7203 A case of undifferentiated shock found to be due to voriconazole-related primary adrenal insufficiency

Abstract

Abstract Disclosure: K.X. Zhang: None. C. Bergwitz: None. Primary adrenal insufficiency can be a rare effect observed with azole antifungal therapy, classically ketoconazole, via inhibition of cortisol and aldosterone synthesis. Whether primary AI can be observed with newer triazole drugs used for neutropenic prophylaxis and treating invasive fungal infections is far less understood. We describe a case of a 65-year-old man with medical history notable for COPD and gout, who was on voriconazole for Aspergillus pneumonia, and admitted to the medical ICU with confusion and undifferentiated shock. His potassium was 6.5 mmol/L, sodium 133 mmol/L, bicarbonate 18 mmol/L, and blood pressure 72/63 requiring pressor support. Voriconazole was withdrawn. He also had a fever to 101.7F that was attributed to a gout flare, and he received a course of high dose prednisone. His shock and electrolyte abnormalities quickly resolved, and he was discharged on isavuconazole. At the 1 week mark, he was found to have a morning cortisol 2.3 ug/dL, potassium 5.4 mmol/L, and sodium 134 mmol/L, along with fatigue, nausea, and hypotension, which prompted resumption of steroid and mineralocorticoid replacement. One month after completing his course of isavuconazole, morning cortisol normalized to 11.0 ug/dL and ACTH 22.3 pg/mL. We present a convincing clinical story supporting the etiology of this patient’s initial shock as primary adrenal insufficiency related to a voriconazole effect. This case illustrates how iatrogenic AI can be a missed diagnosis in the emergency room setting. Primary AI has classically been reported following ketoconazole therapy, but there are only 4 reports of primary AI involving the newer triazole posaconazole, and none for voriconazole or isavuconazole. Due to the rarity of this effect, AI due to voriconazole was not on the initial shock differential and timely endocrine labs to seal the diagnosis (morning cortisol, ACTH, and renin/aldosterone levels) were not obtained. If our patient had not received steroids serendipitously for gout, he may have been at risk for adrenal crisis. Whereas central AI is more common and induced by chronic use of systemic steroids, it is important to also think about AI caused by antifungal therapy with newer azoles. Presentation: 6/3/2024