What is the appropriate dosage of hydrocortisone (Solu Cortef) for secondary adrenal insufficiency?

Appropriate Dosage of Hydrocortisone (Solu-Cortef) for Secondary Adrenal Insufficiency

For chronic maintenance therapy in secondary adrenal insufficiency, hydrocortisone should be dosed at 15-25 mg daily in divided doses, typically 10-20 mg in the morning and 5-10 mg in the early afternoon. 1

Maintenance Dosing Regimens

The standard approach uses divided doses to approximate physiological cortisol secretion:

• Typical regimen: 10 mg at 7:00 AM, 5 mg at 12:00 PM, and 2.5-5 mg at 4:00 PM 1
• Alternative regimens: 15 + 5 mg, 10 + 10 mg, or 10 + 5 + 5 mg depending on individual response 1
• Simplified two-dose regimen: 15 mg morning + 5 mg early afternoon for patients with compliance issues 1

The last dose should be taken no later than 4-6 hours before bedtime to avoid insomnia. 2

Severity-Based Dosing Algorithm

Mild/Asymptomatic (Grade 1)

• Maintenance dose: Hydrocortisone 10-20 mg orally in the morning, 5-10 mg in early afternoon 1
• Alternatively, prednisone 5-10 mg daily (equivalent to 20-40 mg hydrocortisone) 1

Moderate Symptoms (Grade 2)

• Stress dosing: 2-3 times maintenance dose (20-30 mg morning, 10-20 mg afternoon) 1
• Taper back to maintenance over 5-10 days 1

Severe/Life-Threatening (Grade 3-4)

• Emergency IV dosing: Hydrocortisone 100 mg IV bolus immediately 1
• If diagnosis uncertain and stimulation testing needed, use dexamethasone 4 mg instead 1
• Hospital management: Continue with normal saline (at least 2 L) plus IV stress-dose corticosteroids 1
• Taper to maintenance over 7-14 days after discharge 1

Critical Differences from Primary Adrenal Insufficiency

Secondary adrenal insufficiency does NOT require mineralocorticoid (fludrocortisone) replacement because the renin-angiotensin-aldosterone system remains intact. 1 This is a key distinction—fludrocortisone 0.05-0.2 mg daily is only needed in primary adrenal insufficiency. 1, 3

Dosing Pitfalls and Optimization

Common Dosing Errors

Research demonstrates that 79% of patients at 8:00 AM and 55% at 4:00 PM are either over- or under-treated with standard regimens. 4 The best simulated regimen (10 + 5 + 5 mg at 7:30 AM, 12:00 PM, and 4:30 PM) still leaves approximately 54% of patients outside physiological targets. 4

Monitoring for Appropriate Dosing

• Over-replacement signs: Weight gain, insomnia, peripheral edema, Cushingoid features 2, 3
• Under-replacement signs: Lethargy, nausea, poor appetite, weight loss, persistent fatigue 2, 3
• Clinical assessment is primary: Laboratory cortisol levels are not reliable for monitoring adequacy 2

Drug Interactions Requiring Dose Adjustment

Medications that increase hydrocortisone requirements: 1

• Anti-epileptics and barbiturates
• Antituberculosis medications (rifampin)
• Topiramate
• Etomidate

Substances that decrease requirements: 1

• Grapefruit juice
• Liquorice (should be avoided)

Special Situations

Stress Dosing Education

All patients must be educated on doubling or tripling their dose during febrile illness, infection, or minor stress. 5, 6 For major stress (surgery, severe infection), IV hydrocortisone 100 mg is required. 1

Procedural Coverage

Endocrine consultation is mandatory prior to any surgical procedure for stress-dose planning. 1 Patients should continue their regular hydrocortisone on the day of procedures with consideration for supplemental dosing. 7

Emergency Preparedness

• Medical alert bracelet identifying adrenal insufficiency 1
• Emergency injectable hydrocortisone kit 2
• Written sick-day rules for dose adjustment 6

Alternative Glucocorticoid Options

Prednisolone 4-5 mg daily (equivalent to 20-25 mg hydrocortisone) may be considered only when: 1, 3

• Hydrocortisone is not tolerated
• Marked compliance problems exist
• Severe energy fluctuations occur throughout the day

However, hydrocortisone remains the preferred agent as it most closely mimics physiological cortisol. 1

FDA-Approved Dosing Range

The FDA label states that hydrocortisone tablets may range from 20-240 mg daily depending on disease severity, with dosage requirements being highly individualized. 8 For adrenal insufficiency specifically, the lower end of this range (15-25 mg daily) is appropriate for maintenance therapy. 1, 9