What is the diagnostic approach and treatment for adrenal insufficiency?

Diagnostic Approach and Treatment for Adrenal Insufficiency

The diagnosis of adrenal insufficiency requires measurement of morning serum cortisol and ACTH levels, followed by a cosyntropin stimulation test when results are equivocal, while treatment consists of glucocorticoid replacement (hydrocortisone 15-25 mg daily in divided doses) and mineralocorticoid replacement (fludrocortisone 0.05-0.2 mg daily) for primary adrenal insufficiency. 1

Diagnostic Approach

Initial Assessment

• Consider adrenal insufficiency in patients with:
  • Unexplained collapse, hypotension, vomiting, or diarrhea
  • Fatigue, weight loss, anorexia
  • Hyperpigmentation (in primary adrenal insufficiency)
  • Hyponatremia, hyperkalemia, acidosis, or hypoglycemia 2, 1

Laboratory Testing Algorithm

1. First-line tests:

   • Morning serum cortisol and ACTH levels (8 AM)
     • Low cortisol (<140 nmol/L or <5 μg/dL) with elevated ACTH (>300 pg/mL) suggests primary adrenal insufficiency
     • Low cortisol with low/normal ACTH suggests secondary adrenal insufficiency 1, 3

2. Confirmatory testing:

   • Cosyntropin stimulation test (when morning cortisol is equivocal)
     • Administer 0.25 mg cosyntropin IV or IM
     • Measure cortisol at baseline, 30, and 60 minutes
     • Normal response: cortisol >550 nmol/L at any timepoint 1, 4
     • For children under 2 years: use 0.125 mg cosyntropin 1

3. Etiologic evaluation:

   • Test for 21-hydroxylase autoantibodies (positive in ~85% of primary adrenal insufficiency cases) 1
   • Additional testing based on suspected cause:
     • Adrenal imaging if tuberculosis, hemorrhage, or infiltrative disease suspected
     • Pituitary imaging if secondary adrenal insufficiency suspected 3

Diagnostic Pitfalls

• Never delay treatment of suspected adrenal crisis for diagnostic testing 2, 1
• Medications affecting test results:
  • Glucocorticoids and spironolactone should be stopped on the day of testing
  • Estrogen-containing medications should be stopped 4-6 weeks before testing
  • For patients on long-acting glucocorticoids, a longer washout period is needed 1, 4
• In conditions affecting cortisol binding globulin (pregnancy, oral contraceptives, liver disease), urinary free cortisol provides more accurate assessment 1

Treatment

Maintenance Therapy

1. Glucocorticoid replacement:

   • Hydrocortisone 15-25 mg daily in divided doses (typically 2/3 in morning, 1/3 in afternoon)
   • Alternative: prednisone 3-5 mg daily 1, 3

2. Mineralocorticoid replacement (for primary adrenal insufficiency only):

   • Fludrocortisone 0.05-0.2 mg daily 1
   • Monitor effectiveness through blood pressure, serum electrolytes, and plasma renin activity 2

3. DHEA replacement (optional):

   • Consider for patients with persistent symptoms despite adequate primary replacement
   • Typical dose: 25-50 mg orally once daily in the morning 1

Stress Dosing Protocol

• Minor illness/stress: Double or triple usual daily dose
• Moderate stress: Hydrocortisone 50-75 mg/day in divided doses
• Severe stress/adrenal crisis: Hydrocortisone 100 mg IV immediately, followed by 100-300 mg/day as continuous infusion or divided doses every 6 hours 1

Adrenal Crisis Management

1. Immediate interventions:

   • Hydrocortisone 100 mg IV immediately
   • IV saline infusion (initial rate ~1 L/hour)
   • Frequent hemodynamic monitoring and electrolyte measurement 2

2. Additional measures:

   • Consider ICU admission for severe cases
   • Prophylaxis for gastric stress ulcers
   • Low-dose heparin
   • Antibiotics if infection suspected 2

Follow-up and Monitoring

Annual Assessment

• Clinical evaluation:

  • Overall well-being, weight, blood pressure
  • Questions about quality of daily replacement therapy
  • Self-medication during illness and previous adrenal crises 2, 1

• Laboratory monitoring:

  • Serum electrolytes
  • Screening for other autoimmune disorders:
    • Thyroid function (TSH, FT4, TPO-Ab)
    • Plasma glucose, HbA1c
    • Complete blood count
    • Vitamin B12 levels 2, 1

• Bone mineral density assessment every 3-5 years 1

Patient Education

• All patients must receive education on:
  • Recognizing early symptoms of adrenal crisis
  • Wearing medical alert identification
  • Carrying a steroid alert card
  • Having an emergency hydrocortisone injection kit
  • When and how to adjust medication during illness or stress 1

By following this diagnostic and treatment algorithm, clinicians can effectively identify and manage adrenal insufficiency, reducing the risk of life-threatening adrenal crises and improving patients' quality of life.