The Dexamethasone Suppression Test (DST) measures how cortisol levels respond after a person takes the synthetic steroid drug, dexamethasone. It is primarily used to help diagnose conditions involving the overproduction of cortisol, most notably Cushing’s Syndrome. The test assesses the feedback control system that regulates cortisol production.
The Hormonal Mechanism of Suppression
The DST works by interacting with the body’s Hypothalamic-Pituitary-Adrenal (HPA) axis, which is the system that controls the release of cortisol. In a healthy person, the hypothalamus releases corticotropin-releasing hormone, which prompts the pituitary gland to secrete adrenocorticotropic hormone (ACTH. ACTH then travels through the bloodstream to the adrenal glands, stimulating them to produce and release cortisol.
Cortisol acts as a natural brake on this system, creating a negative feedback loop by signaling the pituitary gland to reduce its ACTH output when cortisol levels are high. Dexamethasone is a powerful, synthetic version of cortisol that mimics this natural feedback signal. When administered, the drug binds to the same receptors as natural cortisol, effectively exaggerating the “high-level” signal.
In a person with a normally functioning HPA axis, the pituitary gland detects the presence of dexamethasone and responds by halting the release of ACTH. This suppression of ACTH leads to a significant decrease in the adrenal glands’ own production of cortisol. A healthy response to the test, therefore, is a distinct drop in circulating cortisol.
In conditions like Cushing’s Syndrome, the HPA axis is often disregulated and does not respond appropriately to this feedback signal. The source of the excess cortisol continues to produce cortisol despite the presence of high levels of dexamethasone. This failure to suppress the body’s own cortisol production is the underlying principle of an abnormal DST result.
Administration Protocols and Types of DST
The Dexamethasone Suppression Test uses different protocols tailored for initial screening or for differentiating the cause of hypercortisolism. The two main categories are the Low-Dose DST and the High-Dose DST. The most common screening method is the Low-Dose Overnight DST, which is simple and convenient for patients.
For the Low-Dose Overnight test, the patient takes a single 1-milligram tablet of dexamethasone orally late in the evening, usually between 11:00 PM and midnight. A blood sample is then collected the following morning, typically between 8:00 AM and 9:00 AM, to measure the resulting cortisol level. This quick protocol is highly sensitive for detecting potential excess cortisol production.
A more comprehensive screening approach is the Low-Dose Standard DST, which lasts 48 hours. The patient takes a smaller dose of 0.5 milligrams of dexamethasone every six hours over two days, for a total of eight doses. A blood sample is drawn six hours after the final dose, or a 24-hour urine collection is completed on the second day for a urinary free cortisol measurement. This extended period of exposure to the drug provides a more sustained suppression challenge to the HPA axis.
The High-Dose DST is used after initial screening suggests a problem and aims to identify the specific source of cortisol overproduction. The overnight version involves taking an 8-milligram dose of dexamethasone at 11:00 PM, followed by a blood draw the next morning. The Standard High-Dose DST involves taking 2 milligrams of dexamethasone every six hours for 48 hours, followed by a final cortisol measurement. The higher dose helps distinguish pituitary tumors from other causes of cortisol excess by overcoming partial resistance to suppression.
Analyzing Cortisol Levels and Results
The interpretation of the DST relies on comparing the patient’s post-dexamethasone cortisol level to established suppression cut-off values. In the Low-Dose Overnight DST, a normal suppression is generally defined as a morning serum cortisol level falling below 1.8 micrograms per deciliter (mcg/dL). A result above this threshold suggests a failure of the HPA axis to suppress and is considered a positive screening result for hypercortisolism, or Cushing’s Syndrome.
The lack of suppression indicates that the body is producing cortisol independent of the normal feedback mechanisms. This abnormal response suggests that the source of the excess cortisol is autonomous, meaning it is not being properly regulated by the pituitary gland’s ACTH signal. Further testing is required after a positive low-dose result to confirm the diagnosis of Cushing’s Syndrome.
If Cushing’s Syndrome is confirmed, the High-Dose DST helps differentiate the cause. If the cortisol level suppresses by more than 50% during the High-Dose test, it suggests a pituitary tumor (Cushing’s Disease), as these cells often retain some sensitivity to the large dose. Conversely, failure to suppress suggests a source outside the pituitary, such as an adrenal tumor or an ACTH-producing tumor located elsewhere.
Factors Affecting Test Accuracy
Several physiological states and medications can interfere with the results of the Dexamethasone Suppression Test. These interferences can cause a false positive result, suggesting a lack of suppression in a person who does not actually have Cushing’s Syndrome. Conditions that mimic hypercortisolism, often called pseudo-Cushing states, include severe physical or emotional stress, chronic alcoholism, and major depressive disorder.
Certain medications can increase the clearance of dexamethasone, lowering its effective concentration and causing a false non-suppression result. These include anticonvulsant drugs like phenytoin and phenobarbital, which accelerate the metabolism of dexamethasone by the liver. Patients are advised to stop taking these medications well in advance of the test, if medically possible.
Other drugs, such as those containing estrogen like oral contraceptives, can increase the level of a protein that binds to cortisol in the blood. This increase in total cortisol, even if the free, active cortisol is normal, may lead to a falsely high test result.