Recent developments on DHEA supplementation in the substitutive therapy of primary adrenal insufficiency

Primary adrenal insufficiency is the consequence of the bilateral destruction or impaired function of the adrenal cortex. The reduction of the adrenocortical cell mass is responsible for a deficiency of glucocorticoids and, in some cases, of mineralcorticoids. The substitutive therapy with hydrocortisone, or cortisone acetate and fludrocortisone is life-saving and the current oral pharmaceutical preparations allow an adequate treatment of the clinical signs and a satisfactory quality of life, even though the currently available therapy cannot guarantee a correct adaptation of the hormone levels to the physiologic requests. The adrenal cortex also produces DHEA and DHEA-S, whose levels are typically reduced in patients with adrenal insufficiency. Clinical studies have shown that substitutive therapy with DHEA is associated with improvement of patient well-being. However, the unavailability of a large series of data on long-term efficacy and safety has so far limited the routine clinical use of DHEA in adrenal insufficiency therapy. Novel DHEA compounds, reviewed in this article, have been proposed to either reduce the minimum dose of DHEA needed to obtain normal serum levels or to minimise the side effects of the treatment. These recently developed DHEA compounds will enable large clinical studies of DHEA substitution that will increase our understanding of the physiological role of DHEA and will allow a future correct use of this drug in the treatment of adrenal insufficiency.