scholarly journals An automated liver segmentation in liver iron concentration map using fuzzy c-means clustering combined with anatomical landmark data

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Kittichai Wantanajittikul ◽  
Pairash Saiviroonporn ◽  
Suwit Saekho ◽  
Rungroj Krittayaphong ◽  
Vip Viprakasit
Keyword(s):  
Iron Concentration ◽  
Thalassemia Major ◽  
Anatomical Landmark ◽  
Liver Segmentation ◽  
Liver Iron Concentration ◽  
Liver Iron ◽  
Fuzzy C Means ◽  
Landmark Data ◽  
Fuzzy C Means Clustering ◽  
Liver Region

Abstract Background To estimate median liver iron concentration (LIC) calculated from magnetic resonance imaging, excluded vessels of the liver parenchyma region were defined manually. Previous works proposed the automated method for excluding vessels from the liver region. However, only user-defined liver region remained a manual process. Therefore, this work aimed to develop an automated liver region segmentation technique to automate the whole process of median LIC calculation. Methods 553 MR examinations from 471 thalassemia major patients were used in this study. LIC maps (in mg/g dry weight) were calculated and used as the input of segmentation procedures. Anatomical landmark data were detected and used to restrict ROI. After that, the liver region was segmented using fuzzy c-means clustering and reduced segmentation errors by morphological processes. According to the clinical application, erosion with a suitable size of the structuring element was applied to reduce the segmented liver region to avoid uncertainty around the edge of the liver. The segmentation results were evaluated by comparing with manual segmentation performed by a board-certified radiologist. Results The proposed method was able to produce a good grade output in approximately 81% of all data. Approximately 11% of all data required an easy modification step. The rest of the output, approximately 8%, was an unsuccessful grade and required manual intervention by a user. For the evaluation matrices, percent dice similarity coefficient (%DSC) was in the range 86–92, percent Jaccard index (%JC) was 78–86, and Hausdorff distance (H) was 14–28 mm, respectively. In this study, percent false positive (%FP) and percent false negative (%FN) were applied to evaluate under- and over-segmentation that other evaluation matrices could not handle. The average of operation times could be reduced from 10 s per case using traditional method, to 1.5 s per case using our proposed method. Conclusion The experimental results showed that the proposed method provided an effective automated liver segmentation technique, which can be applied clinically for automated median LIC calculation in thalassemia major patients.

Consequences and management of iron overload in sickle cell disease

Hematology ◽  
2013 ◽  
Vol 2013 (1) ◽  
pp. 447-456 ◽  
Author(s):  
John Porter ◽  
Maciej Garbowski
Keyword(s):  
Sickle Cell Disease ◽  
Blood Transfusion ◽  
Iron Overload ◽  
Sickle Cell ◽  
Iron Concentration ◽  
Thalassemia Major ◽  
Iron Loading ◽  
Cell Disease ◽  
Liver Iron Concentration ◽  
Liver Iron

Abstract The aims of this review are to highlight the mechanisms and consequences of iron distribution that are most relevant to transfused sickle cell disease (SCD) patients and to address the particular challenges in the monitoring and treatment of iron overload. In contrast to many inherited anemias, in SCD, iron overload does not occur without blood transfusion. The rate of iron loading in SCD depends on the blood transfusion regime: with simple hypertransfusion regimes, rates approximate to thalassemia major, but iron loading can be minimal with automated erythrocyte apheresis. The consequences of transfusional iron overload largely reflect the distribution of storage iron. In SCD, a lower proportion of transfused iron distributes extrahepatically and occurs later than in thalassemia major, so complications of iron overload to the heart and endocrine system are less common. We discuss the mechanisms by which these differences may be mediated. Treatment with iron chelation and monitoring of transfusional iron overload in SCD aim principally at controlling liver iron, thereby reducing the risk of cirrhosis and hepatocellular carcinoma. Monitoring of liver iron concentration pretreatment and in response to chelation can be estimated using serum ferritin, but noninvasive measurement of liver iron concentration using validated and widely available MRI techniques reduces the risk of under- or overtreatment. The optimal use of chelation regimes to achieve these goals is described.

Safe and Efficient Chelation by Deferasirox In Thalassemia Major Patients with Low Liver and Cardiac Iron Concentrations

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 5168-5168
Author(s):  
Regine Grosse ◽  
Gritta Janka ◽  
Andrea Jarisch ◽  
Peter Nielsen ◽  
Jin Yamamura ◽  
...  
Keyword(s):  
Side Effects ◽  
Conflicts Of Interest ◽  
Iron Concentration ◽  
Iron Chelation ◽  
Thalassemia Major ◽  
Transfusion Rate ◽  
Liver Iron Concentration ◽  
Measurement Interval ◽  
Liver Iron ◽  
Rbc Transfusion

Abstract Abstract 5168 Chelation treatment of iron overload from chronic blood (RBC) transfusion is still a challenge to both, patients and medical caretakers. Different treatment regimes have been recommended so far, especially for chronically transfused patients with low or even normal liver iron concentration. We report the results from 16 regularly transfused patients with thalassemia major (TM) who were on iron chelation treatment under normal to mild liver iron concentration (LIC). All patients received deferoxamine (DFO) treatment before they changed to deferasirox (DSX) treatment. 16 TM patients (mean age 13.6 y) were treated with DSX (median dose 18 mg/kg/d, range: 7 – 33 mg/kg/d) for 6 to 71 months. Liver iron measurements by biomagnetic susceptometry (BLS) and/or MRI-R2 as well as cardiac MRI-R2* were performed in intervals of 6 to 12 months. The median LIC was 782 μ g/g-liver wet weight (range: 460 μ g – 1122 μ g). Median RBC transfusion rate was 8500 ml/y, equivalent to about 2 erythrocyte concentrates per 3 weeks or a daily iron influx of 16.2 mg/d. For each measurement interval, the ratio of daily iron influx and DSX dose rate was calculated. This represents the equilibrium molar efficacy for iron balance. In all 16 TM patients no severe side effects were observed and creatinine was in the normal range of < 0.9 mg/d throughout the treatment with DSX. From baseline DFO treatment interval to the endpoint of DSX treatment, liver iron decreased by 124 – 4689 μ g/g-liver (conversion factor of 6 for mg/g-dry-wgt), while serum ferritin decreased by -596 to 8283 μ g/l. For all measurement intervals, molar chelation efficacies between 18 % and 56 % were calculated at equilibrium with a median efficacy of 31 % (interquartile range = 16 %). This agrees with molar efficacies of DSX reported earlier, but for relatively higher LIC and chelation doses (Blood 2005; 106(11):#2690 and Blood 2007; 110(11):#2776). The cardiac R2* (median R2* = 38 s-1) was either below the normal threshold of 50 s-1 (T2* > 20 ms) or decreased by about 24 %/y under DSX treatment. In these few patients at low LIC, this was even higher than recently reported. Conclusion: Even in patients with normal to mild LIC iron chelation treatment with DSX is safe, does not result in increased creatinine levels or severe side effects and is as efficient as in patients with higher LIC. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Association of Liver Iron Concentration Levels with Myocardial T2* Responses in Transfusion-Dependent Thalassemia Major Patients Treated with Deferasirox and Deferoxamine- Extension of Cordelia Study

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 2155-2155 ◽  
Author(s):  
Dudley J Pennell ◽  
John B Porter ◽  
Antonio Piga ◽  
Jackie Han ◽  
Alexander Vorog ◽  
...  
Keyword(s):  
Research Funding ◽  
Iron Concentration ◽  
Thalassemia Major ◽  
Iron Removal ◽  
Liver Iron Concentration ◽  
Liver Iron ◽  
Time Points ◽  
Cardiac Iron ◽  
Time Point

Abstract Background: Beta thalassemia major patients (pts) are at an increased risk of heart failure, due to the deposition of iron in the heart causing myocardial siderosis. Intensive long-term iron chelation therapy (ICT) is required to obtain a normal myocardial T2* (mT2* >20 ms). Previously published studies suggested that cardiac iron removal lags changes in liver iron, and liver iron concentration (LIC) may affect the rate of removal of cardiac iron (Porter et al, ASH 2013). The objective of these analyses was to evaluate the association of the severity of LIC levels with the change in mT2* responses in pts with myocardial siderosis when treated with deferasirox (DFX) and deferoxamine (DFO) for up to 24 months (mo) in the CORDELIA study. Due to the very low pt numbers in the DFO arm, the results for these pts are not presented here. Methods: The study design, inclusion, and exclusion criteria have been reported previously (Pennell et al, Am J Hematol. 2015). Pts were categorized into LIC <7, 7 to <15 and ≥15 mg Fe/g dry weight (here after mg/g) both at baseline (BL) and specific visits, to assess the relation of absolute LIC and changes in LIC overtime, with mT2* and cardiac iron concentration (CIC), respectively. During the study, mT2* (ms), and LIC (mg/g) were measured every 6 mo at the same time point. CIC (mg/g) was analyzed as a post hoc parameter derived from mT2*. The change in mT2* was assessed as geometric mean (Gmean)±coefficient of variation (CV), ratio of the Gmean at specific time points divided by that at BL (Gmean at specific time point/Gmean BL) and both CIC and LIC as mean±SD, unless otherwise specified. Results: Of 197 pts, 160 (81.2%) completed 12 mo of treatment and 146 (74.1%) entered into the extension study whereas 103 pts continued on initially assigned treatment. Pts completing 24 mo of treatment included 65 (87.8%) of 74 pts (mean age 20.1±6.9 years, 59.5% male) on DFX and the results for these pts are presented as follows. Average actual doses (mg/kg/d) were 26.7±8.9, 31.5±7.4, 38.0±2.9 for LIC <7, 7 to <15, ≥15, respectively, during the extension study. The LIC levels for pts categorized by LIC <7, 7 to <15 and ≥15 improved from BL to Mo 24 as follows: 72% decrease (mean absolute change, -15.1±14.1), 66% decrease (-26.6±13.0), and 19% decrease (-10.2±15.7), respectively. For pts with BL LIC <7, 7 to <15, ≥15, mT2* improved from BL to Mo 24 as follows: 43% increase (14.0±18.1 to 21.6±31.1; mean abs change, 7.8±4.0), 50% increase (12.3±34.4 to 19.1±46.4; 8.0±6.0), and 30% increase (11.1±30.8 to 14.5±40.8; 4.1±5.0). The CIC values improved from BL to Mo 24 by 38% (1.8±0.4 to 1.1±0.5), 40% (2.3±0.9 to 1.4±0.7), and 23% (2.6±1.0 to 1.9±1.0), respectively. The mT2* responses for pts categorized according to visit specific LIC levels (LIC <7, 7 to <15, ≥15) from BL to Mo 12 were 22% increase (mean abs change, 3.7±4.3) in LIC <7, 21% increase (2.7±2.0) in LIC 7 to <15, and 7% increase (1.5±3.2) in LIC ≥15. From BL to Mo 24, mT2* increased by 51% (mean abs change, 7.8±5.3), 35% (4.1±2.5), and 11% (2.0±4.4), respectively. The CIC levels improved from BL to Mo 24 by 40% (mean abs change, -1.0±0.8) in LIC <7, 31% (-1.0±0.6) in LIC 7 to <15, and 6% (-0.1±0.8) in LIC ≥15. The change in mT2* (Gmean ratio) at Mo 6, 12, 18 and 24 are shown in the Figure A. The mT2* response was higher in pts who achieved a lower LIC category (LIC <7) at respective time points and this change in mT2* was more apparent at 18 and 24 mo of treatment with DFX. Discussion: Overall, DFX treatment resulted in a substantial decrease in LIC and improved mT2*. These results suggest a greater difference in mT2* improvement and CIC reduction in pts who achieved lower LIC during treatment with DFX. This divergence was progressive with time, being maximal at Mo 24. Thus, a therapeutic response in LIC with DFX may be associated with a greater likelihood of improving mT2*. Pts with high LIC ≥15 may require an effective long-term treatment with higher doses of ICT to have an improvement in mT2*, suggesting that cardiac iron removal is likely to be slow in heavily iron overloaded pts. These results are consistent with the previous report which showed a significant decrease in LIC and increased mT2* responses at Mo 36 in pts who attained lower end-of-year LIC levels when treated with DFX (Porter et al, ASH 2013) and highlight the potential value of monitoring the liver and cardiac responses during ICT. To further understand the kinetics between liver and cardiac iron removal, prospective investigation is warranted. Disclosures Pennell: Novartis: Consultancy, Research Funding; Apotex: Consultancy, Research Funding. Porter:Celgene: Consultancy; Novartis: Consultancy, Honoraria, Research Funding; Shire: Consultancy, Honoraria. Piga:Acceleron: Research Funding; Cerus: Research Funding; Apopharma: Honoraria, Research Funding, Speakers Bureau; Novartis: Research Funding; Celgene Corporation: Honoraria. Han:Novartis: Employment. Vorog:Novartis: Employment. Aydinok:Cerus: Research Funding; Sideris: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

scholarly journals Water Only Sequence: An Accurate Method to Estimate Hepatic Siderosis in Patients with Thalassemia Major and Intermedia

2020 ◽  
Vol 17 (2) ◽  
Author(s):  
Mehrzad Lotfi ◽  
Mohammad Reza Rouhezamin ◽  
Bijan Bijan ◽  
Sepideh Sefidbakht ◽  
Mehran Karimi ◽  
...  
Keyword(s):  
Chemical Shift ◽  
Iron Overload ◽  
Iron Concentration ◽  
Major Complication ◽  
Accurate Method ◽  
Thalassemia Major ◽  
Liver Iron Concentration ◽  
Liver Iron ◽  
Mr Relaxometry ◽  
Sensitivity Specificity

Background: Thalassemia is a common hemoglobinopathy in Iran. Iron overload is a major complication of thalassemia, and an accurate quantification of iron deposition is the mainstay of treatment planning. The liver is the main organ for storage of iron, and quantification of hepatic siderosis is a reliable estimation of total iron overload. Objectives: The aim of this study was to determine the accuracy of chemical shift sequences (CSS), especially a water only sequence (WOS), to estimate hepatic siderosis in thalassemia patients. Patients and Methods: During a seven-month period, from May to December 2016, one hundred and two known cases of thalassemia major and intermedia underwent liver MRI. The liver iron concentration was estimated using T2* MR relaxometry. The iron signal percentage and fraction were calculated using chemical shift sequences and correlated with estimated liver iron concentration (LIC). Results: The correlation coefficient of in-phase and opposed-phase sequences was 0.566 in estimating hepatic siderosis, which was improved by employing water only sequence (0.640). The sensitivity, specificity and positive predictive value were 90.5%, 94.4% and 98.7% for the in-phase and opposed-phase sequences and 82.1%, 94.4% and 98.6% for the water only sequence, respectively. Conclusion: Chemical shift sequences, including a water only sequence, are accurate for the assessment of hepatic siderosis. Water only sequences can effectively minimize the confounding effect of fatty liver.

Association Between Cardiac Iron Clereance and Hepatic Siderosis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4833-4833
Author(s):  
Alessia Pepe ◽  
Laura Pistoia ◽  
Domenico D'Ascola ◽  
Maria Rita Gamberini ◽  
Francesco Gagliardotto ◽  
...  
Keyword(s):  
Iron Overload ◽  
Iron Concentration ◽  
Thalassemia Major ◽  
Hepatic Iron ◽  
Liver Iron Concentration ◽  
Liver Iron ◽  
Cardiac Iron ◽  
Follow Up Study ◽  
Hepatic Iron Overload

Abstract Introduction. The aim of this multicenter study was to evaluate in thalassemia major (TM) if the cardiac efficacy of the three iron chelators in monotherapy was influenced by hepatic iron levels over a follow up of 18 months. Methods. Among the 2551 TM patients enrolled in the MIOT (Myocardial Iron Overload in Thalassemia) network we evaluated prospectively the 98 patients those with an MR follow up study at 18±3 months who had been received one chelator alone between the 2 MR scans and who showed evidence of significant cardiac iron (global heart T2*<20 ms) at the basal MRI. Iron overload (IO) was measured by T2* multiecho technique. We used cardiac R2* (equal to 1000/T2*) because cardiac R2* is linearly proportional to cardiac iron and hepatic T2* values were converted into liver iron concentration (LIC) values. Results. We identified 3 groups of patients: 47 treated with deferasirox (DFX), 11 treated with deferiprone (DFP) and 40 treated with desferrioxamine (DFO). Percentage changes in cardiac R2* values correlated with changes in LIC in both DFX (R=0.469; P=0.001) and DFP (R=0.775; P=0.007) groups. All patients in these 2 groups who lowered their LIC by more than 50% improved their cardiac iron (see Figure 1). Percentage changes in cardiac R2* were linearly associated to the log of final LIC values in both DFX (R=0.437; P=0.002) and DFP groups (R=0.909; P<0.0001). Percentage changes in cardiac R2* were not predicted by initial cardiac R2* and LIC values. In each chelation group patients were divided in subgroups according to the severity of baseline hepatic iron overload (no, mild, moderate, and severe IO). The changes in cardiac R2* were comparable among subgroups (P=NS) (Figure 2). Conclusion. In patients treated with DFX and DFP percentage changes in cardiac R2* over 18 months were associated with final LIC and percentage LIC changes. In each chelation group percentage changes in cardiac R2* were no influenced by initial LIC or initial cardiac R2*. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures Pepe: Chiesi Farmaceutici and ApoPharma Inc.: Other: Alessia Pepe is the PI of the MIOT project, that receives no profit support from Chiesi Farmaceutici S.p.A. and ApoPharma Inc..

scholarly journals Association between serum ferritin and liver iron concentration with cardiac iron in pediatric thalassemia major patients

2016 ◽  
Vol 18 (S1) ◽  
Author(s):  
Antonella Meloni ◽  
Maddalena Casale ◽  
Aldo Filosa ◽  
Maria Giovanna Neri ◽  
Lorella Pitrolo ◽  
...  
Keyword(s):  
Serum Ferritin ◽  
Iron Concentration ◽  
Thalassemia Major ◽  
Liver Iron Concentration ◽  
Liver Iron ◽  
Cardiac Iron

Effect of Antioxidant Therapy On Hepatic Fibrosis and Liver Iron Concentrations In Beta-Thalassemia Major Patients

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5292-5292
Author(s):  
Mohsen Saleh Elalfy ◽  
Atef Attia ◽  
Abd El Basat Sayed ◽  
Fatma Ibrahim ◽  
Amer Mohammed ◽  
...  
Keyword(s):  
Vitamin A ◽  
Hepatic Fibrosis ◽  
Antioxidant Status ◽  
Reduced Glutathione ◽  
Iron Concentration ◽  
Thalassemia Major ◽  
Beta Thalassemia ◽  
Liver Iron Concentration ◽  
Liver Iron ◽  
Ms Therapy

Abstract Abstract 5292 Objective: Repeated blood transfusion my lead to peroxidative tissue injury in thalassemia ptients due to secondary iron overload. The aim of the study was to assess the effects of antioxidant vitamins on the oxidative stress, antioxidant status, erythrocytes, hemoglobin derivatives. Also to demonstrate their effects on hepatic status in multitransfused beta-thalassemia major patients. Methods: The study was a prospective follow up study. It involved thirty β-thalassemia major patients aged 4–17 years (15 males and 15 females) recruited from Hematology Oncology Department, Ain Shams University. They were compared to a 20 healthy age and sex matched subjects served as controls. Patients were treated with oral dose of vitamin E (400 mg/day if patient weight < 20 kg and 600 mg/day in patient weight at least 20 kg), low dose of vitamin C (100 mg/day) and vitamin A (25000 IU/ week) for twelve months. Investigations were performed before and after 6 and twelve months of therapy: liver transaminases, serum ferrittin, hepatitis status for HBV, HCV, hepatic fibroscan elastography (TE) for assessment of liver fibrosis and hepatic MRI R2* to measure liver iron concentration (LIC). Assessment of the oxidant /antioxidant capacity by measuring: reduced glutathione, malondialdehyde, ascorbic acid, catalase enzyme, superoxide dismutase, glutathione reductase as well as glutathione peroxidase determination. Results: All patients were on iron chelation therapy: 12 patients received deferiprone (DFP) (75 mg/kg per day orally), 8 patients received deferoxamine (DFO) (30–50 mg/kg per day subcutaneously at least 5 times/week), and 10 patients received a combination of DFO (30–50 mg/kg per day, 2–3 days/week) and DFP (75 mg/kg per day, 7 days/week). In the studied thalassemics 40.0% and 54% were HCV RNA and hepatitis B surface antigen positive. The basal levels of vitamin A, E and C were 3.1, 4, and 2.6 times significantly lower in thalassemia patients compared to controls(p<0.001). Malondialdehyde concentration was 3.4 times higher while reduced glutathione level was 3.2 times lower in studied thalassemics compared to controls(p=0.02,p=0.04). Levels of vitamin A, C, E, reduced glutathione and hemoglobin were significantly elevated during the study period on antioxidant therapy(P=0.03, P=0.02, P<0.001)).This was paralleled by a significant decline in the oxidative-stress marker malondialdehyde (7.87±2.2,8.2±3,11.6±4.1nmol/L;at baseline, after 6 and 12 ms therapy respectively, p<0.001) and serum ferritin levels(2887±1009,2456±1122,2114±990 μg/L, p=0.05). After twelve months of vitamins treatment, there were highly significant improvements of enzymatic antioxidants parameters as compared with before treatment in thalassemia patients. Alanine transaminase, aspartate transaminase, superoxide dismutase and glutathione peroxidase were significantly decreased(p<0.001) while catalase and glutathione reductase activities were significantly elevated(p<0.005). The extent of hemolysis of erythrocytes in studied patients decreases markedly after treatment compared to baseline (p<0.001).There was significant improvement of hepatic fibrosis after 12ms of therapy as 20% of patients had high TE values (FibroScan>12kPa) at baseline compared to 16% after 12 ms therapy (P=0.04).And 56% of patients had value of (>6kPa) at baseline compared to 66%, 70% at 6 and 12months therapy respectively(p=0.03). Levels of liver iron concentration were progressively decreased during the study period compared to baseline (22.4±6.7, 19.4±4.8, 14.4±3.6 mg/gm) in MRI R2* at baseline, after 6 and 12 months therapy respectively<0.001. CONCLUSIONS: Antioxidants vitamins are effective in clinical practice for regulation of antioxidant status as well as improvement of liver iron concentration and hepatic fibrosis in multitransfused thalassemia major patients. Disclosures: No relevant conflicts of interest to declare.

Lack of Correlation between Serum Ferritin and Liver Iron Concentration in Beta-Zero Thalassemia Intermedia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3620-3620 ◽  
Author(s):  
Renzo Galanello ◽  
Nicolina Giagu ◽  
Susanna Barella ◽  
Liliana Maccioni ◽  
Raffaella Origa
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Regulatory Protein ◽  
Iron Concentration ◽  
Iron Chelation ◽  
Dry Weight ◽  
Thalassemia Major ◽  
Thalassemia Intermedia ◽  
Liver Iron Concentration ◽  
Liver Iron

Abstract Serum ferritin and liver iron concentration (LIC) are the most commonly used methods for assessment of iron overload in thalassemia. While in patients with thalassemia major a significant correlation has been found between these two parameters, data are lacking in patients with thalassemia intermedia. In this study we measured the serum ferritin and LIC in 22 adult patients with beta-zero thalassemia intermedia never transfused (14 patients) or sporadically transfused, i.e. less than 10 units in total (8 patients), who maintained a mean hemoglobin of 8.8 ± 1.1 g/dl. Serum ferritin levels were measured by an automated chemiluminescence immunoassay analyzer, whereas LIC was determined by atomic absorption in liver biopsies. We compared the results obtained in those patients with those obtained in 22 regularly transfused (mean annual Hb = 11.3 ± 0.3 g/dl) and iron chelated thalassemia major patients, matched by sex, age and liver iron concentration. We also determined serum erythropoietin (s-epo) and serum transferrin receptor (s-TfR) in a cohort of the two patient groups (12 thalassemia intermedia; 15 thalassemia major). Mean LIC was 11.3 ± 6 mg/g dry weight tissue in thalassemia intermedia, and 11.8 ± 7 mg/g d.w. in thalassemia major group. Mean serum ferritin (at least 2 determinations from each patient within ± 2 months of liver biopsy) was 627 ± 309 ng/ml in thalassemia intermedia and 2748 ± 2510 ng/ml in thalassemia major. The difference was statistically significant (p = 0.0001). LIC was weakly correlated with serum ferritin in thalassemia major patients (r2=0.46; p=0.001) and uncorrelated in patients with thalassemia intermedia (r2=0.04; p=0.37) (Figure). S-epo and s-TfR were significantly higher in thalassemia intermedia than in thalassemia major [s-epo 467 ± 454 mU/ml versus 71 ± 44 mU/ml (p<0.001); s-TfR 43 ± 13 mU/ ml versus 13 ± 6 mU/ml (p<0.0001)]. The discrepancy between LIC and serum ferritin in thalassemia intermedia patients may be due to the higher levels of s-epo (secondary to anemia) in those patients, which through the iron regulatory protein 1 determine an up-regulation of s-TfR and a repression of ferritin translation (Weiss et al 1997). The mechanism of iron overload may also be mediated by hepcidin, whose synthesis could be suppressed as a consequence of anemia. The observation reported has important implications for iron chelation in patients with thalassemia intermedia. In such patients serum ferritin levels have little value for the monitoring of iron overload. Figure Figure

Pituitary Iron and Volume Predicts Hypogonadal Hypogonadism in Transfusional Iron Overload

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1094-1094
Author(s):  
Leila Noetzli ◽  
Ashok Panigrahy ◽  
Steven D Mittelman ◽  
Aleya Hyderi ◽  
Ani Dongelyan ◽  
...  
Keyword(s):  
Iron Overload ◽  
Chelation Therapy ◽  
Iron Concentration ◽  
Thalassemia Major ◽  
Iron Deposition ◽  
Iron Loading ◽  
Volume Loss ◽  
Z Score ◽  
Liver Iron Concentration ◽  
Liver Iron

Abstract Abstract 1094 Introduction: Hypogonadotropic Hypogonadism (HH) is one of the most common morbidities in patients with transfusion-dependent anemias such as thalassemia major. Unfortunately, pituitary dysfunction is difficult to detect prior to puberty because of immaturity of the hypothalamic-pituitary-gonadal axis. We used MRI to measure pituitary R2 and volume to determine at what age these patients develop pituitary iron overload and volume loss. Additionally, we aimed to stratify the risk of clinical HH based on pituitary R2 and pituitary volume, and determine predictors of pituitary iron deposition and volume loss. Methods: We recruited 56 patients (52 with thalassemia major and 4 with Blackfan-Diamond syndrome) to have pituitary MRIs to measure pituitary R2 and volume. Diagnosis of HH was determined by either lack of secondary pubertal characteristics by age 13 for females or age 14 for males, by primary or secondary amenorrhea in females ages 16 or older, or by the need for testosterone administration in males. Patients also had pancreas R2*, heart R2*, and liver iron concentration measured by MRI. Normative pituitary R2 and volume trends were determined by a cohort of 100 control patients. Results: Patients were 20.4 ± 12.1 years old and well distributed by sex (31 males, 25 females). All subjects received blood transfusions every 2–4 weeks and were on appropriate chelation therapy as indicated by their physician. Mean pituitary R2 Z-score was 4.5 and mean anterior pituitary volume Z-score was −0.9. Figure 1 shows pituitary R2 values as a function of age, superimposed on normal trends from the control population. Patients with transfusional iron overload began to develop pituitary iron overload in the first decade of life; however, significant iron deposition were observed beginning in the second decade. Heavy pituitary iron deposition (Z-score > 5) and volume loss (Z-score < −2.5) were predictive of HH (Figure 2). Volume loss was highly specific (87%) but identified only half of HH cases. The remaining HH patients had heavy pituitary iron (Z-score > 5), but preserved pituitary volume. Pituitary R2 correlated significantly with serum ferritin as well as liver iron concentration, pancreatic R2*, and cardiac R2* by MRI. Discussion: Pituitary iron loading begins as early as the first decade of life in chronically transfused patients, meriting a pituitary MRI in children under 10 years old. Severe pituitary iron loading as well as volume loss throughout the second decade of life, and are predictive of HH, warranting more intensive screening in this age group. However, many patients with moderate-to-severe pituitary iron overload retained normal gland volume and function, representing a potential therapeutic window. This may also be explained by improvements in gland function observed following intensive chelation therapy. Serial tracking of pituitary iron and volume trends on age-appropriate nomograms should improve diagnostic accuracy and toxicity prophylaxis. Disclosures: Wood: Novartis: Research Funding; Ferrokin Biosciences: Consultancy; Cooleys Anemia Foundation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

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