Such salt-losing forms of adrenal insufficiency causing combined glucocorticoid and mineralocorticoid insufficiency can occur in several well-defined conditions, such as defects in steroidogenesis (e.g. steroidogenic acute regulatory protein (STAR), CYP11A1, HSD3B2, CYP21), following adrenal destruction (e.g. haemorrhage, adrenoleukodystrophy, autoimmune), or with forms of congenital adrenal hypoplasia (e.g. X-linked (DAX1), steroidogenic factor-1, IMAGe).22,23. Here, CYP21A2 is linked to chronic primary adrenal insufficiency.