What is the treatment for hypocortisolism (low cortisol levels)?

Treatment for Hypocortisolism (Low Cortisol Levels)

Hypocortisolism requires physiologic glucocorticoid replacement therapy, typically with hydrocortisone 15-20 mg daily in divided doses (morning and afternoon), patient education on stress dosing, and a medical alert bracelet/card. 1

Diagnosis Before Treatment

Before initiating treatment, it's important to determine whether the hypocortisolism is:

• Primary adrenal insufficiency: Characterized by high ACTH, low cortisol, often with hyperkalemia 1
• Secondary adrenal insufficiency: Low or low-normal ACTH with low cortisol, due to pituitary or hypothalamic disorders 1

Diagnostic tests include:

• Morning cortisol level (8 am preferred)
  • <3 μg/dL strongly suggests adrenal insufficiency

  • 15 μg/dL makes it unlikely 1

• ACTH stimulation test (250-μg) with cortisol measured at baseline, 30 and 60 minutes
  • Peak cortisol <18 μg/dL confirms adrenal insufficiency 1

Treatment Algorithm Based on Severity

Severe Symptoms (hypotension, severe electrolyte disturbances)

• Immediately administer IV hydrocortisone 100 mg or dexamethasone 4 mg 1
• Provide at least 2L normal saline IV
• Hospitalize for close monitoring
• Withhold immune checkpoint inhibitors if applicable 2
• Refer to or consult endocrinologist 2

Moderate Symptoms (fatigue/mood alteration but hemodynamically stable)

• Initiate oral prednisolone 0.5-1 mg/kg once daily after pituitary axis assessment 2
• If no improvement in 48 hours, treat as severe with IV methylprednisolone 2
• Alternatively, use 2-3 times maintenance dose (prednisone 20 mg daily or hydrocortisone 20-30 mg morning, 10-20 mg afternoon) 1
• Taper to maintenance over 5-10 days
• Do not stop steroids completely 2

Mild Symptoms (mild fatigue, anorexia)

• Replace with hydrocortisone 20/10 mg (morning/afternoon) 2, 1
• For primary adrenal insufficiency, add fludrocortisone 0.05-0.1 mg daily for mineralocorticoid replacement 1
• For secondary adrenal insufficiency, mineralocorticoid replacement is rarely necessary 2

Dosing Regimen

The optimal dosing regimen for hydrocortisone is:

• Thrice daily: Research shows that twice-daily regimens lead to very low cortisol levels by mid-afternoon, while thrice-daily dosing maintains more physiologic levels throughout the day 3
• Typical dosing: 10 mg on waking, 5 mg at lunch, 5 mg in early evening

Patient Education and Monitoring

All patients must receive:

1. Stress dosing instructions:

   • Minor stress (mild fever, minor illness): Double oral daily dose for duration of illness 1
   • Moderate stress (moderate illness, dental procedures): Triple oral dose or hydrocortisone 50-100 mg IM 1
   • Major stress (surgery, severe illness): Hydrocortisone 100 mg IV/IM every 6-8 hours 1

2. Medical alert bracelet/card identifying steroid dependence 1

3. Regular monitoring:

   • Blood pressure
   • Electrolytes
   • Glucose
   • Symptoms of under-replacement (fatigue, weakness, nausea, hypotension) or over-replacement 1

Special Considerations

• Tapering from exogenous steroids: For patients with iatrogenic adrenal insufficiency, reduce dose by 10-20% every 1-2 weeks, then by 1 mg every 2-4 weeks once at physiologic replacement dose 1

• Drug-induced secondary adrenal insufficiency: Minimize by gradual reduction of dosage. In stressful situations during recovery period, hormone therapy should be reinstituted 4

• Pregnancy: Hydrocortisone requirements may increase, particularly in the third trimester, with parenteral hydrocortisone planned for delivery 1

Common Pitfalls to Avoid

1. Abrupt discontinuation of steroids: This can precipitate adrenal crisis 4

2. Inadequate stress dosing: Patients need increased doses during illness, surgery, or other stressors 1

3. Overlooking mineralocorticoid replacement: Essential in primary but not typically needed in secondary adrenal insufficiency 1

4. Failure to educate patients: Patients must understand the importance of adherence to replacement therapy and stress dosing 1

5. Inadequate monitoring: Regular assessment of symptoms and laboratory parameters is necessary to ensure optimal replacement 1