What are the signs and symptoms of iron overload (hemochromatosis)?

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From the Guidelines

Iron overload typically presents with non-specific signs and symptoms, including chronic fatigue, joint pain, and diabetes, which can progress to end-organ failure, particularly affecting the pancreas and liver 1.

Key Signs and Symptoms

The signs and symptoms of iron overload are varied and can be subtle in the early stages. Key manifestations include:

  • Chronic fatigue
  • Joint pain
  • Abdominal discomfort
  • Decreased libido
  • Bronze or gray skin discoloration
  • Liver enlargement and dysfunction, potentially leading to cirrhosis
  • Heart problems, such as arrhythmias and heart failure
  • Diabetes due to pancreatic damage
  • Arthritis
  • Erectile dysfunction in men
  • Menstrual irregularities in women
  • Psychological symptoms, including depression, memory fog, and irritability

Causes and Diagnosis

Iron overload is most commonly caused by hereditary hemochromatosis, multiple blood transfusions, or certain anemias 1. Diagnosis can be challenging due to the non-specific nature of the symptoms, but serum iron parameters, such as transferrin saturation and ferritin levels, can provide clues 1. MRI can also be helpful in detecting and quantifying iron overload in the liver, spleen, pancreas, heart, and brain 1.

Treatment and Management

Treatment of iron overload typically involves regular phlebotomy to reduce iron levels and prevent further organ damage 1. The goal of treatment is to reduce ferritin levels to <50 µg/L during the induction phase and <100 µg/L during the maintenance phase 1. Early detection and treatment are crucial to prevent irreversible organ damage and improve quality of life.

From the Research

Signs and Symptoms of Iron Overload

The signs and symptoms of iron overload can be diverse and affect various organs in the body. Some common signs and symptoms include:

  • Elevated liver enzymes, which can be an indicator of liver damage or disease 2
  • Hyperferritinemia, which is an excess of ferritin in the blood, and can be caused by a variety of conditions, including chronic liver disease, malignancy, infections, kidney failure, and rheumatic conditions 2
  • Fatigue, weakness, and shortness of breath, which can be caused by the accumulation of excess iron in the body 3
  • Joint pain and arthritis, which can be caused by the deposition of excess iron in the joints 3
  • Skin pigmentation, such as bronzing or darkening of the skin, which can be caused by the accumulation of excess iron in the skin 3
  • Diabetes mellitus, which can be caused by the damage to the pancreas and other organs caused by excess iron 3
  • Hormonal abnormalities, such as hypogonadism or amenorrhea, which can be caused by the damage to the endocrine glands caused by excess iron 3
  • Dysfunctional immune system, which can be caused by the damage to the immune cells and organs caused by excess iron 3

Organ-Specific Damage

Iron overload can cause damage to various organs in the body, including:

  • Liver: Iron overload can cause liver damage, fibrosis, and cirrhosis, which can lead to liver failure and other complications 2, 4, 5
  • Heart: Iron overload can cause heart damage, cardiomyopathy, and heart failure, which can lead to serious cardiovascular complications 3, 4
  • Pancreas: Iron overload can cause pancreatic damage, diabetes mellitus, and other endocrine disorders 3
  • Joints: Iron overload can cause joint pain, arthritis, and other musculoskeletal disorders 3
  • Skin: Iron overload can cause skin pigmentation, such as bronzing or darkening of the skin, and other dermatological disorders 3

Diagnostic Testing

Diagnostic testing for iron overload typically includes:

  • Serum ferritin levels: Elevated ferritin levels can indicate iron overload 2
  • Transferrin-iron saturation: Elevated transferrin-iron saturation can indicate iron overload 2
  • Genetic testing: Genetic testing for HFE mutations can help diagnose hereditary hemochromatosis 2
  • Liver biopsy: Liver biopsy can help diagnose liver damage and fibrosis caused by iron overload 2
  • Magnetic resonance imaging (MRI): MRI can help diagnose iron overload and liver damage 2

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Iron overload disorders.

Hepatology communications, 2022

Research

Chronic iron overload and toxicity: clinical chemistry perspective.

Clinical laboratory science : journal of the American Society for Medical Technology, 2001

Research

Iron and the liver.

Liver international : official journal of the International Association for the Study of the Liver, 2016

Research

The Role of Iron and Iron Overload in Chronic Liver Disease.

Medical science monitor : international medical journal of experimental and clinical research, 2016

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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