Adrenal insufficiency may be caused by the destruction or altered function of the adrenal gland with a primary deficit in
cortisol secretion (
primary adrenal insufficiency) or by hypothalamic-pituitary pathologies determining a deficit of
ACTH (secondary
adrenal insufficiency). The clinical picture is determined by the
glucocorticoid deficit, which may in some conditions be accompanied by a deficit of mineralcorticoids and adrenal
androgens. The substitutive treatment is aimed at reducing the signs and symptoms of the disease as well as at preventing the development of an addisonian crisis, a clinical emergency characterized by
hypovolemic shock. The oral substitutive treatment should attempt at mimicking the normal circadian profile of
cortisol secretion, by using the lower possible doses able to guarantee an adequate quality of life to patients. The currently available
hydrocortisone or
cortisone acetate preparations do not allow an accurate reproduction of the physiological secretion pattern of
cortisol. A novel dual-release formulation of
hydrocortisone, recently approved by EMEA, represents an advancement in the optimization of the clinical management of patients with
adrenal insufficiency. Future clinical trials of
immunomodulation or immunoprevention will test the possibility to delay (or prevent) the autoimmune destruction of the adrenal gland in autoimmune
Addison's disease.