Symptoms and Treatment of Addison's Disease
Addison's disease (primary adrenal insufficiency) requires lifelong replacement of glucocorticoids and mineralocorticoids, with hydrocortisone (10-30mg daily in divided doses) and fludrocortisone (typically 0.1mg daily), along with patient education on stress dosing to prevent potentially fatal adrenal crises. 1, 2, 3
Clinical Presentation
Chronic Symptoms
- Nonspecific symptoms (often leading to delayed diagnosis):
- Fatigue and weakness
- Malaise and anorexia
- Weight loss
- Nausea and diarrhea
- Joint and back pain 4
Cutaneous Manifestations
- Hyperpigmentation (pathognomonic finding):
- Darkening of sun-exposed areas
- Increased pigmentation of:
- Palmar creases
- Frictional surfaces
- Vermilion border of lips
- Recent scars
- Genital skin
- Oral mucosa 4
Laboratory Abnormalities
- Primary adrenal insufficiency:
- High ACTH, low cortisol
- Electrolyte disturbances (↓Na, ↑K)
- Hyperpigmentation present
- Secondary adrenal insufficiency:
- Low ACTH, low cortisol
- Generally normal electrolytes
- No hyperpigmentation 2
Acute Adrenal Crisis
- Life-threatening emergency requiring immediate treatment
- Characterized by:
Diagnosis
- Screening: Basal plasma cortisol is insensitive
- Confirmatory test: Synthetic ACTH stimulation test (250 μg)
- Definitive diagnosis: Elevated ACTH and renin levels with low cortisol 4
- Most patients have circulating antibodies against 21-hydroxylase (in autoimmune etiology) 5
Treatment Approach
Maintenance Therapy
Glucocorticoid replacement:
Mineralocorticoid replacement:
- Fludrocortisone 0.1mg daily (range: 0.1mg three times weekly to 0.2mg daily)
- Reduce to 0.05mg daily if transient hypertension develops 3
Monitoring adequacy of replacement:
- Clinical assessment (energy levels, weight, blood pressure)
- Electrolytes
- Plasma renin activity (for mineralocorticoid adjustment) 2
Special Situations
Surgery and Medical Procedures
Major surgery with long recovery:
- 100mg hydrocortisone IM before anesthesia
- Continue 100mg IM every 6 hours until oral intake possible
- Then double oral dose for 48+ hours before tapering 1
Minor surgery/dental procedures:
- 100mg hydrocortisone IM before procedure
- Double oral dose for 24 hours 1
Pregnancy
- Increase hydrocortisone by 2.5-10mg daily in third trimester
- Fludrocortisone dose may need to be increased during late pregnancy
- During delivery: 100mg hydrocortisone bolus, repeated every 6 hours if necessary 1
Physical Activity
- Regular, accustomed activity: No dose adjustment needed
- Intense/prolonged exercise: Increase hydrocortisone and salt intake
- Marathon-type events: Extra 5mg hydrocortisone before the event 1
Adrenal Crisis Management
- Immediate treatment:
- 100mg hydrocortisone IV bolus
- Follow with 100-300mg/day as continuous infusion or divided doses
- Rapid IV isotonic saline administration
- Hourly blood glucose monitoring if fasting >4 hours 2
Patient Education and Prevention
Essential education points:
- Stress dosing instructions
- Emergency injectable hydrocortisone use
- Medical alert bracelet/card
- Recognition of early warning signs of adrenal crisis 2
Follow-up monitoring:
- Regular assessment of replacement adequacy
- Watch for signs of over-replacement (weight gain, hypertension)
- Monitor for signs of under-replacement (fatigue, nausea, hypotension) 2
Common Pitfalls to Avoid
- Delayed diagnosis due to nonspecific symptoms
- Inadequate stress dosing during illness or procedures
- Failure to recognize adrenal crisis promptly
- Insufficient patient education about emergency management
- Inappropriate glucocorticoid dosing leading to under or over-replacement 2
With proper treatment and patient education, the survival rate of patients with Addison's disease can approach that of the general population 6.