Is an abnormal ferritin level a concern in a 67-year-old female with normal transferrin levels?

Abnormal Ferritin with Normal Transferrin Saturation in a 67-Year-Old Female

An abnormal ferritin level with normal transferrin saturation in a 67-year-old female should be evaluated but is not typically concerning for hereditary hemochromatosis and may reflect other underlying conditions that require further assessment.

Understanding Ferritin and Transferrin Saturation

• Ferritin is a storage protein for iron and an acute phase reactant that can be elevated in inflammatory conditions, while transferrin saturation reflects iron that is readily available for erythropoiesis 1
• Normal transferrin saturation (typically <45-50%) with elevated ferritin is not consistent with hereditary hemochromatosis, which typically presents with both elevated transferrin saturation and ferritin 1
• In healthy individuals, transferrin is normally not saturated more than 50% with iron under normal physiological conditions 2

Clinical Significance of Isolated Ferritin Elevation

• An isolated elevated ferritin with normal transferrin saturation is commonly seen in:

  • Inflammatory conditions (as ferritin is an acute phase reactant) 1
  • Dysmetabolic iron overload syndrome associated with alcohol excess or NAFLD 1
  • Chronic liver diseases 1
  • Metabolic syndrome 3

• The American Association for the Study of Liver Diseases guidelines state that "a variety of disease conditions unrelated to iron overload may cause a nonspecific rise in serum ferritin, and in the absence of an elevated transferrin saturation, this rise may be nonspecific" 1

Diagnostic Approach

• For patients with suspected iron metabolism disorders, both transferrin saturation and ferritin should be measured together as the first step in testing 1
• The EASL guidelines recommend that "individuals with clinical and biochemical signs of hemochromatosis, elevated transferrin saturation and high serum ferritin concentrations, or otherwise unexplained persistently elevated transferrin saturation should be genetically tested for hemochromatosis" 1
• In the absence of elevated transferrin saturation, genetic testing for hemochromatosis is not routinely indicated 1

When to Consider Further Evaluation

• If the patient has other symptoms or risk factors, consider evaluating for:

  • Inflammatory conditions (check CRP, ESR) 1
  • Liver disease (check liver enzymes, abdominal ultrasound) 1
  • Metabolic syndrome (check lipid panel, glucose) 3
  • Chronic kidney disease (check renal function) 1

• In patients with unexplained hyperferritinemia, MRI may be used to quantify hepatic iron concentrations if clinically indicated 1

Monitoring Recommendations

• For patients with isolated ferritin elevation and normal transferrin saturation:
  • Periodic monitoring of iron studies (ferritin and transferrin saturation) 1
  • Evaluation of underlying conditions that may cause ferritin elevation 1
  • Assessment of other markers of inflammation or metabolic dysfunction 3

Conclusion

• Normal transferrin saturation with abnormal ferritin in a 67-year-old female is more likely to represent an inflammatory state or metabolic disorder rather than true iron overload 1
• The British Society of Gastroenterology recommends that iron deficiency should be confirmed by iron studies prior to investigation, with serum ferritin being the single most useful marker, but other blood tests (e.g., transferrin saturation) can be helpful if a false-normal ferritin is suspected 1
• Without elevated transferrin saturation, the risk of hereditary hemochromatosis is low, and genetic testing is not routinely indicated 1