What is the role of the dexamethasone (corticosteroid) suppression test in diagnosing adrenal insufficiency?

Dexamethasone Suppression Test Has No Role in Diagnosing Adrenal Insufficiency

The dexamethasone suppression test is designed to diagnose Cushing's syndrome (cortisol excess), not adrenal insufficiency (cortisol deficiency), and should never be used for this purpose. 1, 2

Why Dexamethasone Suppression Testing is Inappropriate for Adrenal Insufficiency

• The dexamethasone suppression test evaluates whether exogenous glucocorticoid can suppress endogenous cortisol production—this assesses for autonomous cortisol hypersecretion, not cortisol deficiency 3, 2
• In patients with adrenal incidentalomas, the low-dose dexamethasone suppression test identifies subtle glucocorticoid excess, with post-test cortisol levels correlating with adenoma size 3
• The test is specifically designed to detect Cushing's syndrome, where cortisol levels fail to suppress appropriately after dexamethasone administration 2

The Correct Diagnostic Approach for Adrenal Insufficiency

Initial Testing

• Morning (8 AM) serum cortisol and plasma ACTH are the first-line diagnostic tests for suspected adrenal insufficiency 4
• Basal cortisol <250 nmol/L (<9 μg/dL) with elevated ACTH in acute illness is diagnostic of primary adrenal insufficiency 4
• Basal cortisol <400 nmol/L with elevated ACTH raises strong suspicion of adrenal insufficiency 4

Confirmatory Testing: The Cosyntropin (ACTH) Stimulation Test

• The cosyntropin stimulation test is the gold standard for confirming adrenal insufficiency, not the dexamethasone suppression test 4, 5
• Administer 0.25 mg cosyntropin (Synacthen) intramuscularly or intravenously 4
• Measure serum cortisol at baseline and 30 minutes (and/or 60 minutes) post-administration 4
• A peak cortisol value >550 nmol/L (>18-20 μg/dL) is normal 4
• A peak cortisol <500-550 nmol/L (<18-20 μg/dL) is diagnostic of adrenal insufficiency 4

Distinguishing Primary from Secondary Adrenal Insufficiency

• Primary adrenal insufficiency: high ACTH with low cortisol 4
• Secondary adrenal insufficiency: low ACTH with low cortisol 4
• Primary adrenal insufficiency often presents with both hyponatremia (90% of cases) and hyperkalemia (only 50% of cases) 4
• Secondary adrenal insufficiency may have additional pituitary hormone deficiencies 4

Critical Pitfall: Dexamethasone Can Confound Adrenal Testing

• Exogenous steroids including dexamethasone can suppress the hypothalamic-pituitary-adrenal axis and cause iatrogenic secondary adrenal insufficiency 6, 1
• The FDA label explicitly warns that dexamethasone and other corticosteroids may interfere with dexamethasone suppression tests, which should be interpreted with caution 1
• Patients on corticosteroids for management of other conditions will have low morning cortisol as a result of iatrogenic secondary adrenal insufficiency 6
• Dexamethasone suppression testing can predict later development of impaired adrenal function after glucocorticoid therapy, but this is assessing iatrogenic suppression, not diagnosing pre-existing adrenal insufficiency 7

When to Use Dexamethasone in Adrenal Insufficiency Context

• Dexamethasone 4 mg IV is preferred for emergent treatment of suspected adrenal crisis when the diagnosis is not yet confirmed and you still need to perform ACTH stimulation testing 6
• Unlike hydrocortisone, dexamethasone does not cross-react with cortisol assays, allowing diagnostic testing to proceed after emergency treatment 6
• Once adrenal insufficiency is confirmed, switch to hydrocortisone 100 mg IV for ongoing treatment 6

Emergency Management Takes Priority

• Treatment of suspected acute adrenal insufficiency should NEVER be delayed for diagnostic procedures 4
• If clinically unstable with suspected adrenal crisis: give IV hydrocortisone 100 mg immediately (or dexamethasone 4 mg if diagnosis uncertain) plus 0.9% saline infusion 6, 4
• Draw blood for cortisol and ACTH before treatment if possible, but do not delay treatment 4