Main Article Content
Abstract. Introduction: Chronic blood transfusion is the mainstay of care for individuals with ?-thalassemia major (BTM). However, it causes iron-overload that requires monitoring and management by long-term iron chelation therapy in order to prevent endocrinopathies and cardiomyopathies, that can be fatal. Hepatic R2 MRI method (FerriScan®) has been validated as the gold standard for evaluation and monitoring liver iron concentration (LIC) that reflects the total body iron-overload. Although adequate oral iron chelation therapy (OIC) is promising for the treatment of transfusional iron-overload, some patients are less compliant with it and others suffer from long-term effects of iron overload.
Objective: The aim of our study was to evaluate the prevalence of endocrinopathies and liver dysfunction, in relation to LIC and serum ferritin level, in a selected group of adolescents and young adult BTM patients with severe hepatic iron overload (LIC from 15 to 43 mg Fe/g dry weight).
Patients and Methods: Twenty-four selected BTM patients with severe LIC, due to transfusion-related iron-overload, followed at the Hematology Section, National Center for Cancer Care and Research, Hamad Medical Corporation of Doha (Qatar), from April 2015 to July 2017, were retrospectively evaluated. The prevalence of short stature, hypogonadism, hypothyroidism, hypoparathyroidism, impaired fasting glucose (IFG), diabetes, and adrenal insufficiency was defined and assessed according to the International Network of Clinicians for Endocrinopathies in Thalassemia (ICET) and American Diabetes Association criteria.
Patients have been transfused over the past 19.75 ± 8.05 years (ranging from 7 to 33 years). The most common transfusion frequency was every 3 weeks (70.8%). At the time of LIC measurements, the mean age of patients was 21.75 ± 8.05 years, mean LIC was 32.05 ± 10.53 mg Fe/g dry weight (range: 15 to 43 mg Fe/g dry weight). Their mean serum ferritin level was 4,488.6 ± 2,779 µg/L. The overall prevalence of growth failure was 26.1% (6/23), IFG was 16.7% (4/24), sub-clinical hypothyroidism was 14.3% (3/21), hypogonadism was 14.3% (2/14), diabetes mellitus was 12.5% (3/24), and biochemical adrenal insufficiency was 6.7% (1/15). The prevalence of hepatitis C positivity was 20.8% (5/24). No case of clinical hypothyroidism, adrenal insufficiency or hypoparathyroidism was detected in this cohort of patients. The prevalence of IFG impaired fasting glucose was significantly higher in BTM patients with very high LIC (>30 mg Fe/g dry liver) versus those with lower LIC (p = 0.044). LIC was correlated significantly with serum ferritin levels (r = 0.512; p = 0.011), lactate dehydrogenase (r = 0.744; p = 0.022) and total bilirubin (r = 0.432; p = 0.035).
Conclusions: A significant number of BTM patients, with high LIC and endocrine disorders, still exist despite the recent developments of new oral iron chelating agents. Therefore, physicians’ strategies shall optimize early identification of those patients in order to optimise their chelation therapy and to avoid iron-induced organ damage. We believe that further studies are needed to evaluate if serial measurements of quantitative LIC may predict the risk for endocrine complications. Until these data are available, we recommend a close monitoring of endocrine and other complications, according to the international guidelines.
Downloads month by month
1. Galanello R, Origa R. Beta-thalassemia.Orphanet J Rare Dis. 2010 May 21;5:11. doi: 10.1186/1750-1172-5-11.
2. Ballas SK, Zeidan AM, Duong VH, DeVeaux M, Heeney MM. The effect of iron chelation therapy on overall survival in sickle cell disease and ?-thalassemia: A systematic review. Am J Hematol. 2018;93:943-952.
3.Yassin MA, Soliman AT, De Sanctis V, Abdula MA, Riaz LM, Ghori FF, Yousaf A, Nashwan AJ, Abusamaan S, Moustafa A, Kohla S, Soliman DS. Statural Growth and Prevalence of Endocrinopathies in Relation to Liver Iron Content (LIC) in Adult Patients with Beta Thalassemia Major (BTM) and Sickle Cell Disease (SCD). Acta Biomed. 2018;89(2-S):33-40.
4.St Pierre TG, Clark PR, Chua-anusorn W, Fleming AJ, Jeffrey GP, Olynyk JK, Pootrakul P, Robins E, Lindeman R. Noninvasive measurement and imaging of liver iron concentrations using proton magnetic resonance. Blood. 2005;105:855-861.
5. Verlhac S, Morel M, Bernaudin F, Béchet S, Jung C, Vasile M. Liver iron overload assessment by MRI R2* relaxometry in highly transfused pediatric patients: an agreement and reproducibility study. Diagn Interv Imaging. 2015;96:259-264.
6. De Sanctis V, Soliman AT, Elsedfy H, Skordis N, Kattamis C, Angastiniotis M, Karimi M, Yassin MA, El Awwa A, Stoeva I, Raiola G, Galati MC, Bedair EM, Fiscina B, El Kholy M. Growth and endocrine disorders in thalassemia: The international network on endocrine complications in thalassemia (I-CET) position statement and guidelines. Indian J Endocrinol Metab. 2013;17:8-18.
7. International Diabetes Federation. Definition and diagnosis of diabetes mellitus and intermediate hyperglycaemia: report of a WHO/IDF consultation. Geneva: World Health Organization; 2006.
8.Telfer PT, Prestcott E, Holden S, Walker M, Hoffbrand AV, Wonke B. Hepatic iron concentration combined with long-term monitoring of serum ferritin to predict complications of iron overload in thalassaemia major. Br J Haematol. 2000;110:971-977.
9. De Sanctis V, Elsedfy H, Soliman AT, Elhakim IZ, Soliman NA, Elalaily R, Kattamis C. Endocrine profile of ?-thalassemia major patients followed from childhood to advanced adulthood in a tertiary care center. Indian J Endocrinol Metab. 2016 ;20:451-459.
10.Fung EB, Harmatz PR, Lee PD, Milet M, Bellevue R, Jeng MR, Kalinyak KA, Hudes M, Bhatia S, Vichinsky EP; Multi-Centre Study of Iron Overload Research Group. Increased prevalence of iron-overload associated endocrinopathy in thalassaemia versus sickle-cell disease. Br J Haematol. 2006;135:574-582.
11.Vichinsky E, Butensky E, Fung E, Hudes M, Theil E, Ferrell L, Williams R, Louie L, Lee PD, Harmatz P. Comparison of organ dysfunction in transfused patients with SCD or beta thalassemia. Am J Hematol. 2005;80:70-74.
12.Casale M, Citarella S, Filosa A, De Michele E, Palmieri F, Ragozzino A, Amendola G, Pugliese U, Tartaglione I, Della Rocca F, Cinque P, Nobili B, Perrotta S. Endocrine function and bone disease during long-term chelation therapy with deferasirox in patients with ?-thalassemia major. Am J Hematol. 2014;89:1102-1106.
13. Al-Akhras A, Badr M, El-Safy U, Kohne E, Hassan T, Abdelrahman H, Mourad M, Brintrup J, Zakaria M. Impact of genotype on endocrinal complications in ?-thalassemia patients. Biomed Rep. 2016;4:728-736.
14.Skordis N, Michaelidou M, Savva SC, Ioannou Y, Rousounides A, Kleanthous M, Skordos G, Christou S. The impact of genotype on endocrine complications in thalassaemia major.Eur J Haematol. 2006;77:150-156.
15.Cunningham MJ, Macklin EA, Neufeld EJ, Cohen AR; Thalassemia Clinical Research Network. Complications of beta-thalassemia major in North America. Blood. 2004;104:34-39.
16. Chirnomas D, Smith AL, Braunstein J, et al. Deferasirox pharmacokinetics in patients with adequate versus inadequate response. Blood. 2009; 114:4009–4013.
17.Vichinsky E, Butensky E, Fung E, Hudes M, Theil E, Ferrell L, Williams R, Louie L, Lee PD, Harmatz P. Comparison of organ dysfunction in transfused patients with SCD or beta thalassemia. Am J Hematol. 2005;80:70-74.
18.Gamberini MR, De Sanctis V, Gilli G. 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. Pediatr Endocrinol Rev. 2008M 6 (Suppl 1):158-169.
19. Shalitin S, Carmi D, Weintrob N, Phillip M, Miskin H, Kornreich L, Zilber R, Yaniv I, Tamary H. Serum ferritin level as a predictor of impaired growth and puberty in thalassemia major patients. Eur J Haematol. 2005;74:93-100.
20.Wood JC, Tyszka JM, Carson S, Nelson MD, Coates TD. Myocardial iron loading in transfusion-dependent thalassemia and sickle cell disease. Blood. 2004; 103:1934–1936.
21. Ho PJ, Tay L, Lindeman R, Catley L, Bowden DK. Australian guidelines for the assessment of iron overload and iron chelation in transfusion-dependent thalassaemia major, sickle cell disease and other congenital anaemias. Intern Med J. 2011;41:516-524.
22. Sayani F, Warner M, Wu J, Wong-Rieger D, Humphreys K, Odame I. Guidelines for the Clinical Care of Patients with Thalassemia in Canada. Anemia Institute for Research & Education, Thalassemia Foundation of Canada, ON, Canada.2009.
23. Cappellini MD, Cohen A, Porter J, Taher A, Viprakasit V, editors. Guidelines for the Management of Transfusion Dependent Thalassaemia (TDT) [Internet]. 3rd edition. Nicosia (CY): Thalassaemia International Federation; 2014.