PSAT052 Iatrogenic Cushing's Syndrome With a Remote History of Synthetic Glucocorticoid Use in the Setting of a CYP3A4 Inhibitor – Location Matters

Abstract

Abstract Introduction The most common cause of Cushing's syndrome is iatrogenic due to the exogenous administration of glucocorticoids (GCs). Exogenous GCs disrupt the hypothalamic-pituitary-adrenal (HPA) axis by reducing ACTH production, thereby suppressing cortisol production by the adrenal gland. The degree of HPA axis suppression and recovery varies by the formulation, dose, duration, frequency, timing, and location of GC administration. It is also well known that the clearance of GCs is delayed by inhibitors of cytochrome P450 (CYP) 3A4 isoenzyme. Here we report a case in which a patient on cobicistat developed iatrogenic Cushing's syndrome (ICS) even with a remote history of GC use. Clinical Case A 34-year-old male with Human Immunodeficiency Virus (HIV) on cobicistat and a history of a motor vehicle accident was referred for evaluation of ICS. The patient was started on triamcinolone epidural injections after the accident and developed a ruddy face, weight gain, posterior neck fat redistribution, and purple abdominal striae. He received a total of nine injections over three months at an unknown dose with the last injection being given two years ago. His symptoms improved after stopping the regimen. He received no GCs again until four months prior to presentation when he completed a 4 mg methylprednisolone taper and the cushingoid phenotype returned. Biochemical workup was consistent with HPA axis suppression: morning cortisol <0.5 mcg/dL (4-22 mcg/dL), ACTH <5 pg/mL (6-50 pg/mL), and DHEAS 18 mcg/dL (106-464 mcg/dL). Synthetic glucocorticoid screen was positive for methylprednisolone 5.3 mcg/dL (n <0.10 mcg/dL) and triamcinolone 0.29 mcg/dL (n <0.1 mcg/dL). The patient denied any surreptitious GC use. We concluded the patient still had unmetabolized triamcinolone even after two years due to drug interactions from cobicistat, which is a CYP3A4 inhibitor. Moreover, epidural triamcinolone has the longest half-life, 523 hours, compared to oral or intraarticular injections. Clinical Lesson: GCs are primarily metabolized in the liver by CYP3A4. Very few cases have been reported with the use of cobicistat and the cushingoid phenotype typically appears within 3-6 months of the GC use. However, our patient had detectable triamcinolone and return of ICS two years after epidural injections. It is not enough to know whether a patient received GCs; it is also essential to know how it was given and the location of the injection as the half-lives vary depending on said location. This case reinforces the importance of pharmacovigilance and performing a thorough medication reconciliation, as even a remote history of steroid use in the setting of CYP3A4 inhibitors could lead to ICS. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.