Does prior administration of steroids (corticosteroids) interfere with Cosyntropin (tetracosactide) ACTH (Adrenocorticotropic Hormone) stimulation testing?

From the Guidelines

Steroids should be discontinued before a cosyntropin ACTH stimulation test to avoid false results, with the duration of discontinuation depending on the type and duration of steroid use, as evidenced by recent guidelines 1. When considering the impact of steroids on cosyntropin ACTH stimulation testing, it's crucial to understand that exogenous steroids can suppress the hypothalamic-pituitary-adrenal (HPA) axis, leading to reduced endogenous cortisol production. This suppression can result in an inadequate cortisol response to ACTH stimulation, potentially leading to a false diagnosis of adrenal insufficiency.

Key Considerations

• The duration for which steroids should be discontinued before the test varies based on the steroid's duration of action: short-acting steroids like prednisone, prednisolone, and hydrocortisone should be stopped 24-48 hours before testing 1.
• Intermediate-acting steroids, such as methylprednisolone, should be discontinued 48-72 hours prior to the test.
• Long-acting steroids, including dexamethasone, require at least 72 hours of discontinuation, and depot preparations like triamcinolone acetonide need several weeks.
• Inhaled, topical, and intra-articular steroids can also interfere if used at high doses or for prolonged periods, as noted in guidelines for managing patients on long-term systemic steroids 1.

Clinical Implications

The decision to discontinue steroids before cosyntropin ACTH stimulation testing must balance the risk of false test results against the potential clinical risks of temporarily stopping steroid therapy. If steroids cannot be safely discontinued, this should be clearly documented and considered when interpreting test results. In urgent situations where steroid therapy cannot be interrupted, alternative approaches, such as using dexamethasone, which does not cross-react with most cortisol assays, may be considered, though this is not ideal 1.

Patient Education and Management

Patients on corticosteroids require education on stress dosing, the use of emergency steroid injectables, and when to seek medical attention for impending adrenal crisis, highlighting the importance of comprehensive management plans 1.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION • In general, stop glucocorticoids and spironolactone on the day of cosyntropin for injection testing For long-acting glucocorticoids, stop for a longer period before cosyntropin for injection testing. (2.1) DRUG INTERACTIONS • Drug effects on plasma cortisol levels: o Glucocorticoids and spironolactone: May falsely elevate plasma cortisol levels. Stop these drugs on day of cosyntropin for injection testing Long-acting glucocorticoids may need to be stopped for a longer period before cosyntropin for injection testing. (7)

Steroids, specifically glucocorticoids, can interfere with cosyntropin ACTH stimulation testing by falsely elevating plasma cortisol levels. To minimize this interference, it is recommended to:

• Stop glucocorticoids and spironolactone on the day of testing
• Stop long-acting glucocorticoids for a longer period before testing 2
• Stop estrogen-containing drugs 4 to 6 weeks before testing 2, 2

From the Research

Interference of Steroids on Cosyntropin ACTH Stimulation Testing

• The administration of steroids prior to cosyntropin ACTH stimulation testing can interfere with the test results, as it may suppress the adrenal gland's response to ACTH 3.
• A study found that patients receiving high-dose dexamethasone therapy had a compromised serum cortisol response to the ACTH stimulation test after 96 hours of therapy, suggesting that the test may not be reliable in this setting 3.
• However, the same study suggested that the ACTH stimulation test may still be used to diagnose adrenal insufficiency within the first 3 days after initiation of empiric glucocorticoid therapy 3.

Factors Affecting Test Results

• The time of day the test is performed, type of assay, and sample source used for cortisol measurement can affect the clinical value of the ACTH stimulation test 4.
• The use of specific cortisol assays, such as monoclonal antibody immunoassays or LC-MS/MS, may require lower thresholds for a normal response 5.
• Baseline cortisol levels <2 μg/dL may be predictive of subnormal stimulated cortisol values 5.

Diagnostic Considerations

• Clinicians should consider the clinical presentation and likelihood of adrenal insufficiency before testing when interpreting the results of the ACTH stimulation test 4.
• The test should be used in conjunction with other diagnostic tools, such as insulin-induced hypoglycemia testing, to confirm the diagnosis of adrenal insufficiency 6.
• A low-dose ACTH stimulation test may be more sensitive than a high-dose test in detecting subtle adrenal insufficiency 6, 7.