What is the initial approach to managing primary adrenal insufficiency?

Approach to Primary Adrenal Insufficiency

Immediate Recognition and Emergency Management

If adrenal crisis is suspected clinically (hypotension, vomiting, altered mental status, unexplained collapse), immediately administer hydrocortisone 100 mg IV bolus and start rapid isotonic saline infusion at 1 L/hour—never delay treatment waiting for laboratory confirmation. 1, 2, 3

Clinical Presentation to Recognize

Primary adrenal insufficiency presents with:

• Hyperpigmentation in sun-exposed areas, skin creases, and mucous membranes (due to elevated ACTH)—this distinguishes primary from secondary adrenal insufficiency 2, 4
• Salt craving (specific for primary adrenal insufficiency due to aldosterone deficiency) 2
• Postural hypotension leading to dizziness, syncope, or collapse 2, 3
• Profound fatigue, unintentional weight loss, anorexia, muscle pain, nausea, and vomiting 4, 5

Laboratory Findings

• Hyponatremia (present in ~90% of cases) 2, 3
• Hyperkalemia (present in ~50% of cases) 2, 3
• Mild hypercalcemia (10-20% of cases) 2, 3
• Increased creatinine from prerenal renal failure 1, 3

Critical Pitfall: The absence of hyperkalemia does not exclude primary adrenal insufficiency—it is present in only half of cases. 3

Diagnostic Approach

Step 1: Draw Blood Before Treatment (But Never Delay Treatment)

Obtain early-morning (8 AM) samples for:

• Serum cortisol
• ACTH
• DHEAS
• Sodium, potassium, creatinine, urea, glucose 1, 2, 4

Diagnostic criteria: Serum cortisol <250 nmol/L (<5 µg/dL) with elevated ACTH confirms primary adrenal insufficiency 2, 4

Step 2: Confirm with Cosyntropin Stimulation Test (If Needed)

• Administer cosyntropin 250 µg
• Measure cortisol at 30 and 60 minutes
• Normal response: cortisol exceeds 550 nmol/L (20 µg/dL) 2
• Abnormal response: failure to reach this threshold confirms adrenal insufficiency 2

Step 3: Determine the Underlying Cause

Test for 21-hydroxylase autoantibodies (21OH-Ab) first—positive in ~85% of primary adrenal insufficiency cases in Western Europe (autoimmune Addison's disease) 1, 2, 3

If 21OH-Ab is negative: Obtain CT scan of adrenals to evaluate for:

• Adrenal hemorrhage
• Tuberculosis
• Tumor/metastases
• Infiltrative processes 1, 2, 3

Acute Crisis Management

Immediate Treatment Protocol

1. Hydrocortisone 100 mg IV bolus immediately (saturates mineralocorticoid receptors) 1, 2, 3
2. Isotonic saline 1 L over first hour, then continue 3-4 L total over 24-48 hours with frequent hemodynamic monitoring 1, 2, 3
3. Continue hydrocortisone 100-300 mg/day as continuous IV infusion OR 100 mg IV/IM every 6 hours 1, 6, 3
4. Treat precipitating causes (infections, bleeding, etc.) 1, 6

Critical Pitfall: Do NOT add separate mineralocorticoid (fludrocortisone) during acute crisis—high-dose hydrocortisone provides adequate mineralocorticoid activity. 3

Transition to Oral Therapy

• Taper parenteral glucocorticoids over 1-3 days once patient can tolerate oral medications 1, 6
• Restart fludrocortisone when hydrocortisone dose falls below 50 mg/day 1, 3

Chronic Maintenance Therapy

Glucocorticoid Replacement

Hydrocortisone 15-25 mg daily in 2-3 divided doses (preferred over longer-acting agents like prednisone) 1, 2, 6, 4

Mineralocorticoid Replacement (Required for Primary Adrenal Insufficiency)

Fludrocortisone 50-200 µg daily as single morning dose 1, 2, 6, 7

Critical Pitfall: Chronic under-replacement with mineralocorticoids combined with low salt intake is a common cause of recurrent adrenal crises. 1, 3

Stress Dosing Guidelines

Minor Illness with Fever

Double or triple the usual oral glucocorticoid dose 1, 2, 6

Major Surgery

• Hydrocortisone 100 mg IM just before anesthesia
• Continue 100 mg IM every 6 hours until able to eat and drink
• Then double oral dose for 24-48 hours before tapering to normal 1, 2, 6

Vomiting or Inability to Take Oral Medications

Use parenteral hydrocortisone 100 mg IM immediately 1, 3, 5

Critical Pitfall: Even mild gastrointestinal upset can precipitate crisis because patients cannot absorb oral medication when they need it most. 1, 3

Patient Education and Crisis Prevention

All patients must:

• Wear medical alert identification jewelry 2, 3
• Carry emergency injectable hydrocortisone 100 mg IM and know how to self-administer 2, 3, 5
• Understand when and how to increase steroid doses during illness, injuries, or stress 1, 2
• Carry a steroid emergency card 5

Critical Pitfall: Never start thyroid hormone replacement before adequate glucocorticoid replacement in patients with multiple hormone deficiencies—this can trigger adrenal crisis. 2, 3

Annual Follow-Up and Monitoring

Clinical Assessment

• Evaluate symptoms, weight, blood pressure (including orthostatic measurements) 1, 2
• Assess for signs of under-replacement (weight loss, postural hypotension, hyperpigmentation) or over-replacement 1

Laboratory Monitoring (Annual)

• Serum sodium and potassium 1, 2
• Glucose and HbA1c (screen for diabetes) 1, 2
• Complete blood count 1, 2
• Thyroid function tests (TSH, FT4, TPO antibodies) annually—autoimmune thyroid disease is common 1, 2
• Vitamin B12 levels annually—autoimmune gastritis is common 1, 2
• Screen for celiac disease if episodic diarrhea present 1

Critical Pitfall: Serum and urine cortisol measurements are usually impossible to interpret in patients on replacement therapy and should not be used for monitoring. 1