When to test for adrenal insufficiency?

When to Test for Adrenal Insufficiency

Adrenal insufficiency should be considered in all patients presenting with unexplained collapse, hypotension, vomiting, diarrhea, hyperpigmentation, hyponatremia, hyperkalaemia, acidosis, or hypoglycemia. 1 Testing should never be delayed if adrenal crisis is suspected, as immediate treatment is essential.

Clinical Presentations That Warrant Testing

High Suspicion Scenarios

• Patients with unexplained:
  • Fatigue (50-95% of cases)
  • Nausea and vomiting (20-62%)
  • Anorexia and weight loss (43-73%)
  • Hypotension or orthostatic hypotension
  • Hyponatremia with hyperkalemia
  • Hyperpigmentation (in primary adrenal insufficiency)
  • Hypoglycemia (especially in children)

Specific Patient Populations

• Patients with autoimmune disorders (particularly thyroid disease, celiac disease)
• Patients with pituitary disorders or tumors
• Patients who have recently tapered or discontinued supraphysiological doses of glucocorticoids
• Patients on medications that can affect adrenal function:
  • High-dose azole antifungals
  • Opioids (can suppress corticotropin production)
• Patients with history of pituitary surgery, radiation, or hemorrhage
• Women with postpartum hemorrhage
• Patients with suspected adrenal hemorrhage or infarction

Diagnostic Algorithm

First-Line Testing

1. Morning serum cortisol and plasma ACTH (approximately 8 AM) 1, 2
   • Cortisol <100 nmol/L (<5 μg/dL) with elevated ACTH: Diagnostic of primary adrenal insufficiency
   • Cortisol <100 nmol/L with low/normal ACTH: Suggests secondary adrenal insufficiency
   • Cortisol 100-400 nmol/L (5-10 μg/dL): Requires confirmatory testing

Confirmatory Testing

1. Synacthen (cosyntropin) stimulation test 1, 3

   • Standard dose: 250 μg ACTH administered IV or IM
   • Measure cortisol at baseline and 60 minutes post-administration
   • Peak cortisol <500 nmol/L suggests adrenal insufficiency
   • Note: May give false normal results in recent-onset secondary adrenal insufficiency

2. Insulin Tolerance Test (ITT) - Gold standard for secondary adrenal insufficiency 3, 4

   • Required when:
     • Secondary adrenal insufficiency is strongly suspected despite normal Synacthen test
     • Evaluation of entire hypothalamic-pituitary-adrenal axis is needed
   • Contraindicated in patients with seizure disorders, cardiovascular disease, or elderly

Special Considerations

• In patients currently on glucocorticoids, laboratory confirmation should be delayed until treatment can be safely discontinued 5
• In children under 2 years, hypoglycemia, dehydration, and convulsions are common presentations 5
• In patients with fatigue and early morning cortisol <400 nmol/L with low/normal ACTH, consider ITT as studies show significant rates of adrenal insufficiency in this population 6

Important Caveats

• Never delay treatment of suspected acute adrenal crisis for diagnostic testing 1
• The spectrum of adrenal insufficiency ranges from overt crisis to subtle dysfunction that may only manifest during stress 4
• Standard ACTH stimulation tests may miss mild or recent-onset secondary adrenal insufficiency 4
• Patients with autoimmune disorders are at higher risk of developing adrenal insufficiency and should be monitored regularly 1
• Annual screening for associated autoimmune conditions is recommended in patients with established adrenal insufficiency 1

Emergency Management Reminder

If adrenal insufficiency is suspected in an acutely ill patient, immediate administration of hydrocortisone 100mg IV/IM and isotonic saline should precede diagnostic testing 1. This is a life-saving intervention that should never be delayed.