What are the symptoms of iron overload?

Symptoms of Iron Overload

Iron overload presents with a spectrum of symptoms ranging from non-specific early manifestations like chronic fatigue and joint pain to severe end-organ damage including cirrhosis, cardiomyopathy, and diabetes, with many patients remaining asymptomatic in early stages. 1

Early and Non-Specific Symptoms

• Chronic fatigue is one of the most common presenting symptoms of iron overload, often appearing before other manifestations become evident 1, 2
• Joint pain (arthropathy) frequently occurs and may be mistaken for other rheumatologic conditions 1, 3
• Abdominal pain can be present as iron accumulates in hepatic tissue 1, 2
• Skin pigmentation changes (bronze or gray discoloration) develop as iron deposits in dermal tissues 4, 1

Cardiac Manifestations

The cardiac symptoms represent a critical concern as they are the leading cause of death in patients with chronic transfusion therapy 4:

• Exertional shortness of breath typically presents first, resulting from left ventricular diastolic dysfunction with restrictive physiology 4
• Cardiomyopathy progresses from diastolic dysfunction to dilated cardiomyopathy with systolic dysfunction 4, 1
• Cardiac dysrhythmias including bradyarrhythmias from conduction system involvement and supraventricular arrhythmias can lead to sudden death 4, 1
• Heart failure may become refractory to standard treatment in advanced cases 4, 1

A critical pitfall: Patients may be completely asymptomatic early in the disease despite significant cardiac iron deposition, making early screening essential in at-risk populations 4.

Hepatic Manifestations

• Elevated liver enzymes often detected on routine laboratory testing 1, 3
• Hepatomegaly on physical examination 3
• Progressive fibrosis leading to cirrhosis if untreated 1
• Hepatocellular carcinoma accounts for approximately 30% of hemochromatosis-related deaths and risk persists even after iron removal in cirrhotic patients 1

Endocrine Manifestations

• Diabetes mellitus develops from pancreatic iron deposition and is a major cause of morbidity 4, 1, 2
• Hypogonadism (hypogonadotrophic) results from pituitary iron accumulation 4, 1

Clinical Presentation Patterns

The spectrum of symptoms varies widely based on disease stage 4:

• Asymptomatic phase: Patients may have no symptoms despite significant iron accumulation, particularly early in the disease process 4
• Symptomatic phase: Non-specific symptoms like fatigue, joint pain, and abdominal discomfort predominate 1, 3
• End-organ damage phase: Terminal heart failure, cirrhosis, diabetes, and other irreversible complications develop 4, 1

Important Clinical Considerations

Early recognition is paramount because cardiac dysfunction and other manifestations are reversible if treatment begins before end-stage heart failure or cirrhosis develops 4, 5. The American College of Cardiology emphasizes that adequate medical therapy can reverse iron overload cardiomyopathy when diagnosed before end-stage disease 4.

Key pitfall to avoid: Delayed diagnosis leads to irreversible organ damage, particularly cardiac and hepatic complications 1, 2. Clinicians should maintain high suspicion for iron overload in patients presenting with unexplained fatigue, joint pain, palpitations, elevated liver enzymes, or hepatomegaly 3.

The cardiac symptoms deserve particular attention as iron accumulation occurs in ventricular myocardium before atrial tissue, and deposition in the conduction system can necessitate pacemaker placement 4. First-degree AV blocks and supraventricular arrhythmias correlate with the extent of cardiac iron deposition 4.