How should a patient with suspected Addison's disease be managed and treated?

Management and Treatment of Addison's Disease

All patients with suspected Addison's disease require immediate diagnostic confirmation followed by lifelong dual hormone replacement with hydrocortisone 15-25 mg daily (divided 2-3 times) plus fludrocortisone 50-200 μg once daily, with aggressive education on stress-dose adjustments to prevent fatal adrenal crisis. 1, 2

Diagnostic Approach

Diagnosis follows a two-step algorithmic approach: 2

• Initial screening: Obtain paired serum cortisol and plasma ACTH levels simultaneously 2
• Diagnostic threshold: Serum cortisol <250 nmol/L with elevated ACTH during acute illness confirms the diagnosis 2
• Confirmatory testing: In equivocal cases, perform synacthen (tetracosactide) stimulation test with 0.25 mg IM or IV—peak serum cortisol <500 nmol/L confirms primary adrenal insufficiency 2
• Expected laboratory findings: Hyponatremia (90% of newly diagnosed cases), hyperkalemia (50% of cases), low DHEAS, androstenedione, and testosterone 2, 3

Glucocorticoid Replacement

Hydrocortisone is the mandatory first-line glucocorticoid: 1, 2

• Standard dosing: 15-25 mg daily divided into 2-3 doses to mimic natural cortisol rhythm 1, 4
• Timing protocol: First dose immediately upon waking, last dose at least 6 hours before bedtime 1
• Pediatric dosing: 6-10 mg/m² body surface area daily 1
• Dose titration: Use the lowest effective dose based on clinical assessment (weight, blood pressure, well-being) rather than laboratory values to minimize side effects 1, 2

Mineralocorticoid Replacement

Fludrocortisone is essential for aldosterone replacement: 1, 4

• Standard dosing: 50-200 μg (0.05-0.2 mg) once daily 1, 4
• FDA-approved dosing: Typical dose is 0.1 mg daily, with range from 0.1 mg three times weekly to 0.2 mg daily 4
• Age considerations: Children and younger adults typically require higher doses 1
• Hypertension management: If essential hypertension develops, reduce (but never completely discontinue) fludrocortisone dose 1, 4
• Dietary guidance: Advise liberal salt and salty food consumption; avoid licorice and grapefruit juice 1

Adrenal Crisis Management

Adrenal crisis is a life-threatening emergency requiring immediate aggressive treatment: 1, 2

• Immediate hydrocortisone: 100 mg IV or IM bolus, then 100 mg every 6-8 hours until recovery 1, 2
• Aggressive fluid resuscitation: Isotonic (0.9%) saline at 1 L/hour initially until hemodynamic improvement, typically 3-4 L over 24-48 hours 1, 2
• Identify precipitant: Aggressively search for and treat underlying triggers (infection, trauma, stress) 1, 2

Stress-Dose Adjustments

Specific protocols for different stress levels: 1

• Minor illness/stress: Double or triple oral glucocorticoid dose 1
• Major surgery: 100 mg hydrocortisone IM before anesthesia, followed by IV or IM dosing and increased oral doses 1
• Pregnancy: Small adjustments to hydrocortisone and fludrocortisone in third trimester; parenteral hydrocortisone during delivery 1
• Intense exercise: Increase hydrocortisone and salt intake for unaccustomed prolonged activity 1

Androgen Replacement (Selected Patients)

For women with persistent symptoms despite optimized replacement: 3

• Indication: Persistent lack of libido and/or low energy despite optimized glucocorticoid and mineralocorticoid therapy 3
• Trial therapy: DHEA 25-50 mg daily for 6 months, continue only if clinically effective 3
• Monitoring: Target serum DHEAS, androstenedione, and testosterone levels in normal range 3
• Evidence caveat: Limited objective evidence from large studies; use with caution due to lack of long-term safety data 3

Mandatory Patient Education

Every patient must receive comprehensive crisis prevention education: 1, 2

• Emergency identification: Wear medical alert bracelet/necklace and carry emergency steroid card at all times 1, 2
• Self-management training: Education on dose adjustments during illness and use of emergency injectable hydrocortisone 1, 2
• Crisis recognition: Clear instructions on when to seek immediate medical attention 1

Follow-Up Protocol

Structured annual monitoring is mandatory: 1, 2

• Clinical assessment: General health, weight, blood pressure at least annually 1, 2
• Laboratory monitoring: Serum electrolytes annually 1, 2
• Autoimmune screening: Monitor for new autoimmune disorders, particularly hypothyroidism (50% develop another autoimmune condition) 1, 2, 5
• Bone health: Assess bone mineral density every 3-5 years to monitor for glucocorticoid-induced complications 1

Critical Pitfalls to Avoid

• Never discontinue fludrocortisone completely, even with hypertension—only reduce dose 1, 4
• Never rely on laboratory values alone for dose adjustments; clinical assessment (symptoms, weight, blood pressure) guides therapy 2
• Never underestimate stress-dose requirements—failure to increase glucocorticoids during illness, surgery, or stress precipitates adrenal crisis 1, 2
• Never miss screening for polyendocrine syndromes—approximately 50% have coexisting autoimmune diseases requiring monitoring 2, 5