What does a Total Iron Binding Capacity (TIBC) of 258, Unsaturated Iron Binding Capacity (UIBC) of 180, serum iron level of 78, iron saturation of 30, and a ferritin level of 353 indicate, and what are the next steps?

Iron Panel Interpretation: Elevated Ferritin with Normal Iron Studies

Your iron panel shows elevated ferritin (353 ng/mL) in the context of normal iron saturation (30%) and normal serum iron (78), which indicates this is NOT iron overload but rather reflects inflammation, metabolic dysfunction, or another secondary cause of hyperferritinemia. 1, 2

Understanding Your Results

Your iron studies reveal a specific pattern that helps narrow the diagnosis:

• Iron saturation of 30% is well below the 45% threshold that would suggest iron overload 1, 2
• Ferritin of 353 ng/mL is elevated but below the 1,000 ng/mL threshold associated with significant organ damage risk 2
• TIBC of 258 and serum iron of 78 are within normal ranges, confirming adequate circulating iron 1

This combination—elevated ferritin with normal transferrin saturation (<45%)—means iron overload is highly unlikely, and you should focus on identifying secondary causes of hyperferritinemia. 1, 2

What Causes This Pattern

Over 90% of cases with elevated ferritin and normal iron saturation are caused by non-iron overload conditions 2:

• Chronic inflammation or infection: Ferritin is an acute-phase reactant that rises during any inflammatory process, independent of actual iron stores 1, 3, 4
• Metabolic syndrome/NAFLD: Ferritin elevation reflects hepatocellular injury and insulin resistance rather than iron accumulation 2, 3
• Chronic alcohol consumption: A common cause of hyperferritinemia without true iron overload 1, 2
• Liver disease: Viral hepatitis (B or C), alcoholic liver disease, or NAFLD can elevate ferritin 1, 2
• Obesity: Ferritin correlates strongly with BMI and functions as an inflammatory marker in overweight individuals 3
• Occult malignancy: Solid tumors or lymphomas can cause ferritin elevation 2
• Cell necrosis: Muscle or liver cell damage releases stored ferritin 2

Next Steps: Diagnostic Algorithm

Step 1: Rule Out Common Secondary Causes

Order the following tests immediately 1, 2:

• Liver function tests (ALT, AST): Elevated transaminases suggest hepatocellular injury from NAFLD, viral hepatitis, or alcohol 1, 2
• Inflammatory markers (CRP, ESR): Elevated values indicate active inflammation as the cause of hyperferritinemia 2, 5
• Complete metabolic panel: Assess for metabolic syndrome components (glucose, lipids) 2
• Hepatitis B and C serologies: Screen for viral hepatitis if liver enzymes are abnormal 1, 2

Step 2: Clinical Assessment

Evaluate for specific conditions 2:

• Alcohol consumption history: Chronic alcohol use is a leading cause of this pattern 1, 2
• Metabolic syndrome features: Check BMI, waist circumference, blood pressure, fasting glucose, and lipid panel 2, 3
• Signs of infection: Recent or chronic infections can drive ferritin elevation 2
• Medication review: Certain drugs can cause hepatocellular injury 1
• Symptoms of malignancy: Unexplained weight loss, night sweats, or lymphadenopathy warrant further investigation 2

Step 3: Genetic Testing Is NOT Indicated

Do NOT proceed with HFE genetic testing for hereditary hemochromatosis because your transferrin saturation is <45% 1, 2. Hereditary hemochromatosis requires both elevated ferritin AND elevated transferrin saturation (≥45%) 1. Your normal iron saturation excludes primary iron overload as the cause 2.

Step 4: Imaging If Indicated

Consider abdominal ultrasound or liver MRI only if 1, 2:

• Liver enzymes are persistently elevated
• Clinical suspicion for NAFLD or other liver pathology exists
• You need to quantify hepatic fat content (not iron content, since iron overload is excluded)

Critical Pitfalls to Avoid

• Never use ferritin alone to diagnose iron overload: Always interpret ferritin alongside transferrin saturation 1, 2, 5
• Do not assume iron overload when transferrin saturation is <45%: This pattern virtually excludes hereditary hemochromatosis 1, 2
• Recognize ferritin as an inflammatory marker: In the general population, iron overload is NOT the most common cause of elevated ferritin 1, 2, 4
• Do not order unnecessary genetic testing: HFE testing is only appropriate when transferrin saturation is ≥45% 1, 2

What This Means for You

Your elevated ferritin at 353 ng/mL does not indicate risk of organ damage (threshold >1,000 ng/mL for liver damage risk) 2. The most likely explanation is inflammation, metabolic syndrome, liver disease, or another secondary cause 2, 3. The next step is to identify and treat the underlying condition causing the ferritin elevation, not the ferritin itself 2.

If initial workup (liver enzymes, inflammatory markers, metabolic panel) is unrevealing, consider referral to gastroenterology or hematology for further evaluation of less common causes 2.