Mineralocorticoid effects due to cortisol inactivation overload explain the beneficial use of hydrocortisone in septic shock.

The role of corticosteroids in septic shock remains controversial despite their use for over 50 years. Large prospective trials of their use continue with the aim of resolving the controversy. These may well remain indecisive if basic endocrine principles are ignored. Review of the available evidence suggests that use of synthetic glucocorticoids is harmful but hydrocortisone beneficial. Consideration of the basic properties of the corticosteroids used and their receptors suggest an explanation for their differing therapeutic effects. The harmful synthetic glucocorticoids have no or reduced mineralocorticoid effects in contrast with the significant mineralocorticoid effects of hydrocortisone at the doses which have been found to be beneficial. The potent synthetic mineralocorticoid fludrocortisone is well recognised to raise peripheral resistance by sensitising the resistance vessels to endogenous or exogenous catecholamines and also causes metabolic alkalosis. We provide evidence to support our hypothesis that at the doses of hydrocortisone used, cortisol inactivation overload is the basis of the beneficial effect. The consequent mineralocorticoid effects result in increased sensitivity of the resistance vessels to endogenous and exogenous catecholamines with an increase in peripheral resistance correcting shock. In addition the metabolic alkalotic component of mineralocorticoid effect would tend to correct the prevailing metabolic acidosis. Hydrocortisone also has an attenuating, as opposed to the suppressing effect of synthetic glucocorticoids on the immune response which is also regarded as beneficial.