Medical Student Midwestern University, United States
Introduction: Cushing syndrome is characterized by elevated cortisol levels due to iatrogenic causes, pituitary tumors or from an ectopic focus. Ketoconazole has been shown to effectively decrease cortisol levels without a high risk of toxicities. Here we show a case report of a patient with ectopic Cushing syndrome treated with an alternative steroidogenesis inhibitor, fluconazole.
Case Description: We reported a 75-year-old male with a past medical history significant for atrial fibrillation, hypertension and obstructive sleep apnea. He was admitted to the hospital due to severe hypokalemia of 2.6 mmol/L (reference range 3.6-5.2 mmol/L), a blood sugar of 498 mg/dL (reference range 7-99 mg/dL), elevated PM cortisol levels of 66.1 mcg/dL (reference range 3-13 mcg/dL) and AM Cortisol Levels of 112 (reference range 5-25mcg/dL), thus prompting an endocrinology consult. Further examination of 24-hour urine cortisol displayed elevated levels at 11,656 mcg/24hrs (reference range 4-40 mcg/24hrs). The patient failed a 8mg dexamethasone suppression test with AM cortisol levels of 57.8 mcg/dL (5-25 mcg/dL) with a dexamethasone drug level of 2713 ng/dL (reference range >200 ng/dL), excluding elevated metabolism as cause of failed suppression. Pituitary magnetic resonance imaging showed a normal pituitary gland. Patient was started on 400mg of fluconazole daily with plans to switch to 400 mg ketoconazole in outpatient care.
Outpatient positron emission tomography failed to identify the source of ACTH. Additionally, petrosal sinus sampling failed to detect altered levels of ACTH secretion. Patient was readmitted to hospital one month after original diagnosis with continued hypokalemia of 2.7 mmol/L (reference range 3.6-5.2 mmol/L) and worsening diabetic symptoms. Patient was taken off ketoconazole two weeks after prior discharge, not knowing it was temporary treatment for his Cushing’s syndrome. He was restarted on 400mg fluconazole and on day three of admission, fluconazole dose was increased to 600 mg daily (Endocrinology Metabolism case reports 2019, July 3) with cortisol levels to be monitored. On day one of admission, his AM cortisol levels were 91.5 mcg/dL (reference range 5-25 mcg/dL) and declined to 76.8 mcg/dL, 72.9 mcg/dL, 69.2 mcg/dL, 66.4 mcg/dL, and 60 mcg/dL the following days with fluconazole treatment. The patient was then discharged to outpatient follow-up with continuation of 600mg fluconazole.
Within a week of the latest discharge, the patient presented to the hospital again due to an episode of atrial fibrillation. AM cortisol levels were measured to be 37.2 mcg/dL (reference range 5-25 mcg/dL), showing a 59.3% decrease since his last admission. Patient was then discharged from our care to an outpatient endocrinologist.
Discussion: This case shows that cortisol levels in ectopic Cushing Syndrome can be effectively lowered through fluconazole treatment. This medication has a more favorable side effect profile than other steroidogenesis inhibitors such as metyrapone and mitotane. Fluconazole monotherapy or dual therapy should be investigated further as a viable option for ectopic Cushing Syndrome therapy prior to bilateral adrenalectomy.
.jpg)