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


METHODS
Case report and in vitro study in a University Clinic.


METHODS
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 microM 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 microM (48.3 +/- 1.9% vs. control, P < 0.0001) and 5 microM (80.5 +/- 8.5% vs. control, P < 0.05).


CONCLUSIONS
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.
Department of Medicine III, Clinical Division of Endocrinology and Metabolism, Medical University and General Hospital of Vienna, Austria.
Michaela
M
Riedl
Christina
C
Maier
Georg
G
Zettinig
Peter
P
Nowotny
Wolfgang
W
Schima
Anton
A
Luger
D000236:Adenoma / Q000150:complications / Q000378:metabolism / Q000601:surgery; D000310:Adrenal Gland Neoplasms / Q000150:complications / Q000378:metabolism / Q000601:surgery; D000315:Adrenalectomy; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000627:therapeutic use; D045744:Cell Line, Tumor; D003345:Corticosterone / Q000096:biosynthesis; D003480:Cushing Syndrome / Q000150:complications / Q000188:drug therapy* / Q000209:etiology; D005260:Female; D015725:Fluconazole / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007654:Ketoconazole / Q000008:administration & dosage; D008175:Lung Neoplasms / Q000150:complications / Q000556:secondary; D012008:Recurrence
D000935:Antifungal Agents; D015725:Fluconazole; D007654:Ketoconazole; D003345:Corticosterone