SAT331 A Case Of Iatrogenic Cushing’s Syndrome Due To The Concomitant Use Of Cobicistat With An Inhaled Glucocorticoid Followed By Adrenal Insufficiency Upon Discontinuation Of Cobicistat

Disclosure: L. Noor: None. J. Mullally: None. R. Glassman: None. Cobicistat is an inhibitor of cytochrome P4503A (CYP3A) used to increase the systemic exposure of antiretroviral drugs for treatment of HIV, and because of it’s mechanism of action, can have significant drug interactions. A similar “pharmacologic booster” ritonavir has now been widely reported to cause cases of iatrogenic Cushing’s syndrome when used in combination with glucocorticoids, but the data on this risk with cobicistat is much more limited. This case describes a patient who developed florid Cushing’s syndrome while on cobicistat and inhaled glucocorticoids followed by secondary adrenal insufficiency upon discontinuation of cobicistat. A 60 year old male with past medical history of well-controlled HIV on elvitegravir, cobicistat, emtricitabine and tenofovir, asthma on chronic inhaled fluticasone/salmeterol, presented with several months of progressive abdominal distention, back pain, irritability, easy bruising, proximal muscle weakness and weight gain. On physical exam, he appeared Cushingoid with central obesity, supraclavicular fullness, dorsocervical fat pad, wide violaceous striae on his abdomen and multiple ecchymoses. Iatrogenic Cushing's syndrome was suspected and labs showed undetectable morning serum cortisol and 24 hour urine free cortisol as well as newly elevated A1C of 5.7%. DEXA scan showed osteopenia. CT abdomen pelvis showed small adrenal glands. His HIV medication was switched to a combination of bictegravir, emtricitabine and tenofovir and he subsequently developed significant fatigue, nausea, abdominal discomfort and headaches. He was started on replacement doses of prednisone and his symptoms improved significantly. The prednisone dose is being gradually tapered, with ongoing recovery of the hypothalamic-pituitary-adrenal(HPA) axis, with now low, but detectable cortisol and ACTH levels. We present a unique case of iatrogenic Cushing’s syndrome due to concomitant use of cobicistat with inhaled fluticasone and the subsequent development of secondary adrenal insufficiency upon discontinuation of cobicistat. Cobicistat is an inhibitor of CYP3A which can cause decreased metabolism of exogenous glucocorticoids resulting in HPA axis suppression and exogenous Cushing’s syndrome. Fluticasone causes more cortisol suppression than other inhaled steroids because of it’s long half-life, higher binding affinity for glucocorticoid receptors and high lipophilicity. Concomitant u