What is the treatment for central hypocortisolism?

Treatment of Central Hypocortisolism

The standard treatment for central hypocortisolism is hydrocortisone replacement therapy at a total daily dose of 15-20 mg, typically divided with 2/3 in the morning and 1/3 in early afternoon to mimic physiological cortisol rhythm. 1

Diagnosis and Etiology

Central hypocortisolism (secondary adrenal insufficiency) is characterized by:

• Low morning cortisol with inappropriately low ACTH levels
• Caused by pituitary or hypothalamic disorders affecting ACTH production
• Unlike primary adrenal insufficiency, mineralocorticoid replacement is typically not needed

Treatment Approach

First-Line Treatment: Glucocorticoid Replacement

1. Hydrocortisone (HC) is the preferred glucocorticoid replacement:

   • Total daily dose: 15-20 mg 1, 2
   • Standard dosing schedule: 2-3 divided doses 2
     • Two-dose regimen: 2/3 in morning (upon awakening), 1/3 in early afternoon
     • Three-dose regimen: Morning, noon, and late afternoon (not after 6 PM to avoid insomnia)

2. Cortisone acetate (CA) is an alternative:

   • Requires activation to hydrocortisone by hepatic 11β-hydroxysteroid dehydrogenase type 1
   • Available in 25 mg and 5 mg tablets 2
   • Slightly delayed onset of action compared to hydrocortisone

Dosing Considerations

• Weight-based dosing of 8.1 mg/m²/day may be used in some cases 3
• Three-times-daily regimens may provide more physiological cortisol levels 4
• Lower doses (15 mg/day) may be sufficient and reduce risk of bone loss while maintaining quality of life 5
• Avoid evening doses (after 6 PM) to prevent insomnia

Monitoring and Dose Adjustment

• Clinical assessment is the primary method for monitoring adequacy of replacement 2
• Signs of over-replacement: weight gain, insomnia, peripheral edema
• Signs of under-replacement: fatigue, nausea, hypotension, hyponatremia
• Plasma ACTH and serum cortisol are not useful parameters for dose adjustment 2

Patient Education and Emergency Management

1. Stress dosing education:

   • Increase dose 2-3 times during minor illness or stress
   • For severe illness or surgery, parenteral hydrocortisone is required

2. Emergency preparedness:

   • Patients should wear medical identification (bracelet/card) 2, 1
   • Emergency injectable hydrocortisone kit should be provided
   • Patients and family members should be trained in administration

3. Adrenal crisis prevention:

   • Delays in hydrocortisone administration during emergencies can be fatal 2
   • Patients should be educated to increase doses during concurrent illnesses or injury

Special Considerations

• Drug interactions: CYP3A4 inducers/inhibitors can affect hydrocortisone clearance 2
• Surgical management: Patients require stress-dose steroids for procedures
• Central hypothyroidism: When both cortisol and thyroid hormones are deficient, always replace cortisol first to prevent precipitating an adrenal crisis 2

Long-term Follow-up

• Annual clinical assessment for adequacy of replacement
• Monitor for symptoms of under- or over-replacement
• Assess for development of other pituitary hormone deficiencies
• Bone health monitoring may be warranted with long-term therapy

Common Pitfalls to Avoid

1. Replacing thyroid hormone before cortisol in patients with multiple pituitary deficiencies (can precipitate adrenal crisis) 2
2. Failing to provide adequate stress-dose instructions
3. Administering evening doses too late (can cause insomnia)
4. Using plasma cortisol levels to adjust maintenance doses
5. Inadequate patient education about emergency management

Central hypocortisolism requires lifelong replacement therapy with careful attention to dose adjustments during times of stress or illness to prevent potentially life-threatening adrenal crisis.