Editorial: Primary Adrenal Insufficiency - Quality of Life and Long-Term Outcome With Current Treatment Strategies

Primary adrenal insufficiency (PAI) is a life-threating disease characterized by inadequate secretion of glucocorticoids (GCs), mineralocorticoids (MCs), and androgens from the adrenal cortex. Conventional treatment consists of lifelong replacement with GCs (i.e. hydrocortisone or cortisone acetate, administered twice or thrice daily) and MCs (i.e. fludrocortisone 0.05 to 0.2 mg). Androgen replacement is less frequent administered in women (1). Current replacement treatment strategies fail to restore physiological cortisol exposure and patients with PAI still have poor outcome, with increased morbidity, mortality, and impaired quality of life (QoL) (1–3). The poor outcome has mainly been related to increased exposure to cortisol and inadequate cortisol coverage during stress-related events and illness. Indeed, conventional GC replacement results in peaks and trough of GC concentrations throughout the day. Overexposure to cortisol has been associate to poor QoL, similar to that found in patients with Cushing ́s syndrome (4). Similarly, underexposure to cortisol may result in fatigue, higher frequency of adrenal crisis and lower QoL (5). A novel GC replacement treatment, dual-release oral hydrocortisone has been shown to provide a more circadian-based serum cortisol profile and has be associated to a better QoL as compared to conventional therapy (6). It is important to take in mind that MC deficiency may also play a role on long-term outcome in patients with PAI. Available evidence suggests that the current standard MC replacement may be inadequate in some patients. Indeed, signs and symptoms related to MC underreplacement are commonly reported, as hyponatremia, salt craving, and postural hypotension (7, 8). MC receptor plays an important role in cognition, thus MC underreplacement may contribute to poor QoL (9). There are still several aspects on outcome in patients with PAI that remain poorly understood. The aim of the present Research Topic is to provide an overview of the current knowledge and a better understanding of QoL and long-term outcomes in PAI. In one of the world’s largest registries, including 494 patients with PAI from Norway, Didriksen et al. have analysed how clinical characteristics and PAI-associated diseases affect QoL. QoL was measured using RAND-36 (generic) and AddiQoL (-30 and -8, disease-specific). QoL was