What is the recommended treatment regimen for Addison's disease using fludrocortisone (mineralocorticoid)?

Fludrocortisone Treatment for Addison's Disease

Most patients with Addison's disease require fludrocortisone 50-200 μg (0.05-0.2 mg) once daily as mineralocorticoid replacement, with the dose titrated based on blood pressure, serum electrolytes, and salt cravings rather than plasma renin activity. 1, 2

Standard Dosing Regimen

• Start with fludrocortisone 0.1 mg (100 μg) once daily as the typical initial dose, though the FDA-approved range is 0.1 mg three times weekly to 0.2 mg daily 3
• The dose range of 50-200 μg daily covers most patients, with children and younger adults often requiring higher doses within this range 1, 2
• Administer as a single daily dose, as the long half-life of fludrocortisone does not require divided dosing 2

Dose Titration and Monitoring

Monitor adequacy of replacement using blood pressure, serum sodium and potassium levels, and assessment of salt cravings—not plasma renin activity. 1, 2

• Check blood pressure at each visit; postural hypotension indicates insufficient mineralocorticoid replacement or inadequate salt intake 1
• Measure serum electrolytes (sodium and potassium) at least annually to detect hyponatremia or hyperkalemia 2, 4
• Ask specifically about salt cravings, as persistent cravings suggest under-replacement 1

Common Pitfall: Under-Replacement

Historical evidence shows that doses of 0.05-0.1 mg are often insufficient. A landmark study found that patients receiving these conventional doses remained sodium and water depleted with elevated plasma renin activity despite "adequate" treatment, and most required 0.2 mg to maintain proper sodium balance 5. This under-replacement is common and sometimes compensated for by over-replacement of glucocorticoids, potentially predisposing patients to adrenal crises 1.

Dose Adjustments in Special Situations

Hypertension

• If essential hypertension develops, reduce the fludrocortisone dose but never discontinue it completely 1, 2
• Add a vasodilator antihypertensive agent rather than stopping mineralocorticoid replacement 1

Pregnancy

• Increase fludrocortisone dose during late pregnancy as serum progesterone has anti-mineralocorticoid effects 1
• Plasma renin activity is not useful for dose adjustment during pregnancy as it normally increases; rely instead on blood pressure, serum electrolytes, and salt cravings 1

Drug Interactions

• Diuretics and medications affecting blood pressure or electrolytes may require fludrocortisone dose adjustments 1
• Patients must avoid licorice and grapefruit juice, as both potentiate the mineralocorticoid effect of hydrocortisone and can cause excessive mineralocorticoid activity 1, 2

Integration with Glucocorticoid Therapy

• Fludrocortisone is always administered in conjunction with glucocorticoid replacement (hydrocortisone 15-25 mg daily or cortisone acetate 18.75-31.25 mg daily in divided doses) 1, 2, 3
• During acute adrenal crisis or high-dose glucocorticoid therapy, restart fludrocortisone only when the hydrocortisone dose falls below 50 mg daily, as high doses of hydrocortisone provide sufficient mineralocorticoid activity by saturating the 11β-HSD type 2 enzyme 1

Patient Education

• Advise patients to consume salt and salty foods ad libitum (freely according to taste) 1, 2
• During intense physical activity or hot conditions, increase both fluid and salt intake to replace sweat losses 1
• All patients should wear medical alert identification and carry an emergency steroid card 2