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Practice Lesson of the week

Cushing's syndrome without excess cortisol

BMJ 2006; 332 doi: (Published 23 February 2006) Cite this as: BMJ 2006;332:469
  1. D R Woods, specialist registrar1,
  2. C S Arun, specialist registrar (,
  3. P A Corris, professor2,
  4. P Perros, consultant1
  1. 1 Department of Endocrinology, Freeman Hospital, Newcastle upon Tyne NE7 7DN
  2. 2 Department of Respiratory Medicine, Freeman Hospital
  1. Correspondence to: C S Arun
  • Accepted 26 August 2005

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.

Case report

A 55 year old man with bronchiectasis and asthma developed an exacerbation of allergic bronchopulmonary aspergillosis. His regular medication included long acting and short acting inhaled β2 agonists (formoterol and terbutaline respectively), the leucotriene receptor antagonist montelukast (10 mg once daily), alendronate (75 mg weekly), amitriptyline (50 mg daily at night), and codeine phosphate (60 mg as required). In addition, he had been taking inhaled fluticasone (1-1.5 mg twice daily) for over two years with …

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