ACTH stimulation test
From Standard of Care
Assesses the functioning of the adrenal glands stress response by measuring the adrenal response to adrenocorticotropic hormone (ACTH).
ACTH hormone is produced in the pituitary gland that stimulates the adrenal glands to release cortisol, dehydroepiandrosterone (DHEAS) and aldosterone.
A small amount of synthetic ACTH is injected, and the amount of cortisol, and sometimes aldosterone, the adrenals produce in response is measured.
The test is used to diagnose or exclude primary and secondary adrenal insufficiency, Addison's disease and related disrders.
The test can distinguish whether the cause is adrenal with low cortisol and aldosterone production or the pituitary with low ACTH production).
Gold standard assay of adrenal insufficiency, and is primarily used to determine the presence of Addison's disease and pituitary impairment.
The test is sensitive 97% for primary adrenal insufficiency, but less so to secondary adrenal insufficiency at 57-61%.
In the low-dose short test, 1 µg of an ACTH drug is utilized and conventional-dose short test, 250 µg of drug is injected: tests last for about an hour and provide the same information.
The prolonged-stimulation test can last up to 48 hours and can differentiate between primary, secondary, and tertiary adrenal insufficiency.
The test is performed fasting and Should not be done if the patient is on glucocorticoids, as it will affect test results.
Stress and spironolactone, contraceptives, licorice, estrogen, androgens, progesterone therapy may also affect test results.
Commonly reported reactions to the administration of ACTH are nausea, anxious sweating, dizziness, itchy skin, redness and or swelling of injection site, palpitations and facial flushing, which are transient.
Cortisol stimulation should double from a baseline of 20-30 µg/dl within 60 minutes in a healthy individual.
Baseline cortisol level in people with adrenal insufficiency is usually near 15 µg/dl.
A suboptimal ACTH stimulation test that raises the cortisol concentration to 20 µg/dl would support the diagnosis of primary adrenal insufficiency.
In Addison's disease, baseline cortisol is below 10 µg/dl and rises no more than 25 percent after ACTH administration.
ACTH stimulates cortisol from the low baseline value encountered in patients suffering from secondary adrenal insufficiency.
In secondary adrenal insufficiency ACTH stimulation resulting in a greater than 14-fold increase in serum concentration over 30 minutes, although typically serum cortisol levels will double or triple from baseline.
In secondary adrenal insufficiency the lower the baseline cortisol, the more likely cortisol levels will increase by a large amount.
An ACTH plasma test should always be performed at the same time as the ACTH stimulation test and a normal ACTH value should be just into the upper third of the range (assuming a range of 10–60 ng/L).
The ACTH plasma and ACTH stimulation test together provide a clearer picture, particularly for secondary adrenal insufficiency.
In primary adrenal insufficiency and Addison's diseas ACTH levels will be high.
In Addison's disease, ACTH may be way above the normal range and may reach levels in the hundreds, or thousands.
For secondary adrenal insufficiency ACTH levels will be low, usually below 35, but most people with secondary fall within the range limit.
Rarely, the cause of low ACTH is from low cortisol releasing hormone in the hypothalamus.
ACTH and cortisol releasing hormone impairment can both occur with a head injury.
The test can be used to test adrenal production of aldosterone to determine if primary or secondary hypoaldosteronism.
