Fluconazole treatment in severe ectopic Cushing syndrome

Area of Science:

• Endocrinology
• Pharmacology
• Oncology

Background:

• Severe Cushing syndrome (SCS) is a medical emergency requiring prompt reduction of serum cortisol.
• Ectopic ACTH syndrome (EAS) is a rare cause of SCS, often associated with neuroendocrine tumors.
• Management of SCS involves controlling hypercortisolism, frequently preceding definitive treatment like adrenalectomy.

Purpose of the Study:

• To report the efficacy of intravenous fluconazole in managing severe Cushing syndrome secondary to ectopic ACTH syndrome.
• To highlight fluconazole as a potential alternative treatment for hypercortisolism when standard therapies are contraindicated or unavailable.

Main Methods:

• A case report of a 39-year-old woman with metastatic neuroendocrine tumor and ectopic ACTH syndrome presenting with severe Cushing syndrome.
• Administration of intravenous fluconazole, initially at 400 mg/day, escalated to 600 mg/day, and then reduced to 400 mg/day due to elevated transaminases.
• Monitoring of clinical status, cortisol levels, and liver function tests.

Main Results:

• Intravenous fluconazole led to a significant decrease in cortisol levels (up to 55% within one week).
• The patient experienced clinical improvement, including enhanced mental state and hemodynamic stability.
• Fluconazole facilitated successful bilateral adrenalectomy by stabilizing the patient's condition.

Conclusions:

• Intravenous fluconazole can be an effective therapeutic option for rapidly lowering cortisol levels in severe Cushing syndrome caused by ectopic ACTH syndrome.
• Fluconazole serves as a valuable alternative when ketoconazole is not tolerated or etomidate is unavailable.
• While generally well-tolerated, potential hepatotoxicity necessitates monitoring of liver function during fluconazole treatment.