What is the approach to diagnose adrenal insufficiency in an outpatient setting?

Testing for Adrenal Insufficiency in Outpatient Clinic

The gold standard for diagnosing adrenal insufficiency in an outpatient setting is the ACTH stimulation test (Synacthen/cosyntropin test), which requires administration of 0.25 mg cosyntropin intramuscularly or intravenously, followed by measurement of serum cortisol after 30 and/or 60 minutes. 1

Initial Evaluation

First-Line Laboratory Testing

• Morning cortisol level (8 AM) with simultaneous plasma ACTH measurement
  • Morning cortisol >350 nmol/L (>13 μg/dL) effectively rules out adrenal insufficiency 1, 2
  • Morning cortisol <85 nmol/L (<3 μg/dL) is highly specific for adrenal insufficiency 1
  • Intermediate values (85-350 nmol/L) require further testing 1

ACTH Stimulation Test (Gold Standard)

• Standard test procedure:
  1. Obtain baseline cortisol sample
  2. Administer 0.25 mg cosyntropin IV or IM 3
  3. Measure serum cortisol at 30 and 60 minutes post-administration 3
  4. Normal response: peak cortisol >550 nmol/L (>18 μg/dL) 1, 3
  5. Stimulated cortisol <550 nmol/L suggests adrenal insufficiency 4, 1

Interpreting Results

Primary vs. Secondary Adrenal Insufficiency

• Primary adrenal insufficiency:

  • Low cortisol with elevated ACTH levels
  • Test for 21-hydroxylase antibodies (21OH-Ab) 4
  • If 21OH-Ab negative, consider CT of adrenal glands 4

• Secondary adrenal insufficiency:

  • Low cortisol with low or inappropriately normal ACTH levels
  • Consider MRI of pituitary gland 1

Important Considerations

Medication Interference

• Stop these medications before testing: 1, 3
  • Glucocorticoids: stop on the day of testing (longer for long-acting formulations)
  • Spironolactone: stop on the day of testing
  • Estrogen-containing drugs: stop 4-6 weeks before testing

Timing Considerations

• Morning samples (8 AM-12 PM) are preferred for optimal diagnostic accuracy 5
• Afternoon samples may be acceptable for outpatients but have different thresholds 5

Pitfalls to Avoid

1. Never delay treatment if adrenal crisis is suspected - give hydrocortisone immediately and obtain blood samples for cortisol and ACTH before treatment 4
2. Consider cortisol binding globulin levels in conditions that may affect them (cirrhosis, nephrotic syndrome) 3
3. Be aware of assay variability - cutoff values may vary according to the specific assay used 3

Follow-Up Testing

• If adrenal insufficiency is confirmed, screen for associated autoimmune conditions:
  • Thyroid function tests (TSH, FT4, TPO-Ab) 4
  • Plasma glucose and HbA1c 4
  • Complete blood count 4
  • B12 levels 4
  • Consider celiac disease testing in patients with diarrhea 4

By following this systematic approach to testing for adrenal insufficiency in the outpatient setting, clinicians can ensure accurate diagnosis and appropriate management of this potentially life-threatening condition.