Figures 1 - 2: Comparison of Figure 1 (out of phase) with Figure 2 (in phase) demonstrates a diffuse drop out of T1 signal in the liver parenchyma on the longer TE sequence during the in phase. This is consistent with susceptibility artifact caused by iron deposition.

Figures 3 - 4: Comparison of Figure 3 (out of phase) with Figure 4 (in phase) demonstrates a marked and diffuse drop out of T1 signal in the pancreas during the in phase. This is consistent with susceptibility artifact caused by iron deposition.

Figure 5: Axial STIR image demonstrates a focal lesion in the hepatic dome with mildly increased signal intensity. This lesion proved to be a hepatoma.

Figure 6: Post contrast VIBE image demonstrates heterogeneous liver enhancement consistent with cirrhosis and signs of portal hypertension including spontaneous spleno-renal shuts and splenomegaly.

Primary hemochromatosis.

Hemochromatosis is characterized by a progressive increase in total body iron stores with abnormal iron deposition in multiple organs. Primary hemochromatosis is a genetic disorder, whereas secondary hemochromatosis can be the result of a variety of disorders including congenital (e.g. thalassemia, sideroblastic anemia) and acquired (e.g. myelodysplasia, hypoplastic anemia) anemias, excess iron intake, and secondary to liver disease.

In primary hemochromatosis, also known as “bronze diabetes” and idiopathic hemochromatosis, the liver is the main organ for abnormal iron deposition. Iron is a direct hepatotoxin causing oxidative damage leading to perilobular fibrosis. As the disease progresses, the liver becomes cirrhotic and broad fibrous septa surrounding large areas of relatively normal liver parenchyma develop leading to micronodular cirrhosis. Other sites of abnormal iron deposition include the pancreas, heart, anterior pituitary gonadotropin-producing cells, and joints.

Secondary hemochromatosis, also called hemosiderosis, can be due to a wide variety of causes. Patients who receive multiple blood transfusions secondary to a variety of anemias can develop iron overload. The reticuloendothelial system (RES) becomes saturated, and additional iron deposits are seen in the parenchymal cells of the liver, pancreas, spleen, heart, and bone marrow where it can cause end-organ damage. Patients with extremely high rates of erythropoiesis can also develop hemosiderosis. These patients include those with chronic hemolytic disorders, sickle-cell disease, and congenital spherocytosis. The hyperplastic bone marrow in these patients leads to an increased demand for iron which results in increased absorption of iron even in the presence of large iron stores. The iron is first deposited in the RES and then redistributed to parenchymal cells of the liver, pancreas, and other organs.

The liver is the most common site of involvement in both primary and secondary hemochromatosis. Hepatomegaly is often present and is most marked in the left lobe. Portal hypertension is mild and variceal bleeding and splenomegaly is uncommon. In primary hemochromatosis, the liver is the main organ for abnormal iron deposition, and if untreated may lead to cirrhosis. Hepatocellular carcinoma is not commonly seen in patients with hemochromatosis without cirrhosis. The pancreas also is commonly involved by primary hemochromatosis. Patients with early hemochromatosis (non-cirrhotic) frequently have insulin resistance, while patients with cirrhosis and hemochromatosis often have insulin-dependent diabetes mellitus (IDDM). Cardiac involvement includes cardiomyopathy and arrhythmias and is a common cause of death in patients with primary hemochromatosis. Arthropathy is also a common clinical manifestation with primary hemochromatosis. It can occur early during the course of the disease and can often be the presenting complaint.

Increased iron in the liver can be detected and quantified by MRI. Iron deposition causes magnetic susceptibility artifact, which leads to spin dephasing and results in decreased signal intensity on T2-weighted MRI images. T2*-weighted gradient echo images with longer TE values are most sensitive to magnetic susceptibility artifact, thus are the best sequences to detect increased iron in the liver. In determining whether the signal intensity of the liver is abnormally low, skeletal muscle can be used as a control. If the liver demonstrates signal intensity equal to or lower than that of skeletal muscle on T2-weighted images, increased iron accumulation in the liver can be diagnosed.

Most patients with primary hemochromatosis do not have involvement of the spleen. Iron deposition occurs in the parenchymal cells of the liver (hepatocytes) and not in the reticuloendothelial system (Kupffer cells and spleen). Therefore, a diagnostic feature of primary hemochromatosis is that the signal intensity of the spleen is not substantially decreased on T2-weighted images. In patients with primary hemochromatosis, iron deposition can occur in the pancreas. However, pancreatic involvement is uncommon in patients without cirrhosis. Patients with primary hemochromatosis can also develop hepatocellular carcinoma. Because these tumor cells do not contain excess iron, they are shown as high-signal intensity masses relative to the iron-overloaded liver on MR images. In patients with hemochromatosis, non-siderotic nodules that are not hemangiomas or cysts are highly suspicious for hepatocellular carcinoma.

Patients with secondary hemochromatosis due to transfusional overload first accumulate iron in the RES.. Iron overload in the RES results in low signal intensity of the spleen, liver, and bone marrow on MR images. As the RES becomes saturated with iron, iron may deposit in the parenchymal cells of the liver, pancreas, and heart. In these patients, fibrosis in the liver is usually mild and cirrhosis is rare. Note that the signal intensity of the spleen in usually normal in primary hemochromatosis, whereas the signal intensity of the pancreas is normal with most cases of secondary hemochromatosis associated with transfusional overload.

References:

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2. Okuda K, Mitchell DG, Itai Y, and Ariyama J (eds.). Hepatobiliary Diseases: Pathophysiology and Imaging. Oxford: Blackwell Science, c2001. pp. 451-456.
3. Gandon Y, Guyader D, Heautot JF, et al. Hemochromatosis: Diagnosis and Quantification of Liver Iron with Gradient-Echo MR Imaging. Radiology. 1994; 193: 533-8.
4. Joffe, Sandor. Hemochromatosis. (2001). eMedicine.