What is the recommended mineralocorticoid replacement regimen for primary adrenal insufficiency?

Mineralocorticoid Replacement Dosing for Primary Adrenal Insufficiency

Most patients with primary adrenal insufficiency should take 50–200 µg of fludrocortisone as a single daily dose, with the typical starting dose being 100 µg (0.1 mg) daily. 1

Standard Dosing Regimen

• The physiological replacement range is 50–200 µg (0.05–0.2 mg) of fludrocortisone taken once daily upon awakening. 1

• The FDA-approved standard dosing is 0.1 mg (100 µg) daily, with a range extending from 0.1 mg three times weekly to 0.2 mg daily in some cases. 2

• Fludrocortisone must be administered daily as a single morning dose—never on alternate days—because mineralocorticoids are vital for maintaining blood pressure and electrolyte homeostasis, and the medication's pharmacokinetics do not support alternate-day dosing. 3

Age-Related Dosing Considerations

• Children and younger adults often require higher doses within or even exceeding the upper range (up to 500 µg daily in some cases) due to physiological mineralocorticoid resistance in infancy. 1, 3

• Older adults may require lower doses within the 50–100 µg range. 1

Monitoring Parameters to Guide Dosing

The dose should be titrated based on clinical and biochemical parameters:

• Blood pressure assessment in both supine and standing positions: Orthostatic hypotension suggests under-replacement, while sustained hypertension suggests over-replacement. 1, 3

• Clinical symptoms: Salt cravings and lightheadedness indicate under-replacement; peripheral edema indicates over-replacement. 1

• Serum electrolytes: Low sodium or high potassium warrant dose increases. 3, 4

• Plasma renin activity (PRA): The goal is to maintain PRA in the upper normal range, as this indicates adequate mineralocorticoid replacement. 4, 5 Recent evidence shows a dose-dependent relationship between fludrocortisone and renin levels (r = -0.131), with higher doses associated with lower renin. 6

Common Pitfalls and Critical Management Points

• Under-replacement is common and dangerous: It is often compensated for by over-replacement of glucocorticoids and predisposes patients to recurrent adrenal crises. 1, 5

• Never stop fludrocortisone completely when hypertension develops: Instead, reduce the dose, but continue mineralocorticoid replacement. If blood pressure remains elevated, add a vasodilator rather than discontinuing fludrocortisone. 1, 3

• Avoid medications that interact with fludrocortisone: Diuretics, acetazolamide, NSAIDs, carbenoxolone, and liquorice should be avoided as they can unpredictably alter mineralocorticoid effects. 1, 3

• Grapefruit juice and liquorice potentiate the mineralocorticoid effect of hydrocortisone and should be avoided. 1

Special Circumstances Requiring Dose Adjustment

Pregnancy

• Fludrocortisone dose often needs to be increased during late pregnancy due to the anti-mineralocorticoid effects of progesterone. 1, 4

• PRA is not a reliable parameter for dose adjustment during pregnancy as it normally increases; instead, monitor salt cravings, blood pressure, and serum electrolytes. 1

Long-Term Follow-Up

• An overall reduction in fludrocortisone dose may be observed in patients with longer follow-up (>60 months), suggesting that initial doses can sometimes be reduced over time. 6

Dietary Recommendations

• Patients should be advised to consume salt and salty foods ad libitum to support the mineralocorticoid regimen. 1, 3

• Avoid potassium-containing salt substitutes. 3