Does hydrocortisone (cortisol) increase total leukocytes (white blood cell count)?

Hydrocortisone Increases Total Leukocyte Count

Yes, hydrocortisone does increase total leukocyte (white blood cell) count. This effect is well-documented and can be clinically significant when interpreting laboratory results in patients receiving corticosteroid therapy.

Mechanism and Magnitude of Effect

• Hydrocortisone causes leukocytosis primarily by increasing the number of circulating neutrophils (polymorphonuclear cells) in the bloodstream 1, 2
• The increase in white blood cell count peaks approximately 48 hours after hydrocortisone administration 1
• The magnitude of increase is dose-dependent:
  • High-dose hydrocortisone can increase WBC count by up to 4.84 × 10^9/L 1
  • Medium-dose hydrocortisone typically increases WBC count by approximately 1.7 × 10^9/L 1
  • Low-dose hydrocortisone causes minimal increases of around 0.3 × 10^9/L 1

Cellular Mechanisms

• Hydrocortisone reduces the expression of neutrophil adhesion molecules, particularly:
  • Mac-1 (CD11b) - decreased by approximately 40-50% 3
  • L-selectin (CD62L) - decreased by approximately 17-30% 3
• This reduced adhesion molecule expression decreases neutrophil margination (adherence to vessel walls) and increases the number of circulating neutrophils 4, 3
• Hydrocortisone also increases the velocity of rolling leukocytes along vessel walls, reducing their ability to extravasate into tissues 4

Differential Effects on White Blood Cell Types

• The leukocytosis from hydrocortisone is predominantly due to increased neutrophils 2
• Other white blood cell changes typically include:
  • Monocytosis (increased monocytes) 2
  • Eosinopenia (decreased eosinophils) 2
  • Variable lymphopenia (decreased lymphocytes) 2

Clinical Implications

• Hydrocortisone-induced leukocytosis can persist for the duration of therapy, though it may decrease somewhat over time even with continued treatment 2
• When interpreting WBC counts in patients on hydrocortisone, clinicians should consider that:
  • Increases up to 4.84 × 10^9/L within 48 hours after high-dose steroids may be due to the medication alone 1
  • Larger increases, especially after low-dose steroids, suggest other causes of leukocytosis such as infection 1
• The FDA drug label for hydrocortisone (IV) specifically lists leukocytosis as a known adverse reaction 5

Important Considerations for Clinical Practice

• Hydrocortisone-induced leukocytosis can complicate the diagnosis of infection, particularly in immunocompromised patients 2
• Key differentiating features between steroid-induced leukocytosis and infection:
  • Steroid-induced leukocytosis rarely shows a significant "left shift" (>6% band forms) 2
  • Toxic granulation in neutrophils is uncommon in steroid-induced leukocytosis but often present in infection 2
• In septic shock management, hydrocortisone at doses of 200 mg/day may be used when fluid resuscitation and vasopressors fail to restore hemodynamic stability 6

Understanding this predictable effect of hydrocortisone on white blood cell count is essential for accurate laboratory interpretation and avoiding unnecessary diagnostic procedures or treatments when evaluating patients on corticosteroid therapy.