Do inducers of drug metabolism also induce thyroid hormones and thereby cause hypothyroidism and its myriad complications? Lending credence to that eventuality is a study (A. Garoufi and colleagues, European Journal of Neurology 21(1):118-123, 2014) that prospectively followed anticonvulsant-treated, epileptic children over a long term while assaying their thyroid function and lipid profiles.
The authors studied 23 children whose seizure disorders were being treated with oxcarbazepine monotherapy (reported to have approximately two-thirds the potency of carbamazepine in vitro with respect to induction of CYP3A4), measuring at baseline and at both eight and eighteen months of treatment their thyroid function (serum free levothyroxine, triiodothyronine, and thyrotropin (TSH)), lipid profile (serum total triglyceride, high and low density lipoprotein cholesterol, total serum cholesterol) and liver function (serum gamma glutamyltransferase (GGT)).
Results at eight and/or eighteen months were consistent with significant reductions in thyroid function, accompanied by changes in their lipid profiles consistent with complications of hypothyroidism: free thyroxine concentrations were significantly reduced (and serum TSH concentrations significantly elevated) at both eight and eighteen months of treatment, contemporaneous with significant elevations of total serum cholesterol (at eight months) and (at both eight and eighteen months) significant increases of low density lipoprotein cholesterol. (No changes were observed throughout study in serum triiodothyronine, high density lipoprotein cholesterol, or serum triglycerides.)
Serum GGT and low density lipoprotein cholesterol were positively correlated at both follow-up intervals, as were serum total cholesterol and serum TSH.
The authors attribute the changes they observed at both eight and eighteen months of treatment with oxcarbazepine monotherapy consistent with thyroid dysfunction and hypothyroid-related abnormalities of serum lipids deemed proxies for later development of cardiovascular disease. They attribute their patient’s abnormal thyroid functions to oxcarbazepine-emergent induction of free levothyroxine (as has been reported previously apropos of carbamazepine). Their work broaches a possibility that other, equally and more potent hepatic inducers also may induce metabolism of levothyroxine and result in clinically significant hypothyroidism, hypothyroidism-related abnormal lipid metabolism, and acceleration or worsening of atherosclerotic cardiovascular disease.