Fluconazole Is Potential Treatment for Severe Cushing’s Syndrome, Case Report Contends

Fluconazole — a treatment for fungal infections that can lower cortisol levels — could be a potential therapy for severe Cushing’s syndrome caused by ACTH-secreting tumors located outside the pituitary gland, a case report suggests.

According to the report, “Fluconazole treatment in severe ectopic Cushing syndrome,” published in the journal Endocrinology, Diabetes & Metabolism Case Reports, fluconazole may be a suitable alternative when standard-of-care treatments are not tolerated or available.

Severe Cushing’s syndrome demands immediate treatment to lower cortisol levels and prevent further complications. Usual treatments include metyrapone and ketoconazole, but these medications are not available in all countries and might cause adverse side effects.

Researchers in Argentina reported the case of a 39-year-old woman who was successfully treated with fluconazole after developing severe ectopic Cushing’s syndrome.

The patient had a tumor in the pancreas removed via a surgery called Whipple procedure.

Three years after the surgery, the woman developed metastatic tumors in her liver. She received treatment, but the tumors continued to grow. At that time, the patient also reported extreme fatigue, weakness, delirium, and growth of hair in the face, chest, and back.

Lab exams showed anemia (low red blood cell count), high blood sugar, very low potassium, high levels of cortisol in the urine and blood, and high adrenocorticotropic hormone (ACTH) — a hormone produced by the pituitary gland that controls cortisol levels. The woman was diagnosed with severe Cushing’s syndrome and started treatment with ketoconazole.

The doctors decided to remove the patient’s adrenal glands, which are located over the kidneys, to control cortisol levels.

When she was admitted for surgery, the woman had internal bleeding in her abdomen, unstable vital signs, and heart dysfunction due to anemia and low potassium.

She was admitted to the intensive care unit to stabilize her vital signs. The doctors found a gastric ulcer that was treated with endoscopy.

Treatment with high doses of intravenous fluconazole was started to control cortisol levels. The patient also received other medications to increase potassium and blood cell levels.

After 18 days of treatment, the patient had stable vital signs, reduction of delirium, and controlled cortisol levels. The woman did not develop liver failure, and markers of liver function remained within a healthy range during the treatment.

“Intravenous fluconazole effectively decreased cortisol levels in a patient with [severe ectopic Cushing’s syndrome]. After the improvement of her medical condition, successful bilateral adrenalectomy could be performed,” the scientists wrote.

The patient remained in the hospital after the surgery because she had sepsis — toxicity in the blood — due to herpes infection. After sepsis was controlled, the woman underwent chemoembolization, a procedure that delivers high doses of chemotherapy and cuts the blood supply of liver tumors, which reduced tumor size.

Two years after the surgery, the patient “is in good general health and has an active life as a mother,” the investigators said.

Previous case reports support that fluconazole is a good alternative treatment for Cushing’s syndrome. But this was the first case showing that the treatment works in severe cases. Still, more studies are necessary to establish the safety and effectiveness of fluconazole in Cushing’s syndrome.