Type of test Blood

Normal findings

Rapid test: cortisol levels increase > 7 mcg/dL higher than baseline

 24-hour test: cortisol levels > 40 mcg/Dl

 3-day test: cortisol levels > 40 mcg/dL

Test explanation and related physiology

 This test is performed in patients found to have an adrenal insufficiency. An increase in plasma free or total cortisol levels after the infusion of an ACTH-like drug indicates that the adrenal gland is normal and is capable of functioning if stimulated. In that case, the cause of the adrenal insufficiency would lie within the pituitary gland (hypopituitarism, which is called secondary adrenal insufficiency). If little or no rise in cortisol levels occurs after the administration of the ACTH-like drug, the adrenal gland is the source of the problem and cannot secrete cortisol. This is called primary adrenal insufficiency (Addison disease), which may be caused by adrenal hemorrhage, infarction, autoimmunity, metastatic tumor, surgical removal of the adrenal glands, or congenital adrenal enzyme deficiency.

This test can also be used in the evaluation of patients with Cushing syndrome. Patients with Cushing syndrome caused by bilateral adrenal hyperplasia have an exaggerated cortisol elevation in response to the administration of the ACTH-like drug. Those experiencing Cushing syndrome as a result of hyperfunctioning adrenal tumors (which are usually autonomous and relatively insensitive to ACTH) have little or no increase in cortisol levels over baseline values.

Cosyntropin (Cortrosyn) is a synthetic subunit of ACTH that has the same corticosteroid-stimulating effect as endogenous ACTH in healthy persons. During this test, cosyntropin is administered to the patient, and the ability of the adrenal gland to respond is measured by plasma cortisol levels.

The rapid stimulation test is only a screening test. A normal response excludes adrenal insufficiency. An abnormal response, however, requires a 24-hour to 3-day prolonged ACTH stimulation test to differentiate primary insufficiency from secondary insufficiency. It should be noted that the adrenal gland can also be stimulated by insulin-induced hypoglycemia as a stressing agent. When insulin is the stimulant, cortisol and glucose levels are measured.

Interfering factors

* Drugs that may cause artificially increased cortisol levels include corticosteroids, estrogens, and spironolactone.

 Procedure and patient care

 • See inside front cover for Routine Blood Testing.

 • Fasting: yes

 • Blood tube commonly used: red

Rapid test

 • Obtain a baseline plasma cortisol level. This should be done 30 minutes before cosyntropin (ACTH-like drug) administration.

 • Administer an IV injection of cosyntropin over a 2-minute period as prescribed.

 • Measure plasma cortisol levels 30 and 60 minutes after drug administration.

 24-hour test

 • Obtain a baseline plasma cortisol level.

 • Start an IV infusion of synthetic cosyntropin.

 • Administer the solution as prescribed for 24 hours.

• After 24 hours, obtain another plasma cortisol level.

 3-day test

 • Obtain a baseline plasma cortisol level.

 • Administer the prescribed dose of cosyntropin IV over an 8-hour period for 2 to 3 consecutive days.

 • Measure plasma cortisol levels at 12, 24, 36, 48, 60, and 72 hours after the start of the test.

 Abnormal findings

 In adrenal insufficiency

 Increase higher than normal response (secondary adrenal insufficiency) Hypopituitarism

 Exogenous steroid ingestion

 Endogenous steroid production from a nonendocrine tumor

 Normal or lower than normal response (primary adrenal insufficiency)

Addison disease

 Adrenal infarction/hemorrhage

 Metastatic tumor to the adrenal gland

Congenital enzyme adrenal insufficiency

 Surgical removal of the adrenal gland

In Cushing syndrome

 Increase higher than normal response

 Bilateral adrenal hyperplasia

 Normal or lower than normal response

 Adrenal adenoma

 Adrenal carcinoma

ACTH-producing nonadrenal tumor

Chronic steroid use

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