Abstract

ABSTRACT: We studied the effect of ketoconazole on glucocorticoid metabolism in three patients before and after a continuous four-hour infusion of ACTH. A single 400 mg oral dose of ketoconazole caused a decrease in serum cortisol concentration, while the concentration of 11-deoxycortisol and its ratio to cortisol increased. The decrease in serum cortisol levels was not accompanied by an increase in plasma ACTH concentration. A four-hour continuous infusion of ACTH resulted in an appropriate elevation of serum cortisol, but with a marked increase in serum concentration of 11-deoxycortisol and its ratio to serum cortisol. We conclude that (1) 400 mg of ketoconazole can decrease cortisol synthesis apparently through a partial block of the 11-β-hydroxylation step; (2) the observed degree of inhibition may not be sufficient to stimulate the hypothalamic-pituitary-adrenal axis or to cause overt symptoms or signs of adrenal insufficiency; and (3) this partial block of the 11-β-hydroxylation step becomes more evident during a continuous, infusion of ACTH, which can stimulate a normal response of cortisol.