Treatment of ACTH-Dependent Relative Adrenal Insufficiency
For ACTH-dependent relative adrenal insufficiency, hydrocortisone replacement therapy at physiologic doses (15-25 mg daily in divided doses) is the recommended treatment, with dose adjustments based on clinical response. 1
Initial Management
- Begin with hydrocortisone 20-30 mg in the morning and 10-20 mg in the afternoon for significant symptoms of adrenal insufficiency 1
- Administer the first dose immediately after waking, and the last dose not less than 6 hours before bedtime to mimic the natural cortisol rhythm 2
- Use the lowest dose compatible with health and a sense of well-being (typically 15-25 mg daily total) 2
- For moderate symptoms, consider starting at 2-3 times maintenance dose and tapering to maintenance over 5-10 days as symptoms improve 1
- For severe symptoms or adrenal crisis, immediate hospitalization with IV hydrocortisone 100 mg bolus followed by 100-300 mg/day as continuous infusion or boluses every 6 hours is required 2
Dose Adjustments and Monitoring
- Titrate the hydrocortisone dose based on symptom response, up to a maximum of 30 mg daily for outpatient management 1
- Monitor for clinical improvement of symptoms including fatigue, nausea, abdominal pain, and hypotension 2
- Assess weight, blood pressure, and serum electrolytes at least annually 2
- If essential hypertension develops while on treatment, reduce the dose but do not stop the medication 2
Special Circumstances
Acute Illness or Stress
- During minor illness: Double the usual oral dose for 24-48 hours, then taper back to normal dose 2
- For severe illness or surgery: Administer 100 mg hydrocortisone IM/IV immediately, followed by 100 mg every 6-8 hours until recovered 2
- For dental procedures: Take an extra morning dose 1 hour prior to the procedure 2
Surgery
- For major surgery: 100 mg hydrocortisone IM just before anesthesia, continue 100 mg IM every 6 hours until able to eat and drink, then double oral dose for 48+ hours before tapering to normal dose 2
- For minor surgery: 100 mg hydrocortisone IM before anesthesia, then double oral dose for 24 hours 2
Patient Education
- All patients need education on stress dosing for sick days and when to seek medical attention for impending adrenal crisis 2
- Provide emergency steroid injectable supplies and training on self-administration 2
- Recommend medical alert bracelet for adrenal insufficiency 2, 1
- Advise patients to take salt and salty foods ad libitum and avoid licorice and grapefruit juice 2
Important Considerations
- Always start corticosteroids first when planning hormone replacement therapy for multiple deficiencies, as other hormones can accelerate cortisol clearance and precipitate adrenal crisis 2
- ACTH stimulation can give false-negative results early in the course of adrenal insufficiency; in cases of clinical uncertainty, opt for replacement and test for ongoing need at 3 months 2
- If prednisone is used instead of hydrocortisone, consider lower doses (average daily dose over two months of 7.5 mg) due to reports of reduced survival on higher doses 2
- For ACTH-dependent adrenal insufficiency, mineralocorticoid replacement (fludrocortisone) is generally not necessary as aldosterone production is maintained 3
Follow-up
- Schedule follow-up in 2-4 weeks to reassess symptoms and adjust medication 1
- Monitor for development of iatrogenic Cushing's syndrome with excessive replacement 1
- Consider testing for recovery of the hypothalamic-pituitary-adrenal axis after 3 months of maintenance therapy, especially if the condition was precipitated by exogenous steroid use 2