Combination Therapy for Adrenal Insufficiency

Rationale for Combination Therapy

Primary adrenal insufficiency requires replacement of both glucocorticoids and mineralocorticoids, as the adrenal cortex normally produces both hormone types 1
Fludrocortisone is specifically designed to replace the mineralocorticoid component, which is vital for maintaining blood pressure, water and electrolyte homeostasis 1
Under-replacement of mineralocorticoids is common and possibly predisposes patients to recurrent adrenal crises 1

Hydrocortisone: 15-25 mg/day in divided doses (typically three doses at 07:00, 12:00, and 16:00) 1
Common regimens include:
- 10 mg + 5 mg + 2.5 mg 1
- 15 mg + 5 mg + 5 mg 1
- 10 mg + 5 mg + 5 mg 1

Fludrocortisone: 50-200 μg (0.05-0.2 mg) daily, usually taken as a single dose upon awakening 1
Higher doses (up to 500 μg daily) may be needed in children, younger adults, or during pregnancy 1

Mineralocorticoid replacement should be evaluated by measuring blood pressure in supine and standing positions (to detect postural hypotension) 1
Measuring plasma renin activity (aim for upper normal range) 1
Signs of excessive mineralocorticoid replacement include suppressed plasma renin activity 1

Overreplacement with glucocorticoids often occurs as compensation for inadequate mineralocorticoid replacement 1
Drug interactions: Several medications can interact with both hydrocortisone and fludrocortisone, including anti-epileptics, barbiturates, and antituberculosis drugs 1
Medications to avoid with fludrocortisone include diuretics, acetazolamide, carbenoxolone, and NSAIDs 1
Patients should eat sodium salt and salty foods without restriction and avoid potassium-containing salts 1

Adrenal crisis requires immediate high-dose hydrocortisone (100 mg bolus followed by 100-300 mg/day) and fluid replacement; mineralocorticoid replacement should be restarted when hydrocortisone dose falls below 50 mg/day 1
Pregnancy may require higher fludrocortisone doses (up to 500 μg daily) in the third trimester due to progesterone's antimineralocorticoid effects 1
Stress situations require increased glucocorticoid doses but generally not increased fludrocortisone 1