What tests are recommended to monitor a patient with hemochromatosis (iron overload disorder)?

Monitoring Tests for Hemochromatosis

Serum ferritin is the primary test for monitoring iron burden during treatment in hereditary hemochromatosis, reliably reflecting total body iron stores, and should be checked monthly during induction phlebotomy or every 4 phlebotomies, with a target maintenance level of 50-100 μg/L. 1, 2

Core Iron Panel Monitoring

During active treatment (induction phase):

• Serum ferritin monthly or every 4 phlebotomies to track iron depletion 2
• Hemoglobin at each phlebotomy session—reduce frequency if <12 g/dL and suspend if <11 g/dL to prevent iatrogenic iron deficiency 2, 3
• Transferrin saturation periodically to assess iron mobilization 1, 2

During maintenance phase:

• Serum ferritin every 2-3 months to maintain target of 50-100 μg/L 2
• Transferrin saturation to ensure adequate iron control 1
• Complete blood count to monitor for anemia from excessive phlebotomy 1, 3

The EASL guidelines emphasize that serum ferritin reliably reflects iron burden during therapy in hereditary hemochromatosis, unlike secondary iron overload where ferritin can be misleading. 1

Liver Disease Surveillance

All patients require baseline and ongoing liver assessment:

• Transaminases (ALT, AST) and platelet count to detect progressive liver disease 1, 2
• Non-invasive fibrosis assessment using transient elastography (liver stiffness <6.4 kPa excludes advanced fibrosis) or FIB-4 score 1, 4
• Patients with ferritin >1,000 μg/L, elevated transaminases, thrombocytopenia, or hepatomegaly warrant more intensive liver evaluation 1

For patients with cirrhosis or advanced fibrosis (F3-F4):

• Abdominal ultrasound every 6 months for hepatocellular carcinoma surveillance, regardless of iron depletion status 1, 2, 4
• Alpha-fetoprotein (AFP) may be added optionally 2
• MRI or CT when ultrasound is technically inadequate 2, 4

The AASLD guidelines note that cirrhotic hemochromatosis patients have a 20-fold increased HCC risk with 3-4% annual incidence, mandating lifelong surveillance even after iron normalization. 1

Cardiac Monitoring in High-Risk Patients

Patients with severe iron overload (very high ferritin) require:

• Electrocardiogram (ECG) to detect arrhythmias and conduction abnormalities 1, 5, 2
• Echocardiography to assess contractile dysfunction 1, 5
• Cardiac MRI with T2 sequences* for myocardial iron quantification in patients with cardiac symptoms or juvenile hemochromatosis 1, 5, 4

The EASL guidelines specifically mandate cardiac MRI for all juvenile hemochromatosis patients given their high risk of cardiac iron deposition and life-threatening cardiomyopathy. 1, 4

Endocrine and Metabolic Monitoring

Screen for common endocrine complications:

• Fasting glucose and/or hemoglobin A1c to detect secondary diabetes from pancreatic iron deposition 5
• Testosterone, LH, and FSH in patients with sexual dysfunction or hypogonadism symptoms, as hypogonadotropic hypogonadism from pituitary iron deposition is common and potentially reversible with treatment 5

Advanced Imaging for Tissue Iron Quantification

MRI R2 sequences* provide non-invasive quantification of hepatic iron concentration and predict the number of phlebotomies required, particularly useful in: 1, 4

• Unclear hyperferritinemia cases
• Patients with additional risk factors (metabolic syndrome, alcohol use)
• Assessment of multi-organ iron distribution (liver, spleen, pancreas, heart)

MRI helps differentiate hemochromatosis (predominant hepatic iron, minimal splenic iron) from other iron overload conditions like ferroportin disease or transfusional overload (increased splenic iron). 4

Critical Monitoring Pitfalls to Avoid

Common errors that compromise patient outcomes:

• Over-phlebotomy leading to iron deficiency: Monitor hemoglobin closely as symptomatic iron deficiency can persist for months and cause significant morbidity 3
• Relying on ferritin alone in inflammatory states: Ferritin is an acute phase reactant and can be falsely elevated by inflammation, liver disease, malignancy, or alcohol consumption 4, 6
• Missing cirrhosis in patients with ferritin <1,000 μg/L: While rare, cirrhosis can occur; use platelet count <200,000/μL combined with elevated transaminases as additional predictors 1, 2
• Discontinuing HCC surveillance after iron depletion: Cirrhotic patients retain elevated HCC risk indefinitely regardless of iron normalization 1, 2

The AASLD guidelines note that in hemochromatosis, unlike secondary iron overload, serum ferritin reliably tracks treatment response, making it the cornerstone of monitoring. 1