What is the treatment for Addison's disease?

Treatment of Addison's Disease

Addison's disease requires lifelong dual hormone replacement with oral hydrocortisone (15-25 mg daily in 2-3 divided doses) and fludrocortisone (50-200 μg once daily), with immediate IV hydrocortisone 100 mg and isotonic saline for adrenal crisis. 1

Glucocorticoid Replacement Therapy

Hydrocortisone is the first-line glucocorticoid for replacement therapy. 1

• Start with 15-25 mg of hydrocortisone daily, divided into 2-3 doses to mimic natural cortisol rhythm 1
• Administer the first dose immediately upon waking and the last dose at least 6 hours before bedtime 1
• Use the lowest effective dose that maintains well-being to minimize side effects 1
• In pediatric patients, dose hydrocortisone at 6-10 mg/m² of body surface area 1
• Alternative option: cortisone acetate 10-37.5 mg daily in divided doses 2

The divided dosing strategy is critical because it attempts to replicate the physiological diurnal cortisol pattern, though current oral formulations cannot perfectly achieve this 3. The FDA-approved labeling supports hydrocortisone 10-30 mg daily in divided doses when combined with fludrocortisone 2.

Mineralocorticoid Replacement Therapy

Fludrocortisone 50-200 μg (0.05-0.2 mg) once daily is required to replace aldosterone. 1, 2

• The usual starting dose is 0.1 mg daily 2
• Children and younger adults may require higher doses within this range 4, 1
• If hypertension develops, reduce the fludrocortisone dose but do not discontinue it completely 4, 1, 2
• Patients should consume salt and salty foods freely (ad libitum) 4, 1
• Avoid licorice and grapefruit juice, as these can interfere with mineralocorticoid activity 4, 1

The FDA labeling confirms dosing from 0.1 mg three times weekly up to 0.2 mg daily, with reduction to 0.05 mg daily if transient hypertension occurs 2.

Management of Adrenal Crisis

Adrenal crisis is a medical emergency requiring immediate treatment without delay for diagnostic procedures. 4, 1

Immediate Actions:

• Administer 100 mg hydrocortisone IV or IM immediately, followed by 100 mg every 6-8 hours until recovery 4, 1
• Infuse isotonic (0.9%) sodium chloride solution at 1 L/hour initially until hemodynamic improvement, typically 3-4 L over 24-48 hours 1
• If possible, obtain blood samples for cortisol and ACTH before treatment, but never delay treatment for diagnostic testing 4
• Identify and treat the underlying precipitant (most commonly infection or gastrointestinal illness) 4, 1

Stress Dosing and Special Situations

Minor Illness or Stress:

• Double or triple the oral glucocorticoid dose during minor illness or stress 1
• Increase salt intake during unaccustomed intense or prolonged exercise 1

Surgery and Invasive Procedures:

• Major surgery requires 100 mg hydrocortisone IM before anesthesia 1
• Continue IV or IM hydrocortisone with increased oral doses perioperatively 4, 1

Pregnancy:

• Small adjustments to both hydrocortisone and fludrocortisone may be needed, particularly during the third trimester 4, 1
• Administer parenteral hydrocortisone during delivery 4, 1

Patient Education and Safety Measures

All patients must receive comprehensive education on emergency management and wear medical alert identification. 1, 5

• Teach patients when to double or triple glucocorticoid doses during illness 1, 5
• Prescribe emergency injectable hydrocortisone for home use 1, 5
• Issue an emergency steroid card 1, 5
• Provide medical alert bracelet or necklace 1, 5

Follow-Up and Monitoring

Patients require at least annual review with specific assessments. 4, 1, 5

• Measure weight and blood pressure at each visit 1, 5
• Check serum electrolytes (sodium and potassium) annually 1, 5
• Assess general health, well-being, energy levels, and symptom patterns 5
• Screen periodically for autoimmune hypothyroidism and other autoimmune conditions 4, 5
• Monitor bone mineral density every 3-5 years to detect glucocorticoid-induced osteoporosis 4, 1, 5

Important Monitoring Caveat:

Serum cortisol levels are not useful for monitoring replacement adequacy because hydrocortisone produces highly variable peaks and troughs throughout the day 5. Similarly, ACTH levels remain elevated regardless of replacement adequacy and do not guide dosing 5.

Adrenal Androgen Replacement

There is insufficient evidence to recommend routine replacement of adrenal androgens (DHEA). 4

While some studies have explored DHEA replacement at 20-50 mg daily, the evidence for clinical benefit remains weak 6, and current consensus guidelines do not support routine use 4.