Can Fludrocortisone Elevate White Blood Cell Count?
No, fludrocortisone itself does not cause clinically significant leukocytosis because it is a selective mineralocorticoid with minimal glucocorticoid activity—it is the glucocorticoid component of corticosteroids that causes leukocytosis, not the mineralocorticoid effect.
Understanding the Mechanism
The key distinction lies in understanding which corticosteroid properties cause leukocytosis:
Glucocorticoids cause leukocytosis: Medications like prednisone and hydrocortisone elevate white blood cell counts through their glucocorticoid activity, with increases ranging from 2.4 × 10⁹/L at 48 hours on average, and up to 4.84 × 10⁹/L with high-dose therapy 1
The leukocytosis is dose-dependent: Even small doses of glucocorticoids administered over prolonged periods can induce extreme and persistent leukocytosis, with WBC counts exceeding 20,000/mm³ in some cases 2
Chronic glucocorticoid therapy increases baseline WBC: Patients with acute infections on chronic glucocorticoid treatment show WBC counts averaging 14.9 ± 7.4 × 10⁹/L compared to 12.9 ± 6.4 × 10⁹/L in non-treated patients—an average increase of approximately 5 × 10⁹/L 3
Fludrocortisone's Specific Effects
Fludrocortisone is designed as a selective mineralocorticoid replacement:
Primary mechanism: Fludrocortisone causes sodium retention, water expansion, and increases intravascular volume—these are mineralocorticoid effects, not glucocorticoid effects 4
Standard dosing: Typical doses range from 0.05-0.2 mg daily for primary adrenal insufficiency, with higher doses up to 0.5 mg daily in specific populations 4
Monitoring parameters focus on mineralocorticoid effects: Clinical guidelines emphasize monitoring electrolytes (sodium and potassium), blood pressure, and plasma renin activity—not white blood cell counts 4, 5
Clinical Implications for Adrenal Insufficiency Patients
When evaluating leukocytosis in patients with adrenal insufficiency:
Consider the glucocorticoid component: Patients on hydrocortisone (15-25 mg/day) or other glucocorticoid replacement are more likely to have elevated WBC counts from the glucocorticoid, not the fludrocortisone 6
Hydrocortisone has mineralocorticoid activity: Most glucocorticoids possess some mineralocorticoid activity, which is why fludrocortisone dosing should be considered in combination with glucocorticoid therapy 7
Infection versus steroid effect: In patients on glucocorticoid therapy, a shift to the left (>6% band forms) and toxic granulation suggest infection rather than corticosteroid-induced leukocytosis, where these findings are rare 2
Common Pitfall to Avoid
Do not attribute leukocytosis to fludrocortisone when patients are on combination therapy with hydrocortisone or other glucocorticoids—the glucocorticoid component is responsible for any WBC elevation 6, 3. If a patient on fludrocortisone alone (without glucocorticoid replacement) develops leukocytosis, investigate other causes such as infection or inflammatory processes.