Endocrine Abstracts

Introduction: Secondary adrenal insufficiency (AI) is commonly due to exogenous glucocorticoids, other causes being infection, tumour, surgery or radiation. Aldosterone production is usually unaffected. We present two cases of AI in patients with aspergillosis on itraconazole and steroids.

Case 1: A 35 year old lady with aspergillosis was referred with suboptimal response to short synacthen test (SST). She was on itraconazole and required 6 courses of prednisolone 30-40 mg over the past year. Clinically she was well. A second SST showed a cortisol of <20nmol/l (ACTH <5ng/l, Plasma renin 1.1nmol/L/h), 72nmol/l and 108 nmol/l respectively at 0, 30 and 60 minutes.

Case 2: A 57 year old lady with 8 year prednisolone use following previous ICU admission with swine flu, respiratory failure and aspergillosis. She was treated with posaconazole achieving dormant aspergillosis. SST showed cortisol of 55nmol/l, 199nmol/l and 265nmol/l respectively at 0, 30 and 60 minutes (ACTH 8ng/l, Renin 0.3ng/L/L/l).

Discussion: Prolonged exogenous glucocorticoid use is the commonest cause of secondary AI. With concurrent conazole this can be difficult to interpret as they can cause primary or secondary AI. Conazoles such as itraconazole and posaconazole inhibits hepatic enzyme CYP3A4, leading to reduction in metabolism of synthetic glucocorticoids, prolonging exposure causing pituitary suppression. Conazoles also inhibit the steroidogenesis pathway, and although useful in treating Cushing’s syndrome, there is potential adverse effect of primary AI in patients with normal hypothalamo-pituitary-adrenal axis. Infective causes of primary or secondary AI should also be considered the context of active fungal infection thereby challenging conclusions of the cause. Thus imaging and biochemistry profile are important to assess.

Conclusion: There remains an ongoing debate on the cause of AI in aspergillosis patients with concurrent use of conazole and steroid therapy. Clinical history along with relevant investigations is key in determining the underlying pathology therefore guiding management.