What is the treatment for Addison's disease?

Treatment for Addison's Disease

The treatment for Addison's disease requires lifelong hormone replacement with oral hydrocortisone 15-25 mg daily (divided into 2-3 doses) plus fludrocortisone 50-200 μg once daily, with immediate dose escalation during illness or stress to prevent potentially fatal adrenal crisis. 1

Glucocorticoid Replacement Therapy

Hydrocortisone is the first-line glucocorticoid and should be administered in divided doses to mimic natural cortisol rhythm 1:

• Starting dose: 15-25 mg daily, divided into 2-3 doses 1
• Timing is critical: Give the first dose immediately upon waking and the last dose at least 6 hours before bedtime to simulate physiological cortisol patterns 1
• Pediatric dosing: 6-10 mg/m² of body surface area 1
• Use the lowest effective dose to minimize side effects while maintaining patient well-being 1

The FDA-approved alternative glucocorticoids include cortisone (10-37.5 mg daily in divided doses) or hydrocortisone (10-30 mg daily in divided doses) when used with fludrocortisone 2.

Mineralocorticoid Replacement Therapy

Fludrocortisone is essential for aldosterone replacement 2:

• Standard dose: 50-200 μg (0.05-0.2 mg) once daily 1, 2
• Higher doses may be needed in children and younger adults 1
• If hypertension develops, reduce the dose to 0.05 mg daily but do not discontinue completely 1, 2
• Dietary guidance: Patients should consume salt and salty foods freely, while avoiding licorice and grapefruit juice 1

The FDA label confirms that 0.1 mg daily is the usual dose, with a range of 0.1 mg three times weekly to 0.2 mg daily 2.

Management of Adrenal Crisis

Adrenal crisis is a medical emergency requiring immediate treatment without waiting for diagnostic confirmation 3:

Immediate Actions:

• Administer hydrocortisone 100 mg IV or IM bolus immediately 1, 3
• Begin aggressive fluid resuscitation with 0.9% saline at 1 L/hour until hemodynamic improvement 1, 3
• Continue hydrocortisone 100 mg every 6-8 hours (or 100-300 mg/day as continuous infusion) until recovery 1, 3
• Administer 3-4 L of isotonic saline over 24-48 hours 1, 3
• Identify and treat the precipitating cause (infection, trauma, surgery) 1, 3

Transition from Crisis Management:

• When hydrocortisone dose falls below 50 mg/day, restart fludrocortisone 4

Stress Dosing Protocols

Dose adjustments are mandatory during physiological stress to prevent crisis 1:

Minor Illness or Stress:

• Double or triple the oral glucocorticoid dose 1, 3

Major Surgery:

• Administer 100 mg hydrocortisone IM before anesthesia 1, 3
• Continue 100 mg every 6 hours until able to resume oral medication 3

Pregnancy:

• Small dose increases during third trimester (2.5-10 mg additional hydrocortisone daily) 1, 5
• Administer 100 mg hydrocortisone IM at onset of labor 3, 5

Intense Exercise:

• Increase hydrocortisone and salt intake for unaccustomed prolonged or intense physical activity 1, 3

Patient Education and Safety Measures

Comprehensive patient education is essential to prevent adrenal crises 4, 1:

• Teach dose adjustment protocols for illness, vomiting, injuries, and other stressors 4, 1
• Provide emergency injectable hydrocortisone and ensure patients know how to use it 1, 3
• Issue medical alert identification (bracelet/necklace) and emergency steroid card 1, 3, 5
• Educate on when to seek immediate medical attention before reaching a state of incapacity 4, 1

Annual Follow-Up and Monitoring

Regular surveillance is necessary to optimize therapy and detect complications 4, 1:

Clinical Assessment:

• Review at least annually: Assess general health, weight, blood pressure, and quality of life 4, 1
• Laboratory monitoring: Serum sodium, potassium, and plasma renin activity (PRA) to assess mineralocorticoid adequacy 4, 1
• Morning cortisol absorption test (serum or saliva at 0,2,4, and 6 hours post-dose) if under-replacement suspected 4

Screening for Autoimmune Comorbidities:

• Thyroid function (TSH, FT4, TPO antibodies) every 12 months to detect hypothyroidism or thyrotoxicosis 4, 1
• Annual screening: Plasma glucose, HbA1c for diabetes mellitus 4
• Complete blood count and B12 levels annually to screen for pernicious anemia 4
• Tissue transglutaminase antibodies and total IgA in patients with episodic diarrhea to screen for celiac disease 4
• Bone mineral density every 3-5 years to monitor for glucocorticoid-induced osteoporosis 1

Women of Reproductive Age:

• Counsel about risk of premature ovarian insufficiency, especially if side-chain cleavage enzyme antibodies (SCC-Ab) are present 4

Common Pitfalls to Avoid

• Under-replacement with mineralocorticoid and low salt consumption are common causes of recurrent adrenal crises 4
• Failure to increase doses during illness is a leading cause of preventable adrenal crisis 3
• Starting thyroid replacement before adequate glucocorticoid replacement can precipitate adrenal crisis 4
• Poor compliance and undiagnosed psychiatric disorders should be investigated in patients with recurrent crises 4