Is a serum iron concentration of 226 µg/dL considered a critical laboratory value?

Is Serum Iron 226 µg/dL a Critical Laboratory Value?

A serum iron concentration of 226 µg/dL is not a critical laboratory value requiring immediate emergency intervention, but it is significantly elevated and warrants prompt clinical evaluation to exclude hemochromatosis or secondary iron overload. 1

Understanding the Clinical Context

• Normal serum iron ranges from 60-80 µg/dL in healthy subjects. 1
• In patients with hereditary hemochromatosis (HH), serum iron typically ranges from 150-280 µg/dL in asymptomatic patients and 180-300 µg/dL in symptomatic patients. 1
• Your value of 226 µg/dL falls within the range seen in hemochromatosis patients, placing it well above normal but not at a level requiring immediate emergency management. 1

Immediate Diagnostic Algorithm

Step 1: Calculate Transferrin Saturation (TS)

• TS is calculated as (serum iron × 100) ÷ total iron-binding capacity (TIBC). 1
• TS ≥ 45% is abnormal and triggers further evaluation for hemochromatosis. 1
• In HH patients, TS ranges from 45-100% in asymptomatic cases and 80-100% in symptomatic cases. 1

Step 2: Measure Serum Ferritin

• Obtain serum ferritin simultaneously with TS rather than relying on a single test. 1
• Ferritin >1000 µg/L combined with elevated liver enzymes (ALT or AST) and platelet count <200 predicts cirrhosis in 80% of C282Y homozygotes. 1
• Ferritin levels in HH range from 150-1000 µg/L in asymptomatic patients and 500-6000 µg/L in symptomatic patients. 1

Step 3: If Either TS ≥ 45% or Ferritin is Elevated

• Proceed immediately to HFE mutation analysis (C282Y and H63D testing). 1
• Screen for other causes of secondary iron overload: alcoholic liver disease, viral hepatitis, nonalcoholic fatty liver disease, repeated transfusions, or excessive oral iron supplementation. 1

Critical Pitfalls to Avoid

• Do not dismiss elevated serum iron as benign without calculating transferrin saturation. Serum iron alone has poor diagnostic accuracy (sensitivity 63.5%, specificity 38.6%) for iron disorders, but when combined with TIBC to calculate TS, it becomes clinically meaningful. 1, 2
• Serum iron shows marked diurnal variation and can be transiently elevated by recent dietary intake, inflammation, or hemolysis. A single elevated value requires confirmation with repeat testing and correlation with ferritin and TS. 1
• Ferritin is an acute-phase reactant that rises during inflammation, infection, or tissue damage. An elevated ferritin may reflect inflammation rather than true iron overload, making TS the more reliable marker in acute settings. 1

When to Escalate Urgency

While serum iron of 226 µg/dL is not immediately life-threatening, escalate evaluation urgently if:

• Patient has symptoms of organ involvement: fatigue, arthralgia, hepatomegaly, skin hyperpigmentation, diabetes, or cardiac dysfunction. 1
• Liver enzymes (ALT/AST) are elevated, suggesting hepatic iron deposition. 1
• Ferritin exceeds 1000 µg/L, which carries high risk of cirrhosis. 1
• Family history of hemochromatosis exists, as first-degree relatives have significantly increased risk. 1

Distinguishing True Iron Overload from Laboratory Artifact

• Research demonstrates that serum iron markers can be misleading: in chronic kidney disease patients, serum iron and transferrin saturation correlate poorly with actual liver iron concentration measured by MRI. 3
• Serum ferritin protein generated during inflammation contains much less iron than normal ferritin, potentially masking or exaggerating true iron status. 4
• The combination of elevated serum iron with normal or low ferritin suggests recent iron ingestion, hemolysis, or laboratory error rather than chronic iron overload. 5, 6

Bottom line: A serum iron of 226 µg/dL requires same-day calculation of transferrin saturation and measurement of ferritin, followed by HFE genetic testing if either is abnormal, but does not constitute a medical emergency requiring immediate hospitalization or chelation therapy. 1