Pancreatic functions in adolescents with beta thalassemia major could predict cardiac and hepatic iron loading: relation to T2-star (T2*) magnetic resonance imaging

The aim of this study is to assess the correlation between cardiac and hepatic T2* MRI findings with the endocrine and exocrine pancreatic functions in known patients with β-thalassaemia major (β-TM). A total of 50 adolescent patients with β-TM and 44 healthy controls were investigated via: serum amylase, lipase, triglyceride index, oral glucose tolerance test and T2* MRI, to assess iron content in the heart and liver. Diabetes was found in 20%, and 40% of patients had impaired fasting glucose (IFG). Cardiac T2* was less than 10 ms in 22% indicating heavy load with iron in cardiac tissues. There was a significant decrease in median serum amylase (63.5 vs 87.5 IU/L, p=0.003) and lipase (63 vs 90 IU/L, p=0.017) among patients in comparison with the control group. Patients with β-TM and diabetes had lower serum amylase (32 vs 68 IU/L), lipase (28 vs 79 IU/L), cardiac and hepatic T2* MRI (7 vs 25.5 ms; 3 vs 6 ms, p<0.001 for all) than those without diabetes. Similar results were found among patients with IFG when compared with others (p<0.001 for all). Cardiac and hepatic T2* were inversely correlated to triglyceride index (r=−0.376, p=0.014 and r=−0.475, p=0.001, respectively) and positively correlated to amylase (r=0.791 and r=0.790) and lipase (r=0.784 and r=0.783; p<0.001 for all). The endocrine and exocrine pancreatic functions might become an equivalent predictor to cardiac and hepatic iron overload, especially in countries where MRI is not available or where it is expensive. The early occurrence of these abnormalities warrants more intensive chelation therapy.

[1]  T. Coates,et al.  Tissue iron evaluation in chronically transfused children shows significant levels of iron loading at a very young age , 2013, American journal of hematology.

[2]  T. Coates,et al.  Pancreatic iron loading predicts cardiac iron loading in thalassemia major. , 2009, Blood.

[3]  G. Spanos,et al.  MRI assessment of liver iron content in thalassamic patients with three different protocols: comparisons and correlations , 2009, European journal of haematology.

[4]  A. Eleftheriou,et al.  Prevalence of endocrine complications and short stature in patients with thalassaemia major: a multicenter study by the Thalassaemia International Federation (TIF). , 2004, Pediatric endocrinology reviews : PER.

[5]  Anuja Roy,et al.  Medication compliance and persistence: terminology and definitions. , 2008, Value in health : the journal of the International Society for Pharmacoeconomics and Outcomes Research.

[6]  K. Adalet,et al.  Early Detection of Left Ventricular Dysfunction with Strain Imaging in Thalassemia Patients , 2010, Clinical cardiology.

[7]  A. Moshiri,et al.  MRI Evaluation of Liver Iron Concentration in Patients with β-Thalassemia Major , 2011, Hepatitis monthly.

[8]  D N Firmin,et al.  Cardiovascular T2-star (T2*) magnetic resonance for the early diagnosis of myocardial iron overload. , 2001, European heart journal.

[9]  E. Gotsis,et al.  Effect of enhanced iron chelation therapy on glucose metabolism in patients with β‐thalassaemia major , 2006, British journal of haematology.

[10]  Goh As,et al.  Endocrine complications in transfusion dependent thalassaemia in Penang Hospital. , 2008 .

[11]  P. Krishnan,et al.  Efficacy and safety of deferasirox for reducing total body and cardiac iron in Thalassemia , 2012, Indian Pediatrics.

[12]  V. Positano,et al.  Cardiac complications and diabetes in thalassaemia major: a large historical multicentre study , 2013, British journal of haematology.

[13]  L. Astrakas,et al.  Liver, bone marrow, pancreas and pituitary gland iron overload in young and adult thalassemic patients: a T2 relaxometry study , 2007, European Radiology.

[14]  Y. Jang,et al.  Standards of Medical Care in Diabetes-2010 by the American Diabetes Association: Prevention and Management of Cardiovascular Disease , 2010 .

[15]  G. Oudit,et al.  Iron-overload cardiomyopathy: pathophysiology, diagnosis, and treatment. , 2010, Journal of cardiac failure.

[16]  O. Petersen Ca 2 + signaling in pancreatic acinar cells : physiology and pathophysiology , 2009 .

[17]  A. Hoffbrand,et al.  Endocrine Abnormalities in Thalassemia , 1990, Annals of the New York Academy of Sciences.

[18]  D. Pennell,et al.  Cardiovascular function and treatment in β-thalassemia major: a consensus statement from the American Heart Association. , 2013, Circulation.

[19]  D. Pennell,et al.  Continued improvement in myocardial T2* over two years of deferasirox therapy in β-thalassemia major patients with cardiac iron overload , 2011, Haematologica.

[20]  M. Agarwal Deferasirox: Oral, once daily iron chelator — an expert opinion , 2010, Indian journal of pediatrics.

[21]  G. Marchesini,et al.  TyG index, HOMA score and viral load in patients with chronic hepatitis C due to genotype 1 , 2011, Journal of viral hepatitis.

[22]  W. Au,et al.  A T2* magnetic resonance imaging study of pancreatic iron overload in thalassemia major , 2008, Haematologica.

[23]  M. Monajemzadeh,et al.  Evaluation of Serum Insulin, Glucose, Lipid Profile, and Liver Function in β-Thalassemia Major Patients and Their Correlation With Iron Overload , 2010 .

[24]  T. Coates,et al.  Longitudinal analysis of heart and liver iron in thalassemia major. , 2008, Blood.

[25]  G. Adam,et al.  Pancreatic exocrine function and cardiac iron in patients with iron overload and with thalassemia , 2011, Pediatric blood & cancer.

[26]  J. Wood Cardiac iron across different transfusion-dependent diseases. , 2008, Blood reviews.

[27]  V. Basevi Standards of Medical Care in Diabetes—2011 , 2011, Diabetes Care.

[28]  T. Coates,et al.  The effect of deferasirox on cardiac iron in thalassemia major: impact of total body iron stores. , 2010, Blood.

[29]  O. Petersen,et al.  Ca2+ signaling in pancreatic acinar cells: physiology and pathophysiology. , 2009, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[30]  M. S. Kirkman,et al.  Comment on: American Diabetes Association. Standards of Medical Care in Diabetes—2011. Diabetes Care 2011;34(Suppl. 1):S11–S61 , 2011 .

[31]  C. Hillenbrand,et al.  R2* magnetic resonance imaging of the liver in patients with iron overload. , 2009, Blood.

[32]  E. Eracleous,et al.  Low Serum Ferritin Levels are Misleading for Detecting Cardiac Iron Overload and Increase the Risk of Cardiomyopathy in Thalassemia Patients. The Importance of Cardiac Iron Overload Monitoring Using Magnetic Resonance Imaging T2 and T2* , 2006, Hemoglobin.

[33]  J. Tanner,et al.  Standards from birth to maturity for height, weight, height velocity, and weight velocity: British children, 1965. I. , 1966, Archives of disease in childhood.

[34]  V. Positano,et al.  Multislice multiecho T2* cardiovascular magnetic resonance for detection of the heterogeneous distribution of myocardial iron overload , 2006, Journal of magnetic resonance imaging : JMRI.

[35]  A. Hoffbrand,et al.  Pancreatic lipase in serum of patients with beta-thalassemia major. , 1983, Clinical chemistry.

[36]  V. Positano,et al.  Pancreatic iron overload by T2* MRI in a large cohort of well treated thalassemia major patients: Can it tell us heart iron distribution and function? , 2015, American journal of hematology.

[37]  K. E. Allam,et al.  Gradient-echo magnetic resonance imaging study of pancreatic iron overload in young Egyptian beta-thalassemia major patients and effect of splenectomy , 2010, Diabetology & metabolic syndrome.

[38]  N. Gourtsoyiannis,et al.  The pancreas in beta-thalassemia major: MR imaging features and correlation with iron stores and glucose disturbances. , 2007, European radiology.

[39]  S. Keam,et al.  Deferasirox , 2012, Drugs.

[40]  H. Cario,et al.  Insulin sensitivity and β-cell secretion in thalassaemia major with secondary haemochromatosis: assessment by oral glucose tolerance test , 2003, European Journal of Pediatrics.

[41]  W. M. Lam,et al.  Magnetic resonance imaging assessment of cardiac and liver iron load in transfusion dependent patients , 2009, Pediatric blood & cancer.

[42]  L. Gullo,et al.  Morphologic and Functional Evaluation of the Exocrine Pancreas in β‐Thalassemia Major , 1993, Pancreas.

[43]  A. Khalifa,et al.  Abnormal glucose tolerance in Egyptian beta‐thalassemic patients: possible association with genotyping , 2004, Pediatric diabetes.

[44]  A. Araújo,et al.  Pancreatic iron stores assessed by magnetic resonance imaging (MRI) in beta thalassemic patients. , 2012, European journal of radiology.

[45]  J. Reiber,et al.  The reproducibility of cardiac and liver T2* measurement in thalassemia major using two different software packages , 2013, The International Journal of Cardiovascular Imaging.

[46]  M. Francone,et al.  Myocardial iron overload assessed by magnetic resonance imaging (MRI)T2* in multi-transfused patients with thalassemia and acquired anemias. , 2011, European journal of internal medicine.

[47]  R. Shawky,et al.  Thalassemia intermedia: An overview , 2012 .

[48]  V. De Sanctis,et al.  Hypogonadism, diabetes mellitus, hypothyroidism, hypoparathyroidism: incidence and prevalence related to iron overload and chelation therapy in patients with thalassaemia major followed from 1980 to 2007 in the Ferrara Centre. , 2008, Pediatric endocrinology reviews : PER.

[49]  C. Borgna-Pignatti The life of patients with thalassemia major , 2010, Haematologica.

[50]  S. Alavi,et al.  Efficacy and safety of combined oral iron chelation therapy with deferasirox and deferiprone in a patient with beta-thalassemia major and persistent iron overload , 2014, Blood research.

[51]  M. Tsironi,et al.  Thalassemia heart disease: a comparative evaluation of thalassemia major and thalassemia intermedia. , 2005, Chest.

[52]  T. Coates,et al.  Spleen R2 and R2* in iron‐overloaded patients with sickle cell disease and thalassemia major , 2009, Journal of magnetic resonance imaging : JMRI.

[53]  C. Kattamis,et al.  Evolution of glucose intolerance and diabetes in transfused patients with thalassemia. , 2004, Pediatric endocrinology reviews : PER.

[54]  A. El‐Beshlawy,et al.  Screening for beta-thalassaemia carriers in Egypt: significance of the osmotic fragility test. , 2007, Eastern Mediterranean health journal = La revue de sante de la Mediterranee orientale = al-Majallah al-sihhiyah li-sharq al-mutawassit.

[55]  N. Gourtsoyiannis,et al.  The pancreas in β-thalassemia major: MR imaging features and correlation with iron stores and glucose disturbunces , 2007, European Radiology.

[56]  V. Positano,et al.  Multiparametric Cardiac Magnetic Resonance Survey in Children With Thalassemia Major: A Multicenter Study , 2015, Circulation. Cardiovascular imaging.

[57]  C. Ong,et al.  Endocrine complications in transfusion dependent thalassaemia in Penang Hospital. , 2008, The Medical journal of Malaysia.

[58]  Massimo Lombardi,et al.  Regional and global pancreatic T*2 MRI for iron overload assessment in a large cohort of healthy subjects: Normal values and correlation with age and gender , 2011, Magnetic resonance in medicine.

[59]  O. Tangvarasittichai,et al.  Association of iron overload and oxidative stress with insulin resistance in transfusion-dependent beta-thalassemia major and beta-thalassemia/HbE patients. , 2013, Clinical laboratory.

[60]  Dudley J Pennell,et al.  On T2* Magnetic Resonance and Cardiac Iron , 2011, Circulation.