7487 Iatrogenic Cushing’s Syndrome In A Patient On Prezcobix And Fluticasone

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Abstract Disclosure: A.N. Davis: None. M. Nicholson: None. Introduction: The HIV medication Prezcobix contains darunavir, a protease inhibitor which is known to inhibit the hepatic enzyme CYP3A4. This may lead to accumulation of some medications in the blood, including fluticasone. We present a patient with iatrogenic Cushing’s syndrome while on Prezcobix and fluticasone. Case: Patient is a 55-year-old man who presented to clinic 3/13/23 for evaluation for cushingoid appearance at the request of his infectious disease (ID) physician. The patient has history of HIV, asthma, and seasonal allergies and had been taking Prezcobix, inhaled fluticasone, and intranasal fluticasone for over 3 years. Patient noted easy bruising and difficulty with weight loss. Vital signs were remarkable for elevated blood pressure at 165/86 despite taking amlodipine, HCTZ, and carvedilol. He was overweight with BMI 27.2. Physical exam revealed a somewhat rounded face, mild central obesity, no dorsocervical or supraclavicular fat pads, and no purple striae. Labs on 3/8/23 were remarkable for cortisol level <0.40mcg/dL at 4:10PM. Labs on 3/13/23 were remarkable for cortisol <0.40mcg/dL, ACTH level <5.0pg/mL, and urine fluticasone 17-beta carboxylic acid elevated at 540pg/mL (<10pg/mL) at 3:57PM. His ID physician planned to transition the patient off of Prezcobix and onto Tivicay, so patient was started on hydrocortisone 15mg PO daily at 8AM and 5mg daily at 2PM on the day he switched to Tivicay. He was gradually tapered off of hydrocortisone over a 2-3 month period without any symptoms concerning for adrenal insufficiency. His Cortisol level on 7/10/23 off hydrocortisone was 4.98mcg/dL at 7:56AM. Discussion: Prezcobix contains darunavir which is known to inhibit CYP3A4. With most patients, use of inhaled and intranasal fluticasone does not result in physiologically meaningful systemic levels of fluticasone. However, metabolism of fluticasone is dependent on CYP3A4, so systemic levels may increase with use of inhaled fluticasone with Prezcobix resulting in excess of corticosteroids and suppression of the native hypothalamic-pituitary-adrenal (HPA) axis. Fluticasone 17-beta carboxylic acid is a metabolite of fluticasone which is detectable in the urine. Sudden cessation of Prezcobix after prolonged use may result in secondary adrenal insufficiency from prolonged HPA axis suppression. Our case demonstrates how the use of Prezcobix with fluticasone may result in iatrogenic Cushing’s syndrome. Additionally, our case demonstrates that anticipation of secondary adrenal insufficiency after stopping Prezcobix allows for implementation of a safe transition plan. Presentation: 6/1/2024