6713 Voriconazole Usage, An Atypical Cause Of Primary Adrenal Insufficiency

Disclosure: J. Turkiewicz: None. M. Kanin: None. S. Shmadi: None. Introduction: Primary adrenal insufficiency (AI) is a rare, life-threatening clinical entity. AI can be the result of infection, autoimmune processes, genetic conditions, medication, or malignancy. The medications most associated with AI include anti-epileptics, azoles, steroids, monoclonal antibodies, beta-2 agonists, bisphosphonates, opioids, hormone therapies, and protein kinase inhibitors. We present a case of voriconazole induced primary AI. Case Description:A 67 year old man with unspecified psychosis, hypothyroidism, chronic pulmonary aspergillosis, and severe malnutrition presented for hypothermia and was found to have septic shock from a urinary track infection. On admission, history was limited, though he reported poor oral intake and nonspecific abdominal pain. He had a BMI of 18 and was tachycardic, hypotensive, and hypothermic to 35.5 C. He was started on antibiotics including empiric vorincazole therapy for chronic pulmonary aspergillosis, and empiric steroids x4 days with improvement in labs and clinical status. He was then transferred to the inpatient psychiatry unit for ongoing treatment of psychosis. 1 month later, a rapid response was called after the patient was found down. He was confused, lethargic, hypoglycemic and hypotensive. Acute laboratory revealed glucose of 25 mg/dL, sodium of 116 mmol/L, potassium of 3.7 mmol/L, and creatinine of 0.49 mg/dL. TSH level was 4.8 mclU/mL (range 0.3-4.7). Cortisol was 11 mcg/dL at 7:15 AM (range 8-25). He was started on hydrocortisone with improvement in vitals, labs and mentation. ACTH was 14 pg/mL (range 6-59) the following day, though after steroid administration. Weeks later, AM cortisol was 8 with an ACTH of 104 after holding the PM dose of hydrocortisone the night before. Cosyntropin stim test revealed peak cortisol of 13mcg/dL (<15). Voriconazole level: 2.99 ug/mL (range 1-5.5). Abdominal imaging demonstrated normal adrenal glands. CT head was without a sellar mass. The patient was discharged on hydrocortisone, though was lost to follow up. Discussion:AI due to voriconazole is rare, reported to occur <2% of time, with only a few cases in the literature. Ketoconazole and fluconazole are more often linked with AI, through inhibition of steroidogenic enzymes 11b-hydroxylase, 17a-hydroxylase and 18-hydroxylase. Voriconazole, a second-generation azole, is a potent CYP450 enzyme inhibitor, leading to decreased synthesis of steroidogenic enzymes, indirectly decreasing steroidogenesis. AI is typically seen after 3 months or more of use and is reversible with discontinuation. Our patient had been off and on voriconazole for 2 years with plan for chronic use, and had therapeutic range voriconazole levels after treatment for 3 weeks prior to the rapid response. This case demonstrates the risk of precipitating AI with second-generation azoles. Presentation: 6/3/2024