Replacement therapy for Addison's disease: recent developments

Background: The hormone deficiencies in Addison's disease (primary adrenal insufficiency) are conventionally treated with oral glucocorticoid and mineralocorticoid replacement but the available therapies do not restore the physiological hormone levels and biorhythm. Despite such treatment these patients self-report impaired health-related quality of life (HRQoL) and recent research has indicated increased mortality. Objective/methods: We review the literature and recent developments in replacement therapy. Results/conclusion: Patients with Addison's disease require mineralocorticoid replacement, i.e., fludrocortisone 0.05 - 0.20 mg once daily. Starting doses of glucocorticoids should be 15 - 20 mg for hydrocortisone or 20 - 30 mg for cortisone acetate, divided into two or three doses, and preferentially weight-adjusted. There are indications that the synthetic glucocorticoids have undesirable metabolic long-term effects, which make them less suitable as first-line treatment. Timed-release hydrocortisone tablets and continuous subcutaneous hydrocortisone infusion are promising new treatment modalities. Studies of replacement with the adrenal androgen dehydroepiandrosterone (DHEA) in adrenal failure have shown inconsistent benefit on HRQoL. DHEA, or possibly testosterone replacement is likely to be beneficial for selected groups of patients with Addison's disease but this remains to be shown. We here give our opinion of the best treatment and future direction of research in this area.