Antifungal drug fluconazole reduces cortisol levels in Cushing’s patients
Study: Treatment effective without causing significant liver damage
Fluconazole – a treatment for fungal infections – effectively reduced cortisol levels in people with Cushing’s syndrome, without causing significant liver damage, a study in Taiwan showed.
According to researchers, these results suggest that fluconazole “may be an effective and safe option for managing” high cortisol levels in people with Cushing’s syndrome. The efficacy was more significant in individuals with Cushing’s disease, the most common form of the syndrome.
The study, “Clinical efficacy and safety of fluconazole treatment in patients with Cushing’s syndrome,” was published in Therapeutic Advances in Endocrinology and Metabolism.
Fluconazole explored as alternative Cushing’s treatment
Cushing’s syndrome encompasses a group of disorders caused by excessive levels of cortisol, known as hypercortisolism. The most common cause is a pituitary tumor that secretes excess adrenocorticotropic hormone (ACTH), leading to a specific condition known as Cushing’s disease.
Less frequently, Cushing’s syndrome can arise from ACTH-secreting tumors in other organs, known as ectopic Cushing’s, or tumors in the adrenal glands, where cortisol is produced.
Several medications are used to treat Cushing’s, including ketoconazole, an antifungal agent that blocks the activity of several enzymes necessary for cortisol production. However, due to a risk of liver toxicity, fluconazole, another antifungal agent, has been explored as an alternative treatment for Cushing’s.
In this study, researchers at Taipei Veterans General Hospital in Taiwan retrospectively analyzed data from 22 individuals with Cushing’s syndrome who were treated with fluconazole between 2015 and 2020. The treatment was administered orally, at doses ranging from 112.5 mg to 450 mg daily, for periods of two weeks to more than five years.
Participants had a mean age of 54.5 years and were predominantly women (77.3%). Among them, 12 had Cushing’s disease, seven had ectopic Cushing’s, and three had adrenal Cushing’s syndrome.
Normalization of cortisol occurred in about one quarter of patients
Cortisol blood and urine levels in people with ectopic disease were significantly higher than in participants with Cushing’s disease or adrenal Cushing’s. A similar result was observed for ACTH levels. During fluconazole treatment, more individuals in the ectopic group used additional medications than those with Cushing’s disease (85.7% vs. 33.3%).
Following fluconazole treatment, the levels of urinary cortisol reduced significantly by a mean of 39.2%. When looking separately at each Cushing’s type, this effect was only significant in participants with Cushing’s disease.
Overall, normalization of cortisol occurred in about one quarter of the patients, while in almost half, they reduced to below the threshold of 1.5 times the upper limit of normal (ULN). Values above this threshold indicate that a person is producing excessive amounts of cortisol that are sustained over time.
Among 10 patients who received fluconazole for more than one year, five experienced a recurrence of high cortisol levels within the first three to 12 months after treatment.
This study demonstrates that fluconazole is effective in treating patients with [Cushing’s syndrome] … fluconazole was generally well tolerated, with a minimal risk of liver injury, suggesting it may be an effective and safe option for managing hypercortisolism.
The levels of the liver enzyme alanine aminotransferase (ALT) were measured before and after fluconazole administration to assess potential liver damage. Overall, ALT levels increased after treatment, particularly in individuals with Cushing’s disease, where this increase was considered significant.
According to the researchers, there was no severe liver toxicity, since only four participants (18.2%) presented ALT levels above three times the ULN, values which are considered abnormal and may indicate potential liver injury.
“This study demonstrates that fluconazole is effective in treating patients with [Cushing’s syndrome] … Moreover, fluconazole was generally well tolerated, with a minimal risk of liver injury, suggesting it may be an effective and safe option for managing hypercortisolism.”
Although the study’s observation period was approximately 5.5 years, the researchers noted that “further investigation is required to confirm the long-term efficacy and safety of fluconazole treatment.”
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