Therapeutic advances in endocrinology and metabolism · 2025
Clinical efficacy and safety of fluconazole treatment in patients with Cushing's syndrome.
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Liao Tang-Yi, Lin Yi-Chun, Huang Chun-Jui, Hwu Chii-Min, Lin Liang-Yu
Аннотация
BACKGROUND: Ketoconazole is effective for treating Cushing's syndrome (CS) but its use is limited by the risk of hepatotoxicity. Fluconazole, with similar antifungal properties, is being investigated as a potentially safer alternative for managing CS. This study aims to evaluate the efficacy and safety of fluconazole in patients with CS.
METHODS: This retrospective study evaluated a total of 22 patients with CS, including 12 with Cushing's disease (CD), 3 with adrenal Cushing's syndrome (ACS), and 7 with ectopic Adrenocorticotropic hormone (ACTH) syndrome. Fluconazole was administered orally, ranging from 112.5 to 450 mg daily, with the duration varying from 2 weeks to over 5 years. The efficacy of fluconazole was assessed by changes in 24-hour urinary free cortisol (24-h UFC) levels. Additionally, hepatic safety was assessed by monitoring changes in alanine aminotransferase (ALT) levels.
RESULTS: Following fluconazole treatment, 24-h UFC levels significantly decreased from 717.6 ± 1219.4 to 184.1 ± 171.8 µg/day (p = 0.035). ALT levels showed an increase from 38.5 ± 28.4 to 56.5 ± 47.8 U/L, though this change was not statistically significant (p = 0.090). ALT levels exceeding the upper limit of normal range (ULN) were observed in 12 patients (54.5%), with only 4 patients (18.2%) showing ALT levels more than three times the ULN. Out of 10 patients who received treatment for over 1 year, 5 patients (50.0%) experienced a recurrence, with 24-h UFC levels more than 1.5 times the ULN within 3 to 12 months after fluconazole treatment.
CONCLUSION: Fluconazole effectively reduces hypercortisolism in patients with CS without significant liver injury, suggesting it as a viable therapeutic option for CS. While some cases have shown treatment escape, more studies are required to confirm the long-term efficacy.
METHODS: This retrospective study evaluated a total of 22 patients with CS, including 12 with Cushing's disease (CD), 3 with adrenal Cushing's syndrome (ACS), and 7 with ectopic Adrenocorticotropic hormone (ACTH) syndrome. Fluconazole was administered orally, ranging from 112.5 to 450 mg daily, with the duration varying from 2 weeks to over 5 years. The efficacy of fluconazole was assessed by changes in 24-hour urinary free cortisol (24-h UFC) levels. Additionally, hepatic safety was assessed by monitoring changes in alanine aminotransferase (ALT) levels.
RESULTS: Following fluconazole treatment, 24-h UFC levels significantly decreased from 717.6 ± 1219.4 to 184.1 ± 171.8 µg/day (p = 0.035). ALT levels showed an increase from 38.5 ± 28.4 to 56.5 ± 47.8 U/L, though this change was not statistically significant (p = 0.090). ALT levels exceeding the upper limit of normal range (ULN) were observed in 12 patients (54.5%), with only 4 patients (18.2%) showing ALT levels more than three times the ULN. Out of 10 patients who received treatment for over 1 year, 5 patients (50.0%) experienced a recurrence, with 24-h UFC levels more than 1.5 times the ULN within 3 to 12 months after fluconazole treatment.
CONCLUSION: Fluconazole effectively reduces hypercortisolism in patients with CS without significant liver injury, suggesting it as a viable therapeutic option for CS. While some cases have shown treatment escape, more studies are required to confirm the long-term efficacy.