Ferritin - Meaning and Tests to Measure Ferritin Levels

Introduction

Red blood cells need iron to form healthy red blood cells and carry oxygen around the body. Other body parts like the liver, bone marrow, and muscles also need iron. Ferritin estimation is a valuable tool for the clinician, both for evaluating common disease states, such as iron-deficiency anemia, and for evaluating hereditary and acquired iron-overload conditions.

Serum ferritin is usually part of a panel of several blood tests routinely ordered to diagnose and manage these conditions and is a useful marker in most populations. Elevated serum ferritin levels are a diagnostic tool for rare autoimmune or inflammatory disorders.

What Is Ferritin?

Ferritin is a form of protein that stores the majority of iron molecules in the blood, is essential for iron breakdown, and is responsible for various physiologic and pathologic processes. Ferritin is also a serum marker of total iron stored in the blood. In cases of both iron scarcity and overload, serum ferritin is widely used in diagnosis and management. Elevated serum and tissue ferritin are associated with coronary artery disease, malignancy, and stem cell transplantation.

Ferritin is also involved with less common but potential human diseases such as anemias (specially sideroblastic), neurodegenerative disorders (loss of structure or function of neurons), and hemophagocytic syndrome (a hyperinflammatory response that can be life-threatening). The normal range for blood ferritin is suggested as follows:

• For adult men, 24 to 336 micrograms per liter.

• For adult women, 11 to 307 micrograms per liter.

What Is the Ferritin Test?

A ferritin test measures how much iron is stored in the blood. If a ferritin test measures are lower, it simply means that the body's iron stores are low, and there is iron deficiency, resulting in anemia. If a ferritin test measures higher, it indicates an underlying condition that causes the body to store too much iron. It could be liver disease, rheumatoid arthritis, other inflammatory conditions, or even hyperthyroidism. Some types of cancer have also been shown to cause changes in ferritin levels.

1. Lower Than Normal Results: Low levels of ferritin lead to iron-deficiency anemia indicating that too few red blood cells are present in the body. In adults, low iron levels are caused due to long-term blood loss. If the presence of ulcers or tumors is seen in the gut, intestinal bleeding, or prolonged heavy menstrual periods result in frequent loss of iron, then the body produces and develops an iron deficiency. This is also seen with pregnant or breastfeeding women.

2. Higher Than Normal Results: High levels of ferritin can damage the joints, heart, liver, and pancreas. The most common cause of the high levels of ferritin comes from an inherited disease known as hemochromatosis. Many people born with this disease never show symptoms, especially women who lose excess iron through menstruation. But with time, the excess iron starts to build up, and they may feel pain in the joint and belly areas.

To summarize, high ferritin is caused by the following:

• Hemochromatosis - It causes the body to absorb too much iron.

• Porphyria - A group of disorders caused by an enzyme deficiency that affects the nervous system and skin.

• Rheumatoid Arthritis or Another Chronic Inflammatory Disorder - It results from iron overload and deposition in the joint areas of the body.

• Liver Disease - Chronic liver disease decreases the synthetic functions of the liver, including the production of hepcidin, a key protein in iron metabolism.

• Hyperthyroidism - Hypothyroidism also decreases hydrochloric acid (HCl) production, which means food absorption is not very good. Especially iron absorption decreases due to low HCl.

• Leukemia - Excess iron promotes the development of leukemia due to the pro-oxidative nature of iron and its damaging effects on DNA.

• Hodgkin's Lymphoma- Anemia is a frequent finding of Hodgkin's lymphoma (HL) diagnosis, and it exhibits the features of anemia (chronic disease) because of abnormalities in iron metabolism.

• Multiple Blood Transfusions - Increased iron from multiple blood transfusions causes a rise in serum ferritin levels.

• Alcohol Abuse - Alcohol consumption can increase the absorption of iron.

• Taking Too Many Iron Supplements - Iron poisoning occurs when children or adults accidentally intake many iron supplements at once.

Iron Deficiency Anemia

• Iron deficiency anemia is extremely common in developed and undeveloped countries; serum ferritin is routinely used to diagnose and treat anemia.

• Iron deficiency can emerge from a lack of a balanced diet, blood loss, or the body not absorbing iron from food. A healthy adult generally takes an extremely poor diet to get a nutritional iron deficiency. In contrast, a low iron level is found to be the most common nutritional deficiency in children.

• Low serum ferritin is highly specific for iron deficiency anemia. Reference ranges for serum ferritin vary across laboratories. The normal range for men and women includes 30 to 300 ng/ml and 10 to 200 ng/ml, respectively.

• It is widely accepted that serum ferritin less than 12 ng/ml indicates depletion of iron stores. Only two conditions other than iron deficiency can lower serum ferritin:

  1. Ascorbate deficiency is the first step in iron absorption that requires the reduction of ferric iron to ferrous iron, a change that is catalyzed by duodenal ferric reductase. Iron deficiency is associated with high iron absorption, high ferric reductase activity, and high duodenal ascorbate concentrations.

  2. Hypothyroidism also affects hydrochloric acid (HCl) production, resulting in ill absorption of food, especially iron.

What Do the Ferritin Test Results Mean?

Test results are divided based on age and gender. The test results may show intermediate values. Ask the healthcare provider to explain the results. Results are often calculated in nanograms per milliliter (ng/mL). The normal range for ferritin in the given blood serum is:

• Ranges from 20 to 250 ng/mL for adult males.

• Ranges from 10 to 120 ng/mL for adult females, 18 to 39 years.

• Ranges from 12 to 263 ng/mL for females 40 years and older.

• Ranges from 25 to 200 ng/mL for newborns.

• Ranges from 200 to 600 ng/mL at one month old.

• Ranges from 50 to 200 ng/mL at two to five months old.

• Ranges from 7 to 140 ng/mL for children six months to 15 years.

If the results are lower, it may result in iron deficiency anemia. Certain medicines could also cause lower levels. Antacids can cause absorption defects, and nonsteroidal anti-inflammatory medicines can cause blood leakage in the digestive tract.

If the results are towards a higher value, it may suggest:

• Hyperthyroidism - A condition where the thyroid gland is insufficient in producing enough of certain crucial hormones.

• Hemochromatosis - A condition where the body absorbs too much iron from food.

• Liver Dysfunction - Liver fibrosis in chronic hepatitis C and nonalcoholic fatty liver disease

• Inflammatory Diseases - Such as chronic kidney disease and rheumatoid arthritis.

• Cancer - Such as leukemia, lymphoma, or a breast lump.

Higher levels of iron can also result from iron-replacement therapy or a blood transfusion done recently.

What Causes Iron Overload?

Ferritin is also clinically useful in the diagnosis and treatment of iron overload. Because iron is actively regulated at the scene of absorption, there is no physiologic process to eradicate excess iron.

• Most cases of iron overload occur due to abnormal iron absorption or excess iron administration (usually the result of repeated blood transfusions). Excess iron collects within the liver and heart, which causes chronic free-radical induced injury.-overloading, in the long run, affects the heart and liver, manifesting in organ failure.

• Other clinical manifestations include arthropathy (joint disease), skin changes, and endocrine dysfunction resulting from iron deposition.

• The phenotype of advanced iron overload has been termed “bronze diabetes,” representing the triad symptoms- skin hyperpigmentation, diabetes resulting from pancreatic endocrine dysfunction, and liver cirrhosis.

Conclusion

Despite its clear use in assessing body iron stores, cellular mechanisms involved in the secretion of ferritin, which does not contain a canonical leader sequence, remain unknown. This will be important to unravel, particularly as it is becoming clear that extracellular ferritin can subsume many functions unrelated to its classic role as an intracellular iron storage protein. The delineation of precise relationships between ferritin secretion and immunomodulation, iron delivery, and triggering of signaling pathways will all require further investigation.