Why does iron accumulate?
Normally, the body does not know how to actively remove iron, so it regulates its absorption. The liver hormone hepcidin is responsible for this: when there are enough reserves, it closes the entry of iron from the intestines into the blood. In hereditary hemochromatosis, this regulation is disrupted, there is little hepcidin, and iron continues to flow even when the depots are overcrowded. The excess is deposited in the cells of the liver, heart, pancreas and joints, where it triggers oxidative damage and gradually replaces the tissue with scars.
- Hereditary form associated with iron metabolism genes
- Secondary overload due to frequent blood transfusions
- Overload in thalassemia and other anemias with ineffective hematopoiesis
- Chronic liver disease and alcohol abuse
- Long-term unjustified intake of iron supplements
- Iron overload in metabolic syndrome
Symptoms and organ damage
During the first years, the disease proceeds silently because iron accumulates slowly. In men, complaints appear earlier, in women - usually after menopause, since menstruation naturally reduces iron reserves. The typical onset is constant fatigue, joint pain, especially in the second and third metacarpophalangeal joints, and decreased libido. Later, liver enlargement, blood sugar disturbances, changes in skin color to grayish-bronze, heart rhythm disturbances and shortness of breath appear.
- Chronic fatigue and weakness
- Pain and stiffness in the joints of the hands
- Grayish-bronze skin tone
- Enlarged liver, heaviness in the right hypochondrium
- Diabetes mellitus
- Decreased libido, cycle disorders, infertility
- Shortness of breath, edema, arrhythmia with heart damage
What are the dangers of iron overload?
The main target is the liver. Long-term accumulation of iron leads to fibrosis, then to cirrhosis and significantly increases the risk of liver cancer, and this risk persists even after normalization of iron reserves. The cells in the pancreas that produce insulin are damaged and diabetes develops. Deposition in the heart causes cardiomyopathy with heart failure and rhythm disturbances. The pituitary gland also suffers: the production of sex hormones decreases. That is why it is important to identify the disease before irreversible changes occur.
- Fibrosis and cirrhosis of the liver
- Increased risk of hepatocellular cancer
- Diabetes mellitus
- Cardiomyopathy and rhythm disturbances
- Arthropathy with joint destruction
- Hypogonadism and infertility
- Increased susceptibility to certain infections
Diagnostics
The examination begins with two indicators: ferritin and transferrin saturation with iron. Ferritin reflects stores, but also increases during inflammation, so it is assessed together with C-reactive protein. Persistently high transferrin saturation is a more specific sign of overload. If a hereditary form is suspected, genetic analysis is performed. The degree of iron accumulation in the liver is accurately shown by MRI, and the severity of fibrosis is shown by elastography. Liver biopsy is rarely used today, mainly in cases of high ferritin and unclear diagnosis.
- Serum ferritin
- Iron and latent iron binding capacity
- Calculation of transferrin saturation
- Liver tests ALT and AST, glucose and HbA1c
- Genetic research if a hereditary form is suspected
- MRI of the liver to assess iron stores
- Liver elastography, ECG and echocardiography
Treatment and lifestyle
The main method for the hereditary form is therapeutic bloodletting: red blood cells are removed from the blood, and the body uses excess iron to form new ones. At first, procedures are done frequently, until ferritin decreases to target values, then they switch to a maintenance regimen several times a year. If bloodletting is contraindicated, for example in case of anemia or heart disease, iron-binding drugs are used. A complete abstinence from alcohol and from supplements with iron and high doses of vitamin C is required. Diet is of auxiliary importance.
- Therapeutic bloodletting according to the doctor’s scheme
- Control of ferritin and hemoglobin during treatment
- Iron chelators for contraindications to phlebotomy
- Complete abstinence from alcohol
- Refusal of iron supplements and large doses of vitamin C
- Limiting red meat and offal, avoiding raw shellfish
- Liver monitoring and screening for liver cancer in cirrhosis
- Examination of blood relatives