What is the Dexamethasone Suppression Test?
The Dexamethasone Suppression Test (DST) is a diagnostic procedure used to evaluate the function of the hypothalamic-pituitary-adrenal (HPA) axis by assessing how cortisol production is regulated. It is most commonly used in the diagnosis of Cushing’s syndrome, a condition characterized by excessive cortisol levels. Dexamethasone, a synthetic glucocorticoid, mimics the effects of cortisol in the body. The test works by measuring whether dexamethasone can suppress the secretion of adrenocorticotropic hormone (ACTH) from the pituitary gland, and consequently, reduce cortisol production by the adrenal glands. Since cortisol plays a vital role in metabolism, immune function, and the body’s response to stress, the DST is essential for identifying disorders involving cortisol excess or dysregulation.
Table of Contents
Purpose of the Dexamethasone Suppression Test
The main purpose of the DST is to help determine whether the body is producing too much cortisol, a hormone released by the adrenal glands in response to stress and controlled by the hypothalamic-pituitary-adrenal (HPA) axis. The HPA axis regulates cortisol production through a feedback loop involving the hypothalamus, pituitary gland, and adrenal glands. Disruptions in this loop can lead to either excessive or insufficient cortisol production, with various health implications.
The DST is primarily used to:
A. Diagnose Cushing’s Syndrome
The most common use of the DST is to screen for Cushing’s syndrome, a disorder caused by prolonged exposure to elevated cortisol levels. The syndrome may result from:
➧ Cushing’s disease – Caused by a pituitary adenoma secreting excess ACTH (ACTH-dependent).
➧ Adrenal tumors – Benign or malignant tumors in the adrenal cortex producing cortisol independently of ACTH (ACTH-independent).
➧ Ectopic ACTH production – Non-pituitary tumors (e.g., small-cell lung cancer, pancreatic tumors) producing ACTH inappropriately.
In a normal HPA axis, dexamethasone (a potent synthetic glucocorticoid) should suppress ACTH and, subsequently, cortisol secretion. In patients with Cushing’s syndrome, this suppression is often absent or incomplete, helping to confirm the diagnosis.
B. Differentiate Types of Cushing’s Syndrome
There are two main DST approaches for differentiating the cause of Cushing’s syndrome:
➧ Low-dose DST (1 mg overnight or 2 mg over 48 hours): Used primarily to confirm the presence of hypercortisolism.
➧ High-dose DST (8 mg): Helps differentiate Cushing’s disease (where cortisol suppression is partially preserved) from ectopic ACTH secretion or adrenal tumors (where suppression is usually absent).
This step-wise approach allows clinicians to localize the source of cortisol overproduction and guides further imaging or lab evaluation.
C. Evaluate for Subclinical Hypercortisolism
In patients with incidental adrenal masses (adrenal incidentalomas), the DST is often used to assess for subclinical Cushing’s syndrome—a condition with biochemical cortisol excess but without classic clinical signs. Identifying this is important due to its links with increased cardiovascular risk and diabetes.
D. Investigate Cortisol Regulation in Other Conditions
Although less commonly, DST is also used in the context of psychiatric conditions (such as severe depression or psychosis), alcoholism, and obesity, which may show abnormal cortisol dynamics without structural HPA axis disease. In these cases, an abnormal DST may reflect HPA axis dysregulation rather than Cushing’s syndrome and must be interpreted with caution.
The DST is a vital tool in endocrine diagnostics. It serves not only to confirm cortisol excess but also to differentiate between its various causes. However, accurate interpretation requires understanding of the HPA axis, timing of the test, and the patient's clinical context. It is often used alongside other investigations, such as late-night salivary cortisol, 24-hour urinary free cortisol, and plasma ACTH levels.(alert-passed)
How is the Dexamethasone Suppression Test Performed?
The Dexamethasone Suppression Test (DST) involves the administration of dexamethasone, a synthetic glucocorticoid, followed by the measurement of cortisol levels in the blood (and occasionally in urine or saliva). The test evaluates the body’s ability to suppress cortisol production in response to external steroid input, providing insight into the functioning of the hypothalamic-pituitary-adrenal (HPA) axis.
There are two main forms of the DST, each serving a different diagnostic purpose:
A. Low-Dose Dexamethasone Suppression Test
The low-dose DST is typically the first-line screening tool for identifying hypercortisolism, especially in patients suspected of having Cushing’s syndrome.
1. Overnight Low-Dose Test (Most Common):
➧ The patient takes 1 mg of dexamethasone orally at 11 p.m.
➧ Blood cortisol levels are measured the next morning between 8:00 and 9:00 a.m.
➧ In a normal response, cortisol should be suppressed to less than 1.8 µg/dL (50 nmol/L).
2. 48-Hour Low-Dose Test (Less commonly used today):
➧ The patient takes 0.5 mg of dexamethasone every 6 hours for 48 hours.
➧ Serum cortisol and/or 24-hour urinary free cortisol are measured at the end of the test.
➧ This version may be used in more complex or equivocal cases to increase test sensitivity.
B. High-Dose Dexamethasone Suppression Test
If hypercortisolism is confirmed via the low-dose DST, the high-dose DST helps identify the source—whether it is due to Cushing’s disease (pituitary), ectopic ACTH production, or an adrenal tumor.
1. Overnight High-Dose Test
➧ The patient takes 8 mg of dexamethasone orally at 11 p.m.
➧ Morning serum cortisol is measured the next day between 8:00 and 9:00 a.m.
➧ A >50% suppression of cortisol suggests Cushing’s disease (pituitary source), whereas little to no suppression indicates adrenal or ectopic ACTH-producing tumors.
2. 48-Hour High-Dose Test
➧ The patient takes 2 mg of dexamethasone every 6 hours for 48 hours.
➧ Cortisol and/or urinary free cortisol levels are measured after the final dose.
➧ This method provides a more detailed assessment, especially in borderline or ambiguous cases.
Clinical Notes
➧ Medications, stress, obesity, depression, and alcohol use can all affect DST results and may cause false positives or negatives.
➧ In some protocols, plasma ACTH levels are measured in conjunction with DST to aid in diagnosis.
➧ Late-night salivary cortisol and 24-hour urinary free cortisol tests are often used alongside DST to increase diagnostic accuracy.
Interpretation of the Dexamethasone Suppression Test
The DST results are interpreted based on how well cortisol production is suppressed by dexamethasone. In healthy individuals, dexamethasone mimics the effects of cortisol, signaling the pituitary gland to stop producing ACTH, which in turn reduces cortisol production by the adrenal glands.
Normal Response
In individuals with a healthy hypothalamic-pituitary-adrenal (HPA) axis, the administration of dexamethasone results in a significant decrease in serum cortisol levels. For the low-dose overnight test, a morning cortisol level below 1.8 µg/dL (50 nmol/L) generally rules out Cushing’s syndrome. Suppression of cortisol demonstrates intact negative feedback on the pituitary and hypothalamus.
Abnormal Response in Cushing’s Syndrome
When cortisol levels fail to suppress appropriately after dexamethasone administration, this suggests Cushing’s syndrome. The degree of cortisol suppression—or lack thereof—helps identify the source of the abnormal cortisol production:
➧ No suppression after low-dose DST strongly suggests hypercortisolism.
➧ Additional testing with high-dose DST helps distinguish between Cushing’s disease (pituitary adenoma) and non-pituitary causes.
High-Dose DST Interpretation
The high-dose DST is primarily used to differentiate causes of Cushing’s syndrome. Here's how results are interpreted:
➧ Suppression of cortisol by ≥50% from baseline: Suggestive of Cushing’s disease (pituitary adenoma secreting ACTH).
➧ Little or no suppression: Indicates either an adrenal tumor (ACTH-independent) or ectopic ACTH production (e.g., from a small cell lung carcinoma). These causes do not respond to feedback inhibition from dexamethasone.
ACTH Measurements as a Complement
To enhance the diagnostic value of DST, plasma ACTH levels are often measured simultaneously:
➧ Low ACTH with high cortisol: Suggests adrenal cause (autonomous cortisol secretion).
➧ High or inappropriately normal ACTH: Suggests Cushing’s disease or ectopic ACTH production. DST results will help distinguish between the two.
Considerations in Interpretation
It is essential to interpret DST results in conjunction with clinical findings, additional lab tests, and imaging studies. Several factors can affect the accuracy of the DST:
➧ Medications (e.g., phenytoin, rifampin) may increase dexamethasone metabolism.
➧ Obesity, depression, and alcoholism may result in false-positive tests (pseudo-Cushing’s).
➧ Stress and illness can affect cortisol levels, possibly confounding results.
Interpreting the DST involves assessing whether cortisol production is appropriately suppressed and using this information to determine the presence and source of hypercortisolism. While failure to suppress cortisol is a key diagnostic indicator, the full clinical picture must be considered to reach a definitive diagnosis.(alert-passed)
Clinical Applications of the Dexamethasone Suppression Test
The Dexamethasone Suppression Test (DST) is a valuable tool in the evaluation of disorders involving cortisol excess, particularly Cushing’s syndrome. Beyond diagnosis, it plays a critical role in differential diagnosis and monitoring treatment outcomes in endocrine disorders.
A. Diagnosing Cushing’s Syndrome
The DST is considered one of the most reliable initial screening tests for Cushing’s syndrome, a condition characterized by chronically elevated cortisol levels. In healthy individuals, dexamethasone suppresses cortisol production via negative feedback to the hypothalamic-pituitary-adrenal (HPA) axis. However, in individuals with Cushing’s syndrome, this suppression does not occur, or is significantly blunted, indicating dysregulation in the HPA axis. This initial test helps confirm the presence of hypercortisolism.
B. Differentiating Between Cushing’s Disease and Ectopic ACTH Production
The high-dose DST plays a key role in differentiating between Cushing’s disease (caused by a pituitary adenoma producing ACTH) and ectopic ACTH production (caused by non-pituitary tumors, such as small cell lung carcinoma). In Cushing’s disease, cortisol levels are often suppressed by more than 50% with high-dose dexamethasone. In contrast, ectopic ACTH production usually shows little to no suppression, guiding clinicians toward the appropriate source for further diagnostic imaging and intervention.
C. Monitoring Treatment Response and Detecting Recurrence
Following surgical treatment for Cushing’s syndrome (e.g., removal of a pituitary or adrenal tumor), the DST is useful for monitoring therapeutic efficacy. A normal suppression response post-treatment suggests successful intervention, while persistently elevated or rising cortisol levels may indicate incomplete resection or recurrence of disease. The DST thus serves as a non-invasive follow-up tool to assess long-term outcomes in treated patients.
D. Supporting Diagnosis in Other Cortisol-Related Conditions
In select cases, the DST may also be used to help evaluate cortisol regulation abnormalities in pseudo-Cushing states, such as chronic depression, alcohol use disorder, and severe stress. These conditions can mimic true Cushing’s syndrome in clinical presentation but may show a different response to dexamethasone, helping differentiate between physiological and pathological hypercortisolism.
Limitations and Risks of the Dexamethasone Suppression Test
While the Dexamethasone Suppression Test (DST) is a widely used diagnostic tool in endocrinology, it is not without its limitations and potential risks.
A. False Positives and False Negatives
One of the main limitations of the DST is its susceptibility to false-positive and false-negative results. Various non-endocrine conditions, such as depression, alcoholism, obesity, poorly controlled diabetes, and severe stress, can lead to abnormal cortisol suppression patterns that mimic Cushing’s syndrome, potentially leading to a false positive diagnosis. Conversely, some patients with true Cushing’s syndrome, especially those with mild or cyclical forms, may show suppression on low-dose testing, resulting in a false negative outcome.
B. Interference from Medications
Several medications can affect dexamethasone metabolism or cortisol levels, thereby interfering with the test results. Drugs that induce liver enzymes, such as phenytoin, phenobarbital, rifampin, and carbamazepine, can increase the clearance of dexamethasone, leading to insufficient suppression of cortisol. Additionally, oral estrogen therapy can raise cortisol-binding globulin levels, falsely elevating total serum cortisol despite normal free cortisol activity. Clinicians need to review a patient’s medication history before performing the DST.
C. Variation in Cortisol Measurement
The method of cortisol measurement—whether serum, salivary, or urinary—can also affect the accuracy and interpretation of the DST. Factors such as diurnal variation, improper timing of sample collection, and laboratory variability can lead to inconsistent results. This makes standardized timing and methodology crucial when performing the test.
D. Risk of Adverse Effects from Dexamethasone
Dexamethasone is generally well-tolerated at the doses used in suppression testing; however, it may cause temporary side effects in some individuals. These include mood changes, sleep disturbances, increased appetite, or gastrointestinal discomfort. In patients with diabetes or hypertension, dexamethasone may transiently worsen blood glucose or blood pressure control. While serious adverse effects are rare at low doses, clinicians should still monitor vulnerable patients closely.
E. Not Definitive Without Follow-Up Testing
The DST alone is not diagnostic of the specific cause of hypercortisolism. It is typically the first step in a broader diagnostic process. Abnormal DST results usually require follow-up testing, such as ACTH level measurement, CRH stimulation tests, urinary free cortisol, or imaging studies to accurately localize the source of cortisol excess. Thus, DST is part of a diagnostic algorithm rather than a standalone diagnostic tool.
