What is the recommended treatment for a patient with late-onset Addison's disease?

Treatment of Late-Onset Addison's Disease

Patients with late-onset Addison's disease require lifelong dual hormone replacement with oral hydrocortisone 15-25 mg daily (divided into 2-3 doses) plus fludrocortisone 0.05-0.2 mg once daily, with the treatment approach being identical to early-onset disease. 1, 2

Core Replacement Therapy

Glucocorticoid Replacement

• Hydrocortisone is the first-line glucocorticoid, administered in divided doses to mimic natural cortisol rhythm, with the first dose immediately upon awakening and the last dose at least 6 hours before bedtime 1, 2

• The standard starting dose is 15-25 mg daily of hydrocortisone (or 20-30 mg daily of cortisone acetate if hydrocortisone is unavailable), divided into 2-3 doses with the largest dose in the morning 1, 3

• Cortisone acetate is an acceptable alternative to hydrocortisone, though it has a slightly delayed onset as it requires hepatic conversion to active hydrocortisone 1

• Dose adjustments are based entirely on clinical assessment, not laboratory values—plasma ACTH and serum cortisol are not useful for monitoring 1, 3

Mineralocorticoid Replacement

• Fludrocortisone 0.05-0.2 mg once daily is required to replace aldosterone deficiency 2, 4

• The FDA-approved usual dose is 0.1 mg daily, though the range of 0.1 mg three times weekly to 0.2 mg daily may be employed 4

• If hypertension develops during treatment, reduce the fludrocortisone dose to 0.05 mg daily but do not discontinue completely 2, 4

• Patients should consume salt and salty foods freely to compensate for increased renal sodium loss 2

Monitoring for Over- and Under-Replacement

Signs of Over-Replacement (Reduce Dose)

• Weight gain, insomnia, and peripheral edema indicate excessive glucocorticoid exposure 1, 3

Signs of Under-Replacement (Increase Dose)

• Lethargy, nausea, poor appetite, weight loss, and increased (often uneven) pigmentation indicate insufficient replacement 1, 3

• Fine-tuning requires detailed questioning about energy levels throughout the day, mental concentration, daytime somnolence, and pigmentation changes 1

Stress Dosing and Crisis Management

Minor Illness or Stress

• Double or triple the oral glucocorticoid dose during minor illnesses, infections, or stress 2

Major Surgery

• Administer 100 mg hydrocortisone IM immediately before anesthesia 1, 2
• Continue 100 mg hydrocortisone IM every 6 hours until the patient can eat and drink 1
• Then double the oral dose for 24-48 hours before tapering to normal 1

Adrenal Crisis (Life-Threatening Emergency)

• Immediately administer 100 mg hydrocortisone IV or IM bolus without waiting for diagnostic confirmation 1, 2
• Follow with 100 mg hydrocortisone every 6-8 hours until recovery 1, 2
• Simultaneously infuse 0.9% isotonic saline at 1 L/hour initially, with 3-4 L typically required over 24-48 hours 1, 2
• Identify and treat the precipitating cause (infection, trauma, GI illness) 1, 2

Common pitfall: Adrenal crisis occurs at a frequency of 6-8 per 100 patient-years, often precipitated by vomiting/diarrhea or infections—even mild GI upset can be life-threatening as patients cannot absorb oral medication when they need it most 1

Essential Patient Education and Safety Measures

• All patients must wear medical alert identification (bracelet or necklace) and carry an emergency steroid card at all times 1, 2

• Train patients in self-administration of intramuscular hydrocortisone for emergency use 1

• Educate on when to increase doses (illness, stress, exercise) and when to seek immediate medical attention 2

Critical warning: Many patients report having to argue with emergency department staff to receive treatment—this delay can be fatal and must be prevented through improved medical personnel awareness 1

Drug Interactions

• CYP3A4 is the key enzyme affecting hydrocortisone clearance—concomitant medications can significantly alter efficacy 1, 3

• Patients should avoid licorice and grapefruit juice, which can interfere with treatment 2

Follow-Up Schedule

• Review patients at least annually with assessment of general health, weight, blood pressure, and serum electrolytes 2

• Monitor for development of new autoimmune disorders, particularly hypothyroidism, which commonly co-occurs 2

• Assess bone mineral density every 3-5 years to detect complications of glucocorticoid therapy 2

Note on "late-onset" terminology: The treatment approach for Addison's disease is identical regardless of age at diagnosis—whether diagnosed in childhood, adulthood, or late adulthood, the same principles of glucocorticoid and mineralocorticoid replacement apply 1, 2