What is the diagnosis and management for a patient with elevated ferritin levels, slightly elevated white blood cell count, hemoglobin, and hematocrit, and normal iron, iron saturation, and total iron-binding capacity (TIBC), with a complete blood count showing hyperferritinemia, leukocytosis, and erythrocytosis?

Diagnostic Interpretation: Elevated Ferritin with Normal Iron Studies and Mild Leukocytosis

This patient has secondary hyperferritinemia (689 ng/mL) with normal transferrin saturation (21%), which essentially rules out primary iron overload and indicates an inflammatory, metabolic, or cellular damage process rather than hereditary hemochromatosis. 1, 2

Key Laboratory Findings Analysis

Your patient presents with:

• Ferritin 689 ng/mL (elevated but <1000 ng/mL threshold)
• Transferrin saturation 21% (normal, <45%)
• Normal iron parameters (iron 63 µg/dL, TIBC 294 µg/dL)
• Mild leukocytosis (WBC 11.0 with neutrophilia 7.8)
• Mild erythrocytosis (hemoglobin 16.1, hematocrit 48.5)

Primary Diagnostic Conclusion

The normal transferrin saturation (<45%) definitively excludes hereditary hemochromatosis and primary iron overload disorders. 1, 2 The American Association for the Study of Liver Diseases states that transferrin saturation ≥45% is required to suspect iron overload and proceed with HFE genetic testing. 1 Since your patient's TS is 21%, iron overload is not the diagnosis. 2

Most Likely Differential Diagnoses

Based on the pattern of elevated ferritin with normal TS, the following conditions account for >90% of cases: 2

1. Inflammatory/Infectious Process (Most Likely)

• The mild leukocytosis (11.0) with absolute neutrophilia (7.8) suggests active inflammation or occult infection 2
• Ferritin rises acutely as an acute-phase reactant during inflammation, independent of iron stores 2, 3
• Action required: Check inflammatory markers (CRP, ESR) to detect occult inflammation 2

2. Metabolic Syndrome/NAFLD

• Ferritin elevation reflects hepatocellular injury and insulin resistance rather than iron overload in metabolic syndrome 2
• Action required: Assess for metabolic syndrome components (BMI, waist circumference, blood pressure, fasting glucose, lipid panel) and evaluate liver enzymes (ALT, AST) 2

3. Chronic Alcohol Consumption

• Alcohol increases iron absorption and causes hepatocellular injury 2
• Action required: Obtain detailed alcohol consumption history 2

4. Cellular Damage/Necrosis

• Ferritin is released from necrotic or lysed cells 2
• Action required: Check creatine kinase (CK) to evaluate for muscle necrosis 2

5. Occult Malignancy

• Malignancy was the most frequent cause (153/627 cases) in patients with ferritin >1000 µg/L in one large series 4
• Action required: Age-appropriate cancer screening based on clinical context 4

Risk Stratification

Your patient's ferritin of 689 ng/mL is below the critical 1000 µg/L threshold. 1, 2 The American Association for the Study of Liver Diseases states that ferritin <1000 µg/L has a 94% negative predictive value for advanced liver fibrosis and indicates low risk of organ damage. 1, 2 This level does not indicate risk of iron-related organ damage (threshold >1000 ng/mL for liver damage risk, >7500 ng/mL for documented organ damage). 2

Recommended Diagnostic Workup

Immediate next steps:

1. Inflammatory markers: CRP, ESR to detect occult inflammation 2
2. Comprehensive metabolic panel: ALT, AST to assess hepatocellular injury 2
3. Metabolic assessment: Fasting glucose, lipid panel, assess for metabolic syndrome 2
4. Detailed history: Alcohol consumption, medications, recent infections, constitutional symptoms 2
5. Physical examination: Hepatomegaly, signs of chronic liver disease, lymphadenopathy 1

Do NOT order:

• HFE genetic testing (only indicated if TS ≥45%) 1, 2
• Liver biopsy (only indicated if ferritin >1000 µg/L with abnormal liver tests) 1, 2

Management Approach

Treat the underlying condition, not the elevated ferritin. 2 The American College of Gastroenterology recommends treating the underlying condition rather than the elevated ferritin in patients with secondary hyperferritinemia. 2

• If metabolic syndrome/NAFLD: Weight loss and metabolic syndrome management 2
• If inflammatory condition: Disease-specific anti-inflammatory therapy 2
• If infection: Appropriate antimicrobial therapy 2
• Avoid iron supplementation in patients with elevated ferritin 5

Critical Pitfalls to Avoid

• Never use ferritin alone without transferrin saturation to diagnose iron overload 2 - ferritin is an acute-phase reactant elevated in inflammation, liver disease, malignancy, and tissue necrosis independent of iron stores 2
• Do not assume iron overload when TS <45% 2 - in the general population, iron overload is NOT the most common cause of elevated ferritin 2
• Do not order HFE genetic testing when TS is normal (<45%) 1, 2

Follow-Up Monitoring

Monitor based on the underlying condition identified. 5 If no clear cause is found after initial workup, recheck ferritin in 3-6 months along with inflammatory markers and liver enzymes to assess for trend. 2