How to assess for adrenal insufficiency?

Assessment of Adrenal Insufficiency

The diagnosis of adrenal insufficiency requires measurement of morning serum cortisol levels as an initial screening test, followed by an ACTH stimulation test with a peak cortisol cutoff of >18-20 μg/dL to confirm the diagnosis. 1

Initial Evaluation

Clinical Suspicion

• Consider adrenal insufficiency in:
  • Patients with cirrhosis (49% have relative adrenal insufficiency) 1
  • Patients with septic shock refractory to vasopressors 1
  • Patients with unexplained fatigue, weight loss, hypotension, nausea/vomiting 2
  • Recent glucocorticoid withdrawal 2

Laboratory Testing Algorithm

1. First-line screening: Morning (8 AM) serum cortisol 1, 2

   • <5 μg/dL: Highly suggestive of adrenal insufficiency

   • 18-20 μg/dL: Effectively rules out adrenal insufficiency

   • 5-18 μg/dL: Requires confirmatory testing

2. Confirmatory testing: Short ACTH stimulation test 1

   • Administration of 250 μg synthetic ACTH (cosyntropin/Synacthen)
   • Measure cortisol at baseline and 60 minutes post-administration
   • Normal response: Peak cortisol >18-20 μg/dL
   • Diagnostic criterion: Cortisol increase <9 μg/dL confirms relative adrenal insufficiency 1

3. Additional diagnostic tests:

   • ACTH level (differentiates primary from secondary)
   • Electrolytes (Na, K)
   • DHEAS levels 2

Differentiating Primary vs Secondary Adrenal Insufficiency

Parameter	Primary	Secondary
ACTH Level	High	Low
Cortisol Level	Low	Low
Electrolytes	↓Na, ↑K	Generally normal
Hyperpigmentation	Present	Absent

Common Pitfalls to Avoid

1. Relying solely on random cortisol measurements - Always obtain morning cortisol levels 1
2. Misinterpreting cortisol levels in patients already on hydrocortisone - Timing of last dose affects results 1
3. Failing to recognize adrenal crisis - A medical emergency requiring immediate treatment with hydrocortisone 100 mg IV and fluid resuscitation 1, 3
4. Not considering adrenal insufficiency in critically ill patients - Especially those with refractory shock 1
5. Missing concomitant autoimmune conditions - Up to 50% of patients with primary adrenal insufficiency develop other autoimmune disorders 4

Special Considerations

• In suspected secondary adrenal insufficiency, consider pituitary imaging to identify tumors or other pathology 2
• For patients on chronic glucocorticoid therapy, adrenal insufficiency should be suspected upon withdrawal 5
• In critically ill patients with suspected adrenal insufficiency and hemodynamic instability, empiric treatment with hydrocortisone 50 mg IV every 6 hours should be initiated before confirmatory testing 1

Treatment Approach

Once diagnosed, treatment involves:

• Glucocorticoid replacement: Hydrocortisone 15-25 mg daily in divided doses 1, 2
• For primary adrenal insufficiency: Add mineralocorticoid (fludrocortisone 0.05-0.1 mg daily) 1, 2
• Patient education on stress dosing during illness or procedures 1
• Regular monitoring of symptoms, weight, blood pressure, and electrolytes 1

The diagnostic approach to adrenal insufficiency must be systematic and thorough to prevent missed diagnoses and potentially life-threatening adrenal crises.