Antiepileptic drugs are associated with central hypothyroidism

Abstract

Objective: Studies in children have shown an increased frequency of central hypothyroidism (CH) with long-term use of antiepileptic drugs (AEDs). The aim of this study was to search for CH in adults treated with AEDs and find whether the type of AEDs used matters.

Materials and methods: Adult epileptic patients treated at the neurology outpatient clinic at Landspitali University Hospital (LSH) from 1998 to 2011 were included. Patients were invited for a blood test if serum levels for TSH (s-TSH) or free-T₄ (s-fT₄ ) had not already been obtained. CH was defined as s-fT₄ below the reference range (12-22 pmol/L) and normal s-TSH levels (0.30-4.20 mIU/L). Data were analyzed using logistic regression and Mann-Whitney test.

Results: We identified 165 patients (92 women), mean age 45.6 (±15.5, range: 20-92) years. The mean s-fT₄ -level in our group was 14.2 (±2.9, range: 8.1-24.4) pmol/L compared with 16.9 (±6.1) pmol/L in a sample of 13248 measurements at LSH during one year (LSH-group) (P < 0.001). The difference in s-fT₄ -level between men and the LSH-group was significant and also for women (P < 0.001 and P < 0.001, respectively). Thirty-five patients (21%) had CH. A significant association with the use of carbamazepine or oxcarbazepine was found, odds ratio for women 15.0 (95% CI: 4.6-49.5) and 1.8 (95% CI: 0.4-8.3) for men.

Conclusion: 21% of patients treated with AEDs had CH, more often patients taking carbamazepine or oxacarbazepine, and more often women. The s-fT₄ -level was lower among patients treated with AEDs.

Keywords: Antiepileptic drugs; Carbamazepine; Hypopituitarism; Hypothyroidism; Oxcarbazepine.