Is a serum iron of 160 µg/dL within the normal range and what additional testing or management is indicated?

Serum Iron of 160 µg/dL: Interpretation and Management

A serum iron of 160 µg/dL is elevated above the normal range (60-80 µg/dL) and falls within the range seen in asymptomatic hemochromatosis patients (150-280 µg/dL), requiring immediate measurement of transferrin saturation and ferritin to evaluate for iron overload. 1

Understanding the Laboratory Finding

Your serum iron of 160 µg/dL exceeds the normal reference range by approximately 2-fold and overlaps with values characteristic of early hereditary hemochromatosis (HH). 1 However, serum iron alone is insufficient for diagnosis because it shows significant diurnal variation and can be transiently elevated by recent dietary intake, inflammation, or hemolysis. 1

Immediate Next Steps: Complete the Iron Panel

You must obtain transferrin saturation (TS) and serum ferritin simultaneously—never rely on serum iron as a single test. 1 The American Association for the Study of Liver Diseases explicitly states that a combination of TS and ferritin should be obtained rather than relying on a single test. 1

Calculate Transferrin Saturation

• If TS ≥ 45%, this is abnormal and triggers the need for HFE mutation analysis. 1
• Normal TS ranges from 20-50%; patients with asymptomatic HH typically show TS of 45-100%. 1
• TS is calculated as: (serum iron × 100) ÷ total iron-binding capacity. 1

Interpret Ferritin in Context

Ferritin thresholds for concern:

• Men: Normal 20-200 µg/L; asymptomatic HH shows 150-1000 µg/L 1
• Women: Normal 15-150 µg/L; asymptomatic HH shows 120-1000 µg/L 1
• Ferritin >1000 µg/L with elevated liver enzymes (ALT/AST) and platelet count <200 predicts cirrhosis in 80% of C282Y homozygotes. 1

Diagnostic Algorithm Based on Results

Scenario 1: TS ≥ 45% and/or Elevated Ferritin

Proceed immediately to HFE genetic testing (C282Y and H63D mutations). 1 This is the definitive diagnostic step for hereditary hemochromatosis, which affects 28% of male and 1% of female C282Y homozygotes with clinically significant iron overload. 1

If C282Y homozygosity or compound heterozygosity (C282Y/H63D) is confirmed:

• Check liver enzymes (ALT, AST) and platelet count 1
• If ferritin >1000 µg/L with elevated transaminases or platelets <200, perform liver biopsy to assess for cirrhosis 1
• If ferritin <1000 µg/L with normal liver enzymes, initiate therapeutic phlebotomy without biopsy 1
• Screen all first-degree relatives with both HFE mutation analysis and iron studies 1

Scenario 2: TS <45% and Normal Ferritin

No further evaluation for hemochromatosis is needed. 1 The elevated serum iron likely represents physiologic variation, recent dietary intake, or laboratory artifact. Repeat fasting iron studies in 3-6 months if clinical suspicion persists.

Scenario 3: Discordant Results (e.g., elevated iron with low ferritin)

This pattern suggests ongoing blood loss with recent iron supplementation or dietary loading. Check for gastrointestinal bleeding, menstrual blood loss, or other sources of chronic blood loss. 1 Consider celiac disease screening (tissue transglutaminase antibodies) and Helicobacter pylori testing, as both impair iron absorption and can create paradoxical iron patterns. 1, 2

Critical Pitfalls to Avoid

Do not diagnose hemochromatosis based on serum iron alone. 1 The sensitivity and specificity are inadequate without TS and ferritin. 3, 4

Do not overlook inflammation as a confounder. 1 Ferritin is an acute-phase reactant that rises during infection, inflammation, or tissue damage, potentially masking true iron status. 1, 2 If C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) are elevated, ferritin thresholds shift upward to <100 µg/L for diagnosing iron deficiency. 1, 2

Do not delay family screening if hemochromatosis is confirmed. 1 First-degree relatives have a 25% chance of being C282Y homozygotes if one parent is a carrier, and early detection prevents cirrhosis, diabetes, and cardiomyopathy. 1

Target High-Risk Populations

Diagnostic strategies using serum iron markers should target those with:

• Family history of hemochromatosis 1
• Unexplained liver enzyme elevation 1
• Arthritis (especially metacarpophalangeal joints) 1
• Cardiomyopathy or arrhythmias 1
• Diabetes mellitus 1
• Hypogonadism or testicular atrophy 1
• Skin hyperpigmentation 1

In these populations, the combination of elevated serum iron, TS ≥45%, and elevated ferritin has high predictive value for clinically significant iron overload requiring intervention. 1, 3