What is a high-dose dexamethasone (corticosteroid) suppression test?

From the Guidelines

A high-dose dexamethasone suppression test is a diagnostic procedure used to differentiate between various causes of excess cortisol production (Cushing's syndrome), where a high dose of dexamethasone (typically 8 mg orally) is administered at 11 PM, followed by measurement of blood cortisol levels at 8 AM the next morning, with suppression of cortisol production by more than 50% from baseline indicating Cushing's disease (pituitary-dependent hypercortisolism) 1.

Procedure and Interpretation

The test involves administering a high dose of dexamethasone, which is a synthetic glucocorticoid that can suppress the production of cortisol in the body. In patients with Cushing's disease, the high dose of dexamethasone usually suppresses cortisol production by more than 50% from baseline, whereas in patients with ectopic ACTH syndrome or adrenal tumors, cortisol levels typically remain elevated with minimal or no suppression 1.

Clinical Application

This differential response occurs because pituitary tumors retain some sensitivity to negative feedback from glucocorticoids, while ectopic sources of ACTH and autonomous adrenal tumors generally do not. The test is performed after an initial low-dose dexamethasone suppression test has already confirmed the presence of Cushing's syndrome. Patients should avoid medications that affect dexamethasone metabolism (such as phenytoin, rifampin, or estrogens) for at least one week before testing to ensure accurate results 1.

Key Considerations

• The high-dose dexamethasone suppression test is used to differentiate between Cushing's disease and other causes of Cushing's syndrome.
• The test involves administering a high dose of dexamethasone and measuring blood cortisol levels the next morning.
• Suppression of cortisol production by more than 50% from baseline indicates Cushing's disease.
• Patients should avoid medications that affect dexamethasone metabolism before testing.
• The test is performed after an initial low-dose dexamethasone suppression test has confirmed the presence of Cushing's syndrome.

From the FDA Drug Label

DOSAGE REQUIREMENTS ARE VARIABLE AND MUST BE INDIVIDUALIZED ON THE BASIS OF THE DISEASE AND THE RESPONSE OF THE PATIENT. The FDA drug label does not answer the question.

From the Research

Definition and Purpose of High-Dose Dexamethasone Suppression Test

• The high-dose dexamethasone suppression test is a diagnostic tool used to differentiate between various forms of Cushing's syndrome, a condition characterized by excess cortisol production 2, 3, 4, 5, 6.
• The test involves administering a high dose of dexamethasone, a synthetic corticosteroid, to suppress cortisol production in the body.
• The purpose of the test is to determine if cortisol production can be suppressed, which helps to identify the underlying cause of Cushing's syndrome.

Types of High-Dose Dexamethasone Suppression Tests

• Overnight high-dose dexamethasone suppression test: involves administering a single 8-mg dose of dexamethasone overnight 2, 5.
• Standard 2-day test: involves administering 8 mg of dexamethasone over two days 2.
• Very high dose dexamethasone suppression test: involves administering 32 mg of dexamethasone over 24 hours 4.
• Intravenous dexamethasone suppression test: involves administering 4 mg of dexamethasone intravenously 6.

Diagnostic Accuracy and Sensitivity

• The overnight high-dose dexamethasone suppression test has a sensitivity of 92% and a specificity of 100% for diagnosing Cushing's disease 2.
• The very high dose dexamethasone suppression test has a higher diagnostic accuracy than the standard 8-mg test, especially in patients with non-suppressible Cushing's syndrome 4.
• The intravenous dexamethasone suppression test is excellent in ruling out pseudo-Cushing's syndrome and can confirm clinical suspicion of pituitary Cushing's disease 6.

Clinical Utility and Convenience

• The high-dose dexamethasone suppression test is a practical and reliable tool for diagnosing Cushing's syndrome, especially in outpatient settings 2, 5, 6.
• The test is simpler and more convenient than other diagnostic tests, such as the standard 2-day test, which requires an extended inpatient stay 5, 6.