MON-307 Azole Induced Syndrome of Apparent Mineralocorticoid Excess in a Central American Farmer With Pulmonary Histoplasmosis

Abstract Disclosure: R. Dymek: None. K. Liang: None. S. Handler: None. P.E. Knapp: None. D. Wong: None. Background: Syndrome of apparent mineralocorticoid excess (AME) can occur due to inhibition of the 11β-hydroxysteroid dehydrogenase type 2 enzyme. This results in cortisol-mediated overactivation of mineralocorticoid receptors, leading to a state of pseudohyperaldosteronism. AME is a rare and dangerous side effect of azole antifungals, and symptoms typically begin 2 to 225 weeks after starting azole therapy. Clinical Case: A 57-year-old male farmer from Central America presented to the hospital with fevers, dyspnea and abdominal pain, at which time serum and urine antigen testing were positive for Histoplasma capsulatum. After initial treatment with amphotericin, he was transitioned to oral itraconazole 500mg BID and discharged with a potassium of 3.1 mmol/L (3.1-5.3 mmol/L) and blood pressure of 113/63. He presented to clinic 10 days after starting itraconazole with symptoms of palpitations and weakness. His blood pressure was 160/76 and labs were notable for a potassium of 2.5 mmol/L. He was prescribed potassium replacement and continued on itraconazole for two additional months. Due to GI side effects, the patient was switched to posaconazole 300mg daily. Four months later, he presented to the hospital with worsening GI symptoms and was found to have a potassium of 2.6 mmol/L and blood pressure of 161/81. He was treated with aggressive potassium replacement, and chest CT demonstrated worsening pulmonary histoplasmosis, thought to be due to poor antifungal adherence in the setting of GI intolerance. Due to concern for azole-induced AME, further testing was obtained, which showed a supratherapeutic serum posaconazole level of 3580 ng/mL (>700 ng/mL), undetectable aldosterone (supine, 3-16 ng/dL) and suppressed plasma renin activity at 0.05 ng/mL/h (0.25-5.82 ng/mL/h). Following these results, the patient was switched to isavuconazonium, and his hypokalemia and hypertension gradually improved. Potassium and blood pressure at the time of discharge were 3.5 mmol/L and 120/70. Subsequent aldosterone and renin check showed normalization to 7 ng/dL and 1.80 ng/mL/h. His potassium and blood pressure were stable during the remainder of treatment. Conclusion: This patient’s presentation was consistent with AME caused by itraconazole and subsequent posaconazole therapy for pulmonary histoplasmosis. There was evidence of AME within 10 days of starting treatment, which is shorter than what is currently documented in the literature. Therapeutic drug monitoring can reduce the risk, as AME mainly occurs when posaconazole levels exceed 3000 ng/mL. Clinicians should consider AME in patients on azole therapy who present with refractory hypokalemia and hypertension. Proactive surveillance and increased provider awareness of AME, especially in regions where demographic and socioeconomic factors predispose to high burdens of fungal disease, can significantly improve patient outcomes. Presentation: Monday, July 14, 2025