Epub 2007 Jun 22.

Abstract

Objective: To identify risk factors for subclinical hypothyroidism (SCH) (thyroid-stimulating hormone levels >5 mIU/mL) in patients receiving valproate (VPA) therapy.

Study design: 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.

Results: 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.

Conclusion: 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.

MeSH terms

  • Adolescent
  • Age Distribution
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Cohort Studies
  • Dose-Response Relationship, Drug
  • Epilepsy / diagnosis
  • Epilepsy / drug therapy
  • Female
  • Follow-Up Studies
  • Humans
  • Hypothyroidism / chemically induced*
  • Hypothyroidism / diagnosis
  • Hypothyroidism / epidemiology*
  • Incidence
  • Logistic Models
  • Male
  • Multivariate Analysis
  • Probability
  • Reference Values
  • Risk Factors
  • Severity of Illness Index
  • Sex Distribution
  • Thyroid Function Tests
  • Thyrotropin / blood*
  • Valproic Acid / adverse effects*
  • Valproic Acid / therapeutic use

Substances

  • Valproic Acid
  • Thyrotropin