Management of adrenal insufficiency in different clinical settings

Adrenal insufficiency is a rare disease, but its prevalence is increasing. The most frequent cause of primary adrenal insufficiency in western countries is autoimmune adrenalitis, whereas secondary adrenal insufficiency is most often caused by pituitary tumours and their treatment (e.g., surgery). Chronic glucocorticoid replacement consists of hydrocortisone 15-25 mg/day in divided doses and dose monitoring is largely based on clinical judgement. Fludrocortisone 0.05-0.2 mg/day is given for substitution in mineralocorticoid deficiency aiming at normotension, normokalaemia and a plasma renin activity in the upper normal range. It has recently been shown that, despite adequate glucocorticoid and mineralocorticoid replacement well being in patients with adrenal insufficiency is still impaired. Several studies have demonstrated that dehydroepiandosterone 25-50 mg/day p.o. may improve mood, fatigue, well-being and, in women, also sexuality, suggesting that dehydroepiandosterone should become part of the standard treatment regime. However, large Phase III trials of dehydroepiandosterone for adrenal insufficiency are still lacking and it has not yet been approved for the treatment of this disease. Patients with adrenal insufficiency are at risk of adrenal crisis, usually precipitated by major stress, such as severe infection or surgery. Early dose adjustments are required to cover the increased glucocorticoid demand in stress. Careful and repeated education of patients and their partners is the best strategy to avoid this life-threatening emergency. Some recent studies suggest that during sepsis some patients with intact adrenal function may develop transient relative adrenal insufficiency and benefit from administration of hydrocortisone plus fludrocortisone. However, the pathophysiology and diagnosis criteria of relative adrenal insufficiency and its treatment remain unsettled issues.