What is a typical starting dose of Cortef (hydrocortisone) for a patient requiring low-dose therapy?

Low-Dose Hydrocortisone (Cortef) Therapy: Starting Dose Recommendations

For patients requiring low-dose glucocorticoid replacement therapy, the typical starting dose of hydrocortisone (Cortef) is 15-20 mg daily in divided doses, with two-thirds given immediately upon awakening and one-third in the early afternoon (not later than 6 hours before bedtime). 1

Standard Dosing Regimens

Primary Adrenal Insufficiency (Mild to Moderate)

• Total daily dose: 15-25 mg hydrocortisone (or 18.75-31.25 mg cortisone acetate) 1
• Typical split-dose schedule:
  • 10 mg upon awakening (before 9 AM) 1, 2
  • 5 mg in early afternoon (around 2:00 PM, but at least 6 hours before bedtime) 1, 2
• The lowest dose compatible with health and sense of well-being should be used 1

Pediatric Dosing

• 6-10 mg/m² of body surface area daily in divided doses 1

Alternative Equivalent Dosing

• If using prednisone instead: 4-5 mg daily (20 mg hydrocortisone = 5 mg prednisone) 2, 3
• Prednisone can be given as a single 4-5 mg dose upon awakening, or split as 3 mg upon awakening and 1-2 mg at 2:00 PM 2

Dosing Rationale and Timing

The split-dose regimen mimics the physiological diurnal cortisol rhythm, with highest levels in the early morning and declining throughout the day 4. This approach is critical because:

• Hydrocortisone has a short elimination half-life of approximately 1.5 hours 4, 5
• Immediate-release formulations create high peaks and low troughs between doses 5
• Morning administration reduces insomnia risk, a common side effect of evening dosing 2

Dose Titration Guidelines

Signs of Under-Replacement (Increase Dose)

• Lethargy, nausea, poor appetite 2
• Weight loss 2
• Increased skin pigmentation 2
• Maximum daily dose: 30 mg hydrocortisone total 1

Signs of Over-Replacement (Decrease Dose)

• Weight gain, peripheral edema 2
• Insomnia 2
• Bruising, thin skin 1
• Hypertension, hyperglycemia 1

Clinical assessment of symptoms, energy levels, and overall well-being is the primary monitoring method, not laboratory cortisol values 2

Additional Mineralocorticoid Requirements

Most patients with primary adrenal insufficiency also require fludrocortisone 0.05-0.1 mg daily (range 50-200 mcg) 1, 2. Adjust based on:

• Volume status and blood pressure 1
• Serum sodium and potassium levels 1
• Plasma renin (target upper half of reference range) 1

Critical Patient Education Requirements

All patients on hydrocortisone replacement must receive:

• Medical alert identification (bracelet, necklace, or card) 1, 2
• Stress dosing education for concurrent illness or injury 1, 2
• Emergency self-injection supplies of parenteral hydrocortisone 1
• Instructions to double or triple the dose during minor to moderate illness 1

Stress Dosing for Illness

• Moderate illness: 2-3 times maintenance dose (30-50 mg hydrocortisone total or 20 mg prednisone daily) for 2 days, then taper 1, 2
• Severe illness/crisis: 100 mg hydrocortisone IV/IM every 6-8 hours until recovery 1

Important Drug Interactions Affecting Dose

Medications that increase hydrocortisone requirements: 2

• Anticonvulsants and barbiturates
• Antituberculosis medications (rifampin)

Medications/substances that decrease requirements: 2

• Grapefruit juice
• Licorice (avoid entirely)

Common Pitfalls to Avoid

• Never give the last dose within 6 hours of bedtime to prevent insomnia 1, 2
• Do not use laboratory cortisol levels to guide chronic dosing - rely on clinical symptoms 2
• Do not abruptly discontinue after long-term therapy - taper gradually 3
• Do not delay treatment in suspected acute adrenal crisis for diagnostic testing 1
• Avoid doses exceeding 30 mg daily for chronic replacement, as higher doses increase morbidity without additional benefit 1