Correlative Study of Iron Accumulation in Liver, Myocardium, and Pituitary Assessed With MRI in Young Thalassemic Patients

Abstract

Clinical complications resulting from unevenly iron accumulation in individual organs of patients with beta-thalassemia major can affect both expectancy and quality of life. Magnetic resonance imaging (MRI) offers a quantitative, noninvasive, accurate method for estimating iron levels in various tissues, not easily accessible with other techniques. The aim of this study was to evaluate and correlate the level of iron accumulation in different organs (anterior pituitary, myocardium, and liver) assessed with MRI, in children and young adults with beta-thalassemia major. Thirty children and young adults (13 female and 17 male patients) with homozygous beta-thalassemia, treated conventionally, were studied with hepatic, myocardial, and hypophyseal MRI. For liver and myocardium, we calculated the natural logarithm of the signal-to-air ratio in flash 2-dimensional sequences with electrocardiogram gating, whereas for anterior pituitary, the signal intensity was measured in sagittal T2 sequences. All scans were performed within 3 months. In 13 patients, data regarding liver iron concentrations (LIC) assessed by percutaneous liver biopsy were available. The mean of serum ferritin concentrations for 1 year before scans was calculated for each patient. MRI values in myocardium and liver showed a significant negative correlation to age (r=-0.73 and -0.69, respectively). For pituitary MRI, a linear regression with age was recorded in patients over 14 years of age (r=-0.67), whereas a relatively increased signal intensity reduction was recorded in pubertal subjects. Mean serum ferritin concentrations ranged from 252 to 5872 mug/L with an average of 1525+/-1047 mug/L. No statistical significant correlation was noted between mean ferritin levels versus liver, pituitary, and cardiac MRI values (r=-0.49, -0.28, and -0.1, respectively). Mean LIC values assessed by percutaneous biopsy were 13.76+/-11.6 mg/g of dry tissue. A statistically significant negative correlation was observed between liver MRI readings and LIC determined by biopsy (r=-0.89). None of the 3 organs studied with MRI were significantly correlated to each other. Pituitary to liver MRI values and liver to myocardial MRI values were moderately correlated (r=0.34 and 0.42, respectively). Pituitary MRI was not correlated at all to myocardial MRI (r=-0.001). In conclusion, iron accumulation in thalassemic patients is a procedure progressing with age, which seems to act independently in different organs. MRI represents a reliable, noninvasive method for assessing iron overload in various tissues, non-easily accessible with other techniques. Regular scanning, to recognize preclinically excessive iron deposits and intensified chelation therapy, can prevent serious and fatal complications.

A decisional algorithm to start iron chelation in patients with beta thalassemia

“…This needs to be further assessed by larger prospective studies based on repeated measurements of TSAT. Elisabetta Defraia, 4 Carlo Dessì, 4 Maria Loreta Foschini, 4 Nicolina Giagu, 4 Giovan Battista Leoni, 4 Maddalena Morittu, 4 and Renzo Galanello …”

“…1 However, in nonchronically-transfused thalassemia patients, ferritin hepatosecretion does not match liver iron accumulation and neither is serum ferritin representative of extrahepatic siderosis. [1][2][3][4] These inherent limitations in viewing serum ferritin as a reliable marker of iron overload have led us to consider other plasma factors that might be more pertinent to the etiopathology of iron overload and relevant for initiating treatment and assessing its long-term efficacy. 5 Here, we considered labile plasma iron (LPI), the major redox-active and readily chelatable fraction of non-transferrin-bound iron (NTBI), as a more direct marker of impending tissue iron overload and, therefore, as a potential indicator for the initiation of chelation therapy.…”

Accumulation of lipid peroxidation‐derived DNA lesions in iron‐overloaded thalassemic mouse livers: Comparison with levels in the lymphocytes of thalassemia patients

“…This knowledge could be applied to thalassemia patients when average iron levels in the liver exceeds a certain threshold. 41,42 In these cases, increased etheno-DNA adducts would be expected to be formed in the liver.…”

Increased Urinary 8-Oxo-7,8-Dihydro-2′-Deoxyguanosine Excretion in a Sample of Egyptian Children With Beta Thalassemia Major: Marker for Lipid Peroxidation-Induced Dna Damage

“…There was no correlation between serum ferritin levels and either with urinary εdA and εdC or with serum NTBI. Recent studies by the magnetic resonance imaging showed that the total tissue iron does not reflected by serum ferritin alone [20,21]. Total body DNA adducts which are formed in any tissue in the body are excreted in urine after DNA repair.…”