What is the management for hyperferritinemia in an elderly male?

Management of Ferritin 874 μg/L in a 93-Year-Old Male

The first step is to measure transferrin saturation (TSAT) to distinguish between iron overload and the far more common secondary causes of hyperferritinemia, as over 90% of elevated ferritin cases are NOT due to iron overload and do not require phlebotomy. 1, 2

Initial Diagnostic Approach

Measure fasting transferrin saturation immediately - this single test determines your entire management pathway. 1, 2, 3

If TSAT < 45%: Secondary Hyperferritinemia (Most Likely)

This effectively rules out primary iron overload, and the elevated ferritin reflects underlying medical conditions rather than excess iron stores. 1, 3

Systematically evaluate for these common causes (responsible for >90% of cases): 1, 2, 3

• Inflammation/Infection: Check CRP, ESR - ferritin is an acute phase reactant and rises with any inflammatory process 1, 4
• Liver disease: Check AST, ALT, hepatitis B/C serology, assess alcohol consumption, evaluate for NAFLD/metabolic syndrome 1, 2, 4
• Metabolic syndrome: Assess blood pressure, BMI, glucose, lipid panel - dysmetabolic hyperferritinemia is now the most common cause of elevated ferritin in general populations 1, 4, 5
• Malignancy: Consider CT imaging if ferritin is very high (>10,000 μg/L) or clinical suspicion exists, particularly lymphomas 1, 3
• Chronic kidney disease: Common in elderly patients and causes secondary hyperferritinemia 4
• Cell necrosis: Check CK for muscle damage 1, 3

In a 93-year-old, the most likely causes are chronic inflammation, metabolic syndrome, liver disease, or occult malignancy. 4, 6

If TSAT ≥ 45%: Possible Iron Overload

Proceed with HFE genetic testing for C282Y and H63D mutations to evaluate for hereditary hemochromatosis. 1, 2

• C282Y homozygotes: Confirm HFE hemochromatosis diagnosis and initiate therapeutic phlebotomy 1, 2
• Other genotypes or negative testing: Consider non-HFE hemochromatosis or secondary iron overload from transfusions, chronic hemolysis, or other causes 1, 7

Risk Stratification for Liver Disease

At ferritin 874 μg/L (below 1,000 μg/L threshold), the risk of cirrhosis is very low. 1

However, given the patient's age (>40 years), consider liver biopsy if: 1, 2

• Elevated AST or ALT
• Hepatomegaly on examination
• TSAT ≥ 45% with confirmed C282Y homozygosity

Ferritin >1,000 μg/L combined with elevated aminotransferases and platelet count <200 predicts cirrhosis in 80% of C282Y homozygotes, but this patient is below that threshold. 1

Treatment Considerations

If Iron Overload is Confirmed (TSAT ≥ 45% + positive genetics):

Therapeutic phlebotomy is the treatment of choice for hereditary hemochromatosis. 1, 2

• Remove 400-500 mL blood weekly or biweekly until target ferritin 50-100 μg/L is reached 1, 2
• Monitor hemoglobin before each phlebotomy; do not allow it to fall >20% from baseline 2
• However, at age 93, carefully weigh risks vs. benefits of aggressive phlebotomy given cardiovascular status, anemia risk, and limited life expectancy 1
• Phlebotomy can be performed even in patients with advanced fibrosis or cirrhosis 1

If Secondary Hyperferritinemia (TSAT < 45%):

Treat the underlying condition - phlebotomy is NOT indicated. 2, 3, 4

• Address metabolic syndrome components (weight loss, diabetes control, lipid management) 4, 5
• Optimize management of liver disease, reduce alcohol if applicable 1, 4
• Treat infections or inflammatory conditions 1, 3
• Avoid iron supplementation and iron-fortified foods 2
• Consider reducing red meat consumption, which may improve glucose homeostasis and liver markers in dysmetabolic hyperferritinemia 5

Critical Pitfalls to Avoid

Do NOT initiate phlebotomy based on ferritin alone without checking TSAT - this is the most common error, as 90% of hyperferritinemia is not due to iron overload. 1, 4

Do NOT assume hemochromatosis in an elderly patient with first presentation - hereditary hemochromatosis typically manifests earlier in life; late presentation suggests secondary causes. 4, 6

Do NOT overlook occult malignancy - in elderly patients with unexplained hyperferritinemia, maintain high suspicion for underlying hematologic or solid malignancies. 1, 8

If ferritin exceeds 6,000 μg/L, strongly consider hemophagocytic lymphohistiocytosis (HLH) using the H score, as this carries high mortality and requires urgent treatment. 8

Monitoring

• Recheck ferritin and TSAT in 3-6 months if secondary causes are being treated 2, 3
• If phlebotomy is initiated, monitor ferritin monthly or after every 4th phlebotomy during induction phase 2
• Investigate unexpected changes in ferritin or TSAT levels 1

Special Considerations for Age 93

Given advanced age, prioritize quality of life over aggressive iron depletion. The patient's limited life expectancy, comorbidities, and functional status should guide intensity of intervention. 1 Even if iron overload is confirmed, a conservative approach with less frequent phlebotomy or observation may be more appropriate than standard protocols designed for younger patients.