How does thyroxine suppress antiseizure medication?
—Jules G. Minkes, DO, Miami

The interaction among thyroxine, seizures, and anticonvulsants is complex. It has been known for quite some time that thyroid hormone lowers the seizure threshold in humans and can cause seizures in patients with Graves’ disease (Epilepsia. 1980;21:91-96). Thyroxine therapy for hypothyroidism has also been shown to induce seizures in certain cases (Neurology. 1985;135:1792-1793). This pro-seizure effect on the brain is not well defined, other than to say that it is believed to be a direct action on cerebral cells by thyroid hormone. Seizures have also been reported in patients who were previously “controlled” on a stable dose of anticonvulsant when thyroxine replacement therapy was initiated (Neurology. 1996;47:605-606). It is thus not clear that thyroxine “suppresses” antiseizure medications in a direct way. Surprisingly, much of the literature has focused on the effects of anticonvulsant therapy on intrinsic thyroid function rather than the converse. Such medications as carbamazepine and phenytoin have been shown to displace thyroxine from plasma protein-binding sites and potentially increase its clearance. Free thyroxine (T4) and triiodothyronine (T3) will be increased, while serum T4 and T3 levels will be decreased. Authors have speculated, therefore, that thyroid-stimulating hormone should be followed to determine if a patient on anticonvulsants has normal thyroid levels (JAMA. 1996;275:1495-1498).
—Christopher Ruser, MD (102-2)

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