Why Is Her Ferritin Elevated at 377 ng/mL?
A ferritin level of 377 ng/mL is most commonly caused by inflammation, chronic disease, or metabolic conditions rather than true iron overload, and you should systematically evaluate for these secondary causes before considering hereditary hemochromatosis or other iron overload disorders. 1, 2
Understanding Ferritin as a Biomarker
Ferritin is an acute phase reactant that rises during inflammation, making it a marker with high sensitivity but low specificity for iron overload. 1, 2 At 377 ng/mL, this level falls well below the thresholds associated with significant iron overload complications (>1000 ng/mL for liver damage risk, >7500 ng/mL for documented organ damage). 3, 4
Most Common Causes at This Level
The overwhelming majority (>90%) of hyperferritinemia cases in outpatients are due to: 2
- Chronic inflammation - including rheumatologic diseases, chronic infections 2
- Metabolic syndrome/NAFLD - extremely common in modern practice 1, 2
- Chronic alcohol consumption - increases ferritin through multiple mechanisms including increased iron absorption and liver injury 1, 2
- Liver disease - viral hepatitis (B or C), alcoholic liver disease, or NAFLD 1, 2
- Malignancy - solid tumors or lymphomas 2, 5
- Active infection - ferritin rises as part of the acute phase response 3
Diagnostic Algorithm for Ferritin 377 ng/mL
Step 1: Check transferrin saturation (TS) simultaneously 1, 2, 4
- Use morning blood sample (fasting not required) 1
- If TS <45%, iron overload is unlikely and secondary causes predominate 2, 4
- If TS ≥45%, proceed with HFE genetic testing 2, 4
Step 2: Evaluate for inflammatory/secondary causes: 1, 2
- Check inflammatory markers (CRP, ESR) 4
- Assess liver enzymes (ALT, AST) 4
- Review alcohol consumption history 1, 2
- Screen for metabolic syndrome components 2
- Consider viral hepatitis serologies if risk factors present 1, 2
- Evaluate for occult malignancy if clinically indicated 2, 5
Step 3: Interpret the combination: 1, 2, 4
- TS <45% + ferritin 377 = Secondary cause most likely; treat underlying condition 4
- TS ≥45% + ferritin 377 = Consider hereditary hemochromatosis; proceed to HFE genotyping 2, 4
Critical Context: When Ferritin Reflects Inflammation vs. Iron Overload
The distinction between functional iron deficiency and inflammatory iron block is crucial. 3 In inflammatory states, ferritin rises acutely while transferrin saturation often drops, creating a pattern of elevated ferritin with low TS. 3 This is the opposite pattern of true iron overload, where both ferritin and TS are elevated. 3, 2
Important: The association between elevated ferritin and infections is bidirectional—infection causes ferritin to rise, not the other way around. 3 This means you should investigate for active infection as a cause of the elevated ferritin rather than worrying that the ferritin level itself increases infection risk at this level. 3
Common Pitfalls to Avoid
Do not diagnose iron overload based on ferritin alone without checking transferrin saturation. 4 This is the most common error in evaluating hyperferritinemia.
Do not overlook multiple contributing factors. 1 A patient may have both metabolic syndrome and chronic alcohol use, both elevating ferritin independently.
Do not assume hereditary hemochromatosis is the cause without genetic confirmation. 2, 4 In the general population, iron overload is not the most common cause of elevated ferritin. 2
Do not ignore unexpected changes in ferritin levels. 1 Significant fluctuations warrant investigation as they are not normal.