In a patient currently receiving dexamethasone (Decadron) with a morning serum cortisol of 2.6 µg/dL, does this indicate adrenal insufficiency and how should adrenal reserve be evaluated?

Dexamethasone Interferes with Cortisol Measurement—This Value is Uninterpretable

A morning cortisol of 2.6 µg/dL in a patient currently receiving dexamethasone (Decadron) cannot be used to diagnose adrenal insufficiency because dexamethasone suppresses the HPA axis and causes iatrogenic secondary adrenal insufficiency, making this result expected and non-diagnostic. 1

Why This Cortisol Value is Meaningless

• 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 1
• Patients on corticosteroids will have low morning cortisol as a result of iatrogenic secondary adrenal insufficiency, and ACTH will also be low—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

Dexamethasone's Unique Properties

• Dexamethasone suppresses the hypothalamic-pituitary-adrenal axis and causes secondary adrenal insufficiency through ACTH suppression 1
• High-dose dexamethasone therapy (12 mg/day or more) can suppress cortisol production to below 50 µg/L for at least 8 hours, though rapid elimination may allow cortisol to rise 8-12 hours after dosing 2
• Within the first 72 hours of dexamethasone therapy, patients with previously intact HPA axes still show adequate cortisol responses to ACTH stimulation, but by 96 hours, suppression becomes evident 3

What You Should Do Instead

If Dexamethasone is for a Temporary Indication (e.g., cerebral edema, antiemetic):

• Wait until dexamethasone has been discontinued with adequate washout time before attempting any diagnostic testing for adrenal insufficiency 1
• The washout period for dexamethasone is longer than for hydrocortisone due to its longer half-life 1
• After stopping dexamethasone, wait at least 3 months before testing for HPA axis recovery in patients with isolated central adrenal insufficiency from steroid use 1

If the Patient Has Confirmed Adrenal Insufficiency on Established Replacement:

• There is usually no reason to check cortisol levels—the diagnosis is already made 1
• Focus on clinical assessment for signs of over-replacement (weight gain, insomnia, peripheral edema) or under-replacement (lethargy, nausea, poor appetite, weight loss) 1

If You Suspect Acute Adrenal Insufficiency Right Now:

• Never delay treatment of suspected acute adrenal crisis for diagnostic procedures 1, 4
• Give 100 mg IV hydrocortisone immediately plus 0.9% saline infusion at 1 L/hour if the patient is clinically unstable with unexplained hypotension, collapse, or gastrointestinal symptoms 1
• Draw blood for cortisol and ACTH before treatment if possible, but do not delay treatment to obtain these samples 1

Critical Pitfall to Avoid

• Do not attempt ACTH stimulation testing while the patient is on dexamethasone or immediately after stopping it—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

When Diagnostic Testing is Actually Appropriate

• Testing should only be performed after dexamethasone has been discontinued with sufficient washout time (typically several weeks to months depending on duration of use) 1
• The standard approach is morning cortisol and ACTH measurement, followed by cosyntropin stimulation test (0.25 mg IV/IM with cortisol at 30 and 60 minutes) if initial results are indeterminate 1
• A peak cortisol <500 nmol/L (<18 µg/dL) confirms adrenal insufficiency, while >550 nmol/L (>18-20 µg/dL) excludes it 1