Ferritin

Ferritin is found in virtually all cells of the body and serves as the cellular storage repository for iron.^2,3 Ferritin is a macromolecule with an average molecular weight of near 440 kD that varies depending on the iron content. Ferritin consists of a protein shell (apoferritin) of 24 subunits surrounding an iron core consisting of up to 4000 ferric iron ions. The majority of ferritin iron stores are found in the liver, spleen, and bone marrow. Ferritin is present in small concentration correlates with total-body iron stores, making its measurement valuable for the assessment of disorders of iron metabolism.

Low levels of ferritin can be found when iron stores are exhausted, well before the serum iron level has become affected. In the setting of anemia, low serum ferritin is a very specific biomarker for iron deficiency anemia. In fact, there is no clinical situation other than iron deficiency in which extremely low values of serum ferritin are seen; however, some clinical states involving infection or inflammation can cause the ferritin level in the serum of patients with iron deficiency to increase into the normal range. Ferritin is an acute-phase reactant that is thought to play a role in the body's defense against oxidative stress and inflammation. Increased ferritin values can also be observed in malignant disease, including acute leukemia; Hodgkin's disease; and carcinoma of the lung, colon, liver, and prostate. Consequently, serum ferritin in the normal range reflects iron sufficiency only in the absence of these conditions.

Patients with a serum ferritin concentration below the lower limit of the reference interval have a very high probability of being iron deficient; however, given the low sensitivity of a low ferritin level (below the lower limit of normal), a higher ferritin cutoff may be more appropriate for screening for potential iron deficiency in some populations.^4-7 It is exceedingly uncommon for ferritin levels to exceed 100 ng/mL in patients with iron deficiency.^6,7

An elevated ferritin level can result from iron overload due, in part, to increased hepatic ferritin synthesis.⁸ Iron overload can occur in hemochromatosis, other excess iron storage disorders, and in individuals who have received multiple blood transfusions. Ferritin can also become markedly elevated secondary to obesity, chronic alcohol consumption, steatohepatitis, chronic inflammation, viral hepatitis, and malignancy. The increased prevalence of obesity has likely resulted in the increased incidence of ferritin elevations, as fatty liver may be the most common cause of an elevated serum ferritin.⁸ Clinical assessment is required to determine whether the serum ferritin elevation is related to hemochromatosis or another underlying liver disease.⁹ To confirm the diagnosis of hemochromatosis, other iron tests (iron, TIBC), and genetic testing may be performed.