What is the significance and recommended evaluation and management for an elevated ferritin level of 372 µg/L in a 45‑year‑old woman?

Evaluation and Management of Ferritin 372 µg/L in a 45-Year-Old Woman

A ferritin of 372 µg/L in a 45-year-old woman is mildly elevated and requires evaluation of transferrin saturation (TSAT) to determine if this represents iron overload versus secondary hyperferritinemia from inflammation, metabolic syndrome, or liver disease.

Initial Diagnostic Approach

The key discriminating test is transferrin saturation (TSAT), which should be measured immediately 1, 2. This single test determines your next steps:

If TSAT is Normal (<45% in women):

• Iron overload is unlikely 1, 2
• Investigate common causes of secondary hyperferritinemia:
  • Metabolic syndrome (check BMI, blood pressure, glucose, lipids) 2
  • Chronic alcohol consumption 2
  • Inflammation (check CRP) 2
  • Liver disease (check ALT, AST) 2, 3
  • Malignancy (age-appropriate cancer screening) 2

Over 90% of hyperferritinemia cases in outpatients are explained by these conditions 2.

If TSAT is Elevated (≥45% in women):

• Proceed to HFE genetic testing for C282Y and H63D mutations 1, 2
• This level of ferritin (372 µg/L) with elevated TSAT warrants genetic evaluation for hereditary hemochromatosis

Interpretation Based on Genetic Testing

If C282Y homozygote with elevated TSAT:

• Diagnosis of hereditary hemochromatosis is confirmed 3, 4
• No liver biopsy needed since ferritin is <1000 µg/L and assuming normal liver enzymes 3
• Proceed directly to therapeutic phlebotomy 3

If other HFE genotypes (C282Y/H63D compound heterozygote or H63D homozygote):

• First exclude other causes of hyperferritinemia 2
• May require MRI or liver biopsy to confirm hepatic iron overload before diagnosing iron overload disorder 4, 5

If negative for HFE mutations:

• Iron overload from hemochromatosis is unlikely
• Focus on secondary causes listed above 2

Critical Thresholds to Remember

The ferritin level of 372 µg/L is:

• Above the diagnostic threshold for case-finding in women (>200 µg/L) 1
• Below the threshold requiring liver biopsy in confirmed hemochromatosis (<1000 µg/L) 3
• In the range where TSAT becomes the critical discriminating test 1, 2

Common Pitfalls to Avoid

1. Do not assume iron overload based on ferritin alone - ferritin is an acute phase reactant and commonly elevated without iron overload 2, 6

2. Do not order genetic testing before checking TSAT - this wastes resources since most hyperferritinemia is not from hemochromatosis 2

3. Do not perform liver biopsy in C282Y homozygotes with ferritin <1000 µg/L and normal liver enzymes - it's unnecessary for diagnosis 3

4. In premenopausal women, consider menstrual blood loss - this can mask iron accumulation, so a ferritin of 372 µg/L deserves investigation even though she's still menstruating 1

If Hemochromatosis is Confirmed

Treatment targets 4:

• Induction phase: ferritin <50 µg/L
• Maintenance phase: ferritin 50-100 µg/L
• Weekly phlebotomy (500 mL) until target reached 3, 4
• Monitor ferritin monthly during induction 4

Lifestyle modifications 4:

• Avoid iron supplements and iron-fortified foods
• Avoid vitamin C supplements (increases iron absorption)
• Limit alcohol intake
• Avoid raw shellfish (risk of Vibrio vulnificus infection)