Thyroid hormones

Thyroid function test results are frequently abnormal in patients who are given carbamazepine (CBZ) or phenytoin. Thyroxine (T4) and free thyroxine (FT4) are often lowered, down to 70% of their normal values.133,134 TSH- and TRH-stimulating test results usually remain normal, however, and the patients remain clinically euthyroid. Only two patients given CBZ and CBZ plus phenytoin have been reported to have overt hypothyroidism.133

The causes of these changes may be:

• increased conversion of T4 to T3
• induction by the hepatic enzyme-inducing AEDs of peripheral metabolism of the thyroid hormones133
• competition by CBZ and thyroid hormones for thyroid-binding globulin133

If the patient is asymptomatic, the changes are of little clinical importance and require no treatment. In thyroxine-substituted hypothyroid patients, the dose of thyroxine used may need to be adjusted upward to compensate for the increased peripheral metabolism of thyroid hormones with CBZ.133

Hyponatremia

CBZ causes water retention and hyponatremia because of an SIADH-like effect. This effect is more likely to occur with CBZ serum levels above 6 mcg/mL and in the elderly. It may result from a combination of actions:

• a direct ADH-like effect on the renal tubule (reversed by demeclocycline)
• a promoting effect at the hypothalamus133

By contrast, phenytoin inhibits ADH release,133 so adding phenytoin to the regimen of CBZ-treated patients with inappropriate ADH may reverse the unwanted effects.133

Oxcarbazepine also causes hyponatremia in a small fraction of patients. The mechanism of oxcarbazepine-induced hyponatremia is not related to an increase in ADH, but may be due to a direct effect of oxcarbazepine on renal collecting tubules, or to an enhancement of their responsiveness to circulating ADH.135

Cortisol

CBZ causes a clinically asymptomatic increase in free cortisol levels.133

Phenytoin in large doses may increase corticotropin and cortisol levels initially.

Adapted from: Klein P and Herzog AG. Endocrine aspects of partial seizures. In: Schachter SC, Schomer DL, eds. The comprehensive evaluation and treatment of epilepsy. San Diego, CA: Academic Press; 1997. p. 207-232.
With permission from Elsevier (www.elsevier.com).
Reviewed and revised June 2004 by Cynthia Harden, MD, Weill Cornell Medical College.