Carbamazepine and risk of hypothyroidism: a prospective study
Jiri Horacek1, Julius Simko1 & Gerhard Waberzinek1
Author affiliations
1Charles University, Faculty of Medicine and University Hospital, Dept. Internal Medicine, Hradec Kralove, Czech Republic; 2Charles University, Faculty of Medicine and University Hospital, Dept. Neurology, Hradec Kralove, Czech Republic.
While carbamazepine (CBZ) treatment may affect serum thyroid hormone concentrations it rarely leads to clinically important hypothyroidism. This study was aimed to evaluate an early effect of CBZ on thyroid status in hypothyroid patients with thyroid hormone replacement, as compared with patients without a thyroid disorder.
Twenty-nine patients indicated for CBZ treatment were followed prospectively. Their thyrotropin (TSH), total thyroxine (TT4) and free thyroxine (FT4) serum levels were assayed before the start of CBZ medication (150 mg/d in the 1st week, then 450 mg/d), and then at week intervals for 7 weeks. Nineteen patients had no thyroid disorder before CBZ treatment (control group A), whereas 10 patients were treated with L-thyroxine (median 100 ug/d) for hypothyroidism and were stable before CBZ treatment (group B). The fluctuations of thyroid status after the start of CBZ treatment were compared between the groups.
In the control group, TT4 was significantly decreased by ca. 15 to 25%, starting from the 1st week of treatment (Friedman, P<0.001), while FT4 was decreased by only ca. 10 to 15%, and the significance (P<0.001) was delayed till the 2nd week. There was a concomitant increase in FT4/TT4 ratio (P<0.001) and a mild, non-significant increase in TSH (P=0.073) never exceeding normal range. Conversely, in group B with hormonal replacement, a similar TT4 and FT4 decline was followed by significantly increasing TSH levels (P=0.011), while the FT4/TT4 ratio was not significantly changed (P=0.218). In 3 of 10 patients TSH rose over 5 mU/L in the 3rd and 4th week, and the treatment had to be modified.
In patients with no thyroid disorder, CBZ caused subtle hormonal changes of no clinical relevance, due to adaptive response. In hypothyroid patients with replacement therapy this adaptation is lacking, and CBZ may precipitate subclinical or overt hypothyroidism. In this group, thyroid function monitoring early in the course of CBZ treatment seems advisable.
The study has been supported by research project MZO 00179906