What is the diagnostic approach and treatment for adrenal insufficiency?

Diagnostic Approach and Treatment for Adrenal Insufficiency

The diagnosis of adrenal insufficiency requires paired measurement of serum cortisol and plasma ACTH, with treatment never delayed by diagnostic procedures in suspected acute cases. 1

Diagnostic Approach

Initial Evaluation

• Consider adrenal insufficiency in patients with:
  • Unexplained collapse, hypotension, vomiting, or diarrhea
  • Hyperpigmentation, hyponatremia, hyperkalemia, acidosis, hypoglycemia 1

Laboratory Testing

1. First-line tests:

   • Morning (8 AM) serum cortisol and plasma ACTH 1, 2
   • Basic metabolic panel (Na, K, CO2, glucose) 1
   • Dehydroepiandrosterone sulfate (DHEAS) 2

2. Interpretation of results:

   • Primary adrenal insufficiency: Low cortisol (<5 μg/dL), high ACTH, low DHEAS 2
   • Secondary adrenal insufficiency: Low cortisol, low or low-normal ACTH and DHEAS 2
   • Acute illness: Cortisol <250 nmol/L with increased ACTH is diagnostic; cortisol <400 nmol/L with increased ACTH raises strong suspicion 1

3. Confirmatory testing:

   • ACTH stimulation test (Synacthen test): Administer 0.25 mg cosyntropin IV/IM, measure cortisol at baseline and 30-60 minutes 1
   • Peak cortisol <500 nmol/L confirms adrenal insufficiency 1
   • For secondary adrenal insufficiency, insulin tolerance test may be more sensitive 3

Etiologic Diagnosis

1. Primary adrenal insufficiency:

   • Measure 21-hydroxylase (anti-adrenal) autoantibodies 1
   • If antibodies negative, proceed with adrenal CT imaging 1
   • In males, measure very long-chain fatty acids to check for adrenoleukodystrophy 1

2. Secondary adrenal insufficiency:

   • Consider MRI of brain with pituitary/sellar cuts in patients with multiple endocrine abnormalities or new severe headaches/vision changes 1

Treatment Approach

Acute Adrenal Crisis

1. Immediate management:

   • Hydrocortisone 100 mg IV bolus immediately, followed by 100-300 mg/day as continuous infusion or divided doses every 6 hours 1
   • Rapid IV administration of isotonic (0.9%) saline at 1 L/hour initially, then continued at slower rate for 24-48 hours 1
   • Identify and treat precipitating causes (e.g., infection) 1

2. Transition to maintenance therapy:

   • Taper stress-dose corticosteroids to maintenance doses over 7-14 days 1

Maintenance Therapy

1. Glucocorticoid replacement:

   • Hydrocortisone 15-25 mg daily in divided doses (10-20 mg in morning, 5-10 mg in early afternoon) 1, 2
   • Alternative: Prednisone 3-5 mg daily 2
   • Use lowest dose compatible with health and well-being 1

2. Mineralocorticoid replacement (for primary adrenal insufficiency):

   • Fludrocortisone 0.05-0.3 mg daily 2
   • Typically 0.1 mg/day, with higher doses needed for children and younger adults 1
   • Advise patients to consume salt and salty foods freely 1

Patient Education and Crisis Prevention

1. Essential education:

   • Provide steroid emergency card and medical alert bracelet 1
   • Educate on stress dosing during illness, injury, or other stressors 1
   • Provide injectable hydrocortisone for emergency use 2

2. Stress dosing guidelines:

   • Minor illness: Double or triple usual dose 1
   • Major stress/surgery: IV hydrocortisone 100 mg followed by appropriate maintenance 1

Follow-up Care

• Annual review with assessment of health and well-being 1
• Monitor weight, blood pressure, and serum electrolytes 1
• Screen for development of other autoimmune disorders, particularly hypothyroidism 1
• Bone mineral density assessment every 3-5 years 1

Important Pitfalls and Caveats

1. Never delay treatment of suspected acute adrenal insufficiency for diagnostic procedures 1
2. Beware of glucocorticoid-induced adrenal insufficiency in patients who have recently tapered or discontinued supraphysiological doses of glucocorticoids 2
3. Consider using dexamethasone (4 mg) instead of hydrocortisone for initial treatment if diagnosis is uncertain and stimulation testing will be needed 1, 4
4. Secondary adrenal insufficiency may be missed by standard ACTH stimulation tests; consider insulin tolerance test in equivocal cases 3
5. All patients need education on stress dosing and should have emergency injectable glucocorticoids to prevent adrenal crisis 1