Treatment of Low Cortisol Levels (Hypocortisolism)
Hydrocortisone replacement therapy is the primary treatment for hypocortisolism, typically administered in divided doses of 15-25 mg daily to mimic the natural cortisol rhythm, with the highest dose given in the morning. 1, 2
Diagnostic Approach
Before initiating treatment, proper diagnosis is essential:
- Morning cortisol and ACTH levels should be measured between 7-9 AM
- ACTH stimulation test for indeterminate results
- Primary adrenal insufficiency: low cortisol (<250 nmol/L) with high ACTH
- Secondary adrenal insufficiency: low cortisol with low ACTH 2
Treatment Algorithm
1. Initial Replacement Therapy
- First-line medication: Hydrocortisone (HC)
- Alternative: Cortisone acetate (CA) - requires activation to HC by liver enzymes
- Daily dose: 15-25 mg total daily dose 1
- Dosing schedule:
- Three-dose regimen: 10 mg on awakening (7:00 AM), 5 mg at noon, 2.5 mg late afternoon (4:00 PM)
- Two-dose regimen: 15 mg on awakening, 5 mg at noon 1
2. Mineralocorticoid Replacement
- Required for primary adrenal insufficiency
- Fludrocortisone 0.1 mg daily 1, 3
- Monitor blood pressure and serum electrolytes
3. Dose Adjustment
- Clinical assessment is the primary method for monitoring adequacy of replacement
- Underdosing signs: fatigue, nausea, poor appetite, weight loss, increased pigmentation
- Overdosing signs: weight gain, insomnia, peripheral edema 1
4. Special Situations
Acute Illness/Stress
- Double or triple the usual dose during minor illness
- For severe illness: IV hydrocortisone 100 mg and IV normal saline 1, 2
Night Shift Workers
- Adjust timing: 10 mg upon awakening before work instead of 7:00 AM 1
Morning Nausea
- Take first dose earlier and go back to sleep 1
Monitoring and Follow-up
- Regular assessment of symptoms
- Blood pressure and electrolyte monitoring
- No need for routine plasma ACTH or serum cortisol monitoring 1, 2
Medication Interactions
Be aware of medications that affect hydrocortisone metabolism:
- Anti-epileptics/barbiturates: May increase hydrocortisone requirements
- Antifungals: May require dose adjustment
- Antituberculosis drugs: May increase hydrocortisone requirements 1
Important Precautions
- Provide medical alert bracelet for adrenal insufficiency 2
- Patient education on stress dosing
- Never abruptly discontinue therapy - taper gradually to avoid adrenal crisis 4
- Always start corticosteroids before thyroid hormone replacement in patients with multiple hormone deficiencies 2
- Secondary adrenal insufficiency may persist for months after discontinuation of exogenous steroids 4
Emerging Evidence
Recent research suggests that thrice-daily dosing may better replicate the natural cortisol rhythm and improve patient well-being compared to twice-daily regimens 5. Studies have shown that twice-daily regimens result in very low cortisol levels by mid-afternoon, which can be eliminated by using a three-dose schedule 5.
Patients on the conventional immediate-release tablets experience high peaks and low troughs due to the short half-life of hydrocortisone (approximately 1.5 hours), which does not optimally mimic the natural circadian rhythm 6.