Diagnosis and Treatment of Adrenal Insufficiency in the Critically Ill Patient

Kwame Asare, Pharm.D.


Pharmacotherapy. 2007;27(11):1512-1528. 

In This Article


Divided into two major classes, glucocorticoids and mineralocorticoids, corticosteroids have several important functions. Glucocorticoids preferentially regulate carbohydrate, protein, and fat metabolism and indirectly lead to insulin secretion to counterbalance glucocorticoidinduced hyperglycemia. Insulin, in turn, allows glucose entry into the cells.[9] Under normal conditions, the rate of glucose production regulates plasma glucose concentrations; however, at higher levels of plasma glucose, increases in glucose clearance mediated by insulin become more important.[14] Glucocorticoids also possess antiinflammatory and immuno-suppressive effects; they maintain cardiovascular integrity and blood glucose level, as well as a host of other functions.[2] Cortisol is the primary glucocorticoid in humans, accounting for about 95% of all glucocorticoid activity. Recent studies show that it is produced at a rate of 10 mg/day (equivalent to 20-30 mg/day of hydrocortisone) in contrast to earlier studies that indicated a daily rate of 20-30 mg.[15] Table 1 shows typical rates of secretion of the two most active corticosteroids in humans.[12]

Mineralocorticoids, on the other hand, preferentially regulate fluids and electrolytes such as sodium, potassium, and hydrogen ions. Their net effect is sodium conservation, potassium and hydrogen ion excretion, and expansion of the vascular space. Aldosterone is the primary mineralocorticoid in humans, accounting for about 90% of all mineralocorticoid activity. Cortisol, which has only 1/400th the mineralocorticoid activity of aldosterone,[13] also provides a significant amount of mineralocorticoid activity because of its high plasma concentration. Its plasma concentration is nearly 1000 times that of aldosterone.[13]

Corticosteroids may also be grouped according to their relative glucocorticoid and mineralocorticoid activities. The estimated potencies and half-lives of several common corticosteroids are listed in Table 2 . As synthetic glucocorticoids become increasingly longer acting and potent, their mineralocorticoid activity decreases.[16] Several glucocorticoids (e.g., dexamethasone, methylprednisolone) do not have sufficient mineralocorticoid activity to replace aldosterone and, when prescribed, need the addition of a potent mineralocorticoid (e.g., fludrocortisone). Aldosterone has potent mineralocorticoid activity but, at normal doses or normal rates of secretion, has insignificant glucocorticoid activity and therefore acts as a pure mineralocorticoid. It is by far the most potent naturally occurring mineralocorticoid. Aldosterone acts on the distal tubules and collecting ducts of the kidney to promote the reabsorption of sodium and to increase the urinary excretion of potassium and hydrogen ions, in effect promoting sodium retention at the expense of potassium and hydrogen ions. Hence, its deficiency in patients who are adrenally insufficient can lead to sodium loss, volume depletion, hypotension, and vascular collapse. Total loss of aldosterone secretion usually results in death within 3-14 days unless the patient receives an exogenous mineralocorticoid.[13]


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