Endocrine Abstracts

Adrenal suppression and iatrogenic Cushing’s secondary to concomitant inhaled steroid and itraconazole is a potentially common and serious drug interaction. A 55 year old patient with bronchiectasis and asthma developed an exacerbation of allergic bronchopulmonary aspergillosis (ABPA). He had been on inhaled fluticasone for over 2 years. He was commenced on itraconazole. The patient was on holiday 6 weeks after itraconazole was commenced when he noted that his face had become swollen. The patient presented 3 weeks later, complaining of being tired, bruising easily, and being unable to fasten either their trousers or shirt. He was noted to have a buffalo hump, acne, a proximal myopathy, and obvious moon face. Investigation revealed undetectable serum cortisol, 24 hour urine cortisol and ACTH. A short synacthen test was abnormal with a baseline cortisol <20 rising to 82 and 118 nmol·L⁻¹ at 30 and 60 minutes respectively. Seven months after stopping itraconazole the patient felt that his clinical appearance had returned to normal. There was still evidence of hypothalamic-pituitary-adrenal axis suppression consistent with long-term inhaled steroid use: repeat SST demonstrated a baseline cortisol of 21, rising to 164 and 233 nmol·L⁻¹ at 30 and 60 minutes respectively. One month later a 9 am cortisol was 507 nmol·L.

It is most likely that this patient developed clinical Cushing’s syndrome secondary to increased systemic concentrations of fluticasone. This is because of reduction in fluticasone clearance due to the inhibition of the cytochrome P450 CYP3A4 enzyme system by itraconazole. The subsequent adrenal insufficiency was due to the suppression of pituitary ACTH following long term inhaled fluticasone.