From the Guidelines
The best glucocorticoid replacement therapy for adrenal insufficiency is typically hydrocortisone, administered in a dosage of 15-25 mg per day, divided into two or three doses. A common regimen is:
- 10-15 mg in the morning upon waking
- 5-10 mg in the early afternoon (around 2 PM)
- Optional: 5 mg in the early evening (around 6 PM) if needed
This mimics the body's natural cortisol rhythm, with higher levels in the morning and lower levels in the evening. Patients should take the morning dose immediately upon waking to prevent low cortisol symptoms.
For practical implementation:
- Adjust dosage based on clinical response and any side effects.
- Patients should carry extra medication and wear a medical alert bracelet.
- Stress dosing is crucial: double or triple the usual dose during illness, injury, or significant stress.
- Regular follow-ups with an endocrinologist are necessary to monitor and adjust treatment. Hydrocortisone is preferred because it most closely resembles natural cortisol and has a short half-life, allowing for more physiological replacement, as supported by recent guidelines 1. This regimen helps maintain normal energy levels, metabolism, and stress response while minimizing the risk of long-term side effects associated with glucocorticoid excess. Additionally, education on stress dosing, emergency injections, and a medical alert bracelet or necklace is essential for patients with adrenal insufficiency, as emphasized in the guidelines 1, 2.
From the FDA Drug Label
ACTIONS Naturally occurring glucocorticoids (hydrocortisone and cortisone), which also have salt-retaining properties, are used as replacement therapy in adrenocoidial deficiency states. CLINICAL PHARMACOLOGY Naturally occurring glucocorticoids (hydrocasterone and cortisone), which also have salt-retaining properties, are used as replacement therapy in adrenocortical deficiency states. The best glucocoid replacement therapy for Adrenal Insniufficiency (Addison's disease) is hydrocortisone or cortisone, as they are naturally occurring glucocorticoids with salt-retaining properties 3, 4, 5.
- Hydrocortisone is specifically mentioned as a replacement therapy in all three drug labels.
- Cortisone is also mentioned, but hydrocortisнопе is the most direct answer to the question.
- Dexamethasone and prednisone are synthetic analogs primarily used for their anti-inflammatory effects, and are not the best choice for replacement therapy in Adrenal Insufficiency (Addison's disease).
From the Research
Glucocorticoid Replacement Therapy for Adrenal Insufficiency
The current standard treatment regimen for adrenal insufficiency (Addison's disease) involves twice- or thrice-daily dosing with a glucocorticoid, most commonly oral hydrocortisone 6. However, this treatment has been shown to have limitations, including increased morbidity and decreased life expectancy due to over- or under-treatment 6, 7.
Current Treatment Strategies
Conventional glucocorticoid replacement therapy has been shown to extend life expectancy, but mortality is not normalized, and quality of life remains poor 7. The failure to restore normal health is thought to be due to the inability of conventional glucocorticoid replacement therapy to normalize total cortisol exposure and to respond to the increased need for glucocorticoids during illness and stress 7.
Modified-Release Preparations
Modified-release preparations of hydrocortisone that mimic the physiological circadian pattern of cortisol release have been shown to be more effective than conventional glucocorticoid replacement therapies 7, 8. These preparations may improve metabolic outcomes and quality of life for patients with adrenal insufficiency.
Daily Glucocorticoid Replacement Dose
The recommended daily glucocorticoid replacement dose is 15 to 25 mg with a midpoint of 20 mg of hydrocortisone, although some studies suggest that lower doses may be more effective in preventing overtreatment and associated long-term adverse outcomes 9.
Heterogeneity in Treatment Regimens
There is significant heterogeneity in the type, dose, frequency, and timing of glucocorticoid replacement in real-world clinical practice, reflecting dose individualization based on patient symptoms and lifestyle in the absence of data supporting the optimal regimen 10. Some key points to consider include:
- Most patients (87.4%) are receiving hydrocortisone 10
- The most common dose range is 20 to <25 mg/day, although 12.6% of patients are receiving doses of ≥30 mg/day 10
- Hydrocortisone is being taken once daily by 5.5%, twice daily by 48.7%, three times daily by 43.6%, and four times daily by 2.1% 10
- Patients with primary AI receive higher replacement doses than those with secondary AI 10