Cortef (Hydrocortisone): A Comprehensive Overview
Cortef (hydrocortisone) is a natural glucocorticoid hormone that serves as the primary replacement therapy for adrenal insufficiency, binding to both glucocorticoid and mineralocorticoid receptors with moderate glucocorticoid activity and weak mineralocorticoid effects. 1
Pharmacological Properties
Hydrocortisone is a naturally occurring adrenocortical steroid that is readily absorbed from the gastrointestinal tract. It is available in oral tablet formulations of 5 mg, 10 mg, and 20 mg strengths. 2
The pharmacokinetics of hydrocortisone are characterized by:
- Short half-life (approximately 90 minutes) 3
- Rapid absorption after oral administration
- Requires multiple daily dosing to approximate physiological cortisol patterns
Clinical Applications
1. Adrenal Insufficiency
- Primary Adrenal Insufficiency: Requires both hydrocortisone and fludrocortisone replacement 1
- Secondary Adrenal Insufficiency: Typically requires only hydrocortisone 1
- Standard Dosing: 15-25 mg/day in divided doses (typically higher dose in morning) 1
2. Critical Illness-Related Corticosteroid Insufficiency (CIRCI)
- Used in septic shock at higher doses (200-300 mg/day) 4
- Can be administered as continuous infusion or bolus doses every six hours 4
- Duration typically 7-14 days or until clinical improvement 4
3. Other Indications
- Treatment of hyperthyroid states including thyroid storm 5
- Adjuvant analgesic in neuropathic and cancer-related pain 5
- Severe alcoholic hepatitis with encephalopathy 5
Dosing Considerations
Standard Replacement Therapy
- Weight-related, thrice-daily dosing regimen is recommended to better mimic the natural cortisol circadian rhythm 6
- Highest dose given in the morning to replicate physiological peak 6
Critical Illness
- Higher doses (200-300 mg/day) are typically used 4
- Can be given as infusion or as boluses every six hours 4
- For patients requiring mechanical ventilation, early hydrocortisone may improve outcomes in certain populations 4
Monitoring and Dose Adjustment
Monitoring should focus on:
- Clinical symptoms and energy levels
- Weight changes
- Blood glucose levels
- Blood pressure
- Electrolyte balance 1
There is no established biomarker for cortisol activity, making clinical assessment crucial. 6
Potential Side Effects
With physiological replacement doses:
- Generally well-tolerated when dosed appropriately
With supraphysiological doses (long-term):
- Proximal muscle weakness
- Osteopenia
- Hyperglycemia/unmasking of latent diabetes
- Sodium retention and hypertension
- Psychiatric reactions
- Increased risk of infections 7
Special Considerations
Discontinuation
- Inflammation may recur after discontinuing therapy, especially when stopped abruptly 4
- For courses >14 days, tapering is recommended to prevent adrenal insufficiency 4
- Careful monitoring after discontinuation is essential 4
Pregnancy
- Higher doses may be required, particularly in the third trimester 1
Recent Developments
Extended-release hydrocortisone formulations have been developed to enable once or twice-daily dosing, potentially improving:
- Body weight management
- Blood pressure control
- Glucose levels
- Overall quality of life 3
Conclusion
Hydrocortisone (Cortef) remains the cornerstone of replacement therapy for adrenal insufficiency and plays an important role in managing critical illness-related corticosteroid insufficiency. Understanding its pharmacokinetics and the importance of mimicking the natural cortisol rhythm is essential for optimizing patient outcomes.