Does Fludrocortisone (Florinef) Cause Leukocytosis?
Fludrocortisone does NOT typically cause clinically significant leukocytosis, unlike glucocorticoids which reliably increase white blood cell counts. Fludrocortisone is a synthetic mineralocorticoid with minimal glucocorticoid activity, and the mechanism of steroid-induced leukocytosis is specifically mediated through glucocorticoid receptor activation, not mineralocorticoid effects 1, 2, 3.
Mechanism and Evidence
Why Glucocorticoids Cause Leukocytosis (But Fludrocortisone Does Not)
Glucocorticoids cause leukocytosis through demargination of neutrophils from the vascular endothelium and delayed apoptosis of circulating neutrophils, effects mediated specifically through glucocorticoid receptors 1, 2.
The magnitude of leukocytosis is dose-dependent with glucocorticoids: high-dose glucocorticoids can increase WBC counts by up to 4.84 × 10⁹/L within 48 hours, medium doses by 1.7 × 10⁹/L, and low doses by only 0.3 × 10⁹/L 3.
Chronic glucocorticoid therapy increases WBC counts by an average of 5 × 10⁹/L in patients with acute infections 2.
Fludrocortisone's Distinct Pharmacology
Fludrocortisone is a 9-alpha-fluorinated derivative of hydrocortisone with potent mineralocorticoid activity but minimal glucocorticoid effects at standard therapeutic doses 4, 5.
The primary mechanism of action involves sodium retention and potassium excretion through renal tubular effects, not the immunomodulatory effects that cause leukocytosis 6, 4.
Standard therapeutic doses range from 0.05-0.2 mg daily for orthostatic hypotension and adrenal insufficiency, which is far below the glucocorticoid-equivalent doses that would cause leukocytosis 6, 7.
Expected Adverse Effects of Fludrocortisone
What Actually Occurs with Fludrocortisone
Hypokalemia is the predominant and most common adverse effect, requiring potassium supplementation in many patients 6, 8.
Hypernatremia, fluid retention, and hypertension can occur due to mineralocorticoid excess 4.
Hyperglycemia and congestive heart failure are possible with chronic use, though less common than electrolyte disturbances 4.
Monitoring Parameters
Regular monitoring of serum sodium and potassium levels is essential, particularly when combined with renin-angiotensin system blockers 6.
Blood pressure monitoring at each visit is recommended, as excessive mineralocorticoid activity causes hypertension 7.
WBC count monitoring is NOT a standard parameter for fludrocortisone therapy, unlike with glucocorticoid treatment 6, 7, 8.
Clinical Implications
When Leukocytosis Occurs in Patients on Fludrocortisone
If leukocytosis develops in a patient taking fludrocortisone, investigate alternative causes such as infection, inflammatory conditions, or concurrent medications rather than attributing it to the fludrocortisone 1, 2.
Consider whether the patient is also receiving glucocorticoids (hydrocortisone, prednisone, etc.), as patients with adrenal insufficiency often require both mineralocorticoid and glucocorticoid replacement 7.
In patients with congenital adrenal hyperplasia or Addison's disease, any leukocytosis is more likely due to concurrent hydrocortisone therapy than fludrocortisone 7, 5.
Key Distinction from Glucocorticoids
The hematologic effects of glucocorticoids (leukocytosis, neutrophilia, lymphopenia) are well-established, but these are NOT characteristic of pure mineralocorticoid therapy 1, 2.
Fludrocortisone's adverse effect profile is more limited compared to glucocorticoids, with hypokalemia being the predominant concern rather than immunologic or hematologic effects 8.