Management of Disabling Fatigue: Hydrocortisone and Phlebotomy Considerations
For a patient with disabling fatigue and no current medications, oral hydrocortisone therapy may be beneficial, but phlebotomy is not indicated without evidence of iron overload or polycythemia.
Assessment of Adrenal Function
Before initiating hydrocortisone therapy, it's essential to determine if the patient has adrenal insufficiency:
- Evaluate for symptoms of adrenal insufficiency: fatigue, weakness, weight loss, hypotension, hyponatremia, hyperkalemia
- Consider morning cortisol level testing and possibly ACTH stimulation test
- Rule out other causes of fatigue (anemia, thyroid dysfunction, sleep disorders, depression)
Hydrocortisone Therapy Approach
For Suspected Adrenal Insufficiency:
- Start with oral hydrocortisone 20-30 mg daily in divided doses (higher morning dose, lower afternoon dose) 1
- Typical regimen: 15-20 mg in morning, 5-10 mg in afternoon
- Weight-based dosing may be more appropriate: approximately 10-12 mg/m² body surface area per day 2
For Chronic Fatigue Without Adrenal Insufficiency:
- Low-dose hydrocortisone (5-10 mg daily) has shown some benefit in randomized controlled trials 3
- In one study, fatigue scores improved significantly with hydrocortisone compared to placebo (7.2 vs 3.3 point reduction, p=0.009) 3
- 28% of patients reached normal fatigue scores with hydrocortisone compared to 9% with placebo 3
Monitoring and Adjustment
- Assess clinical response after 4 weeks
- Monitor for signs of cortisol excess: weight gain, fluid retention, hypertension, hyperglycemia
- Avoid long-term use without clear evidence of adrenal insufficiency due to risk of adrenal suppression 4
- Higher doses (13 mg/m² morning, 3 mg/m² afternoon) have shown improvement but caused adrenal suppression in 40% of patients 4
Phlebotomy Considerations
Phlebotomy is not recommended for the management of fatigue unless there is evidence of:
- Hemochromatosis or iron overload
- Polycythemia vera or secondary polycythemia
- Porphyria cutanea tarda
Important Caveats
- Hydrocortisone should not be used in patients with sepsis in the absence of shock 5, 6
- Patients on hydrocortisone therapy need education about stress dosing during illness or procedures 5
- If initiating treatment, start with a time-limited trial (4-8 weeks) to assess response
- Long-term corticosteroid use carries risks including osteoporosis, weight gain, and increased infection risk
Follow-up Recommendations
- Reassess symptoms after 4 weeks of therapy
- If beneficial, continue for another 4-8 weeks while monitoring for side effects
- If no improvement after 4-8 weeks, taper and discontinue hydrocortisone
- Consider alternative diagnoses and treatments if no response to hydrocortisone
For patients with disabling fatigue, a trial of low-dose hydrocortisone may be reasonable when other causes have been ruled out, but phlebotomy should only be considered if specific hematologic disorders are identified.