What is the best treatment approach for Covid-19 in patients with adrenal insufficiency?

Treatment of COVID-19 in Patients with Adrenal Insufficiency

Patients with adrenal insufficiency who develop COVID-19 must immediately double their glucocorticoid replacement dose at symptom onset, and if they develop fever, respiratory symptoms, or inability to take oral medications, they require parenteral hydrocortisone 100 mg IV/IM immediately followed by 50 mg every 6 hours or 200 mg/24h continuous infusion to prevent adrenal crisis. 1, 2

Immediate Management at COVID-19 Symptom Onset

Mild COVID-19 Symptoms (No Oxygen Requirement)

• Double the usual oral glucocorticoid replacement dose immediately when any COVID-19 symptoms appear 1, 2
• For patients on standard hydrocortisone: increase to 20 mg every 6 hours (80 mg/day total) if fever develops 2
• Continue doubled doses throughout the acute illness until symptoms resolve 1, 2
• Do NOT add dexamethasone for COVID-19 treatment in patients not requiring oxygen, as it provides no benefit and may cause harm 3, 4

Severe COVID-19 (Oxygen Requirement or Clinical Deterioration)

• Administer 100 mg hydrocortisone IV or IM immediately (patient self-injection if unable to reach hospital) 1, 2
• Follow with either:
  • 50 mg hydrocortisone IV every 6 hours, OR
  • 200 mg hydrocortisone per 24 hours by continuous IV infusion 1, 2
• Add dexamethasone 6 mg once daily for up to 10 days once oxygen requirement is established (SpO2 <94% on room air) 3, 4
• The stress-dose hydrocortisone covers adrenal insufficiency; dexamethasone addresses COVID-19 inflammatory response 4

Critical Distinction: Two Separate Indications for Corticosteroids

This population requires corticosteroids for two distinct reasons that must not be confused:

1. Adrenal insufficiency replacement: Always required, dose escalated during illness 1, 2
2. COVID-19 anti-inflammatory therapy: Only indicated when oxygen support is needed 3, 4

The European Respiratory Society explicitly states that dexamethasone should not be given to COVID-19 patients without oxygen requirement, as the RECOVERY trial showed potential harm (mortality 17.0% vs 13.2%, RR=1.22) 3. However, patients with adrenal insufficiency must maintain adequate glucocorticoid replacement at all times to avoid adrenal crisis 5, 1.

Prevention Strategies

Patient Preparation

• Ensure patients have sufficient glucocorticoid supplies (at least 2-3 months) 2
• Provide steroid emergency self-injection kit with 100 mg hydrocortisone 2
• Issue steroid emergency card documenting their condition 2
• Reinforce sick day rules education: double dose immediately with any illness 1, 2

Monitoring Requirements

• Daily oxygen saturation monitoring for all COVID-19 positive patients with adrenal insufficiency 3
• Immediate escalation to parenteral therapy if unable to tolerate oral medications 1, 2
• Watch for emergency warning signs: persistent vomiting, severe weakness, confusion, hypotension 1

Common Pitfalls to Avoid

Critical Error #1: Withholding or reducing glucocorticoids in mild COVID-19 due to concerns about immunosuppression. The guidelines emphasize maintaining sufficient doses to avoid adrenal insufficiency or disease aggravation, even in COVID-19 positive patients 5. Adrenal crisis is life-threatening and must be prevented 1, 2.

Critical Error #2: Adding dexamethasone 6 mg for COVID-19 treatment before oxygen is required. This provides no benefit in non-hypoxic patients and may increase mortality 3, 4. Wait until SpO2 falls below 94% on room air before initiating COVID-19-specific corticosteroid therapy 3.

Critical Error #3: Failing to recognize that stress-dose hydrocortisone (200 mg/day) and therapeutic dexamethasone serve different purposes and may both be needed in severe cases 4, 1, 2.

Special Considerations

For Patients on Modified-Release Hydrocortisone or Prednisolone

• Switch to immediate-release hydrocortisone 20 mg every 6 hours during acute illness 2
• This allows more flexible dosing and better stress coverage 2

Risk Assessment

• Patients with adrenal insufficiency face increased infection risk but current evidence does not suggest they develop more severe COVID-19 than the general population 2, 6
• The primary danger is adrenal crisis, not COVID-19 severity itself 1, 2
• Stringent social distancing is recommended due to vulnerability during any infection 2

Pediatric Dosing

• Weight-based hydrocortisone dosing applies: 50-100 mg/m² IV bolus, then 50-100 mg/m²/24h continuous infusion 2