title: Adrenal insufficiency: review of clinical outcomes with current glucocorticoid replacement therapy.
abstract: Glucocorticoid replacement therapy in patients with adrenal insufficiency (AI), whether primary (Addison's disease) or secondary (due to hypopituitarism), has been established for some 50 years. The current standard treatment regimen involves twice- or thrice-daily dosing with a glucocorticoid, most commonly oral hydrocortisone. Based on previous small-scale studies and clinical perception, life expectancy with conventional glucocorticoid replacement therapy has been considered normal, with a low incidence of adverse events. Data from the past 10-15 years, however, have shown that morbidity remains high and life expectancy is reduced. The increased morbidity and decreased life expectancy appear to be due to both increased exposure to cortisol and insufficient cortisol coverage during infections and other stress-related events. This is thought to reflect a failure of treatment to replicate the natural circadian rhythm of cortisol release, together with a failure to identify and deliver individualized cortisol exposure and to manage patients adequately when increased doses are required. The resulting over- or under-treatment may result in Cushing-like symptoms or adrenal crisis, respectively. This review summarizes the morbidity and mortality seen in patients receiving the current standard of care for AI and suggests areas for improvement in glucocorticoid replacement therapy.
authors.affiliation: Department of Endocrinology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Gudmundur
authors.initials: G
authors.lastname: Johannsson
authors.forename: Alberto
authors.initials: A
authors.lastname: Falorni
authors.forename: Stanko
authors.initials: S
authors.lastname: Skrtic
authors.forename: Hans
authors.initials: H
authors.lastname: Lennernäs
authors.forename: Marcus
authors.initials: M
authors.lastname: Quinkler
authors.forename: John P
authors.initials: JP
authors.lastname: Monson
authors.forename: Paul M
authors.initials: PM
authors.lastname: Stewart
mesh_terms: D000309:Adrenal Insufficiency / Q000188:drug therapy*; D005938:Glucocorticoids / Q000009:adverse effects / Q000627:therapeutic use*; D020249:Hormone Replacement Therapy / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D016896:Treatment Outcome
chemical_list: D005938:Glucocorticoids