What Needs to be Ordered for Adrenal Insufficiency
Immediate Laboratory Testing
Order a morning (8 AM) serum cortisol and plasma ACTH as your first-line diagnostic tests – these paired measurements can often establish the diagnosis without further testing 1, 2.
Interpreting Initial Results:
- Basal cortisol <250 nmol/L (<9 μg/dL) with elevated ACTH in acute illness is diagnostic of primary adrenal insufficiency 1, 2
- Basal cortisol <400 nmol/L with elevated ACTH in acute illness raises strong suspicion 2
- Morning cortisol 140-400 nmol/L (5-14.5 μg/dL) requires confirmatory testing with cosyntropin stimulation test 1
Basic Metabolic Panel:
Order sodium, potassium, CO2, and glucose to assess for characteristic electrolyte abnormalities 1:
- Hyponatremia is present in 90% of newly diagnosed cases and is the most common electrolyte abnormality 1
- Hyperkalemia occurs in only ~50% of cases, so its absence does not rule out adrenal insufficiency 1, 2
Confirmatory Testing: Cosyntropin Stimulation Test
If morning cortisol is intermediate (140-400 nmol/L), perform the standard cosyntropin stimulation test 3, 1:
Test Protocol:
- Administer 0.25 mg cosyntropin (Synacthen/tetracosactide) intramuscularly or intravenously 3, 2
- Measure serum cortisol at 30 and/or 60 minutes post-administration 3, 2
- Peak cortisol >550 nmol/L (>18-20 μg/dL) is normal 3, 1, 2
- Peak cortisol <500-550 nmol/L is diagnostic of adrenal insufficiency 1, 2
Critical Timing Consideration:
The test should preferably be performed in the morning, though this is not strictly necessary 2. Obtain a basal sample of serum cortisol and ACTH before Synacthen administration 2.
Etiologic Workup (After Diagnosis is Confirmed)
First-Line Etiologic Test:
Measure 21-hydroxylase (anti-adrenal) autoantibodies – this is the first step in determining the underlying cause, as autoimmunity accounts for ~85% of primary adrenal insufficiency cases in Western populations 3, 1.
If Autoantibodies are Negative:
Order CT imaging of the adrenals to evaluate for 3, 1:
- Adrenal hemorrhage
- Tumors or metastatic disease
- Tuberculosis (look for calcifications)
- Other structural abnormalities
For Male Patients with Negative Antibodies:
Measure very long-chain fatty acids (VLCFA) to screen for adrenoleukodystrophy 3, 1.
Medications to Order
For Acute/Suspected Adrenal Crisis:
NEVER delay treatment for diagnostic procedures if adrenal crisis is suspected 3, 1, 2. Order immediately:
- IV hydrocortisone 100 mg bolus, followed by 100 mg every 6-8 hours 1, 4
- 0.9% saline infusion at 1 L/hour (at least 2L total) 3, 1
- Draw blood for cortisol and ACTH before treatment if possible, but do not delay treatment 3, 1
Alternative if diagnosis uncertain and you still want to perform testing later: Use dexamethasone 4 mg IV instead of hydrocortisone, as it does not interfere with cortisol assays 1.
For Chronic Maintenance Therapy:
Glucocorticoid Replacement (all patients):
- Hydrocortisone 15-25 mg daily in divided doses (typically 10 mg at 7 AM, 5 mg at noon, 2.5-5 mg at 4 PM) 1, 5, OR
- Prednisone 3-5 mg daily 1, 5, OR
- Cortisone acetate 25-37.5 mg daily in divided doses 1
Mineralocorticoid Replacement (primary adrenal insufficiency only):
- Fludrocortisone 0.05-0.2 mg daily (typical range 50-200 µg, may need up to 500 µg in younger adults) 1, 6, 5
- Secondary adrenal insufficiency does NOT require mineralocorticoid replacement 1
Additional Testing for Patients with Autoimmune Etiology
Order annual screening for associated autoimmune conditions 1:
- Thyroid function tests (TSH, free T4)
- Plasma glucose or HbA1c
- Complete blood count
- Vitamin B12 levels
- Tissue transglutaminase antibodies (celiac screen)
Critical Safety Considerations
If Patient Has Concurrent Hypothyroidism:
Start corticosteroids several days BEFORE initiating thyroid hormone replacement to prevent precipitating adrenal crisis 1, 7. This is absolutely critical and potentially life-saving.
Patient Education and Emergency Supplies:
- Medical alert bracelet or necklace indicating adrenal insufficiency
- Injectable hydrocortisone 100 mg IM kit with self-injection training
- Written instructions on stress-dosing (double or triple dose during illness, fever, or physical stress)
Common Pitfalls to Avoid
- Do not rely solely on electrolyte abnormalities – hyponatremia may be only marginally reduced and hyperkalemia is absent in ~50% of cases 1, 2
- Do not delay treatment of suspected adrenal crisis for diagnostic testing – mortality is high if untreated 3, 1
- Do not start thyroid hormone before corticosteroids in patients with both conditions 1, 7
- Do not perform testing while patient is on exogenous steroids (prednisolone, dexamethasone, inhaled fluticasone) as these can suppress the HPA axis and confound results 2