Endocrine Abstracts

57 year old with a low 0900 h cortisol (40 nmol/l) was referred for an urgent short Synacthen test (SST). Recently during a respiratory clinic visit, he had complained of feeling very tired but there were no other symptoms to suggest adrenal insufficiency. He had a background history of ABPA, Asthma and hypothyroidism. His current medications were Symbicort Inhaler, Vitamin D3, Levothyroxine, Montelukast and Itraconazole. He had been on Symbicort for over 2 years and his Itraconazole was started about a year ago. He had achieved excellent control of his ABPA on Itraconazole. He had not received any oral steroids over the last 3 months. His initial SST was positive with cortisol of 31 nmol/l, 96 nmol/l and 160 nmol/l at 0,30 and 60 min respectively. He was started on standard hydrocortisone replacement therapy. Unfortunately, he did not have a baseline ACTH however rest of his pituitary profile was normal. He also had negative Adrenal antibodies. His adrenal glands were normal on a recent CT thorax. We did a PubMed search and found several case reports of adrenal suppression caused by concomitant use of Itraconazole and certain inhalers. On follow up clinic visit 2 weeks after starting Hydrocortisone replacement he had gained close to 5 kg in weight and his face looked very plethoric. Itraconazole is a potent inhibitor of enzyme CYP3A4 which is part of Cytochrome P450. Of the inhaled corticosteroids Fluticasone and Budesonide are very dependent on CYP3A4 enzyme pathway while Beclometasone is metabolised through a different pathway. At this point, we changed his inhaled steroid to Beclometasone. He tolerated the switch well. We reduced his hydrocortisone dose with advice to double the dose on sick days. About 4 months later he had a repeat SST with cortisol of 183 nmol/l, 343 nmol/l and 397 nmol/l at 0, 30 and 60 min respectively. At this point, his Hydrocortisone was further reduced to 5 mg once a day with a plan of stopping it in the next 2 to 3 weeks. He had a repeat SST 2 months later which was normal with cortisol’s of 149, 445 and 504 at 0, 30 and 60 min respectively. This case highlights the potential hazards of inhaled steroid and certain medications such as Itraconazole. And there are other medications such as certain Macrolides, anti-retrovirals which also inhibit enzyme CYP3A4. These effects can be reduced/avoided by simply changing the inhaled steroid.