Should a patient with adrenal insufficiency (AI) taking cortisol replacement therapy, such as hydrocortisone, hold their morning dose before a blood test to check cortisol levels?

Should Patients Hold Their Morning Cortisol Dose Before Testing?

Yes, patients with adrenal insufficiency on cortisol replacement therapy must hold their morning hydrocortisone dose before checking cortisol levels, as exogenous steroids will falsely elevate the measured cortisol and make the test completely uninterpretable. 1

Why This Matters

• Hydrocortisone must be held for 24 hours before testing, while other synthetic steroids like prednisone require even longer washout periods before endogenous adrenal function can be accurately assessed 1
• Morning cortisol measurements in patients actively taking corticosteroids are not diagnostic because the assay measures both endogenous cortisol and therapeutic steroids, with cross-reactivity varying by assay 2
• Therapeutic glucocorticoid use causes iatrogenic secondary adrenal insufficiency by suppressing the hypothalamic-pituitary-adrenal axis, making cortisol levels unreliable without proper washout 1

The Clinical Problem

• If you're checking a morning cortisol to assess whether a patient still needs replacement therapy or to evaluate HPA axis recovery, the test is meaningless if they've taken their dose 1
• Patients on corticosteroids for management of other conditions will have low morning cortisol as a result of iatrogenic secondary adrenal insufficiency, and ACTH will also be low in these patients 3
• Laboratory confirmation of adrenal insufficiency should not be attempted in patients given corticosteroids until treatment is ready to be discontinued 2

Practical Testing Protocol

• For HPA axis recovery testing: Have the patient hold hydrocortisone for 24 hours, then draw morning (8 AM) cortisol and ACTH 1
• For ACTH stimulation testing: The patient should hold their morning dose, present fasting, and you can perform the cosyntropin test to assess adrenal reserve 1
• In cases of clinical uncertainty with ongoing steroid use, opt for empiric glucocorticoid replacement and test for ongoing need at 3 months rather than attempting diagnostic testing while on steroids 1

Critical Safety Considerations

• Never delay treatment of suspected acute adrenal insufficiency for diagnostic procedures—if the patient is clinically unstable with suspected adrenal crisis, give IV hydrocortisone 100 mg immediately 1
• 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 3, 1
• The Endocrine Society recommends testing for HPA axis recovery after 3 months of maintenance therapy with hydrocortisone in patients with isolated central adrenal insufficiency from steroid use 1

When Testing Isn't the Right Question

• If the patient is on established replacement therapy for confirmed adrenal insufficiency, there's usually no reason to check cortisol levels—the diagnosis is already made 3
• Approximately one-third to one-half of patients taking 5-20 mg prednisolone daily fail to achieve target cortisol concentrations on short Synacthen testing, even when they may have adequate adrenal reserve, demonstrating the test's unreliability in this population 1
• Wait until the patient has been weaned off corticosteroids before performing definitive HPA axis testing 1