What is the diagnostic approach for adrenal insufficiency?

Diagnostic Approach for Adrenal Insufficiency

The diagnosis of adrenal insufficiency should be made through paired measurement of serum cortisol and plasma ACTH, with the ACTH stimulation test (using 0.25 mg cosyntropin) as the confirmatory test when results are equivocal. 1

Initial Diagnostic Evaluation

• Clinical suspicion: Consider adrenal insufficiency in patients with:

  • Unexplained collapse, hypotension, vomiting, or diarrhea
  • Hyperpigmentation (in primary adrenal insufficiency)
  • Hyponatremia, hyperkalemia, acidosis, hypoglycemia 1

• First-line laboratory tests:

  • Morning (8 AM) serum cortisol with paired ACTH measurement 1, 2
  • Interpretation of baseline cortisol:
    • <85 nmol/L (<3 μg/dL): Highly specific for adrenal insufficiency 2

    • 350 nmol/L (>10 μg/dL): Effectively rules out adrenal insufficiency 2

    • Intermediate values: Require confirmatory testing 1

Confirmatory Testing

• ACTH stimulation test (gold standard):

  • Administration: 0.25 mg cosyntropin IV or IM 1, 3
  • Timing: Measure serum cortisol at baseline, 30 minutes, and 60 minutes post-administration 3
  • Interpretation:
    • Peak cortisol <500 nmol/L: Diagnostic of adrenal insufficiency 1
    • In acute illness: Cortisol <400 nmol/L with elevated ACTH strongly suggests primary adrenal insufficiency 1

• Important considerations:

  • Stop glucocorticoids and spironolactone on the day of testing 3
  • For long-acting glucocorticoids, stop for a longer period before testing 3
  • Estrogen-containing medications should be stopped 4-6 weeks before testing 3

Determining the Etiology

• Primary adrenal insufficiency:

  • Low cortisol with elevated ACTH levels 4
  • Measure 21-hydroxylase (anti-adrenal) autoantibodies 1
  • If antibodies are negative, perform CT imaging of adrenal glands 1
  • In male patients, measure very long-chain fatty acids to check for adrenoleukodystrophy 1

• Secondary adrenal insufficiency:

  • Low cortisol with low or inappropriately normal ACTH levels 4
  • Consider pituitary imaging (MRI) 5
  • Evaluate other pituitary hormones 5

• Tertiary adrenal insufficiency (glucocorticoid-induced):

  • History of supraphysiological glucocorticoid use 4
  • Low cortisol with low or normal ACTH levels 4

Special Considerations

• Never delay treatment of suspected acute adrenal insufficiency for diagnostic procedures 1

  • Draw blood for cortisol and ACTH before starting treatment
  • Immediately administer hydrocortisone 100 mg IV and isotonic saline 1

• Potential diagnostic pitfalls:

  • Medications affecting cortisol levels or cortisol binding globulin 2
  • Conditions altering cortisol binding globulin levels 2
  • Newer cortisol assays may require different cutoff values 5

Management After Diagnosis

• Glucocorticoid replacement:

  • Hydrocortisone 15-25 mg daily in split doses 1, 4
  • First dose immediately after waking, last dose not <6 hours before bedtime 1

• Mineralocorticoid replacement (for primary adrenal insufficiency):

  • Fludrocortisone 50-200 μg as a single daily dose 1
  • Advise patients to take salt and salty foods ad libitum 1

• Patient education:

  • Wear medical alert identification and carry a steroid alert card 1
  • Increase doses during illness, injury, or stress 2
  • Self-injection of parenteral hydrocortisone in emergency situations 1

By following this structured diagnostic approach, clinicians can effectively identify and manage adrenal insufficiency, preventing potentially life-threatening adrenal crises and improving patient outcomes.