What is the initial workup and treatment for suspected adrenal insufficiency?

Initial Workup and Treatment for Suspected Adrenal Insufficiency

The initial workup for suspected adrenal insufficiency should include morning cortisol and ACTH levels, followed by a short ACTH stimulation test for confirmation, while treatment consists of hydrocortisone 15-25 mg daily in divided doses with fludrocortisone 0.05-0.1 mg daily for primary adrenal insufficiency. 1

Diagnostic Approach

Initial Assessment

• Evaluate for clinical features of adrenal insufficiency:
  • Primary adrenal insufficiency: fatigue (50-95%), nausea/vomiting (20-62%), anorexia, weight loss (43-73%), hypotension, salt craving, and hyperpigmentation 2
  • Secondary adrenal insufficiency: similar symptoms but without hyperpigmentation or electrolyte disturbances 1, 2

Laboratory Testing Algorithm

1. Morning (8 AM) serum cortisol and ACTH levels 1, 2

   • Interpretation:
     • Morning cortisol <5 μg/dL with high ACTH: strongly suggests primary adrenal insufficiency
     • Morning cortisol <5 μg/dL with low/normal ACTH: suggests secondary adrenal insufficiency
     • Morning cortisol 5-10 μg/dL: intermediate, requires further testing
     • Morning cortisol >18-20 μg/dL: effectively rules out adrenal insufficiency

2. Short ACTH (cosyntropin/Synacthen) stimulation test 1, 3

   • Gold standard confirmatory test
   • Administer 250 μg of cosyntropin
   • Measure cortisol at baseline and 60 minutes post-administration
   • Normal response: peak cortisol >18-20 μg/dL
   • Abnormal response confirms adrenal insufficiency

3. Additional diagnostic tests 1, 2

   • Electrolytes (hyponatremia, hyperkalemia in primary adrenal insufficiency)
   • Dehydroepiandrosterone sulfate (DHEAS) levels (low in adrenal insufficiency)
   • For secondary adrenal insufficiency with inconclusive ACTH stimulation test:
     • Insulin tolerance test (gold standard for secondary adrenal insufficiency) 3
     • Metyrapone test as an alternative 4

Differential Diagnosis

• Primary adrenal insufficiency: autoimmune adrenalitis, tuberculosis, fungal infections, adrenal hemorrhage, metastatic disease 2
• Secondary adrenal insufficiency: pituitary tumors, pituitary surgery, radiation, inflammatory conditions, medications (opioids) 2
• Glucocorticoid-induced adrenal insufficiency: recent tapering or discontinuation of supraphysiological glucocorticoid doses 2

Treatment Protocol

Immediate Management

• If adrenal crisis is suspected or patient is hemodynamically unstable:
  • Administer hydrocortisone 100 mg IV immediately 1
  • Initiate normal saline infusion 1
  • Do not delay treatment while awaiting test results 3

Maintenance Therapy

1. Glucocorticoid replacement 1, 2

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

2. Mineralocorticoid replacement (for primary adrenal insufficiency) 1, 5, 2

   • Fludrocortisone 0.05-0.1 mg daily
   • FDA-approved for primary and secondary adrenocortical insufficiency in Addison's disease and salt-losing adrenogenital syndrome 5

Stress Dosing Protocol 1

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

Patient Education and Follow-up

Critical Patient Education

• Provide emergency hydrocortisone injection kit 1
• Instruct on stress dosing during illness 1, 6
• Recommend medical alert identification (bracelet/necklace) 1
• Warn about avoiding exposure to chickenpox or measles if on immunosuppressive doses 6

Monitoring

• Regular assessment of overall well-being, weight, and blood pressure 1
• Monitor electrolytes and morning cortisol levels 1
• Annual screening for other autoimmune disorders (for primary adrenal insufficiency) 1
• Bone mineral density assessment every 3-5 years 1

Common Pitfalls and Caveats

• Diagnostic pitfalls 7:

  • Time of day affects cortisol levels; morning samples are preferred
  • Different cortisol assays have different reference ranges
  • Clinical presentation should be considered alongside test results

• Treatment pitfalls 6, 8:

  • Abrupt discontinuation of glucocorticoids can precipitate adrenal crisis
  • Secondary adrenocortical insufficiency may persist for months after discontinuation of therapy
  • Inadequate stress dosing during illness is a common cause of adrenal crisis
  • Despite optimal replacement therapy, patients may still experience reduced quality of life and increased mortality 8

• Special considerations:

  • Patients with hypothyroidism or cirrhosis have enhanced effects of corticosteroids 6
  • Use corticosteroids cautiously in patients with infections, ulcerative colitis, peptic ulcer, hypertension, osteoporosis, or myasthenia gravis 6