Cardiovascular and metabolic impact of glucocorticoid replacement therapy

Cortisol in man is essential for life. Excess cortisol as in Cushing's syndrome and during pharmacological glucocorticoid (GC) therapy is associated with increased cardiovascular morbidity and mortality. Recent data from patients with adrenal insufficiency (AI) have demonstrated that currently used replacement regimens are associated with a poor cardiovascular outcome. In particular, a more than doubled vascular mortality rate has been observed in patients with primary AI. The unphysiological GC replacement, both in terms of the total daily dose and the pattern of delivery, may explain this poor outcome together with an inadequate treatment during an intercurrent illness. The mechanism may be both an induction of classical metabolic risk factors for vascular disease, such as obesity and hypertension, but also an unphysiological cortisol exposure to the vascular endothelium and the immune system that may induce an accelerated atherosclerotic process. This review summarizes some of the cardiovascular data associated with GC excess and outcome data in patients with AI. Studies that have compared various regimens for replacement therapy will be addressed and recent developments that may improve outcome in patients with AI will be discussed.