Amphotericin-Induced Apparent Mineralocorticoid Excess (AME)

Introduction: AME is a syndrome characterized by a genetic or acquired deficiency in 11 beta-Hydroxysteroid dehydrogenase type 2 (11 beta-HSD2), which results in overactivation of the mineralocorticoid receptor. Licorice and certain medications such as azoles are known to induce AME. Amphotericin has a different mechanism of action, and to our knowledge, there are no prior case reports of AME induced by amphotericin. Case Description: 64 year-old female with newly diagnosed acute myeloid leukemia, was admitted to the hospital for induction chemotherapy. Hospital course was complicated by neutropenic fever, secondary to mucormycosis of the abdomen, for which she was started on amphotericin B. Three days after the initiation of this medication, patient developed persistent hypokalemia, metabolic alkalosis and difficult to control hypertension for which Nephrology was consulted. Upon chart review, patient’s blood pressure in office visits and on the first 25 days of admission had been <120/80 mm/Hg. Work-up for secondary hypertension revealed increased Cortisol/cortisone ratio on 24 hour urine collection of 0.6. Rest of work-up, including renal artery dopplers and metanephrines was unremarkable. Aldosterone and renin were low at 1.9 ng/dL and 1.1 ng/mL/hr respectively. Creatinine remained unchanged at her baseline of 0.5-0.7 mg/dL. Patient’s blood pressure was controlled with maximum doses of Nifedipine and Lisinopril, showing a dramatic improvement after addition of spironolactone. Blood pressure, potassium and bicarbonate levels normalized after completion of amphotericin therapy. Discussion: After review of all medications given in the Hospital, the only one with a clear temporal relation with the onset of hypertension was amphotericin B. This medication has a different mechanism of action than azoles, and to our knowledge, this is the first case report of amphotericin-induced apparent mineralocorticoid excess syndrome. Hypokalemia is a known side effect of hypokalemia secondary to amphotericin B, which is known to be secondary to tubular toxicity causing concentration gradients between the cytoplasm of distal tubule cells and the tubular lumen.This case can potentially explain a different mechanism of hypokalemia.