Eur J Endocrinol
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DOI: 10.1530/eje.1.02120
European Journal of Endocrinology, Vol 154, Issue 4, 519-524
Copyright © 2006 by European Society of Endocrinology
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CASE REPORT

Long term control of hypercortisolism with fluconazole: case report and in vitro studies

Michaela Riedl1, Christina Maier1, Georg Zettinig2, Peter Nowotny1, Wolfgang Schima3 and Anton Luger1

1 Departments of Medicine III, Clinical Division of Endocrinology and Metabolism, 2 Nuclear Medicine and 3 Radiology, Medical University and General Hospital of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria

(Correspondence should be addressed to A Luger; Email: anton.luger{at}meduniwien.ac.at)

Abstract

Objectives: To evaluate the efficacy of fluconazole as an alternative treatment for controlling hypercortisolism in Cushing’s syndrome and to determine its effect on glucocorticoid production in vitro.

Design: Case report and in vitro study in a University Clinic.

Case: An 83 year old patient presented with recurrence of Cushing’s syndrome due to pulmonary metastases three years after unilateral adrenalectomy. During a near fatal episode of sepsis she was started on fluconazole 200 mg/day intravenously which normalised cortisol excretion. The therapy was continued orally for 18 months. Upon temporary discontinuation and reintroduction of treatment, cortisol levels increased and normalized, respectively. At month 16, fluconazole had to be increased to a dose of 400 mg/day to keep cortisol excretion in the normal range. Disease progression was slow and no side effects occurred.

In vitro results: Fluconazole in a concentration of 500 µM nearly abolished corticosterone production over 24 h from the adrenal adenoma cell line Y-1 (8.6 ± 0.5% compared with control, P < 0.0001) and significantly reduced corticosterone production in concentrations of 50 µM (48.3 ± 1.9% vs. control, P < 0.0001) and 5 µM (80.5 ± 8.5% vs. control, P < 0.05).

Conclusion: These results demonstrate for the first time that fluconazole normalises cortisol concentrations in vivo in a patient with Cushing’s syndrome with adrenal carcinoma and inhibit glucocorticoid production in vitro in a cell line. Thus, fluconazole might be useful in controlling glucocorticoid excess in Cushing’s syndrome and because of its lower toxicity might be preferable to ketoconazole.







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