Since the adrenal cortex and medulla are intimately interrelated, the effects of
anticonvulsant drugs may affect both of these hormonal systems.
Anticonvulsants are commonly used long-term for the treatment of
epilepsy,
chronic pain syndromes and
affective disorders. In patients where adrenal function needs to be evaluated, the clinician should be aware of the potential interactions between
anticonvulsant medication and the hypothalamo-pituitary-adrenal axis.
Carbamazepine,
phenytoin and
phenobarbitone induce the liver P450
cytochrome enzyme system and stimulate
steroid clearance. Therefore, patients investigated for
Cushing's syndrome may show a falsely positive
dexamethasone suppression test, and patients with
adrenal insufficiency on
steroid replacement may require increased doses of
steroids; furthermore, increased
corticosteroid-binding-globulin levels are also associated with chronic
anticonvulsant administration. In addition, concomitant treatment with
benzodiazepines, probably acting via the
GABA pathway, can also alter the
ACTH/
cortisol response to stressful stimuli. Direct and indirect evidence suggest that
benzodiazepines,
acetazolamide and
magnesium sulphate can also interfere with the renin-angiotensin-aldosterone system. Finally, to our knowledge, no systemic data are yet available in the human on the effect of
antiepileptics on the function of the adrenal medulla and/or
catecholamine metabolism; however, as the adrenal medulla receives part of its blood supply from the cortex, it is possible that alterations of cortical hormonal composition might affect adrenal medulla function overall.