Iatrogenic Cushing Syndrome In An Hiv-Infected Patient Secondary to Concomitant Therapy With Genvoya and Epidural Triamcinolone

Abstract

ABSTRACT: Objective: We report the first known case of Cushing syndrome and secondary adrenal insufficiency in a patient with concomitant use of epidural triamcinolone and Genvoya® (elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 10 mg) for the human immunodeficiency viruses (HIV). The prompt recognition of this drug-drug interaction is critical to avoid adverse outcomes when glucocorticoids are used with anti-retroviral treatment containing cobicistat, a potent cytochrome P450 3A (CYP3A4) inhibitor. Methods: The patient was evaluated by determining morning serum cortisol concentrations, the serum cortisol response to cosyntropin, and a urine synthetic glucocorticoid panel that is capable of measuring triamcinolone. We also employed the Naranjo Nomogram for Causality as well as a Drug Interaction Probability scale to assess medication-related adverse effects. Long term outcome was assessed by measuring morning serum cortisol and adrenocorticotropic hormone levels. Results: A 76-year-old female with HIV on Genvoya® presented with fatigue, weight loss, and hyperglycemia. She had received multiple epidural triamcinolone injections for chronic back pain before her presentation. We hypothesized that the patient’s presentation of Cushing syndrome and adrenal insufficiency was caused by the inhibition of triamcinolone metabolism by cobicistat. The patient’s antiretroviral therapy was changed to a regimen without cobicistat. She was started on maintenance hydrocortisone to prevent an adrenal crisis. A repeat urine glucocorticoid panel, within 3 days of the patient’s HIV regimen being changed, showed a significant decrease in triamcinolone levels. Conclusion: It is essential to avoid drugs that include cobicistat when administering glucocorticoids that are metabolized via the CYP3A4 pathway due to the risk of developing Cushing syndrome and secondary adrenal insufficiency. Abbreviations: ART antiretroviral therapy CYP3A4 cytochrome P450 3A4 HIV human immunodeficiency viruses HPA hypothalamic-pituitary-adrenal ICS iatrogenic Cushing syndrome