title: Rapid onset of iatrogenic adrenal insufficiency in a patient with cystic fibrosis-related liver disease treated with inhaled corticosteroids and a moderate CYP3A4 inhibitor.
abstract: OBJECTIVE
  To report the rapid onset of adrenal insufficiency and subsequent development of Cushing syndrome precipitated by a CYP3A4-mediated drug-drug interaction that may have been enhanced by the presence of cystic fibrosis (CF)-related liver disease.
  
  
  METHODS
  A 9-year-old girl with CF and cirrhosis experienced a decline in lung function that led to a diagnosis of asthma. After initiation of asthma therapy with inhaled fluticasone 110 μg/actuation, the patient experienced improvement in lung function to baseline. Seven weeks after the initiation of inhaled fluticasone, she developed vaginal candidiasis and was prescribed fluconazole 100 mg/day, a CYP3A4 inhibitor. Three days after starting fluconazole, she developed polyuria and polydipsia and was found to have severe hyperglycemia, which led to the diagnosis of Cushing syndrome. Fluticasone was discontinued, and the patient's adrenal function normalized.
  
  
  CONCLUSIONS
  Patients with CF are commonly prescribed complex medication regimens that may affect drug metabolism. CYP3A4 inhibitors may significantly decrease metabolic clearance in patients using chronic inhaled corticosteroids. Iatrogenic Cushing syndrome has been reported in patients with CF treated concomitantly, and for extended duration, with inhaled corticosteroids and CYP3A4 inhibitors. This case highlights rapid onset of adrenal insufficiency in a patient with CF-related liver disease treated briefly with a moderate CYP3A4 inhibitor. Use of the Horn drug interaction probability scale indicates that the interaction between fluticasone and fluconazole was probable.
  
  
  CONCLUSIONS
  CYP3A4-mediated drug interactions represent a significant risk in patients treated with long-term inhaled corticosteroids. The presence of clinically significant CF-related liver disease may enhance this risk.
authors.affiliation: Pediatric Cystic Fibrosis Center, University of Alabama at Birmingham, Birmingham, AL, USA. whoover@peds.uab.edu
authors.forename: Wynton C
authors.initials: WC
authors.lastname: Hoover
authors.forename: LaCrecia J
authors.initials: LJ
authors.lastname: Britton
authors.forename: Jay
authors.initials: J
authors.lastname: Gardner
authors.forename: Tracy
authors.initials: T
authors.lastname: Jackson
authors.forename: Hector
authors.initials: H
authors.lastname: Gutierrez
mesh_terms: D000280:Administration, Inhalation; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D000309:Adrenal Insufficiency / Q000139:chemically induced*; D000730:Androstadienes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000935:Antifungal Agents / Q000009:adverse effects / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy* / Q000209:etiology; D002181:Candidiasis, Vulvovaginal / Q000150:complications / Q000188:drug therapy; D056487:Chemical and Drug Induced Liver Injury, Chronic / Q000150:complications*; D002648:Child; D003480:Cushing Syndrome / Q000139:chemically induced; D003550:Cystic Fibrosis / Q000150:complications* / Q000503:physiopathology; D065692:Cytochrome P-450 CYP3A Inhibitors; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D015725:Fluconazole / Q000009:adverse effects / Q000627:therapeutic use; D000068298:Fluticasone; D006801:Humans; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D000935:Antifungal Agents; D065692:Cytochrome P-450 CYP3A Inhibitors; D004791:Enzyme Inhibitors; D015725:Fluconazole; D000068298:Fluticasone