What lab tests diagnose adrenal insufficiency and what are the typical patient symptoms?

Diagnosing Adrenal Insufficiency: Laboratory Tests and Clinical Symptoms

The diagnosis of adrenal insufficiency requires early-morning (8 AM) measurements of serum cortisol, ACTH (adrenocorticotropin), and DHEAS (dehydroepiandrosterone sulfate), followed by ACTH stimulation testing when results are inconclusive. 1, 2

Diagnostic Laboratory Tests

First-Line Testing

• Early morning (8 AM) serum cortisol:
  • Low cortisol (<5 µg/dL) strongly suggests adrenal insufficiency
  • Intermediate values (5-10 µg/dL) require further testing 2
• ACTH level:
  • Primary adrenal insufficiency: High ACTH
  • Secondary adrenal insufficiency: Low or low-normal ACTH 1, 2
• DHEAS level: Typically low in both primary and secondary adrenal insufficiency 2

Confirmatory Testing

• ACTH stimulation test (cosyntropin test):
  • Standard dose: 250 µg ACTH administered
  • Low dose: 1 µg ACTH (more sensitive for central adrenal insufficiency) 3, 4
  • Measure cortisol before and 60 minutes after administration
  • Cortisol level below 500 nmol/L (18 µg/dL) at 30-60 minutes indicates adrenal insufficiency 2, 4

Additional Laboratory Findings

• Electrolyte abnormalities:
  • Primary adrenal insufficiency: Hyponatremia and hyperkalemia
  • Secondary adrenal insufficiency: Generally normal electrolytes 1
• Mild hypercalcemia may be present 1
• Prerenal renal failure markers may be elevated 1

Clinical Symptoms

Common Symptoms

• Fatigue (50-95% of patients) 2
• Gastrointestinal symptoms:
  • Nausea and vomiting (20-62%)
  • Abdominal pain
  • Anorexia and weight loss (43-73%) 1, 2
• Cardiovascular symptoms:
  • Hypotension (often orthostatic)
  • Refractory shock (in severe cases) 1, 5
• Neurological symptoms:
  • Cognitive impairment
  • Altered mental status (in adrenal crisis) 1, 2
• Musculoskeletal symptoms:
  • Muscle cramps
  • Generalized weakness 1

Symptoms Specific to Primary Adrenal Insufficiency

• Skin hyperpigmentation (particularly in skin folds, scars, and mucous membranes)
• Salt craving 1, 2

Symptoms Specific to Secondary Adrenal Insufficiency

• Symptoms related to the underlying pituitary disorder
• Absence of hyperpigmentation
• Less severe electrolyte abnormalities 1, 2

Clinical Pitfalls and Considerations

• Morning cortisol levels can be affected by:
  • Time of day the test is performed
  • Type of assay used
  • Sample source 3
• In suspected recent pituitary injury, the low-dose ACTH test may yield false-negative results 4
• Glucocorticoid-induced adrenal insufficiency should be suspected in patients who have recently tapered or discontinued supraphysiological doses of glucocorticoids 2
• In critically ill patients, both very low and very high baseline cortisol levels have been associated with increased mortality 5
• For children younger than 2 years, hypoglycemia, dehydration, and convulsions are frequently observed; in young girls, virilization may suggest congenital adrenal hyperplasia 6
• The circadian rhythm of cortisol is not present until after 4 months of age 6

Remember that adrenal crisis is a medical emergency requiring immediate treatment with hydrocortisone 100 mg IV bolus, followed by continuous infusion or divided doses, along with rapid IV isotonic saline administration 1.