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Neuroradiology Case of the Week

   Case 60

Ravinder Sidhu MD, Jeevak Almast MD, Leena Ketonen MD, PhD,
and P-L Westesson MD, PhD, DDS

Clinical Presentation: A 27-year-old male with sickle cell disease presented with low backache.

Radiological Findings: Sagittal T1, T2-weighted and proton-density MR images showed decreased signal intensity throughout all the vertebrae of the lumbar spine (Fig.1A&B). The vertebrae showed codfish appearance suggestive of osteoporosis. There were central defects at a few of the vertebral bodies (Fig. 1C). A note was made of bulging discs from L2/3 to the L5/S1 level. On axial T2-weighted MR image, liver parenchyma showed diffuse hypointense signal (Fig. 2).

Diagnosis: Secondary hemochromatosis due to iron overload by repeated blood transfusions

Discussion:  The regular and frequent administration of red blood cell transfusions to patients with hemoglobinopathies such as thalassemia, sickle cell disease and hemophilia has prolonged the survival and eliminated the consequences of anemia. However, it has exacerbated the problem of tissue iron overload thus leading to secondary hemochromatosis. In hemochromatosis, there is an inappropriate increase in iron absorption from the gastrointestinal tract. This excess preferentially deposits iron within parenchymal cells of liver, spleen, pancreas, heart and other organs leading to cellular damage and organ dysfunction. Iron within transfused red blood cells and myoglobin, however is deposited primarily in the reticuloendothelial cells of the liver, spleen, and bone marrow. Reticuloendothelial iron deposition tends not to produce clinically significant organ dysfunction [1].
    Since liver is the principal organ responsible for the storage and detoxification of iron, and also the first and foremost organ damaged by heavy iron overload, the standard for the diagnosis of hemochromatosis is liver biopsy with determination of the hepatic iron index value [2]. Liver biopsy, however is invasive and may be associated with complications, therefore, other non-invasive methods have been proposed such as computed tomography attenuation measurements, bulk magnetic susceptibility, nuclear resonance scattering of gamma rays, and non-invasive evaluation of skin iron by means of diagnostic x-ray fluorescence spectrometry. Although, computed tomography demonstrates an increase in the attenuation of liver in hepatic iron overload, it is relatively insensitive to mild degrees of increased hepatic iron, especially if there is associated fatty change in liver [3-5].
    Magnetic resonance imaging has been considered a promising noninvasive modality to estimate hepatic iron concentration. Reticuloendothelial deposits of ferritin and its denatured form, hemosiderin, are the major store of body iron. They appear hypointense on MR images due to an increased 1/T2 caused by the magnetic properties of hemosiderin and ferritin. Standard spin-echo sequences have been shown to be sensitive, but not specific, for distinguishing mild from marked degrees of iron excess. Gradient-echo sequences are more sensitive to the filed inhomogeneities induced by paramagnetic substances such as iron.
    It is important to establish the diagnosis of hemochromatosis as treatment with phlebotomy in the early stage can be helpful. Secondly, if the hemochromatosis is of an idiopathic type, then human leukocyte antigen typing or serum ferritin and transferritin saturation could be performed for family screening tests for hemochromatosis.

References:

1. Gomori JM, Horev G, Tamary H, Zandback J, Kornreich L, Zaizov R, Freud E, Krief O, Ben-Meir J, Rotem H. Hepatic iron overload: quantitative assessment. Radiology 1991; 179:367-369.
2. Villeneuve JP, Bilodeau M, Lepage R, Cote J, Lefebvre M. Variability in hepatic iron concentration measurement from needle-biopsy specimens. J Hepatol 1996; 25:172-177.
3. Long JA, Doppman JL, Nienhuis AW, Mills SR. Computed tomographic analysis of beta-thalassemia syndrome with hemochromatosis: pathologic findings with clinical and laboratory correlations. J Comput Assist Tomogr 1980; 4:159-165.
4. Oliveri NF, Grisaru D, Daneman A, Matin DJ, Rose V, Freedman MH. Computed tomography scanning of the liver to determine efficacy of iron chelation therapy in thalassemia major. J Pediatrics 1989; 114:427-430.
5. Geodesy R, Goldfarb A, Dagan I, Rachmilewitz EA. Noninvasive analysis of skin iron and zinc levels in beta-thalasemia major and intermedia. J Lab Clin Med 1985; 105:44-51.