Adrenal Insufficiency Diagnosis and Management

Initial Diagnostic Workup

The American College of Endocrinology recommends obtaining morning (8 AM) cortisol and ACTH levels together to determine the type of adrenal insufficiency 1, 2
Low cortisol with high ACTH indicates primary adrenal insufficiency, while low cortisol with low or inappropriately normal ACTH indicates secondary (central) adrenal insufficiency 1, 2, 3
A basic metabolic panel (sodium, potassium, CO2, glucose) should be ordered to assess for characteristic electrolyte abnormalities, with hyponatremia occurring in 90% of newly diagnosed cases 1, 2

The Endocrine Society recommends proceeding with stimulation testing when morning cortisol falls in the indeterminate range (140-500 nmol/L or 5-18 mcg/dL) 2
The standard protocol involves administering 0.25 mg (250 mcg) cosyntropin (Synacthen) intramuscularly or intravenously, with serum cortisol measured at baseline, 30 minutes, and 60 minutes post-administration 1, 2
Peak cortisol <500 nmol/L (<18 mcg/dL) at either 30 or 60 minutes is diagnostic of adrenal insufficiency, while peak cortisol >550 nmol/L (>18-20 mcg/dL) is normal and excludes adrenal insufficiency 1, 2

For primary adrenal insufficiency, measure 21-hydroxylase (anti-adrenal) autoantibodies first, as autoimmunity accounts for ~85% of primary adrenal insufficiency in Western populations 2
If autoantibodies are negative, obtain CT imaging of the adrenals to evaluate for hemorrhage, metastatic disease, tuberculosis, or other structural causes 1, 2

For Grade 1: Asymptomatic or Mild Symptoms, initiate hydrocortisone 15-20 mg daily in divided doses, with fludrocortisone 0.05-0.1 mg daily added for primary adrenal insufficiency 1, 2, 3
For Grade 2: Moderate Symptoms, initiate outpatient treatment at 2-3 times maintenance dose (hydrocortisone 30-50 mg total daily or prednisone 20 mg daily) 1, 2
For Grade 3-4: Severe Symptoms, hospitalize for IV hydrocortisone 50-100 mg every 6-8 hours, with at least 2 liters of 0.9% normal saline administered 1, 3

Teach patients to double or triple their usual dose during illness, fever, injury, or significant physical stress, and provide emergency injectable hydrocortisone 100 mg IM kit with self-injection training 1, 2
All patients must wear a medical alert bracelet or necklace indicating adrenal insufficiency, and be educated on warning signs of impending adrenal crisis 1, 2, 3