Volume 15, Issue 4 (September 2023 2023)                   Iranian Journal of Blood and Cancer 2023, 15(4): 212-235 | Back to browse issues page

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Faranoush P, Elahinia A, Ziaee A, Faranoush M. Review of endocrine complications in transfusion-dependent thalassemia. Iranian Journal of Blood and Cancer 2023; 15 (4) :212-235
URL: http://ijbc.ir/article-1-1401-en.html
Review of endocrine complications in transfusion-dependent thalassemia
Pooya Faranoush1 , Ali Elahinia1 , Amir Ziaee1 , Mohammad Faranoush *2
1- Pediatric Growth and Development Research Center, Iran University of Medical Sciences, Tehran-Iran
2- Pediatric Growth and Development Research Center, Iran University of Medical Sciences, Tehran-Iran , faranoush47@gmail.com
Abstract:   (2673 Views)

Beta thalassemia is an inherited genetic disorder that often leads to transfusion dependence. One of the significant issues that these patients face is increased iron accumulation in their bodies due to the nature of the disease and regular blood transfusions. Iron overload can cause hemosiderosis and tissue damage in various organs, including the heart, liver, and endocrine systems. Endocrine problems are one of the most common complications in transfusion-dependent thalassemia, and addressing these complications can significantly improve patients' health-related quality of life. The prevalence of endocrinopathy is high, especially in patients with poor compliance with therapy. The most common endocrine disorders include hypogonadism, growth disturbances, short stature, delayed puberty, acquired hypothyroidism and hypoparathyroidism, adrenal dysfunction, osteoporosis, diabetes, fertility issues, and complications during pregnancy. Timely diagnosis and treatment of endocrine disorders can improve patients' quality of life and reduce social problems. This article reviews the literature on the various endocrine complications encountered in thalassemia.
 

Keywords: Iron overload, Endocrinopathy, Thalassemia, Blood transfusion
Full-Text [PDF 7941 kb]   (977 Downloads)    
: Review Article | Subject: Pediatric Hematology & Oncology
Received: 2023/06/23 | Accepted: 2023/08/22 | Published: 2023/09/17
References
1. De Sanctis V, Elsedfy H, Soliman AT, Elhakim IZ, Soliman NA, Elalaily R, et al. Endocrine profile of β-thalassemia major patients followed from childhood to advanced adulthood in a tertiary care center. Indian J Endocrinol Metab. 2016;20(4):451-9. [DOI:10.4103/2230-8210.183456]
2. Singer, S. T., Wu, V., Mignacca, R., Kuypers, F. A., Morel, P., Vichinsky, E. P., & Lee, J. M. (2015). Altered growth and micropenis in male patients with transfusion-dependent thalassemia. Journal of Pediatric Hematology/Oncology, 37(6), 435-440.
3. Kattamis A, Forni GL, Aydinok Y, Viprakasit V. Changing patterns in the epidemiology of β-thalassemia. Eur J Haematol. 2020;105(6):692-703. [DOI:10.1111/ejh.13512]
4. Ehsanipour F, Faranoush P, Foroughi‐Gilvaee MR, Sadighnia N, Fallahpour M, Motamedi M, et al. Evaluation of immune system in patients with transfusion‐dependent beta‐thalassemia in Rasoul‐e‐Akram Hospital in 2021: A descriptive cross‐sectional study. Health Science Reports. 2022;5(6):e871. [DOI:10.1002/hsr2.871]
5. Nasiri A, Rahimi Z, Vaisi-Raygani A. Hemoglobinopathies in Iran: An Updated Review. Int J Hematol Oncol Stem Cell Res. 2020;14(2):140-50. [DOI:10.18502/ijhoscr.v14i2.2679]
6. Zamani M, Poustchi H, Shayanrad A, Pourfarzi F, Farjam M, Noemani K, et al. Prevalence and determinants of anemia among Iranian population aged ≥35 years: A PERSIAN cohort-based cross-sectional study. PLoS One. 2022;17(2):e0263795. [DOI:10.1371/journal.pone.0263795]
7. Hadipour Dehshal M, Tabrizi Namini M, Hantoushzadeh R, Yousefi Darestani S. β-Thalassemia in Iran: Things Everyone Needs to Know About This Disease. Hemoglobin. 2019;43(3):166-73. [DOI:10.1080/03630269.2019.1628774]
8. Mehrvar A, Azarkeivan A, Faranoush M, Mehrvar N, Saberinedjad J, Ghorbani R, et al. Endocrinopathies in patients with transfusion-dependent beta-thalassemia. Pediatr Hematol Oncol. 2008;25(3):187-94. [DOI:10.1080/08880010801938207]
9. Fleming RE, Ponka P. Iron overload in human disease. N Engl J Med. 2012;366(4):348-59. [DOI:10.1056/NEJMra1004967]
10. Faranoush P, Jahandideh A, Nekouian R, Mortazavi P. Evaluation of the in vitro and in vivo effect of liposomal doxorubicin along with oncolytic Newcastle disease virus on 4T1 cell line: Animal preclinical research. Veterinary Medicine and Science. 2023. [DOI:10.1002/vms3.1109]
11. Cao A, Galanello R. Beta-thalassemia. Genet Med. 2010;12(2):61-76. [DOI:10.1097/GIM.0b013e3181cd68ed]
12. de Sanctis V. Endocrine Complications. Thalassemia Reports. 2018;8(1):7479. [DOI:10.4081/thal.2018.7479]
13. Taher AT, Weatherall DJ, Cappellini MD. Thalassaemia. Lancet. 2018;391(10116):155-67. [DOI:10.1016/S0140-6736(17)31822-6]
14. Musallam KM, Taher AT, Cappellini MD, Sankaran VG. Clinical experience with fetal hemoglobin induction therapy in patients with β-thalassemia. Blood. 2013;121(12):2199-212; quiz 372. [DOI:10.1182/blood-2012-10-408021]
15. Vichinsky E. Advances in the treatment of alpha-thalassemia. Blood Rev. 2012;26 Suppl 1:S31-4. [DOI:10.1016/S0268-960X(12)70010-3]
16. Weatherall DJ. The inherited diseases of hemoglobin are an emerging global health burden. Blood. 2010;115(22):4331-6. [DOI:10.1182/blood-2010-01-251348]
17. Arab-Zozani M, Kheyrandish S, Rastgar A, Miri-Moghaddam E. A Systematic Review and Meta-Analysis of Stature Growth Complications in β-thalassemia Major Patients. Ann Glob Health. 2021;87(1):48. [DOI:10.5334/aogh.3184]
18. Soliman AT, Yassin MA, De Sanctis V. Final adult height and endocrine complications in young adults with β-thalassemia major (TM) who received oral iron chelation (OIC) in comparison with those who did not use OIC. Acta Biomed. 2018;89(2-s):27-32.
19. Inati A, Noureldine MA, Mansour A, Abbas HA. Endocrine and bone complications in β-thalassemia intermedia: current understanding and treatment. Biomed Res Int. 2015;2015:813098. [DOI:10.1155/2015/813098]
20. Shamshirsaz AA, Bekheirnia MR, Kamgar M, Pourzahedgilani N, Bouzari N, Habibzadeh M, et al. Metabolic and endocrinologic complications in beta-thalassemia major: a multicenter study in Tehran. BMC Endocr Disord. 2003;3(1):4. [DOI:10.1186/1472-6823-3-4]
21. Taher AT, Musallam KM, Karimi M, El-Beshlawy A, Belhoul K, Daar S, et al. Overview on practices in thalassemia intermedia management aiming for lowering complication rates across a region of endemicity: the OPTIMAL CARE study. Blood. 2010;115(10):1886-92. [DOI:10.1182/blood-2009-09-243154]
22. Toumba M, Sergis A, Kanaris C, Skordis N. Endocrine complications in patients with Thalassaemia Major. Pediatr Endocrinol Rev. 2007;5(2):642-8.
23. Musallam KM, Cappellini MD, Wood JC, Motta I, Graziadei G, Tamim H, et al. Elevated liver iron concentration is a marker of increased morbidity in patients with β thalassemia intermedia. Haematologica. 2011;96(11):1605-12. [DOI:10.3324/haematol.2011.047852]
24. Esteghamati A, Etemad K, Koohpayehzadeh J, Abbasi M, Meysamie A, Noshad S, et al. Trends in the prevalence of diabetes and impaired fasting glucose in association with obesity in Iran: 2005-2011. Diabetes Res Clin Pract. 2014;103(2):319-27. [DOI:10.1016/j.diabres.2013.12.034]
25. Vogiatzi MG, Macklin EA, Fung EB, Vichinsky E, Olivieri N, Kwiatkowski J, et al. Prevalence of fractures among the Thalassemia syndromes in North America. Bone. 2006;38(4):571-5. [DOI:10.1016/j.bone.2005.10.001]
26. Aessopos A, Farmakis D, Andreopoulos A, Tsironi M. Assessment and treatment of cardiac iron overload in thalassemia. Hemoglobin. 2009;33 Suppl 1:S87-92. [DOI:10.3109/03630260903347401]
27. De Sanctis V, Soliman AT, Elsedfy H, Yassin M, Canatan D, Kilinc Y, et al. Osteoporosis in thalassemia major: an update and the I-CET 2013 recommendations for surveillance and treatment. Pediatr Endocrinol Rev. 2013;11(2):167-80.
28. Soliman A, De Sanctis V, Elsedfy H, Yassin M, Skordis N, Karimi M, et al. Growth hormone deficiency in adults with thalassemia: an overview and the I-CET recommendations. Georgian Med News. 2013(222):79-88.
29. De Sanctis V, Soliman AT, Yassin MA, Di Maio S, Daar S, Elsedfy H, et al. Hypogonadism in male thalassemia major patients: pathophysiology, diagnosis and treatment. Acta Biomed. 2018;89(2-s):6-15.
30. Christoforidis A, Kazantzidou E, Tsatra I, Tsantali H, Koliakos G, Hatzipantelis E, et al. Normal lumbar bone mineral density in optimally treated children and young adolescents with beta-thalassaemia major. HORMONES-ATHENS-. 2007;6(4):334. [DOI:10.14310/horm.2002.1111030]
31. Christoforidis A, Perifanis V, Tsatra I, Vlachaki E, Athanassiou-Metaxa M. Evolution of OGTT in patients with β-thalassaemia major in relation to chelation therapy. Diabetes Research and Clinical Practice. 2007;76(1):6-11. [DOI:10.1016/j.diabres.2006.07.010]
32. Ladis V, Chouliaras G, Berdousi H, Kanavakis E, Kattamis C. Longitudinal study of survival and causes of death in patients with thalassemia major in Greece. Annals of the New York Academy of Sciences. 2005;1054(1):445-50. [DOI:10.1196/annals.1345.067]
33. Angastiniotis M, Christou S, Kolnakou A, Pangalou E, Savvidou I, Farmakis D, et al. The Outcomes of Patients with Haemoglobin Disorders in Cyprus: A Joined Report of the Thalassaemia International Federation and the Nicosia and Paphos Thalassaemia Centres (State Health Services Organisation). Thalassemia Reports. 2022;12(4):143-56. [DOI:10.3390/thalassrep12040019]
34. Teleanu RI, Sarman MA, Epure DA, Matei M, Roşca I, Roza E. Autosomal Dominant Hypocalcemia Type 1 and Neonatal Focal Seizures. Children. 2023;10(6):1011. [DOI:10.3390/children10061011]
35. Delvecchio M, Cavallo L. Growth and endocrine function in thalassemia major in childhood and adolescence. J Endocrinol Invest. 2010;33(1):61-8. [DOI:10.1007/BF03346551]
36. Soliman AT, Adel A, Al Yafei F, et al. Comprehensive management of endocrine complications in β-thalassemia. Front Endocrinol (Lausanne). 2021;12:624305. doi:10.3389/fendo.2021.624305.
37. Hamed EA, El-Metwally TH, El-Farahaty RM, et al. Endocrine complications in thalassemia major: a multicenter study in Egypt. Hematology. 2021;26(1):53-61. doi:10.1080/16078454.2020.1866356.
38. Vitrano A, Musallam KM, Giardina PJ. Updates and current strategies in the management of endocrine complications of thalassemia. Best Pract Res Clin Endocrinol Metab. 2021;35(3):101499. doi:10.1016/j.beem.2021.101499.
39. Faranoush M, Rahiminejad M, Karamizadeh Z, Ghorbani R, Owji S. Zinc Supplementation Effect on Linear Growth in Transfusion Dependent β Thalassemia. Iranian Journal of Blood and Cancer. 2008;1(1):29-32.
40. Taher AT, Saliba AN, Musallam KM, et al. Endocrine disorders in β-thalassemia: current perspectives. Metabolism. 2020;112:154354. doi:10.1016/j.metabol.2020.154354. [DOI:10.1016/j.metabol.2020.154354]
41. Shoback D. Clinical practice. Hypoparathyroidism. N Engl J Med. 2008;359(4):391-403. [DOI:10.1056/NEJMcp0803050]
42. Zafardoust S, Ansaripor S, Karimi A, Hosseinirad H, Ataei M. Effects of Adjuvant Growth Hormone Therapy on Poor Ovarian Responders in Assisted Reproductive Technology. Maedica (Bucur). 2022;17(2):336-43.
43. Mohammadian S, Sadeghi-Nejad A. Current State of Growth Hormone Therapy. Int J Endocrinol Metab. 2003;1(2):e94490. .
44. Souza FM, Collett-Solberg PF. Adverse effects of growth hormone replacement therapy in children. Arq Bras Endocrinol Metabol. 2011;55(8):559-65. [DOI:10.1590/S0004-27302011000800009]
45. Gaber MA, Elbana RE, Mahmoud AA. Risk factors for hypogonadism in multitransfused thalassemia major male patients. Menoufia Med J 2022;35:439-44. [DOI:10.4103/mmj.mmj_267_21]
46. Golpayegani M, Faranoush p, Rasouli Mh, Foroughi-Gilvaee M, Sadighnia N, Zandi A, et al. Comparative study on the effects of filgrastim and pegfilgrastim in the treatment of fever and neutropenia in patients with leukemia in the west of Iran. Iranian journal of Pediatric Hematology and Oncology. 2022;12(2):76-85. [DOI:10.18502/ijpho.v12i2.9072]
47. De Sanctis V, Soliman AT, Daar S, Di Maio S. Adverse events during testosterone replacement therapy in 95 young hypogonadal thalassemic men. Acta Biomed. 2019;90(2):228-32.
48. De Sanctis V, Soliman AT, Elsedfy H, Di Maio S. Current practice in treating adult female thalassemia major patients with hypogonadism: An International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescence Medicine survey from Italy. Indian J Endocrinol Metab. 2016;20(6):880-1. [DOI:10.4103/2230-8210.192905]
49. Bhardwaj A, Swe KMM, Sinha NK, Osunkwo I. Treatment for osteoporosis in people with ß-thalassaemia. Cochrane Databaseof Systematic Reviews 2016, Issue 3. Art. No.: CD010429. DOI: 10.1002/14651858.CD010429.pub2. . [DOI:10.1002/14651858.CD010429.pub2]
50. Singhal A, Goyal H. Thyroid dysfunction in beta thalassemia major patients. Thyroid Research and Practice. 2020;17(2):70-5. [DOI:10.4103/trp.trp_4_20]
51. Mokhtari Dowlatabad H, Mamdouh A, Yousefpour N, Mahdavi R, Zandi A, Hoseinpour P, et al. High-Frequency (30 MHz–6 GHz) Breast Tissue Characterization Stabilized by Suction Force for Intraoperative Tumor Margin Assessment. Diagnostics. 2023;13(2):179. [DOI:10.3390/diagnostics13020179]
52. Moharamipour S, Aminifar M, Foroughi-Gilvaee MR, Faranoush P, Mahdavi R, Abadijoo H, et al. Hydroelectric actuator for 3-dimensional analysis of electrophoretic and dielectrophoretic behavior of cancer cells; suitable in diagnosis and invasion studies. Biomaterials Advances. 2023;151:213476. [DOI:10.1016/j.bioadv.2023.213476]
53. Hashemi-madani N, Rahimian N, Khamseh ME, Faranoush P, Malek M, Ghasemi F, et al. Guideline for the diagnosis and treatment of hypothyroidism and hypoparathyroidism in patients with blood transfusion-dependent thalassemia. Iranian Journal of Blood and Cancer. 2023;15(2):89-96. [DOI:10.58209/ijbc.15.2.89]
54. Gamberini MR, Fortini M, De Sanctis V, Gilli G, Testa MR. Diabetes mellitus and impaired glucose tolerance in thalassaemia major: incidence, prevalence, risk factors and survival in patients followed in the Ferrara Center. Pediatr Endocrinol Rev. 2004;2 Suppl 2:285-91.
55. Martirosyan D, Jahanbakhshi F, Foroughi-Gilvaee MR, Mousavi F, Faranoush P, Ashoori MR, et al. Evaluation of the effect of electron beam therapy on oxidative stress and some minerals in patients with type 2 diabetes mellitus. Functional Food Science. 2022;2(5):124-35. [DOI:10.31989/ffs.v2i5.935]
56. He L-N, Chen W, Yang Y, Xie Y-J, Xiong Z-Y, Chen D-Y, et al. Elevated Prevalence of Abnormal Glucose Metabolism and Other Endocrine Disorders in Patients with β-Thalassemia Major: A Meta-Analysis. BioMed Research International. 2019;2019:6573497. [DOI:10.1155/2019/6573497]
57. Mowla A, Karimi M, Afrasiabi A, De Sanctis V. Prevalence of diabetes mellitus and impaired glucose tolerance in beta-thalassemia patients with and without hepatitis C virus infection. Pediatr Endocrinol Rev. 2004;2 Suppl 2:282-4.
58. M. Diab A, S. Abdelmotaleb G, Abdel-Azim Eid K, Sebaey S. Mostafa E, Sabry Ahmed E. Evaluation of glycemic abnormalities in children and adolescents with β-thalassemia major. Egyptian Pediatric Association Gazette. 2021;69(1):9. [DOI:10.1186/s43054-021-00052-4]
59. Aleem A, Al-Momen AK, Al-Harakati MS, Hassan A, Al-Fawaz I. Hypocalcemia due to hypoparathyroidism in beta-thalassemia major patients. Ann Saudi Med. 2000;20(5-6):364-6. [DOI:10.5144/0256-4947.2000.364]
60. De Sanctis V, Soliman AT, Canatan D, Elsedfy H, Karimi M, Daar S, et al. An ICET- A survey on Hypoparathyroidism in Patients with Thalassaemia Major and Intermedia: A preliminary report. Acta Biomed. 2018;88(4):435-44.
61. Matin S, Jahromi MG, Karemizadeh Z, Haghpanah S, De Sanctis V, Soliman A, et al. The Frequency of Adrenal Insufficiency in Adolescents and Young Adults with Thalassemia Major versus Thalassemia Intermedia in Iran. Mediterr J Hematol Infect Dis. 2015;7(1):e2015005. [DOI:10.4084/mjhid.2015.005]
62. Baldini M, Mancarella M, Cassinerio E, Marcon A, Ambrogio AG, Motta I. Adrenal insufficiency: An emerging challenge in thalassemia? Am J Hematol. 2017;92(6):E119-e21. [DOI:10.1002/ajh.24726]
63. Bhardwaj A, Swe KMM, Sinha NK, Osunkwo I. Treatment for osteoporosis in people with ß‐thalassaemia. Cochrane Database of Systematic Reviews. 2013(3). [DOI:10.1002/14651858.CD010429]
64. Gaudio A, Morabito N, Catalano A, Rapisarda R, Xourafa A, Lasco A. Pathogenesis of Thalassemia Major-associated Osteoporosis: A Review with Insights from Clinical Experience. J Clin Res Pediatr Endocrinol. 2019;11(2):110-7. [DOI:10.4274/jcrpe.galenos.2018.2018.0074]
65. Rossi F, Perrotta S, Bellini G, Luongo L, Tortora C, Siniscalco D, et al. Iron overload causes osteoporosis in thalassemia major patients through interaction with transient receptor potential vanilloid type 1 (TRPV1) channels. Haematologica. 2014;99(12):1876-84. [DOI:10.3324/haematol.2014.104463]
66. Goldberg EK, Lal A, Fung EB. Nutrition in Thalassemia: A Systematic Review of Deficiency, Relations to Morbidity, and Supplementation Recommendations. J Pediatr Hematol Oncol. 2022;44(1):1-11. [DOI:10.1097/MPH.0000000000002291]
67. Goldberg EK, Neogi S, Lal A, Higa A, Fung E. Nutritional Deficiencies Are Common in Patients with Transfusion-Dependent Thalassemia and Associated with Iron Overload. J Food Nutr Res (Newark). 2018;6(10):674-81. [DOI:10.12691/jfnr-6-10-9]
68. Fung EB. Nutritional deficiencies in patients with thalassemia. Ann N Y Acad Sci. 2010;1202:188-96. [DOI:10.1111/j.1749-6632.2010.05578.x]
69. Ansari S, Baghersalimi A, Azarkeivan A, Nojomi M, Hassanzadeh Rad A. Quality of life in patients with thalassemia major. Iran J Ped Hematol Oncol. 2014;4(2):57-63.
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