Adverse effect of phenytoin on glucocorticoid replacement in a child with adrenal insufficiency

Chronic administration of antiepileptic agents such as phenytoin can increase clearance rates of cortisol and synthetic glucocorticoids through hepatic microsomal enzyme induction. However, data concerning an adverse interaction between antiepileptic and steroid drugs are scarce. We herein report an adolescent boy with primary adrenal insufficiency that developed glucocorticoid deficiency after added phenytoin treatment. The patient had an increased requirement for hydrocortisone replacement, and two episodes of vomiting, hyponatremia and mild hypoglycemia. His ACTH levels were markedly elevated. Fifteen days after stopping phenytoin, his serum ACTH concentration returned to normal range. Even though the hydrocortisone dose was gradually decreased, hyponatremia and vomiting have not recurred. In conclusion, we suggest that drugs such as phenytoin affecting hepatic clearance of synthetic glucocorticoids and mineralocorticoids should not be preferred for therapy in patients with adrenal insufficiency. If their use is vital, one should be aware of increased replacement requirements for steroid drugs, and patients should be closely monitored.