What is the typical outpatient dosing regimen for hydrocortisone in patients with Addison's disease?

Outpatient Hydrocortisone Dosing for Addison's Disease

For stable outpatients with Addison's disease, initiate hydrocortisone 15-25 mg daily divided into 2-3 doses, with two-thirds given in the morning upon awakening and one-third in early afternoon, plus fludrocortisone 0.05-0.1 mg once daily. 1

Standard Maintenance Regimen

Glucocorticoid Replacement

• Total daily dose: 15-25 mg hydrocortisone (or 15-20 mg per current consensus) 1
• Typical dosing schedule:
  • Two-dose regimen: 10 mg upon awakening, 5 mg in early afternoon (4-6 hours before bedtime) 1
  • Three-dose regimen: 10 mg morning, 5 mg afternoon, 5 mg evening 2
  • The first dose should be taken immediately upon awakening to mimic physiologic cortisol rhythm 1

Mineralocorticoid Replacement

• Fludrocortisone 0.05-0.1 mg once daily is required for primary adrenal insufficiency 1
• Titrate based on volume status, sodium levels, and renin (target upper half of reference range) 1
• Maximum dose typically 0.2 mg daily 3

Alternative Glucocorticoid Options

Cortisone Acetate

• Dose range: 25 mg daily in divided doses (12.5 mg twice daily or 12.5 + 6.25 + 6.25 mg three times daily) 3
• Requires hepatic conversion to hydrocortisone, causing slightly delayed onset 1
• No evidence shows superiority over hydrocortisone 1

Prednisolone (Select Cases Only)

• Reserved for patients with marked energy fluctuations throughout the day despite optimized hydrocortisone 1
• Typical doses: 4-5 mg upon awakening, or 3 mg morning plus 1-2 mg at 14:00 hours 1
• Equivalency: Hydrocortisone 20 mg = Prednisone 5 mg 1, 4
• Avoid dexamethasone for maintenance therapy 1

Dose Titration and Monitoring

Clinical Assessment (Not Laboratory Values)

• Plasma ACTH and serum cortisol are NOT useful for dose adjustment 1
• Monitor primarily through clinical symptoms:
  • Over-replacement signs: Weight gain, insomnia, peripheral edema, bruising, thin skin, hypertension, hyperglycemia 1
  • Under-replacement signs: Lethargy, nausea, poor appetite, weight loss, increased/uneven pigmentation 1

Fine-Tuning Strategies

• Assess daily energy patterns, mental concentration, daytime somnolence 1
• Ask about timing of energy "dips" during the day 1
• Maximum maintenance dose: 30 mg hydrocortisone daily for residual symptoms 1
• If morning nausea/poor appetite occurs, take first dose earlier then return to sleep 1

Sick Day Management (Mild-Moderate Stress)

• Double the regular oral maintenance dose during febrile illness, minor procedures, or intercurrent illness 2, 5
• Continue doubled dose for 24-48 hours after stress resolves, then return to normal 1, 5
• For vomiting/inability to absorb oral medication, patients must use emergency injectable hydrocortisone 100 mg IM 2

Critical Patient Education Requirements

Emergency Preparedness

• All patients must have:
  • Emergency hydrocortisone injection kit (100 mg) for self-administration 2
  • Medical alert bracelet/necklace 1, 2
  • Steroid emergency card 1, 2
• Education on stress dosing for sick days is mandatory 1, 4

Common Pitfall to Avoid

• Never start thyroid hormone, testosterone, or estrogen replacement before stabilizing on corticosteroids, as these accelerate cortisol clearance and can precipitate adrenal crisis 2, 4

Special Dosing Situations

Night Shift Workers

• Adjust schedule to work pattern (e.g., 10 mg upon awakening before work instead of at 07:00 hours) 1

Intense Physical Activity

• For marathon running or prolonged exercise: add 5 mg hydrocortisone before the event 1
• Increase salt and fluid intake during hot conditions or intense activity 1

Drug Interactions

• CYP3A4 inducers/inhibitors affect hydrocortisone clearance and may require dose adjustment 1

Monitoring Schedule

• Annual consultation should assess replacement adequacy, self-medication practices during illness, and history of adrenal crises 1
• Normal skin pigmentation and blood pressure indicate adequate replacement 1
• Postural hypotension suggests insufficient mineralocorticoid or low salt intake 1