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Cushing's Syndrome Due to Interaction Between Inhaled Corticosteroids and Itraconazole

Registrar, Department of Endocrinology, Auckland Hospital, Auckland, New Zealand

Warwick Bagg, MD

Senior Lecturer in Medicine, Department of Medicine, University of Auckland; Physician, Department of Internal Medicine, Auckland Hospital

Mark G Thomas, MD

Associate Professor of Infectious Diseases, Department of Molecular Medicine and Pathology, University of Auckland; Physician, Department of Infectious Diseases, Auckland Hospital

Jennifer A Lucas, MBChB

Lecturer in Medicine, Department of Medicine, University of Auckland; Physician, Department of Internal Medicine, Auckland Hospital; Research Fellow in Bone Disease, Department of Medicine, University of Auckland

Rob Ticehurst, BSc Hons

Senior Pharmacist, Pharmacy Department, Auckland Hospital

Peter N Black, MBChB

Associate Professor of Medicine and Clinical Pharmacology, Department of Medicine, University of Auckland; Physician, Department of Internal Medicine, Auckland Hospital

Reprints: Mark J Bolland MBChB, Department of Endocrinology, Auckland Hospital, Private Bag 92-024, Auckland 1, New Zealand, fax 64 9 3074993, mbolland{at}adhb.govt.nz

OBJECTIVE: To report a case of an interaction between inhaled corticosteroids and itraconazole causing iatrogenic Cushing's syndrome and provide a review of the relevant literature.

CASE SUMMARY: A 70-year-old white woman on long-term treatment with high-dose inhaled corticosteroids for asthma was diagnosed as having Scedosporium apiospermum infection of the skin and subcutaneous tissues. As a result, she was treated with itraconazole for 2 months. She subsequently developed Cushing's syndrome due to a probable cytochrome P450-mediated interaction between itraconazole and budesonide. She also had secondary adrenal insufficiency requiring prolonged treatment with replacement hydrocortisone.

DISCUSSION: Budesonide is a potent glucocorticoid that is metabolized in the liver by the CYP3A4 isoenzyme to inactive metabolites. Itraconazole is a potent cytochrome P450 inhibitor. It can inhibit the metabolism of oral or inhaled corticosteroids, producing cortisol excess leading to Cushing's syndrome and adrenal insufficiency. An assessment of causality indicated a possible adverse interaction between itraconazole and budesonide.

CONCLUSIONS: The combination of itraconazole and inhaled corticosteroids is increasingly being used to treat conditions such as allergic bronchopulmonary aspergillosis. Clinicians need to be aware of the potential for an interaction between such a combination.

Key Words: budesonide, Cushing's syndrome, itraconazole

Published Online, December 5, 2003. www.theannals.com, DOI 10.1345/aph.1D222

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