Risk factors for development of subclinical hypothyroidism during valproic acid therapy.
OBJECTIVE
To identify risk factors for subclinical hypothyroidism (SCH) (thyroid-stimulating hormone levels >5 mIU/mL) in patients receiving valproate (VPA) therapy.


METHODS
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.


CONCLUSIONS
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.
Mikati
M A
MA
Department of Pediatrics, American University of Beirut Medical Center, Beirut, Lebanon. mamikati@aub.edu.lb <mamikati@aub.edu.lb>
Tarabay
H
H
Khalil
A
A
Rahi
A C
AC
El Banna
D
D
Najjar
S
S
D000293:Adolescent; D017677:Age Distribution; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004827:Epilepsy / Q000175:diagnosis / Q000188:drug therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007037:Hypothyroidism / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology*; D015994:Incidence; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D011336:Probability; D012016:Reference Values; D012307:Risk Factors; D012720:Severity of Illness Index; D017678:Sex Distribution; D013960:Thyroid Function Tests; D013972:Thyrotropin / Q000097:blood*; D014635:Valproic Acid / Q000009:adverse effects* / Q000627:therapeutic use
D014635:Valproic Acid; D013972:Thyrotropin