Treatment of Adrenal Insufficiency Due to Adrenal Histoplasmosis
Liposomal amphotericin B (3.0-5.0 mg/kg daily intravenously for 1-2 weeks) followed by itraconazole (200 mg three times daily for 3 days and then 200 mg twice daily for at least 12 months) is the recommended treatment for adrenal insufficiency due to adrenal histoplasmosis. 1
Initial Treatment Phase
Antifungal Therapy
First-line therapy:
Transition to oral therapy:
- Itraconazole 200 mg three times daily for 3 days, then 200 mg twice daily 1
- Duration: At least 12 months, with some experts preferring 18-24 months due to risk of relapse 1
- Blood levels of itraconazole should be obtained after at least 2 weeks of therapy to ensure adequate drug exposure (target >1 μg/mL) 1
Glucocorticoid Replacement
- Initiate hydrocortisone 15-25 mg daily in divided doses for maintenance therapy 2
- For primary adrenal insufficiency, add fludrocortisone 0.05-0.1 mg daily for mineralocorticoid replacement 2
Monitoring and Follow-up
Antifungal Therapy Monitoring
- Monitor for drug toxicity (liver function tests, renal function)
- Check itraconazole blood levels after 2 weeks of therapy 1
- Follow adrenal morphology with imaging studies periodically
- Consider repeat adrenal biopsy if clinical response is inadequate or relapse is suspected 3
Adrenal Function Monitoring
- Regular assessment of overall well-being, weight, blood pressure, and serum electrolytes 2
- Morning cortisol levels and ACTH stimulation tests to assess adrenal recovery
- Annual screening for other autoimmune disorders 2
Special Considerations
Duration of Treatment
- Evidence suggests that histoplasmosis can persist in adrenal tissue despite seemingly adequate treatment
- A case report documented persistence of histoplasma in adrenal biopsy 7 years after initial 9-month treatment with itraconazole 3
- This supports the recommendation for prolonged therapy (at least 12 months) with regular monitoring 1
Stress-Dose Steroid Management
- Patients require stress-dose steroids during periods of illness or stress:
- Minor illness/stress: Double or triple usual daily dose
- Moderate stress: Hydrocortisone 50-75 mg/day in divided doses
- Severe stress: Hydrocortisone 100 mg IV immediately, followed by 100-300 mg/day as continuous infusion or divided doses every 6 hours 2
Patient Education
- All patients need education on stress dosing
- Provide medical alert bracelet for adrenal insufficiency 2
- Instruct on self-administration of injectable hydrocortisone for emergency situations
Treatment Alternatives
Second-Line Options
- If itraconazole is not tolerated or ineffective:
Treatment Failure
- If treatment fails after at least 12 weeks of itraconazole therapy:
- Return to amphotericin B therapy
- If using amphotericin B exclusively, a total course of at least 35 mg/kg is recommended 1
Prognosis
- Mortality without treatment is approximately 80% but can be reduced to 25% with appropriate antifungal therapy 1
- Long-term adrenal insufficiency is common even after successful treatment of the infection
- Patients may require lifelong glucocorticoid replacement therapy
Pitfalls to Avoid
- Inadequate duration of antifungal therapy (should be at least 12 months)
- Failure to monitor itraconazole blood levels
- Inadequate glucocorticoid replacement, especially during stress
- Relying solely on serum cortisol levels without considering timing of last hydrocortisone dose 2
- Failure to provide patient education on stress dosing and emergency management
The evidence strongly supports prolonged antifungal therapy for adrenal histoplasmosis, with careful monitoring of both the infection and adrenal function throughout treatment and follow-up.