Cushing's syndrome without excess cortisol

In patients taking inhaled corticosteroids the biochemical detection of a suppressed hypothalamicpituitary-adrenal axis is well documented.1 2 Fluticasone propionate is the most potent inhaled glucocorticoid,3 4 and adrenocortical insufficiency has been reported in 12% of patients on a high dose of inhaled fluticasone.1 5 The incidence of addisonian crises is lower, but crises may occur during intercurrent illness or after dose reduction or withdrawal.5

Itraconazole is an orally active antifungal triazole that inhibits cytochrome P450 dependent CYP3A4 and consequently decreases the clearance of synthetic glucocorticoids.6 The combination of long term inhaled steroid with oral itraconazole may exacerbate suppression of the hypothalamic-pituitary-adrenal axis. In a cohort of 25 patients with cystic fibrosis, six were reported to have adrenal insufficiency.7 However, overt Cushing's syndrome as a result of this drug combination is less well understood. We report the rapid development and the resolution of iatrogenic Cushing's syndrome in a patient taking itraconazole for six weeks in addition to inhaled fluticasone.