What dose of fludrocortisone should be given to an adult with primary adrenal insufficiency, how should it be titrated and monitored, what are its contraindications, and what alternatives exist if it is not tolerated?

Fludrocortisone Management in Primary Adrenal Insufficiency

Initial Dosing

Start fludrocortisone at 100 μg (0.1 mg) once daily in the morning, with a typical range of 50-200 μg daily for most adults with primary adrenal insufficiency. 1, 2

• The medication must be taken as a single morning dose every day—never attempt alternate-day dosing, as this creates dangerous gaps in mineralocorticoid coverage and increases adrenal crisis risk 1
• Children and younger adults often require substantially higher doses (up to 500 μg daily) due to physiological mineralocorticoid resistance in infancy 1, 2

Titration Strategy

Adjust the dose based on three key parameters: blood pressure (both supine and standing), serum electrolytes (sodium and potassium), and clinical symptoms (salt cravings, lightheadedness, or edema). 1, 2

Increase the dose when:

• Orthostatic hypotension persists despite adequate sodium intake 2
• Serum sodium is low or potassium is high 2
• Patient reports persistent salt cravings or lightheadedness 1, 2

Decrease the dose when:

• Hypertension develops (reduce dose but never stop completely—stopping mineralocorticoid replacement can trigger adrenal crisis) 3, 1, 2
• Peripheral edema appears 1, 2
• Patient develops signs of fluid overload 2

Monitoring Protocol

Assess patients at least annually with measurement of weight, blood pressure (supine and standing), and serum electrolytes. 2

• Target plasma renin activity in the upper normal range (though this is less reliable during pregnancy) 3, 2
• Monitor for clinical symptoms at each visit: salt cravings indicate under-replacement, while peripheral edema suggests over-replacement 1, 2
• Under-replacement is common and sometimes compensated for by over-replacement of glucocorticoids, which predisposes patients to recurrent adrenal crises 3, 1, 2

Special Situations Requiring Dose Adjustment

Pregnancy:

• Increase fludrocortisone dose during late pregnancy due to progesterone's anti-mineralocorticoid effects 3, 2, 4
• Monitor using salt cravings, blood pressure, and serum electrolytes rather than plasma renin activity (which normally increases during pregnancy) 3

Drug Interactions:

• Drospirenone-containing contraceptives may require higher fludrocortisone doses 3, 2
• Phenytoin dramatically increases fludrocortisone metabolism—doses may need to increase from 50 μg to as high as 2000 μg daily 5
• Diuretics and drugs affecting blood pressure/electrolytes require dose adjustments 3, 2

Contraindications and Precautions

Avoid these substances as they interact with fludrocortisone:

• Liquorice and grapefruit juice (potentiate mineralocorticoid effect) 3, 2, 4
• Diuretics, acetazolamide, carbenoxolone, and NSAIDs 2, 4
• Potassium-containing salt substitutes (often marketed as "healthy") 2, 4

Critical pitfall: If essential hypertension develops, add a vasodilator rather than stopping mineralocorticoid replacement—only reduce the fludrocortisone dose 3, 1, 2

Alternatives if Not Tolerated

There are no true alternatives to fludrocortisone for mineralocorticoid replacement in primary adrenal insufficiency. However, management strategies include:

• Increase dietary salt intake liberally (patients should consume salt and salty foods without restriction) 1, 2, 4
• Consider that some glucocorticoids possess mineralocorticoid activity—immediate-release hydrocortisone may provide more mineralocorticoid effect than modified-release formulations due to different pharmacokinetic profiles 6
• Recent data suggest fludrocortisone prescription appears independent of glucocorticoid replacement therapy, with no clear association between hydrocortisone-equivalent doses and fludrocortisone requirements 6

Critical Safety Points

Abrupt discontinuation of fludrocortisone triggers adrenal crisis characterized by hypotension, hyponatremia, hyperkalemia, and potentially life-threatening cardiovascular collapse. 2

• If discontinuation is necessary, taper over at least 1-3 days under medical supervision 2
• Educate all patients about the life-threatening risks of missing doses or abrupt discontinuation 2
• Even mild gastrointestinal upset can precipitate crisis as patients cannot absorb medication when they need it most 3