Sudden Serum Iron Increase Without Supplementation
A rapid increase in serum iron from 50 to 216 µg/dL over 3 weeks without iron supplementation is highly unusual and warrants immediate investigation for laboratory error, acute inflammation, hemolysis, or underlying iron overload disorders like hemochromatosis.
Understanding the Clinical Context
Serum iron levels normally exhibit significant variability and are influenced by multiple factors beyond true iron stores 1:
- Diurnal variation: Serum iron rises in the morning and falls at night, with day-to-day fluctuations exceeding those seen with hemoglobin 1
- Post-prandial effects: Iron concentration increases after each meal 1
- Acute phase reactions: Inflammation and infection can paradoxically alter serum iron levels 1
Most Likely Explanations
Laboratory or Timing Issues
- Different testing conditions: If the first test was drawn in the evening or fasting state and the second in the morning or post-prandially, this could partially explain the difference 1
- Laboratory error: Given the magnitude of change, repeat testing is essential to confirm accuracy
- Acute phase reaction resolution: If the initial low value occurred during acute inflammation or infection, resolution could unmask higher baseline iron levels 1
Pathological Causes to Investigate
Hemochromatosis or iron overload disorders 1:
- C282Y homozygotes can have markedly elevated serum iron and transferrin saturation
- Check transferrin saturation (TSAT) and ferritin levels immediately
- If TSAT >45% and ferritin elevated, genetic testing for HFE mutations is indicated 1
Hemolysis 1:
- Acute or chronic hemolysis releases iron from destroyed red blood cells
- Check reticulocyte count, haptoglobin, LDH, and indirect bilirubin
- Review peripheral blood smear
Occult blood transfusion or IV iron administration 2:
- Verify no inadvertent iron administration occurred
- Chronic oral iron supplementation, even over-the-counter products taken without medical indication, can cause iron accumulation 2
Critical Diagnostic Steps
Immediate repeat testing with complete iron panel 1:
- Serum iron (fasting, morning draw)
- Total iron binding capacity (TIBC)
- Transferrin saturation = (serum iron/TIBC) × 100
- Serum ferritin
Interpret ferritin cautiously 1:
- Ferritin is an acute phase reactant and can be elevated with inflammation, liver disease, or malignancy independent of iron stores 1
- Check C-reactive protein concurrently to assess for inflammation 1
- In inflammatory states, ferritin ≥50 µg/L may still represent iron deficiency 1
If iron overload is confirmed 1:
- Transferrin saturation >45% suggests iron overload
- Ferritin >1000 µg/L with elevated transaminases warrants liver biopsy consideration 1
- Genetic testing for hereditary hemochromatosis (HFE gene mutations) 1
Common Pitfalls to Avoid
- Do not assume dietary changes alone: Dietary iron absorption is limited to 2-4 mg/day, insufficient to explain this magnitude of change 1
- Do not ignore the possibility of hemochromatosis: Even without symptoms, C282Y homozygotes can have significant iron elevation and may benefit from prophylactic phlebotomy 1
- Do not overlook medication history: Query specifically about over-the-counter iron supplements, multivitamins with iron, and any parenteral iron that may have been administered in other healthcare settings 2
- Avoid vitamin C supplementation: If iron overload is present, vitamin C accelerates iron mobilization and can increase oxidant stress, particularly during phlebotomy 1
Management Approach
If hemochromatosis is diagnosed 1:
- Initiate weekly phlebotomy (500 mL) as tolerated
- Target ferritin 50-100 µg/L
- Monitor hematocrit/hemoglobin before each phlebotomy
- Check ferritin every 10-12 phlebotomies
- Avoid vitamin C and iron supplements 1
If no clear cause is identified:
- Repeat testing in 2-4 weeks under standardized conditions (fasting, morning draw)
- Consider hematology referral if persistently elevated without explanation
- Screen for occult blood loss if iron parameters suggest true overload 1