Dexamethasone Suppression Test: Purpose, Test Details & Results

Purpose of Dexamethasone Suppression Test

The dexamethasone suppression test (DST) is a critical tool in modern medicine, used to investigate disorders related to the body’s stress hormone system. Whether a doctor is concerned about a hormone imbalance like Cushing’s syndrome or seeking clues about severe mood disorders, the DST offers valuable insight into how the body manages cortisol—a hormone closely tied to both physical and mental health. Understanding why this test is performed helps patients and clinicians target the right diagnosis and tailor effective treatment plans.

Investigating Hormonal Disorders

The DST is most frequently used to help diagnose Cushing’s syndrome—a condition where the body produces too much cortisol. By giving a synthetic steroid (dexamethasone) and measuring how the body’s cortisol responds, doctors can detect abnormal feedback within the hypothalamic-pituitary-adrenal (HPA) axis 3 5.

Key Points:

• In healthy individuals, dexamethasone should suppress cortisol production.
• Failure to suppress suggests possible Cushing’s syndrome or related adrenal disorders.

Understanding Psychiatric Disorders

Beyond hormone disorders, the DST has been extensively studied in psychiatry. Many patients with severe depression, particularly the “endogenous” type, show impaired suppression of cortisol after dexamethasone 2 4 6. This abnormal test result reflects underlying HPA axis dysregulation, which is common in certain mood disorders.

Examples:

• Major depressive disorder: Higher rates of DST non-suppression found 6.
• Bipolar disorder (depressed phase): Also shows higher non-suppression rates 2.
• Mania: Some overlap with depression in DST results, though findings are mixed 7.

Assessing Suicide Risk

Remarkably, DST results can also help predict suicide risk in patients with major depression. Research shows that people with abnormal DST results have a much higher rate of subsequent suicide compared to those with normal results—making DST a unique tool in psychiatric risk assessment 1.

Monitoring Disease Course and Treatment

The DST is sometimes used to monitor endocrine function during treatment for depression. Changes in DST response may precede clinical improvement or signal an impending relapse, helping to guide care 8.

Dexamethasone Suppression Test Details

Curious about what actually happens during a DST? The test involves administering dexamethasone and measuring how your body’s cortisol levels respond over time. Here’s what you need to know about the procedure, sample collection, and what factors can influence the results.

How the Test Is Performed

The DST is simple in principle but requires careful timing and preparation:

• Overnight Test (Low-Dose): The patient takes 1 mg dexamethasone, usually around 11 p.m. Blood is drawn the following morning, typically at 8 a.m., to check cortisol levels 3.
• Extended Protocols: Some protocols include additional samples at 4 p.m. and 11 p.m., or collect urine or saliva over 24-48 hours 2 3 5.
• High-Dose DST: In rare cases, a higher dose (2 mg) is used, particularly in psychiatric research or for differentiating causes of Cushing’s syndrome 7.

Sample Collection Options

• Blood serum: Most common and reliable; measures cortisol and sometimes dexamethasone directly 3 5.
• Urine: 24-hour urine collection for free cortisol or 17-hydroxycorticosteroids 3.
• Saliva: A newer, non-invasive method, especially useful in children or for repeat testing 5.

Factors Affecting the DST

A variety of factors can influence DST accuracy and interpretation:

• Medications: Some drugs can alter dexamethasone metabolism, impacting results 4.
• Dexamethasone Absorption: Variable bioavailability can lead to false results. Measuring dexamethasone levels alongside cortisol can improve specificity 5.
• Sampling Time and Frequency: More sample points increase the test’s sensitivity and reliability 2 5.
• Patient Condition: Severe illness, stress, or even psychiatric medications typically do not affect DST response 8.

Improving Test Accuracy

Recent studies show that measuring both dexamethasone and cortisol at the same time reduces false positives by correcting for poor dexamethasone absorption or metabolism 5. Salivary cortisone has also emerged as a sensitive, patient-friendly marker for certain conditions 5.

Dexamethasone Suppression Test Results & Follow-Up

Interpreting DST results is nuanced. The test doesn’t simply yield a “positive” or “negative”—it’s about patterns, context, and sometimes the need for repeat or additional testing. Here’s how DST results are understood, what they mean for patients, and how clinicians follow up.

Understanding Suppression and Non-Suppression

• Suppression: A drop in cortisol to below a set threshold (e.g., <50 nmol/L) after dexamethasone is considered a “normal” result. This rules out Cushing’s syndrome and is typical in healthy individuals 3 5.
• Non-suppression: If cortisol remains high, this suggests abnormal HPA axis feedback. Possible causes include:
  • Cushing’s syndrome (hormonal)
  • Major depressive disorder or bipolar disorder (psychiatric) 1 2 6 7

Diagnostic Sensitivity and Specificity

• Cushing’s Syndrome: DST is highly sensitive but not perfectly specific. Some patients with Cushing’s syndrome may still suppress cortisol (false negatives), so a normal result does not completely exclude the diagnosis. Additional tests may be needed 3 5.
• Psychiatric Disorders: Nonsuppression is common in endogenous depression (up to 70% of cases), but can also be seen in other psychiatric or neurological illnesses—limiting specificity 2 6 7.
• Suicide Risk: In major depression, DST non-suppression is associated with a much higher long-term risk of suicide (26.8% vs. 2.9%), outperforming traditional risk factors 1.

False Positives and Negatives

• False positives may occur if dexamethasone isn’t properly absorbed, or if other conditions (e.g., stress, certain medications) interfere. Measuring dexamethasone levels alongside cortisol helps reduce these errors 4 5.
• False negatives can happen in some patients with Cushing’s, as dexamethasone may occasionally suppress cortisol even when disease is present 3.

Results Over Time and Follow-Up

• In depression, DST results may normalize weeks before clinical recovery—or become abnormal before a relapse is detected. This makes the test useful for monitoring disease course in some psychiatric patients 8.
• Abnormal DST results are not usually affected by psychotropic medications, making the test robust for psychiatric follow-up 8.

Next Steps After DST:

• If results suggest Cushing’s or other endocrine disorders: Additional hormonal testing and imaging may be required 3 5.
• If results are abnormal in psychiatric patients: It may prompt more intensive monitoring or treatment interventions, especially for suicide risk 1 8.
• Repeat or alternative testing may be used if results are inconclusive or don’t match the clinical picture 3 5.

Conclusion

The dexamethasone suppression test is a powerful diagnostic tool at the crossroads of endocrinology and psychiatry. By measuring how the body’s cortisol responds to dexamethasone, the DST offers insights that shape diagnosis, treatment, and risk assessment for a range of conditions.

Key Points Covered:

• DST Purpose: Used to identify hormonal disorders (especially Cushing’s syndrome), investigate psychiatric conditions (like depression and bipolar disorder), assess suicide risk, and monitor therapy progress 1 2 3 5 6 7 8.
• Test Details: Involves taking dexamethasone orally, followed by precise sampling of blood, urine, or saliva at specific time points. Recent advances include simultaneous dexamethasone and cortisol measurement to improve accuracy 2 3 4 5.
• Results & Follow-Up: Interpretation is context-dependent, with non-suppression indicating potential disease. The test’s sensitivity and specificity vary by condition, and follow-up may include repeat testing or additional diagnostics. DST results can provide early warning of disease relapse or guide suicide prevention efforts 1 2 3 5 6 7 8.

By combining clinical context with careful DST interpretation, healthcare providers can better diagnose complex disorders and improve outcomes for their patients.