What is the recommended dosing regimen for fludrocortisone in adults and children with primary adrenal insufficiency, including starting doses and titration guidelines?

Fludrocortisone Dosing in Primary Adrenal Insufficiency

For adults with primary adrenal insufficiency, start fludrocortisone at 0.1 mg once daily (range 0.05-0.2 mg), and for children, start at 100 mcg (0.1 mg) once daily—a dose that typically remains constant throughout life and does not require adjustment for body surface area. 1, 2

Adult Dosing

• Starting dose: 0.1 mg once daily, taken upon awakening 2
• Dose range: 0.05-0.2 mg daily, with some patients requiring up to 0.3 mg 3, 4
• Frequency: Single daily dose (no need to divide) 3
• Titration approach:
  • If transient hypertension develops, reduce to 0.05 mg daily 2
  • Adjust based on clinical parameters and plasma renin activity (target upper normal range) 1, 5

Pediatric Dosing

• Standard dose: 100 mcg (0.1 mg) once daily 1
• Key principle: The mineralocorticoid dose does NOT require adjustment by body surface area and often remains the same throughout life 1
• Special consideration for infants: Infants, especially in the first 6 months of life, require additional sodium chloride supplementation of 1-2 g/day (17-34 mmol/day) divided in several feedings due to mineralocorticoid resistance in the immature kidney 1
• Higher doses: Children and younger adults may occasionally require higher doses (up to 200 mcg daily or even 500 mcg in the last trimester of pregnancy when progesterone counteracts mineralocorticoids) 3

Monitoring Parameters for Titration

Clinical assessment:

• Salt craving or lightheadedness (suggests inadequate replacement) 1, 3
• Blood pressure in supine and standing positions 1, 3
• Peripheral edema (suggests excessive replacement) 3
• Poor weight gain, dehydration (suggests inadequate replacement) 1

Laboratory monitoring:

• Plasma renin activity or concentration—target upper normal range 1, 5
• Serum sodium and potassium (hyponatremia with hyperkalemia suggests inadequate replacement) 1
• Elevated plasma renin indicates inadequate replacement 1
• Suppressed plasma renin indicates excessive replacement 1

Blood pressure monitoring:

• Hypertension indicates excessive replacement—reduce dose but do not stop 3
• Hypotension suggests inadequate replacement 5
• In infants, monitor blood pressure especially closely during the first year of life as mineralocorticoid sensitivity increases 1

Special Situations Requiring Dose Adjustment

• Pregnancy: May need increased doses, particularly in the last trimester (up to 500 mcg daily) due to progesterone's anti-mineralocorticoid effects 3, 5
• High ambient temperature: May require dose adjustments to avoid sodium depletion 5
• Essential hypertension: Reduce fludrocortisone dose but do not discontinue; monitor for hyperkalemia 3

Critical Pitfalls to Avoid

1. Do not adjust fludrocortisone dose based on body surface area in children—this is a common error. The dose remains relatively constant throughout childhood 1

2. Do not forget sodium supplementation in infants—failure to provide 1-2 g/day of sodium chloride in the first year of life will result in inadequate mineralocorticoid replacement despite appropriate fludrocortisone dosing 1

3. Do not stop fludrocortisone if hypertension develops—reduce the dose instead, as complete cessation can precipitate adrenal crisis 3

4. Do not rely solely on electrolytes for monitoring—plasma renin activity is the most sensitive marker for adequacy of mineralocorticoid replacement 1, 5

5. Advise patients to take salt and salty foods ad libitum—unrestricted sodium intake is an essential third component of therapy alongside glucocorticoid and mineralocorticoid replacement 3