Function of the adrenal cortex during therapy with fluconazole in intensive care patients

An impairment of cortisol synthesis can be assumed for the new antimycotic fluconazole based on its chemical structure (triazole derivative) and mechanism of action (inhibition of ergosterol synthesis). In healthy volunteers, however, no influence on steroid hormone production could be found. The present study was undertaken to clarify whether this is also true for critically ill, long-term patients in an intensive care unit. The basal cortisol and adrenocorticotropic hormone (ACTH) levels were determined by means of radioimmunoassay in 11 patients being treated with antimycotics at fixed times. Antimycotic treatment was carried out using either fluconazole (n = 6) or a combination of amphotericin B and flucytosine (n = 5) for 14 days. Seven days after cessation of the treatment the above-mentioned hormones were again determined. Patients with the same baseline criteria who did not require antimycotic treatment (n = 8) served as controls. During the entire study period adequate cortisol synthesis was found after ACTH stimulation in all three patient groups. They all presented with relatively raised basal cortisol levels (range 16.4-31.0 micrograms dl-1) and an increase in ACTH-stimulated cortisol synthesis from 31% (group ampho B/flucytosine) to 78% (group fluconazole). The basal ACTH values were always within the normal range (9.2-16.4 pg ml-1). Neither the basal ACTH levels nor the basal cortisol levels as well as the cortisol levels determined after the ACTH test showed adrenocortical suppression in the patients of all three groups. Thus, according to the present results clinically relevant impairment of cortisol synthesis after treatment with fluconazole can be excluded.