Differential but infrequent alterations of hepatic enzyme levels and thyroid hormone levels by anticonvulsant drugs.

OBJECTIVE

To assess the differential effects of antiepileptic drugs (AEDs) on hepatic enzyme and thyroid hormone levels and to assess the frequency and degree of these alterations.

STUDY DESIGN

Retrospective analysis of hepatic enzyme (serum aspartate aminotransferase and alanine aminotransferase) and thyroid hormone (thyroxine, T uptake; and free thyroxine index) levels obtained during a 10-year period in a large unselected outpatient population of patients with epilepsy.

PATIENTS

Unselected (for age, sex, race, type of epilepsy, or degree of control) epileptic subjects (n = 642 for determination of hepatic enzyme levels and n = 317 for determination of thyroid hormone levels) attending the largest outpatient epilepsy center in the Midwest. Infants (younger than 1 year) and those receiving more than two AEDs were excluded.

OUTCOME MEASURE

Hepatic enzyme and thyroid hormone level alterations vis-à-vis the type of AED, serum AED levels, and monotherapy vs bitherapy.

RESULTS

Aspartate aminotransferase level alterations were mainly due to valproate or phenobarbital, and alanine aminotransferase alterations were due to phenytoin. Significant enzyme level elevations were infrequent (2% [14/642] of patients), mild, usually associated with bitherapy, transient, and confined to aspartate aminotransferase level. Persistent elevations of both aspartate aminotransferase and alanine aminotransferase levels occurred in only one patient, and he had underlying liver disease. Phenytoin was most and phenobarbital least likely to influence the thyroid indexes. Although bitherapy was more likely to produce biochemical alterations of thyroid hormone levels compared with monotherapy, clinically significant thyroid hormone level alterations were seen in only one of 317 patients, and this patient was known to have hypothyroidism.

CONCLUSIONS

Antiepileptic drugs affect hepatic enzyme and thyroid hormone levels differentially, and bitherapy alters them more than monotherapy does. However, alterations are mostly mild and clinically insignificant and do not justify routine testing, except in those known to have a coexisting hepatic or thyroid abnormality, those who develop symptoms of hepatic or thyroid involvement while receiving AEDs, and perhaps those receiving bitherapy with high serum AED levels.