What is the initial step in the workup of suspected adrenal insufficiency?

Initial Workup of Suspected Adrenal Insufficiency

The initial step in the workup of suspected adrenal insufficiency is to measure early-morning (approximately 8 am) serum cortisol and corticotropin (ACTH) levels. 1

Diagnostic Approach

Initial Testing

• Obtain early-morning (around 8 am) measurements of:
  • Serum cortisol
  • ACTH
  • Dehydroepiandrosterone sulfate (DHEAS)

Interpretation of Initial Results

• Primary adrenal insufficiency:

  • Low morning cortisol (<5 µg/dL)
  • High ACTH levels
  • Low DHEAS levels
  • Often accompanied by electrolyte abnormalities (↓Na, ↑K) 2, 1

• Secondary adrenal insufficiency:

  • Low or intermediate morning cortisol (5-10 µg/dL)
  • Low or low-normal ACTH levels
  • Low DHEAS levels
  • Generally normal electrolytes 2, 1

Confirmatory Testing

For patients with intermediate early-morning cortisol levels (5-10 µg/dL), proceed with:

• Repeat early-morning cortisol testing, or
• ACTH stimulation test (cosyntropin test):
  • Measure cortisol before and 60 minutes after administration of cosyntropin (250 µg)
  • Inadequate response confirms adrenal insufficiency 1, 3

Clinical Presentation to Guide Testing

Key Symptoms Suggesting Adrenal Insufficiency

• Fatigue (50%-95% of cases)
• Nausea and vomiting (20%-62%)
• Anorexia and weight loss (43%-73%)
• Abdominal pain
• Muscle cramps
• Cognitive impairment
• Hypotension, especially postural 2, 1, 4

Distinguishing Features

• Primary adrenal insufficiency:

  • Skin hyperpigmentation
  • Salt craving
  • Hyponatremia and hyperkalemia 2, 4

• Secondary adrenal insufficiency:

  • No hyperpigmentation
  • Generally normal electrolytes 2

Common Pitfalls and Caveats

• Delayed diagnosis is common due to non-specific symptoms; maintain high clinical suspicion 4, 5
• Timing matters: Cortisol levels should be measured in the early morning when they are naturally highest 1, 3
• Glucocorticoid-induced adrenal insufficiency should be suspected in patients who have recently tapered or discontinued supraphysiological doses of glucocorticoids 1
• Don't wait for confirmatory testing if adrenal crisis is suspected; treat immediately with hydrocortisone 100 mg IV bolus and isotonic saline 2, 3
• Don't miss the underlying cause: Primary adrenal insufficiency can be caused by autoimmune destruction, congenital adrenal hyperplasia, medications, infections, or surgical removal of adrenal tissue 1

Urgent Management Considerations

If adrenal crisis is suspected during the diagnostic workup:

• Administer hydrocortisone 100 mg IV bolus immediately
• Follow with 100-300 mg/day as continuous infusion or divided doses every 6 hours
• Provide rapid IV administration of isotonic saline
• Identify and treat the underlying cause (often infections) 2, 3

Early detection and proper management of adrenal insufficiency are crucial to prevent adrenal crisis, which can be life-threatening if not promptly treated 4, 3, 5.