Answer:

• a diagnostic test to determine the functional reserve of the adrenal gland for the production of cortisol (also called hydrocortisone, the predominant glucocorticoid produced by the body).

Background:

• In patients with normal adrenocortical function, neurogenic stimuli will cause the release of corticotropin-releasing factor (CRF) from the hypothalamus.  CRF is transported to the anterior pituitary where corticotropin is secreted .  Corticotropin then stimulates the adrenal cortex to secrete cortisol and several other steroidal substances.

• Physiological effects of glucocorticoids include the regulation of protein, carbohydrate, lipid and nucleic acid metabolism; maintaining the vascular responsiveness to circulating vasoconstrictors and opposing the increase in capillary permeability during acute inflammation; and inhibition of the production and action of the mediators of inflammation.

• Cortisol levels respond within minutes to stress.  Elevated levels will protect the organism  under stress; deficiency under stress may lead to hypotension, shock and death.  Patients may be deficient due to prior steroid use, immunosuppresion, or infarction of the adrenal glands.

• Cosyntropin is a synthetic polypetide which is identical to the portion of corticotropin that has full biological activity.   It is the preferred agent for stimulation tests as it is far less immunogenic than exogenously produced corticotropin and less likely to produce allergic reactions.

Performing the test:

• obtain a baseline cortisol level (7 ml red top tube);
• administer 250 ug (0.25 mg) cosyntropin in 50 ml NS IV over 5 minutes (may also be given IM);
• obtain second cortisol level 30 minutes post infusion of cosyntropin.

Interpreting the results:

• criterion for a normal response is a stimulated cortisol level of >500 nmol/L (>18 ug/dL) and a minimal stimulated increment of >200 nmol/L (>7 ug.dL) above baseline;
• test performed only on Wednesdays thus may be delay in obtaining results;
• baseline serum levels will be higher in the morning than in the evening due to diurnal variations, but the test may be done at any time of the day;
• baseline levels may be higher in patients receiving hydrocortisone, oral contraceptives or pregnant patients, severely ill patients;
• LHSC lab uses the luminescent assay, which may erroneously measure spironolactone, hydrocortisone and cortisone; these agents should be held on the day of the test.  Prednisone, dexamethasone, betamethasone and methylprednisilone will not be measured and may be given on the day of the test.

Comparison to Suppression test:

• suppression tests are used to document hypersecretion of the adrenal glands (such as in Cushing's syndrome)
• when blood levels of glucocorticoid are increased in normal individuals, less corticotropin is released from the pituitary and less steroid is produced by the adrenal gland.  The integrity of this feedback mechanism can be tested clinically by giving a glucocorticoid and judging the suppression of cortisol secretion
• the best screening test is administration of dexamethasone 1 mg po at midnight with measurement of plasma cortisol at 8 am the next morning.  This value should be <140 nmol/L (<5 ug/dL) in normal individuals.

References:

American Hospital Formulary Service Drug Information, 2000.
Harrison's Principles of Internal Medicine, 14th Edition.