What is the best way to titrate hydrocortisone (cortisol) dose in adrenal insufficiency?

Hydrocortisone Dose Titration in Adrenal Insufficiency

Initial Dosing Strategy

Start with 15-25 mg hydrocortisone daily in divided doses, with the first dose immediately upon awakening and the last dose at least 6 hours before bedtime, then titrate to the lowest dose compatible with health and sense of well-being. 1

The standard regimen consists of:

• 10-20 mg upon awakening (before 9 AM)
• 5-10 mg in early afternoon (around 12-2 PM)
• Optional third dose of 2.5-5 mg at 4 PM if needed 2, 3

Clinical Titration Algorithm

Step 1: Establish Baseline Dose

• Begin with 15-20 mg total daily dose for most adults 2
• For children, use 6-10 mg/m² body surface area 1
• Primary adrenal insufficiency requires fludrocortisone 50-200 µg daily in addition to hydrocortisone 1

Step 2: Monitor Clinical Response (NOT Laboratory Values)

Clinical assessment is the primary method for dose adjustment, not cortisol levels. 2, 4

Signs of over-replacement requiring dose reduction:

• Weight gain 2, 4
• Insomnia 2, 4
• Hypertension 1
• Peripheral edema 4

Signs of under-replacement requiring dose increase:

• Persistent fatigue and lethargy 2, 4
• Nausea, poor appetite, weight loss 2, 4
• Orthostatic hypotension 1
• Increased skin pigmentation (primary AI only) 4

Step 3: Adjust in Small Increments

• Decrease or increase by 2.5-5 mg at appropriate intervals 5
• Titrate to the lowest dose that maintains adequate clinical response 1
• Allow 1-2 weeks between adjustments to assess response 6, 7

Severity-Based Dosing Modifications

Grade 1 (Mild/Stable)

• Maintenance: 15-20 mg daily in divided doses 2

Grade 2 (Moderate Stress/Illness)

• Increase to 2-3 times maintenance (30-50 mg total daily) 1, 2
• Taper back to maintenance over 5-10 days 1, 3

Grade 3-4 (Severe/Adrenal Crisis)

• Immediate IV hydrocortisone 100 mg bolus, then 100 mg every 6-8 hours 1
• Administer 1-2 liters normal saline at 1 L/hour initially 1
• Taper to maintenance over 7-14 days after recovery 1, 3

Critical Dose Adjustments for Drug Interactions

Medications requiring INCREASED hydrocortisone dose:

• Anticonvulsants (phenytoin, carbamazepine) 2, 3
• Barbiturates 2, 3
• Rifampin 2, 3
• Topiramate 2

Substances requiring DECREASED dose (or avoidance):

• Grapefruit juice - avoid 1, 3
• Licorice - avoid 1, 3

Special Situations Requiring Dose Modification

Surgery/Major Procedures

• Hydrocortisone 100 mg IV at induction, followed by 200 mg/24 hours continuous infusion 2, 8
• This is superior to intermittent bolus dosing for maintaining physiologic cortisol levels 8

Pregnancy

• Small adjustments may be needed in the third trimester 1
• 100 mg IV hydrocortisone during labor and delivery 2

Minor Illness/Fever

• Double or triple the usual dose during febrile illness or infection 2, 3
• Continue until recovery, then return to maintenance 6, 9

Common Pitfalls to Avoid

1. Do not use cortisol levels to guide chronic dosing - clinical assessment is superior 2, 4
2. Do not give the last dose within 6 hours of bedtime - this causes insomnia 1
3. Do not forget mineralocorticoid replacement in primary AI - fludrocortisone is essential and should be titrated based on blood pressure, electrolytes, and plasma renin 1, 2
4. Do not delay treatment for diagnostic testing in suspected crisis - give hydrocortisone immediately 1

Essential Patient Education for Safe Titration

• All patients must wear medical alert identification 1
• Provide emergency injectable hydrocortisone with self-injection training 1
• Educate on stress dosing: double/triple dose for minor illness, seek emergency care for vomiting/severe illness 2, 3
• Annual follow-up with assessment of weight, blood pressure, and electrolytes 1