Carbamazepine (Tegretol^R) Inhibits in Vivo Iodide Uptake and Hormone Synthesis in rat Thyroid Glands

Abstract

Decreased serum concentrations of T3 and T4 occur in patients treated with the anticonvulsant drug carbamazepine (CBZ), but with rare exception, these patients remain euthyroid. The mechanism that accounts for diminished hormone levels is unknown, and our objective was to study the direct effect of CBZ on iodide uptake and hormone synthesis in thyroid glands of CBZ-treated and pair-fed control rats. Chronic ingestion (per os) of CBZ in male rats reduced the four hour thyroid 131I-iodide uptake by approximately 60%. This inhibition occurred after the animals had received sufficient CBZ to attain plasma CBZ concentrations of 0.8 microgram/ml. Continued treatment with CBZ ranging from 560 to 800 mg/kg/day for 14 days did not result in further inhibition of iodide uptake even though the plasma CBZ concentrations had increased 6-20 fold. No inhibition of iodide uptake was apparent when the animals initially received CBZ ranging from 40 to 152 mg/kg body weight for 22 days when there were no detectable levels of plasma CBZ. Overall growth rates of CBZ-treated rats were slightly (6-10%) less than the pair-fed control animals. Plasma T4 concentrations were reduced by 18% (p less than 0.05) in the CBZ-fed animals, while T3 concentrations were diminished by 53% (p less than 0.01). CBZ appeared to alter thyroidal iodide transport because the thyroid:plasma iodide ratios were decreased by 26% in the drug-treated rats. The distribution of radioiodine in thyroidal iodoamino acids was essentially the same in both groups of rats but the absolute quantities of radioiodine were more than 2.5 times greater in the control rats. CBZ failed to inhibit peroxidase-catalyzed iodide and guaiacol oxidation in vitro. No differences in thyroid gland morphology were noted in the two groups of animals, but weights of the glands from the CBZ-fed animals increased by 25% after 42 days. It is concluded that CBZ, or its metabolites, has a direct inhibitory effect on iodide utilization and hormone synthesis by the thyroid gland.

Effect of antiepileptic drug therapy on thyroid hormones among adult epileptic patients: An analytical cross-sectional study

“…[ 16 17 ] In addition, study done by Villa and Alexander also suggested that iodine uptake inhibition by the thyroid gland might be one of the other mechanism by which carbamazepine can induce thyroid dysfunction. [ 18 ] Although mechanistic approach based study was not conducted, the present study showed screening for thyroid hormones is recommended for patients periodically taking long-term conventional AEDs than for the newer drugs, thereby thyroid dysfunction induced complications can be prevented in the epileptic patients. The small sample size was the limitation in our study; therefore, further prospective studies are required to be mediated on a larger scale of adult epileptic patients to confirm our results.…”

Thyroid Function in Men Taking Carbamazepine, Oxcarbazepine, or Valproate for Epilepsy

“…TSH responses to TRH are normal in patients taking CBZ, and therefore pituitary interference by the drug seems unlikely (1,5). It has also been suggested that CBZ may inhibit iodine uptake by the thyroid gland (25).…”

The Effect of Anticonvulsant Drugs on Serum Thyroid-Stimulating Hormone

“…This mechanism was supported by Surks et al who postulated the drug-induced inhibitory response of thyroid releasing hormone on TSH release [21]. Villa and Alexander proposed another mechanism for carbamazepine induced thyroid dysfunction due to the inhibition of iodine uptake by the thyroid gland [22].…”