The Dexamethasone Suppression Test (DST) evaluates the regulatory function of the body’s stress response system. This test measures how the hypothalamic-pituitary-adrenal (HPA) axis responds to the synthetic steroid dexamethasone. By administering this drug and measuring subsequent cortisol levels, physicians determine if the body appropriately suppresses its own hormone production. The DST is primarily utilized to assess for disorders of cortisol excess, providing a direct physiological assessment of endocrine control.
The Role of Cortisol and Hypercortisolism
Cortisol is a glucocorticoid hormone produced by the adrenal glands. It plays roles essential for life, including regulating metabolism, managing the immune system, and controlling blood pressure. It is known as the “stress hormone” because its release increases rapidly during times of physical or psychological stress. Normally, cortisol levels fluctuate throughout the day, peaking in the morning and dropping to their lowest point late at night.
The production of cortisol is tightly controlled by the HPA axis through a negative feedback loop. The hypothalamus releases corticotropin-releasing hormone (CRH), which stimulates the pituitary gland to release adrenocorticotropic hormone (ACTH). ACTH prompts the adrenal glands to secrete cortisol. When cortisol levels rise, the hormone feeds back to the hypothalamus and pituitary, signaling them to reduce CRH and ACTH release, thereby shutting down further cortisol production.
Hypercortisolism is a state where the body has an abnormally high amount of circulating cortisol over a prolonged period. The most recognized condition resulting from chronic hypercortisolism is Cushing’s syndrome. This excess cortisol can lead to symptoms like a rounded face, trunk weight gain, easy bruising, and muscle weakness. The DST operates on the principle that in a healthy person, dexamethasone mimics cortisol and engages the negative feedback loop, causing a significant drop in natural cortisol levels.
Understanding the Different DST Procedures
The Dexamethasone Suppression Test involves a set of protocols tailored to different diagnostic goals, primarily involving low-dose and high-dose variations. Low-dose tests are used for initial screening to confirm hypercortisolism. The most common screening method is the Overnight Low-Dose DST, where the patient takes 1 milligram (mg) of dexamethasone orally between 11 PM and midnight. A blood sample is collected the following morning, typically between 8 AM and 9 AM, to measure the resulting cortisol level.
The 48-Hour Low-Dose DST is a more definitive screening test. It involves taking 0.5 mg of dexamethasone every six hours for two full days. This prolonged exposure provides a robust assessment of HPA axis function. Low-dose protocols are highly sensitive in detecting hypercortisolism, as a healthy HPA axis should be completely suppressed by this small dose.
If low-dose tests confirm hypercortisolism, a High-Dose DST is performed to determine the underlying cause. This procedure uses a larger dose of the drug, such as 8 mg given overnight, or 2 mg every six hours for 48 hours. The higher dose differentiates between a problem originating in the pituitary gland (Cushing’s disease) and other causes. These other causes include a tumor in the adrenal gland or an ectopic tumor elsewhere in the body.
Patient Preparation and Factors Affecting Accuracy
Accurate DST results depend on managing factors that interfere with cortisol metabolism. Patients must inform their physician of all medications, as many common drugs significantly impact test outcomes. Certain anti-seizure medications, like phenytoin or phenobarbital, and antibiotics like rifampicin, can speed up the liver’s breakdown of dexamethasone. This accelerated breakdown leads to a false lack of suppression.
Conversely, conditions that increase cortisol-binding globulin, such as pregnancy or the use of oral contraceptives containing estrogen, can lead to artificially elevated total cortisol levels and potentially a false positive result. Acute illness, severe psychological stress, and alcohol use disorder can also cause a temporary elevation in cortisol, mimicking hypercortisolism. To ensure a reliable result, physicians advise patients to discontinue certain medications under supervision and to avoid stressful situations leading up to the test.
Interpreting the Test Results
The results of the DST are interpreted by measuring the concentration of cortisol remaining in the blood after the dexamethasone has been administered. For the standard overnight 1 mg DST, a normal result indicates that the HPA axis has been successfully suppressed. This means the morning serum cortisol level is typically less than 1.8 micrograms per deciliter (mcg/dL). A value above this threshold is considered an abnormal result, suggesting a failure of the feedback mechanism and indicating a high likelihood of hypercortisolism.
If the low-dose test is abnormal, the high-dose DST helps pinpoint the origin of the problem. If the high dose causes a significant reduction in cortisol (usually a decrease of more than 50% from baseline), the result points toward Cushing’s disease. Cushing’s disease is caused by a pituitary tumor producing excess ACTH. If the high dose fails to suppress cortisol production, the cause is likely an adrenal gland tumor or a non-pituitary tumor producing ACTH (ectopic source), as these sources operate independently of pituitary control.
Following a positive screening test, physicians often order additional tests, such as a 24-hour urine cortisol collection or a late-night salivary cortisol test, to confirm Cushing’s syndrome. To ensure the test was not flawed, it is necessary to measure the concentration of dexamethasone in the patient’s blood sample. If the dexamethasone level is too low, it suggests the patient did not absorb the pill or metabolized it too quickly, rendering the cortisol result unreliable.