The Dexamethasone Suppression Test (DST) is a common endocrine tool used by physicians to evaluate the function of the body’s natural stress response system, which involves the regulation of the hormone cortisol. The test involves administering dexamethasone, a potent synthetic steroid, and then measuring the subsequent change in the body’s cortisol levels. This procedure assesses the negative feedback loop that normally controls cortisol production. A normal response confirms a healthy regulatory system, while an abnormal response suggests a disorder of hormonal control.
Identifying the Diagnostic Need
Physicians primarily order the DST when they suspect a patient is suffering from chronic hypercortisolism, which is a prolonged overproduction of the hormone cortisol. This condition is frequently associated with Cushing’s syndrome (ICD-10 code E24).
Classic symptoms that raise suspicion include unexplained, rapid weight gain, particularly concentrated in the torso and face (central obesity). Patients may also present with thin, fragile skin that bruises easily, muscle weakness, and new-onset high blood pressure or diabetes. The DST is utilized as a screening and confirmatory test to determine if these symptoms are caused by a failure of the body’s cortisol control mechanism.
The Science Behind the Suppression
The DST works by directly challenging the Hypothalamic-Pituitary-Adrenal (HPA) axis. This axis normally operates on a negative feedback loop to maintain balance. The hypothalamus releases corticotropin-releasing hormone (CRH), which signals the pituitary gland to release adrenocorticotropic hormone (ACTH).
ACTH then travels through the bloodstream to the adrenal glands, prompting them to synthesize and release cortisol. When cortisol levels rise, this signals back to the pituitary and hypothalamus to slow down the release of CRH and ACTH, reducing the adrenal glands’ output of cortisol. Dexamethasone is a potent synthetic glucocorticoid that mimics the effect of natural cortisol.
When administered, dexamethasone binds to receptors on the pituitary gland, sending a strong artificial signal that cortisol levels are high. In a healthy person, this signal should effectively suppress the pituitary’s production of ACTH. The resultant drop in ACTH causes the adrenal glands to stop making their own cortisol, leading to a significant decrease in circulating cortisol levels. A failure to suppress cortisol indicates that the HPA axis has lost its sensitivity to this feedback mechanism, which is characteristic of hypercortisolism.
Step-by-Step Procedure
The simplest and most common version is the overnight DST, used for initial screening. The patient takes a single 1-milligram dose of dexamethasone orally late in the evening. A blood sample is collected the next morning to measure the resulting cortisol level.
If the screening test is abnormal, a low-dose DST is often performed for confirmation, which involves a multi-day regimen to improve accuracy. This protocol generally requires the patient to take a smaller dose, such as 0.5 milligrams, every six hours for a total of two days. Blood or 24-hour urine samples are collected before the test and on the final day to assess the degree of cortisol suppression. Patients are instructed to avoid certain medications beforehand, as these can interfere with the test’s results.
The high-dose DST is reserved for cases where hypercortisolism has already been confirmed but the source of the excess hormone needs to be identified. This test often uses a higher dose, such as 8 milligrams, given overnight or over two days, to see if the higher concentration can overcome the resistance to suppression.
Interpreting the Outcomes
The interpretation of the DST hinges on whether the cortisol level successfully drops below a specific threshold after the dexamethasone is administered. A normal, or “negative,” result on the overnight test is defined by a morning plasma cortisol level less than 1.8 micrograms per deciliter. This successful suppression confirms that the HPA axis is functioning correctly and rules out a diagnosis of Cushing’s syndrome.
An abnormal, or “positive,” result means the cortisol level remains elevated above the suppression threshold, indicating autonomous or unregulated cortisol production. If the low-dose DST also shows a lack of suppression, it confirms the presence of hypercortisolism. The high-dose DST is then used to differentiate the cause.
If the high dose does suppress cortisol, it suggests the problem is a pituitary tumor (Cushing’s disease), which still retains some feedback sensitivity. If the high-dose dexamethasone fails to suppress cortisol levels, the cause is likely an adrenal tumor or an ectopic source of ACTH production, such as a tumor elsewhere in the body. The specific pattern of suppression or lack thereof across the low- and high-dose tests provides a roadmap for physicians to pinpoint the location of the hormonal abnormality.