How to evaluate the adrenal axis in a patient on corticosteroids (steroids)?

Evaluating Adrenal Axis in Patients on Corticosteroids

Laboratory confirmation of adrenal insufficiency should not be attempted in patients on high-dose corticosteroids until treatment is ready to be discontinued, as therapeutic steroids interfere with cortisol assays and can give inaccurate results. 1

Timing of Evaluation

The appropriate timing for adrenal axis evaluation depends on the corticosteroid being used:

• Hydrocortisone: Must be held for at least 24 hours before testing
• Other corticosteroids: Must be held for longer periods (typically 48-72 hours)
• Long-acting glucocorticoids: May need to be stopped for an extended period before testing
• Estrogen-containing medications: Should be stopped 4-6 weeks before testing as they increase cortisol binding globulin levels 1, 2

Testing Protocol

1. Initial Screening:

   • Morning (8-9 AM) serum cortisol level
   • Note: This is not diagnostic in patients currently on corticosteroids 1

2. ACTH Stimulation Test (gold standard):

   • Administer 0.25 mg cosyntropin (synthetic ACTH) IV or IM for adults
   • For children: 0.125 mg (birth to <2 years) or 0.25 mg (2-17 years) 2
   • Obtain baseline cortisol level before administration
   • Measure cortisol levels at exactly 30 and 60 minutes after administration
   • Normal response: Stimulated cortisol level >18 mcg/dL at either 30 or 60 minutes 2
   • Interpretation: Levels <18 mcg/dL suggest adrenocortical insufficiency

3. Important Caveats:

   • ACTH stimulation can give false-negative results early in hypophysitis as adrenal reserve declines slowly 1
   • In cases of clinical uncertainty, opt for replacement therapy and test for ongoing need at 3 months

Recovery Assessment Protocol

For patients with suspected adrenal insufficiency who have been on corticosteroids:

1. Central (Secondary) Adrenal Insufficiency:

   • Test HPA axis recovery after 3 months of maintenance therapy with hydrocortisone 1
   • Consider endocrinology consultation for recovery and weaning protocols

2. Transition Protocol:

   • Switch to hydrocortisone (physiologic replacement) before testing
   • Typical maintenance dose: 15-20 mg daily in divided doses (2/3 morning, 1/3 afternoon) 1

Special Considerations

• Immune Checkpoint Inhibitor-Related Adrenal Insufficiency:

  • May present as isolated central adrenal insufficiency with low ACTH
  • Test HPA axis recovery after 3 months of maintenance therapy 1

• Long-term Inhaled Corticosteroids:

  • Can cause HPA axis suppression, especially at high doses 3, 4
  • Recovery may take months to years after discontinuation 5

• Short-term High-dose Therapy:

  • Can cause adrenal suppression even after just 5 days of therapy 6
  • Suppression may persist for 7 days or longer after discontinuation

Pitfalls to Avoid

1. Premature Testing: Testing while still on corticosteroids leads to inaccurate results

2. Ignoring Medication Interactions:

   • Glucocorticoids and spironolactone may falsely elevate cortisol levels
   • Estrogen increases cortisol binding globulin levels 2

3. Relying Solely on Morning Cortisol:

   • Single cortisol measurements have limited reliability 7
   • ACTH stimulation test provides more accurate assessment

4. Missing Central vs. Primary Distinction:

   • Low ACTH with low cortisol indicates central (secondary) adrenal insufficiency
   • High ACTH with low cortisol indicates primary adrenal insufficiency 1

5. Precipitating Adrenal Crisis:

   • Always start corticosteroids first when planning hormone replacement for multiple deficiencies
   • Other hormones can accelerate cortisol clearance and precipitate adrenal crisis 1

By following this systematic approach to adrenal axis evaluation in patients on corticosteroids, you can accurately diagnose adrenal insufficiency and implement appropriate replacement therapy while avoiding potentially dangerous complications.