Which laboratory studies should be obtained in a patient with suspected adrenal (Addison’s) crisis?

Laboratory Studies for Suspected Adrenal (Addison's) Crisis

In a patient with suspected adrenal crisis, immediately draw blood for serum cortisol, plasma ACTH, electrolytes (sodium, potassium), creatinine, BUN, and glucose before administering hydrocortisone, but never delay treatment while awaiting results. 1, 2

Immediate Laboratory Panel (Draw Before Treatment, Do Not Wait for Results)

Essential Hormone Studies

• Serum cortisol – a level <250 nmol/L (<9 μg/dL) with elevated ACTH in acute illness is diagnostic of primary adrenal insufficiency 1, 2
• Plasma ACTH – markedly elevated ACTH (>300 pg/mL) with low cortisol confirms primary adrenal insufficiency, while low or inappropriately normal ACTH with low cortisol indicates secondary adrenal insufficiency 1, 2

Critical Electrolytes and Metabolic Studies

• Serum sodium – hyponatremia is present in approximately 90% of newly presenting adrenal crisis cases 1, 2
• Serum potassium – hyperkalemia occurs in only ~50% of primary adrenal insufficiency cases, so its absence does not rule out the diagnosis 1, 2
• Serum creatinine and BUN – increased levels reflect prerenal renal failure from volume depletion 2
• Serum glucose – hypoglycemia may occur, particularly in children, and requires frequent monitoring 2

Additional Diagnostic Studies

• Blood cultures and infection workup – infections (especially gastrointestinal illness) are the most common precipitating factor for adrenal crisis 2
• Serum calcium – mild to moderate hypercalcemia occurs in 10-20% of patients with adrenal crisis 2

Critical Clinical Pitfalls to Avoid

Never delay hydrocortisone 100 mg IV bolus and 0.9% saline infusion while waiting for laboratory confirmation—mortality increases significantly with treatment postponement. 1, 2 The classic teaching that you need laboratory confirmation before treating is dangerously wrong in suspected adrenal crisis; clinical suspicion alone mandates immediate therapy 2.

Common Diagnostic Errors

• Do not rely on the presence of hyperkalemia to make the diagnosis – it is absent in approximately 50% of cases, particularly in secondary adrenal insufficiency where mineralocorticoid function is preserved 1, 2
• Do not assume normal cortisol excludes adrenal insufficiency in critically ill patients – approximately 10% of patients with confirmed primary adrenal insufficiency present with normal basal cortisol concentrations when ACTH is markedly elevated 3
• Do not wait for supine hypotension to develop – orthostatic (postural) hypotension occurs earlier and represents a critical warning sign 2

Confirmatory Testing After Stabilization

Cosyntropin (Synacthen) Stimulation Test

• Administer 0.25 mg (250 mcg) cosyntropin IV or IM with baseline serum cortisol measurement, then measure cortisol at exactly 30 and 60 minutes post-administration 1
• Peak cortisol <500 nmol/L (<18 μg/dL) at either 30 or 60 minutes confirms adrenal insufficiency 1
• Peak cortisol >550 nmol/L (>18-20 μg/dL) excludes adrenal insufficiency 1

Etiologic Workup for Primary Adrenal Insufficiency

• 21-hydroxylase autoantibodies – positive in ~85% of autoimmune Addison's disease in Western populations; if positive, no further etiologic testing is needed 1, 2
• CT scan of the adrenals – if autoantibodies are negative, obtain imaging to evaluate for hemorrhage, tumor, tuberculosis, or infiltrative disease 1, 2
• Very long-chain fatty acids (VLCFA) – in males with negative autoantibodies, test for X-linked adrenoleukodystrophy 1

Laboratory Findings That Support the Diagnosis

Expected Patterns in Primary Adrenal Insufficiency

• Low cortisol (<250 nmol/L or <9 μg/dL) with high ACTH (>300 pg/mL) 1, 2
• Hyponatremia (present in 90% of cases) 1, 2
• Hyperkalemia (present in only 50% of cases) 1, 2
• Metabolic acidosis from impaired renal function and aldosterone deficiency 2

Expected Patterns in Secondary Adrenal Insufficiency

• Low cortisol with low or inappropriately normal ACTH 1, 2
• Hyponatremia without hyperkalemia (mineralocorticoid function preserved) 2
• May have additional pituitary hormone deficiencies 1

Special Considerations

If the patient is already on corticosteroids, morning cortisol measurements are not diagnostic because the assay measures both endogenous cortisol and therapeutic steroids. 1 In patients on established glucocorticoid therapy, laboratory confirmation should not be attempted until treatment is ready to be discontinued with adequate washout time 1.

For patients with suspected critical illness-related corticosteroid insufficiency (CIRCI), total cortisol <10 μg/dL (276 nmol/L) or delta cortisol <9 μg/dL (248 nmol/L) after ACTH stimulation defines the condition and is associated with poorer outcomes. 1