Computed Tomography
Noncontrast CT scan in a 47-year-old man with sickle cell disease who had undergone multiple transfusions demonstrates diffuse increased attenuation of the liver, representing abnormal iron deposition. The spleen is small and calcified from autosplenectomy.
Findings
Patients with increased hepatic iron demonstrate diffuse increased attenuation of the liver, usually greater than 75 Hounsfield units on noncontrast examination. The liver vasculature appears particularly prominent because of the increased contrast between the vessels and the high-attenuation liver. Hepatomegaly also may be seen on CT scan.19 Dual-phase (arterial and venous) CT can help detect hepatocellular carcinoma in patients with cirrhosis.
Degree of Confidence
MRI is more sensitive and specific than CT for detection of abnormal hepatic iron deposition.
False Positives/Negatives
Other abnormalities that can cause increased attenuation of the liver on CT include amiodarone toxicity, Thorotrast, glycogen storage disease, gold therapy, and Wilson disease.
Magnetic Resonance Imaging
T2-weighted gradient echo axial image in a patient with hemochromatosis demonstrates diffuse abnormal low signal intensity of the liver. The pancreas and spleen appear normal.
T2-weighted spin echo axial image in a 4-year-old boy with thalassemia demonstrates abnormal low signal intensity of the liver, spleen, and pancreas.
T2-weighted gradient echo axial image in a 24-year-old man with sickle cell disease who had undergone multiple transfusions demonstrates diffuse abnormal low signal intensity of the liver and spleen.
T2-weighted spin echo axial image in a 40-year-old man with alpha-thalassemia demonstrates diffuse abnormal low signal intensity of the liver, spleen, and pancreas.
Findings
Increased iron in the liver can be detected and quantified by MRI. Iron causes magnetic susceptibility artifact, which leads to spin dephasing (T2*-related signal loss). This dephasing results in decreased signal intensity on MRI images.11,19,20,21,22,23,24
- T2-weighted gradient echo images are most sensitive to magnetic susceptibility artifact, thus are the best sequences to detect increased iron in the liver. T2-weighted gradient echo images can be performed as breath-hold images on most scanners. On a 1.5-T scanner, an echo time (TE) of at least 10 milliseconds and a flip angle of less than 30° should be used. The recovery time (TR) is less important and should be chosen based on the number of slices to be obtained and duration of the breath-hold.
- Although less sensitive than T2-weighted gradient echo sequences, spin echo sequences also may demonstrate decreased signal intensity of the liver in patients with increased hepatic iron concentration. Spin echo pulse sequences with a long TE (T2-weighted sequences) are more sensitive than those with a short TE.
- 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, such as the paraspinal muscles, on either T2-weighted gradient echo, or T2-weighted spin echo images, increased iron accumulation in the liver can be diagnosed.
- Most patients with primary hemochromatosis do not have involvement of the spleen; iron deposition in primary hemochromatosis occurs in the parenchymal cells of the liver (hepatocytes) and not in the reticuloendothelial system (Kupffer cells and spleen). Therefore, splenic signal intensity usually is normal in these patients.
- In patients with primary hemochromatosis, iron deposition can occur in the pancreas. Pancreatic involvement is uncommon in patients without cirrhosis. Most cirrhotic patients with primary hemochromatosis have pancreatic involvement and may have type 1 diabetes mellitus. These patients with pancreatic involvement usually demonstrate low signal intensity of the pancreas, regardless of whether they have diabetes.
- Many types of anemia require multiple blood transfusions, resulting in abnormal iron deposition in the reticuloendothelial system. These patients demonstrate MR evidence of iron overload in the liver and spleen with low signal of both organs, particularly on T2-weighted gradient echo images. If the reticuloendothelial system becomes saturated with iron from too many transfusions, iron may deposit in the parenchymal cells of the liver, pancreas, and heart. Therefore, these patients may demonstrate low signal in the liver, spleen, and pancreas.1,8,9,10,11,12
- Patients with thalassemia who have not undergone transfusions may have increased iron in the liver with a similar appearance to that in patients with primary hemochromatosis. If these patients are transfusion-dependent, they may demonstrate low signal in the liver and spleen and possibly the pancreas. Bantu siderosis also may cause decreased signal intensity of the liver and spleen from abnormal iron deposition in these organs.
- Quantitative measurement of hepatic iron content can be performed with MR. Gandon et al evaluated T2 relaxation time and signal intensity ratios of liver to other tissues as a means of quantifying hepatic iron content. T2 relaxation time did not correlate with hepatic iron content as well as the liver-to-tissue signal-intensity ratios. They found the best correlation using a T2-weighted gradient echo sequence and calculating a ratio of the signal intensity of liver to that of fat.
- Bonkovsky et al found the best results using a gradient echo sequence with a repetition time of 18 milliseconds, a TE of 5 milliseconds, and a flip angle of 10°.21 They found the best results with a correlation between the iron concentration in the liver and the natural logarithm of the ratio of signal intensity of the liver to the standard deviation of the background noise. However, to accurately perform quantitative MR, each MR scanner needs to be properly calibrated with patients who have undergone liver biopsy to measure iron content.
- Alustiza et al found that at least 2 different pulse sequences are required to adequately quantify hemochromatosis, and they used T2- and intermediate-weighted gradient echo sequences.20
- In order to accurately perform quantitative MR, each MR scanner must be properly calibrated with patients who have undergone liver biopsy to measure iron content. In the future, if phantoms are developed, it may be possible to calibrate each MR scanner against phantoms. High field-strength magnets are likely to be more accurate at quantifying hepatic iron concentration than mid or low field-strength units.
Degree of Confidence
Quantitative measurement of hepatic iron content by MRI has the advantage of sampling the entire liver, whereas liver biopsy only samples a small area of liver parenchyma. In addition, quantitative measurement of hepatic iron by MRI avoids the risks inherent in percutaneous liver biopsy.
False Positives/Negatives
Although MR is sensitive at detecting abnormal hepatic iron, particularly if performed with optimized technique for this purpose, it may not always determine the etiology of the abnormal iron deposition based on its distribution. However, this is typically not a difficult problem clinically, as the patient's history usually confirms the etiology.
Ultrasonography
Findings
Iron deposits in the liver usually do not alter liver echogenicity. If sonographic liver abnormalities are present, they are usually secondary to cirrhosis. An echogenic pancreas has been described with iron deposition.
More on Hemochromatosis |
| Overview: Hemochromatosis |
 Imaging: Hemochromatosis |
| Follow-up: Hemochromatosis |
| Multimedia: Hemochromatosis |
| References |
| Further Reading |
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References
Schranz M, Talasz H, Graziadei I, Winder T, Sergi C, Bogner K, et al. Diagnosis of hepatic iron overload: a family study illustrating pitfalls in diagnosing hemochromatosis. Diagn Mol Pathol. Mar 2009;18(1):53-60. [Medline].
Pietrangelo A. Inherited metabolic disease of the liver. Curr Opin Gastroenterol. Apr 1 2009;[Medline].
Picot J, Bryant J, Cooper K, Clegg A, Roderick P, Rosenberg W, et al. Psychosocial aspects of DNA testing for hereditary hemochromatosis in at-risk individuals: a systematic review. Genet Test Mol Biomarkers. Feb 2009;13(1):7-14. [Medline].
Phatak PD, Sham RL, Raubertas RF. Prevalence of hereditary hemochromatosis in 16031 primary care patients. Ann Intern Med. Dec 1 1998;129(11):954-61. [Medline].
Gao J, Chen J, Kramer M, Tsukamoto H, Zhang AS, Enns CA. Interaction of the hereditary hemochromatosis protein HFE with transferrin receptor 2 is required for transferrin-induced hepcidin expression. Cell Metab. Mar 2009;9(3):217-27. [Medline].
Deugnier Y, Bourgain C, Mosser J. [Acquired and genetic factors influencing the penetrance of HFE haemochromatosis]. Bull Acad Natl Med. May 2008;192(5):873-81; discussion 881. [Medline].
Bartolo C, McAndrew PE, Sosolik RC. Differential diagnosis of hereditary hemochromatosis from other liver disorders by genetic analysis: gene mutation analysis of patients previously diagnosed with hemochromatosis by liver biopsy. Arch Pathol Lab Med. Jul 1998;122(7):633-7. [Medline].
Mair SM, Weiss G. New pharmacological concepts for the treatment of iron overload disorders. Curr Med Chem. 2009;16(5):576-90. [Medline].
Howard JM, Ghent CN, Carey LS. Diagnostic efficacy of hepatic computed tomography in the detection of body iron overload. Gastroenterology. Feb 1983;84(2):209-15. [Medline].
Jensen PD, Jensen FT, Christensen T. Evaluation of transfusional iron overload before and during iron chelation by magnetic resonance imaging of the liver and determination of serum ferritin in adult non-thalassaemic patients. Br J Haematol. Apr 1995;89(4):880-9. [Medline].
Villari N, Caramella D, Lippi A. Assessment of liver iron overload in thalassemic patients by MR imaging. Acta Radiol. Jul 1992;33(4):347-50. [Medline].
[Best Evidence] McLeod C, Fleeman N, Kirkham J, Bagust A, Boland A, Chu P, et al. Deferasirox for the treatment of iron overload associated with regular blood transfusions (transfusional haemosiderosis) in patients suffering with chronic anaemia: a systematic review and economic evaluation. Health Technol Assess. Jan 2009;13(1):iii-iv, ix-xi, 1-121. [Medline].
Flyer MA, Haller JO, Sundaram R. Transfusional hemosiderosis in sickle cell anemia: another cause of an echogenic pancreas. Pediatric Radiology. 1993;23(2):140-2.
Wang X, Leiendecker-Foster C, Acton RT, Barton JC, McLaren CE, McLaren GD, et al. Heme carrier protein 1 (HCP1) genetic variants in the Hemochromatosis and Iron Overload Screening (HEIRS) Study participants. Blood Cells Mol Dis. Mar-Apr 2009;42(2):150-4. [Medline].
Pedersen P, Milman N. Genetic screening for HFE hemochromatosis in 6,020 Danish men: penetrance of C282Y, H63D, and S65C variants. Ann Hematol. Jan 22 2009;[Medline].
Phatak PD, Bonkovsky HL, Kowdley KV. Hereditary hemochromatosis: time for targeted screening. Ann Intern Med. Aug 19 2008;149(4):270-2. [Medline].
Adams PC, Reboussin DM, Barton JC, Acton RT, Speechley M, Leiendecker-Foster C, et al. Serial serum ferritin measurements in untreated HFE C282Y homozygotes in the Hemochromatosis and Iron Overload Screening Study. Int J Lab Hematol. Aug 2008;30(4):300-5. [Medline].
Acton RT, Barton JC, Passmore LV, Adams PC, McLaren GD, Leiendecker-Foster C, et al. Accuracy of family history of hemochromatosis or iron overload: the hemochromatosis and iron overload screening study. Clin Gastroenterol Hepatol. Aug 2008;6(8):934-8. [Medline].
Kawamoto S, Soyer PA, Fishman EK. Nonneoplastic liver disease: evaluation with CT and MR imaging. Radiographics. Jul-Aug 1998;18(4):827-48. [Medline].
Alustiza JM, Artetxe J, Castiella A, et al. MR quantification of hepatic iron concentration. Radiology. Feb 2004;230(2):479-84. [Medline].
Bonkovsky HL, Rubin RB, Cable EE. Hepatic iron concentration: noninvasive estimation by means of MR imaging techniques. Radiology. Jul 1999;212(1):227-34. [Medline].
Gandon Y, Guyader D, Heautot JF. Hemochromatosis: diagnosis and quantification of liver iron with gradient-echo MR imaging. Radiology. Nov 1994;193(2):533-8. [Medline].
Siegelman ES, Mitchell DG, Outwater E. Idiopathic hemochromatosis: MR imaging findings in cirrhotic and precirrhotic patients. Radiology. Sep 1993;188(3):637-41. [Medline].
Siegelman ES, Mitchell DG, Semelka RC. Abdominal iron deposition: metabolism, MR findings, and clinical importance. Radiology. Apr 1996;199(1):13-22. [Medline].
Villeneuve JP, Bilodeau M, Lepage R. Variability in hepatic iron concentration measurement from needle- biopsy specimens. J Hepatol. Aug 1996;25(2):172-7. [Medline].
Further Reading
Clinical guidelines
Screening for hemochromatosis: recommendation statement.
United States Preventive Services Task Force - Independent Expert Panel. 2006. 5 pages. NGC:004959
Screening for hereditary hemochromatosis: a clinical practice guideline from the American College of Physicians.
American College of Physicians - Medical Specialty Society. 2005 Oct 4. 5 pages. NGC:004540
AASLD practice guidelines: evaluation of the patient for liver transplantation.
American Association for the Study of Liver Diseases - Private Nonprofit Research Organization. 2000 Jan (revised 2005 Jun). 26 pages. NGC:004333
Clinical trials
Treatment of Hemochromatosis
Erythrocyte Apheresis Versus Phlebotomy in Hemochromatosis
Oral Nifedipine to Treat Iron Overload
Related eMedicine topics
Hemochromatosis (Dermatology)
Hemochromatosis (Gastroenterology)
Hemochromatosis, Neonatal
Transfusion-Induced Iron Overload
Keywords
hemochromatosis, haemochromatosis, hereditary hemochromatosis, primary hemochromatosis, secondary hemochromatosis, idiopathic hemochromatosis, hemosiderosis, iron overload, iron toxicity
