Effect of Hydrocortisone on ACTH Stimulation Testing
Exogenous hydrocortisone administration will suppress the HPA axis and invalidate ACTH stimulation test results, requiring discontinuation of all therapeutic steroids before testing. 1
Critical Timing Considerations
Hydrocortisone must be discontinued prior to ACTH stimulation testing to avoid false results, as exogenous glucocorticoids suppress endogenous cortisol production and interfere with accurate assessment of adrenal reserve. 1 This applies to all therapeutic steroids including dexamethasone, betamethasone, prednisone, and prednisolone. 1
Mechanism of Interference
Negative feedback suppression: Hydrocortisone suppresses ACTH secretion from the pituitary gland through negative feedback on the hypothalamic-pituitary-adrenal axis, which can persist even after a single dose. 2
Blunted cortisol response: When hydrocortisone is present in the system, the adrenal glands are already suppressed, preventing accurate measurement of their intrinsic capacity to respond to exogenous ACTH stimulation. 1
Variable suppression patterns: In adrenalectomized patients with Cushing's disease, 200 mg IV hydrocortisone significantly suppressed plasma ACTH levels at 60 minutes, though paradoxical rises can occasionally occur. 2
Recommended Testing Protocol
The 250-μg ACTH stimulation test is the recommended diagnostic approach for evaluating adrenal insufficiency, but only after ensuring the patient is free from exogenous glucocorticoid influence. 3, 1
High-dose (250-μg) over low-dose (1-μg): The task force recommends the high-dose test due to easier practical administration, more standardized protocols, and comparable diagnostic accuracy. 3, 1
Diagnostic thresholds: A peak cortisol level below 18 μg/dL at 30 or 60 minutes indicates adrenal insufficiency. 1
Delta cortisol criterion: In critically ill patients, a delta cortisol <9 μg/dL after cosyntropin administration may indicate Critical Illness-Related Corticosteroid Insufficiency (CIRCI). 1
Clinical Pitfalls to Avoid
Never delay emergency treatment: If acute adrenal insufficiency is suspected, administer stress-dose hydrocortisone (100 mg IV) immediately without waiting for diagnostic testing—treatment takes priority over diagnosis in life-threatening situations. 1, 4
Avoid hemodynamic response testing: The guidelines suggest using the 250-μg ACTH stimulation test rather than hemodynamic response to hydrocortisone (50-300 mg) for diagnosing CIRCI, as no studies have compared their prognostic value and the ACTH test provides more objective data. 3
Account for protein binding changes: During critical illness, extensive changes in cortisol protein binding occur rapidly, complicating comparison between cortisol responses to ACTH testing versus actual stress situations. 5
Special Populations
Critically ill patients: In septic shock, a random plasma cortisol <10 μg/dL may be diagnostic of CIRCI without requiring an ACTH stimulation test. 1
Hypothermic patients: Hypothermia reduces drug clearance by up to 30% at 34°C and causes temperature-dependent enzyme dysfunction affecting cortisol synthesis—reassess adrenal function only after normothermia is achieved. 4