THE FAST AND FURIOUS CUSHING’S SYNDROME

Abstract

Introduction Ritonavir is a commonly prescribed protease inhibitor for human immune deficiency (HIV) treatment. It is a potent inhibitor of hepatic cytochrome P450 (CYP450) enzyme. Interaction between ritonavir and corticosteroids induces iatrogenic Cushing’s Syndrome. We share a case of an acute onset of Cushing’s Syndrome in a young female with HIV. Case A 25-year-old female with stable retroviral disease on ritonavir along with tenofovir, emtricitabine and atazanavir developed Cushing’s syndrome within 2 weeks of receiving injectable hydrocortisone from a general practitioner's clinic for skin itchiness. Facial swelling, hirsutism, abdominal striae, body acne, weight gain and proximal myopathy were noted. Early morning cortisol was 28 nmol/L and the 24-hour urine-free cortisol was 45 nmol/day. She was diagnosed with iatrogenic Cushing’s syndrome with suppression of the hypothalamic-pituitary adrenal (HPA) axis secondary to drug interaction between ritonavir and intravenous hydrocortisone. She was started on oral hydrocortisone 20 mg in the morning and 10 mg in the evening. Throughout her hospitalization and upon discharge, she remained clinically well. She is planning for a Synacthen test on an outpatient basis to reassess her HPA axis. Conclusion Drug interaction between ritonavir and corticosteroids may result in increased levels of plasma corticosteroids, potentiated by the CYP450 metabolism which prolongs the half-life of hydrocortisone, that can lead to Cushing’s syndrome. This highlights the importance of a thorough review of the patient’s medications to prevent drug-todrug interaction. If corticosteroid administration cannot be avoided, the patient needs to be monitored for symptoms of Cushing’s syndrome.