How to check Adrenocorticotropic hormone (ACTH) levels in a patient with a history of adrenal insufficiency who is being treated with high-dose glucocorticoids, such as prednisolone, for vasculitis?

How to Check ACTH Levels in Patients on High-Dose Glucocorticoids

In patients with known adrenal insufficiency currently treated with high-dose prednisolone for vasculitis, checking ACTH levels is not diagnostically useful and should not be performed while on active glucocorticoid therapy. 1

Why ACTH Testing is Not Indicated During Active Glucocorticoid Treatment

Morning cortisol and ACTH measurements in patients actively taking corticosteroids are not diagnostic because:

• The cortisol assay measures both endogenous cortisol and therapeutic steroids, with cross-reactivity varying by assay 1
• Patients on corticosteroids will have low morning cortisol as a result of iatrogenic secondary adrenal insufficiency, and ACTH will also be suppressed—this is expected and not diagnostic 1
• Laboratory confirmation of adrenal insufficiency should not be attempted in patients given corticosteroids until treatment is ready to be discontinued 1

Critical Context for Your Clinical Scenario

If the patient already has confirmed adrenal insufficiency and is on established replacement therapy, there is usually no reason to check cortisol or ACTH levels—the diagnosis is already made. 1

The high-dose prednisolone for vasculitis will suppress the hypothalamic-pituitary-adrenal (HPA) axis regardless of underlying adrenal function 2, 1. This creates a clinical situation where:

• ACTH will be suppressed by the exogenous glucocorticoid 1, 3
• Endogenous cortisol production will be minimal 1
• Any testing will simply confirm expected HPA suppression, not provide diagnostic information 1

When ACTH Testing Becomes Relevant

ACTH stimulation testing should only be considered after glucocorticoid withdrawal, with appropriate washout periods:

Washout Requirements Before Testing

• Hydrocortisone: Must be held for 24 hours before testing 1
• Prednisolone and other steroids: Require longer washout periods before endogenous adrenal function can be accurately assessed 1, 4
• Long-acting glucocorticoids: May need to be stopped for an extended period before testing 4

Timeline for Recovery Assessment

After long-term glucocorticoid therapy (as in vasculitis treatment):

• Recovery from prolonged exposure to high doses may take up to 1 year 5
• In patients with giant cell arteritis on long-term glucocorticoids, mean time until recovery of adrenal function was 14 months (maximum: 51 months) 6
• A normal ACTH test response occurred within 36 months in 85% of patients, but adrenal function never recovered in 5% 6
• Testing for HPA axis recovery should occur after 3 months of maintenance therapy with hydrocortisone in patients with isolated central adrenal insufficiency from steroid use 1

The Proper ACTH Stimulation Test Protocol (When Appropriate)

When glucocorticoid withdrawal is planned and sufficient washout has occurred, the standard high-dose ACTH stimulation test is recommended:

Test Administration

• Administer 0.25 mg (250 mcg) cosyntropin intramuscularly or intravenously 2, 1, 4
• Obtain baseline serum cortisol and ACTH before administration 1, 4
• Measure serum cortisol at exactly 30 and 60 minutes after cosyntropin administration 1, 4

Interpretation

• Peak cortisol >550 nmol/L (>18-20 μg/dL): Normal response, excludes adrenal insufficiency 1
• Peak cortisol <500 nmol/L (<18 μg/dL): Diagnostic of adrenal insufficiency 1

Rationale for High-Dose Test

The high-dose (250-μg) test is preferred over the low-dose (1-μg) test due to:

• Easier practical administration 2
• Comparable diagnostic accuracy for secondary adrenal insufficiency 2
• FDA approval 1
• The low-dose test requires dilution of the commercial preparation at bedside, making it less practical 2, 1

Alternative Approach: Dexamethasone for Emergent Situations

If you need to treat suspected adrenal crisis but still want to perform diagnostic testing later, use dexamethasone 4 mg IV instead of hydrocortisone, as dexamethasone does not interfere with cortisol assays. 1

Management During Vasculitis Treatment

For patients with known adrenal insufficiency on high-dose prednisolone for vasculitis:

• The prednisolone dose for vasculitis (typically 1 mg/kg/day initially, maximum 60 mg/day) far exceeds physiologic replacement needs 2
• No additional glucocorticoid replacement is needed while on high-dose therapy 2
• Duration of glucocorticoid therapy for vasculitis can extend to several years 2
• Some patients may not tolerate complete discontinuation due to recurrent disease or secondary adrenal insufficiency 2

Predictors of Prolonged Adrenal Insufficiency

Risk factors associated with delayed recovery include:

• Glucocorticoid >15 mg/day at 6 months 6
• Glucocorticoid >9.5 mg/day at 12 months 6
• Treatment duration >19 months 6
• Cumulative glucocorticoid dose >8.5 g 6
• Basal cortisol concentration <386 nmol/L 6

Common Pitfalls to Avoid

• Never attempt ACTH or cortisol testing while the patient is on active glucocorticoid therapy—results will be uninterpretable and reflect expected HPA suppression, not true adrenal function 1
• Do not abruptly discontinue glucocorticoids to perform testing in patients on long-term therapy—this risks adrenal crisis 1, 7
• Avoid testing immediately after stopping glucocorticoids—this will yield false-positive results showing "adrenal insufficiency" that simply reflects expected HPA suppression 1
• In cases of long-term steroid exposure, consult endocrinology for a recovery and weaning protocol using hydrocortisone, rather than attempting abrupt discontinuation and early testing 1