What is the management plan for a 15-year-old male patient with elevated ferritin (iron storage protein) levels and no history of iron supplementation?

Management of Elevated Ferritin (158 ng/mL) in a 15-Year-Old Male

Initial Assessment

This ferritin level of 158 ng/mL in a 15-year-old male is mildly elevated but does not indicate iron overload or require aggressive intervention. The most critical next step is measuring fasting transferrin saturation (TS) to distinguish between true iron overload and secondary causes of hyperferritinemia 1, 2.

Immediate Diagnostic Workup

Order the following tests immediately:

• Fasting transferrin saturation (TS) - this is the single most important test to determine if iron overload is present 1, 2
• Complete metabolic panel including ALT and AST to assess for liver disease 1
• Inflammatory markers (CRP and ESR) to detect occult inflammation 1
• Complete blood count with differential to assess for anemia or hematologic abnormalities 1

Algorithmic Approach Based on Transferrin Saturation

If TS ≥45%: Suspect Primary Iron Overload

• Proceed immediately to HFE genotype testing for C282Y and H63D mutations to diagnose hereditary hemochromatosis 1, 2
• However, at ferritin 158 ng/mL with elevated TS, this would be very early detection of hereditary hemochromatosis 1
• Screen first-degree relatives if hereditary hemochromatosis is confirmed 1

If TS <45%: Secondary Causes Are Most Likely

Over 90% of elevated ferritin cases with normal TS are NOT due to iron overload but rather secondary causes 1, 2. In adolescents, the most common causes include:

• Metabolic syndrome/obesity - ferritin elevation reflects hepatocellular injury and insulin resistance 1, 2
• Non-alcoholic fatty liver disease (NAFLD) - check for elevated ALT/AST and consider abdominal ultrasound 1, 2
• Chronic inflammation - assess for rheumatologic conditions, infections 1, 2
• Cell necrosis - check creatine kinase (CK) for muscle injury 1

Risk Stratification by Ferritin Level

At 158 ng/mL, this patient is at extremely low risk for organ damage:

• Ferritin <1000 μg/L has a 94% negative predictive value for advanced liver fibrosis 1, 2
• No evidence of organ damage occurs until ferritin exceeds 1000 μg/L 1
• No liver biopsy or advanced imaging is needed at this level 1

Management Strategy

If TS <45% (Most Likely Scenario):

Treat the underlying condition, not the elevated ferritin itself 1:

• If metabolic syndrome/obesity: Weight loss, dietary modification, exercise 1
• If NAFLD: Lifestyle interventions targeting metabolic risk factors 1
• If inflammation: Disease-specific anti-inflammatory therapy 1
• Do NOT supplement with iron 1
• Do NOT perform phlebotomy - this is only indicated for confirmed iron overload with elevated TS 1

If TS ≥45% and C282Y Homozygote Confirmed:

Even with confirmed hereditary hemochromatosis at this ferritin level:

• Therapeutic phlebotomy can be initiated without liver biopsy since ferritin <1000 μg/L, normal liver enzymes expected, and age <40 years 1
• Target ferritin of 50-100 μg/L 1
• Remove 500 mL blood weekly or biweekly as tolerated 1

Follow-Up Monitoring

• Recheck ferritin and TS in 3-6 months if treating secondary causes 1
• Monitor based on the underlying condition identified 1
• Refer to hepatology if ferritin rises above 1000 μg/L or TS becomes ≥45% on repeat testing 1

Critical Pitfalls to Avoid

• Never use ferritin alone without transferrin saturation to diagnose iron overload - ferritin is an acute phase reactant elevated in inflammation, liver disease, and tissue necrosis independent of iron stores 1, 2
• Do not assume iron overload when TS <45% - in the general population, iron overload is NOT the most common cause of elevated ferritin 1, 2
• Do not supplement with iron or vitamin C 1
• Do not perform phlebotomy without confirmed iron overload (elevated TS and genetic confirmation) 1

Special Considerations for Adolescents

At age 15, this patient is less likely to have developed significant iron overload even if hereditary hemochromatosis is present, as older patients are more likely to have developed iron overload due to increased and ineffective erythropoiesis 3. The ferritin level of 158 ng/mL is well below the 500 mg/L threshold recommended for monitoring in children and adolescents to avoid iron overload risk 3.