Specialist Referral for Iron Overload
This patient should be referred to a hepatologist or gastroenterologist with expertise in iron disorders. 1
Understanding the Laboratory Values
Your patient's labs demonstrate clear iron overload:
- Iron saturation of 61% (significantly elevated above normal <45%)
- Serum iron of 183 mg/dL (elevated)
- Ferritin of 141 ng/mL (mildly elevated for a postmenopausal woman)
- UIBC of 117 mcg/dL (low, consistent with iron overload)
These values indicate biochemical iron overload with elevated transferrin saturation, which requires specialist evaluation. 1
Why Hepatology/Gastroenterology?
The EASL (European Association for the Study of the Liver) 2022 guidelines explicitly state that patients with evidence of significant, unexplained iron overload should be referred for assessment by a specialist in iron disorders. 1 In most healthcare systems, this means hepatologists or gastroenterologists who manage hemochromatosis and related conditions.
The American Association for the Study of Liver Diseases similarly emphasizes that iron overload evaluation and management falls within the gastroenterology/hepatology domain, particularly given the need for:
- Liver biopsy consideration for non-HFE iron overload 1
- Assessment of hepatic iron concentration by MRI 1
- Evaluation for underlying liver disease 2
- Therapeutic phlebotomy management 1, 3
What the Specialist Will Do
Initial Diagnostic Workup
The specialist will pursue:
- HFE genetic testing for C282Y and H63D mutations to evaluate for hereditary hemochromatosis 2, 4
- MRI with quantitative assessment of hepatic iron concentration to confirm and quantify iron overload 1
- Evaluation for secondary causes if HFE testing is negative, including:
Treatment Decisions
If true iron overload is confirmed (not just hyperferritinemia from inflammation), therapeutic phlebotomy will be initiated. 1
The phlebotomy protocol involves:
- Weekly or biweekly removal of 500 mL blood until ferritin reaches 50-100 μg/L 1, 3
- Monitoring hematocrit/hemoglobin before each phlebotomy (allowing no more than 20% decrease) 1, 3
- Checking ferritin every 10-12 phlebotomies 1, 3
- Maintenance phlebotomy thereafter to keep ferritin 50-100 μg/L 1, 3
Critical Distinction: Iron Overload vs. Hyperferritinemia
A key pitfall is assuming all elevated ferritin represents iron overload requiring phlebotomy. 5, 6
In your patient with transferrin saturation >45%, true iron overload is more likely. However, the specialist must distinguish:
- True iron overload (hemochromatosis, secondary iron accumulation) → phlebotomy indicated 1
- Dysmetabolic hyperferritinemia (metabolic syndrome, NAFLD with inflammation but minimal iron) → phlebotomy NOT indicated 4, 5
- Inflammatory hyperferritinemia (ferritin elevated as acute phase reactant) → treat underlying condition 5
In NAFLD patients, hyperferritinemia is due to inflammation without hepatic iron overload in the majority of cases, and phlebotomy should not be performed when hyperferritinemia is related to inflammation. 5
Why Not Hematology?
While hematologists manage iron overload in hematologic disorders (thalassemia, myelodysplastic syndrome requiring transfusions), primary evaluation of unexplained iron overload with these lab values typically begins with hepatology/gastroenterology. 1 Hematology consultation may be added later if a primary hematologic disorder is suspected or if there are difficulties accessing IV iron for complex cases. 1
Urgency Considerations
This referral should be made promptly but is not emergent unless the patient has: