Endocrine Abstracts

A 37-year-old woman was referred to the endocrine team for the assessment of her adrenal axis, as she had been taking high dose prednisolone (20-40 mg) for several years for the management of her brittle asthma. Drug history included inhaled Symbicort 200/6 (SMART regime), tiotropium and montelukast. Her respiratory symptoms improved with the introduction of theophylline, thus enabling her prednisolone to be switched to oral hydrocortisone, with appropriate ’sick- day’ rules advice. In spite of cessation of her prednisolone, the patient paradoxically developed pronounced features of Cushing’s syndrome (central obesity, wide purple striae, bruising and proximal myopathy) over the subsequent months. It was noted much later on review, that she had been concomitantly prescribed long-term oral itraconazole for a fungal skin infection. Biochemical evaluation (whilst taking itraconazole) revealed a morning cortisol of 393 nmol/l, after omitting her evening and morning hydrocortisone dose, with follow- on hydrocortisone day curve revealing similar cortisol values throughout, suggesting an increased hydrocortisone half-life. Her Itraconazole was subsequently stopped and the patient was also advised to reduce her Symbicort, whilst maintaining her usual hydrocortisone replacement. Further biochemical evaluation after six weeks demonstrated a suppressed ACTH level (<5.0ng/l) as well as failed SST (baseline morning cortisol <28 nmol/l, 30 minutes 64 nmol/l) indicating marked ongoing HPA-axis suppression from prolonged steroid therapy. Since cessation of itraconazole, her Cushing’s associated morbidity has been partially ameliorated with central weight loss, improved wound healing, resolution of excessive bruising, restoration of menstrual cycles and improvement in mood. Itraconazole is a potent CYP3A4 enzyme inhibitor and since steroids are metabolised through this pathway, potentiation for steroid toxicity may occur, with simultaneous suppression of the HPA-axis. A medication review on each clinic visit is mandated in order to proactively identify such serious interactions, thereby attenuating the risk of long term morbidity.