A variety of tests that stimulate or suppress cortisol/ACTH levels can be used further to evaluate individuals with signs and symptoms of adrenal hypofunction or hyperfunction or abnormal cortisol levels.

Dexamethasone is a potent glucocorticoid that suppresses ACTH and cortisol production. In the rapid dexamethasone test, 1 mg of oral dexamethasone is given at midnight; cortisol levels are then measured at 8 AM. Normally, plasma cortisol should be no more than 5 to 10 mg/dL after dexamethasone administration. A 5-hour urine collection test for 17-hydroxycorticoids (17-OHCS), metabolites of glucocorticoids, also may be collected as part of the test. Elevated plasma cortisol levels in response to dexamethasone administration are associated with Cushing's syndrome.

Metyrapone is a drug that inhibits certain enzymes required to convert precursor substances into cortisol. When the drug is administered, plasma cortisol levels decrease and ACTH levels subsequently increase in response. The test involves mainly measurement of urinary excretion of 17-OHCS, which should rise if the adenohypophysis is normally responsive to decreased cortisol levels. Plasma cortisol levels are measured to ensure that sufficient suppression has been induced by the metyrapone such that test results will be valid.

Insulin-induced hypoglycemia (serum glucose of 50 mg/dL or less) also stimulates ACTH production. Adenohypophyseal response to hypoglycemia is usually measured indirectly by plasma cortisol levels because the test is more universally available. A normal response is an increase of 6 µg/dL or more over baseline cortisol levels. Lack of response to hypoglycemic stimulation indicates either pituitary or adrenal hypofunction. They can be differentiated either by directly measuring plasma ACTH levels or by administering ACTH preparations and observing cortisol response.

Purified exogenous ACTH or synthetic ACTH preparations (e.g., cosyntropin) may be used diagnostically to stimulate cortisol secretion. The usual response is an increase in plasma cortisol levels of 7 to 18 µg/dL over baseline levels within 1 hour of ACTH administration. Lack of response indicates adrenal insufficiency.⁵³

• The time of day when the test is performed may alter results because cortisol levels vary diurnally, with highest levels being seen on awakening and lowest levels occurring late in the day.
• Stress and excessive physical activity may produce elevated levels.
• Pregnancy, therapy with estrogen-containing drugs, lithium carbonate, methadone, and ethyl alcohol may lead to elevated cortisol levels.
• Therapy with levodopa, barbiturates, phenytoin (Dilantin), and androgens may produce decreased levels.
• Failure to follow dietary restrictions, if ordered, may alter test results.

• Suspected adrenal hyperfunction (Cushing's syndrome) from a variety of causes, as indicated by elevated levels that do not vary diurnally
• Evaluation of effects of disorders associated with elevated cortisol levels (e.g., hyperthyroidism, obesity, and diabetic ketoacidosis)
• Suspected adrenal hypofunction (Addison's disease) from a variety of causes, as indicated by decreased levels
• Monitoring for response to therapy with adrenocorticosteroids:
  • Elevated levels are seen in clients receiving adrenocorticosteroid therapy.
  • Decreased levels may occur for months after therapy is discontinued, resulting from drug-induced atrophy of the adrenal glands.

Nursing Care Before the Procedure

General client preparation is the same as that for any study involving collection of a peripheral blood sample (see Appendix I).

• Some laboratories require an 8-hour fast and activity restriction before the test. Medications that may alter cortisol levels should be withheld for 12 to 24 hours before the study, although this practice should be confirmed with the person ordering the test.
• The client should be informed that it may be necessary to obtain more than one sample and that samples must be obtained at specific times to detect peak and trough levels of cortisol.

At approximately 8 AM, a venipuncture is performed and the sample is collected in a green-topped tube. The sample should be handled gently to avoid hemolysis and sent promptly to the laboratory. If cortisol hypersecretion is suspected, then a second sample may be obtained at approximately 4 PM to determine whether diurnal variation in cortisol levels is occurring.

Nursing Care After the Procedure

Care and assessment after the procedure are the same as for any study involving the collection of a peripheral blood sample.

• Resume food and any medications withheld before the test, as well as usual activities.
• Increased levels: Note and report increased levels in relation to urinary cortisol, serum glucose, and calcium. Assess potential for infection, fluid volume excess (weight gain, edema, increased blood pressure), hyperglycemia (thirst, polyuria, polydipsia), mood changes (euphoria, psychosis), poor body image (moon face, buffalo hump on the back, acne, hair growth in undesirable areas in women, obese trunk, and thin extremities), and bone or joint pain. Monitor I&O. Provide support for psychophysiological changes. Help client to develop coping skills. Instruct client to increase dietary protein; decrease sodium, calories, and carbohydrates; and avoid infections.
• Decreased levels: Note and report decreased levels in relation to electrolyte panel (hyponatremia, hyperkalemia) and serum glucose for hypoglycemia. Assess for fluid volume deficit, long-term administration of corticosteroid therapy, and changes in body image (pigmentation of the skin, masculinization in women). Monitor I&O. Administer ordered corticosteroid regimen. Provide support for physical changes affecting body image. Advise client to avoid situations that cause stress or anxiety. Instruct client in long-term supplemental or replacement cortisone regimen.