What blood test is used to diagnose adrenal insufficiency?

Diagnostic Testing for Adrenal Insufficiency

The primary diagnostic test for adrenal insufficiency is paired measurement of serum cortisol and plasma ACTH, followed by a synacthen (tetracosactide) stimulation test in equivocal cases. 1

Initial Diagnostic Approach

First-Line Testing

• Morning serum cortisol and plasma ACTH (8 AM paired samples)
  • Low cortisol with high ACTH = Primary adrenal insufficiency (PAI)
  • Low cortisol with low/normal ACTH = Secondary adrenal insufficiency

Interpretation of First-Line Results

• Definitive diagnosis without further testing:

  • Morning cortisol <250 nmol/L with elevated ACTH = diagnostic of PAI 1
  • Morning cortisol >300 nmol/L = excludes adrenal insufficiency 2
  • Morning cortisol <110 nmol/L = strongly suggests adrenal insufficiency 2

• Equivocal results requiring further testing:

  • Morning cortisol between 110-300 nmol/L
  • Morning cortisol <400 nmol/L with elevated ACTH during acute illness = strong suspicion of PAI 1

Confirmatory Testing

Synacthen (ACTH Stimulation) Test

• Standard dose: 250 μg synacthen (tetracosactide) administered IM or IV
• Low dose option: 1 μg (more sensitive but requires dilution) 3
• Interpretation:
  • Peak cortisol <500 nmol/L is diagnostic of adrenal insufficiency 1
  • Normal response excludes primary adrenal insufficiency reliably 3

Additional Laboratory Findings

• Electrolytes: Hyponatremia (90% of cases), hyperkalemia (50% of cases) 1
• Other findings: Hypercalcemia (10-20%), mild eosinophilia, lymphocytosis, elevated liver enzymes 1
• Plasma renin activity (PRA): Increased in primary adrenal insufficiency 1
• Aldosterone and DHEAS: Low in primary adrenal insufficiency 1

Special Considerations

Potential Confounding Factors

• Exogenous steroid use: Oral prednisolone, dexamethasone, or inhaled steroids (especially fluticasone) may confound cortisol level interpretation 1
• Timing errors: Cortisol has diurnal variation, so timing of sample collection is critical 4
• Acute illness: May affect cortisol levels; cortisol <400 nmol/L with elevated ACTH during acute illness raises strong suspicion of PAI 1

Secondary Testing for Etiology

After confirming adrenal insufficiency, determine the cause:

• Autoimmune adrenalitis: Measure 21-hydroxylase (anti-adrenal) autoantibodies 1
• Structural causes: CT imaging of adrenals 1
• In males: Test very long-chain fatty acids for adrenoleukodystrophy 1

Important Clinical Pitfalls

1. Never delay treatment of suspected acute adrenal insufficiency for diagnostic procedures 1
2. Beware of false normal results in secondary adrenal insufficiency with the standard synacthen test 5
3. TSH levels may be elevated (4-10 IU/L) in PAI due to lack of cortisol's inhibitory effect on TSH production 1
4. Initiating thyroid replacement before cortisol replacement in patients with multiple hormone deficiencies can precipitate adrenal crisis 4
5. Morning cortisol levels are not diagnostic in patients currently on corticosteroids 4

When to Suspect Adrenal Insufficiency

• Unexplained collapse, hypotension, vomiting, diarrhea
• Hyperpigmentation (primary adrenal insufficiency)
• Hyponatremia, hyperkalemia, acidosis, hypoglycemia
• Fatigue, anorexia, weight loss, nausea, weakness
• Recent discontinuation of long-term steroid therapy 4

Remember that adrenal insufficiency is a potentially life-threatening condition, and treatment should never be delayed if clinical suspicion is high.