A serum hepcidin test is a blood test that measures the amount of hepcidin, a hormone produced by the liver. The term “serum” refers to the clear, liquid portion of blood that is separated from solid components like red and white blood cells. For this test, a blood sample is processed in a lab to isolate the serum, where the hepcidin concentration can be accurately measured.
This measurement provides a snapshot of the hormone’s activity at a specific moment. The process is a straightforward blood draw from a vein in the arm, similar to other routine tests. It is a specialized test ordered when a doctor needs to investigate how the body is regulating its iron levels.
The Role of Hepcidin in Iron Regulation
Hepcidin functions as the primary regulator of iron in the body, acting like a gatekeeper that controls iron’s entry into the bloodstream. Its job is to maintain a balance of iron, ensuring there is enough for bodily functions without accumulating to toxic levels. The hormone achieves this by controlling the absorption of dietary iron, the recycling of iron from old red blood cells, and the release of iron from storage sites.
The mechanism of hepcidin involves its interaction with a protein called ferroportin. Ferroportin acts as an iron channel on the surface of cells that allows iron to exit the cell and enter circulation. When hepcidin levels in the blood are high, it binds to ferroportin, causing the protein to be pulled inside the cell and degraded. This action blocks the channel, trapping iron inside cells and lowering the amount of iron available in the bloodstream.
This regulation occurs at three main locations. The first is in the cells lining the small intestine, called enterocytes, which absorb iron from food. The second is in macrophages, a type of white blood cell that recycles iron from old red blood cells. The third location is in liver cells, which store a significant portion of the body’s iron reserves.
Factors Influencing Hepcidin Levels
The liver adjusts its production of hepcidin in response to several signals to manage iron levels. The body’s own iron status is a primary driver of hepcidin synthesis. When iron stores are high, the liver produces more hepcidin to reduce further iron absorption and lock down stored iron. Conversely, when iron levels are low, hepcidin production is suppressed, allowing more iron to be absorbed and released from stores.
Inflammation and infection are also stimuli for hepcidin production. During an inflammatory response, the body releases signaling molecules called cytokines, with interleukin-6 (IL-6) being a strong inducer of hepcidin. This increase in hepcidin is a defense mechanism; by lowering iron levels in the blood, the body can limit its availability to invading pathogens like bacteria, which require it to multiply.
The body’s need to create new red blood cells, a process known as erythropoiesis, also influences hepcidin levels. When there is a high demand for red blood cell production, such as after blood loss, the bone marrow sends signals that suppress hepcidin production. This suppression maximizes the release of iron from all sources to support the synthesis of hemoglobin, the iron-containing protein in red blood cells.
Interpreting Serum Hepcidin Test Results
The results of a serum hepcidin test provide information for diagnosing and managing disorders related to iron metabolism. The interpretation depends on whether the levels are high or low and must be considered alongside other iron-related tests like serum ferritin and transferrin saturation to form a complete picture.
High levels of hepcidin indicate that iron is being restricted from entering the bloodstream. This is a hallmark of a condition known as anemia of chronic disease or anemia of inflammation. In these cases, the body may have adequate iron stores, but elevated hepcidin traps this iron within cells. This prevents the iron from being used by the bone marrow to make new red blood cells, leading to anemia. Conditions like chronic kidney disease, autoimmune disorders, and chronic infections are often associated with high hepcidin.
Low hepcidin levels signify that the body is attempting to maximize iron availability. This is the expected response in iron deficiency anemia, where the body suppresses hepcidin to increase iron absorption. However, inappropriately low hepcidin is a feature of genetic hemochromatosis. In this inherited disorder, a genetic defect prevents the liver from sensing high iron levels, resulting in persistently low hepcidin production. This leads to uncontrolled iron absorption and a toxic buildup of iron in organs like the liver, heart, and pancreas.
Hepcidin in Medical Treatment
The understanding of hepcidin’s role has opened new avenues for medical treatments aimed at correcting iron imbalances. Therapeutic strategies focus on either lowering hepcidin levels or mimicking the hormone’s action, depending on the underlying disease.
For conditions characterized by high hepcidin, such as anemia of chronic disease, the goal is to lower hepcidin or block its effect on ferroportin. Researchers are developing drugs, known as hepcidin antagonists, that can interfere with the hormone’s ability to bind to and degrade ferroportin. These therapies aim to release the trapped iron from storage, making it available for red blood cell production and potentially alleviating the anemia.
In contrast, for diseases caused by hepcidin deficiency, like hemochromatosis, the therapeutic strategy is to increase hepcidin’s effect. This can be achieved with hepcidin agonists, which are molecules that mimic the hormone, or with drugs that stimulate the body’s own hepcidin production. One approach involves silencing a gene called TMPRSS6, which acts as a brake on hepcidin synthesis. Inhibiting TMPRSS6 allows hepcidin levels to rise, reducing excessive iron absorption and protecting the body from iron overload.