Serum ferritin levels and endocrine disorders in children with thalassemia major

Main Article Content

Evi Dewiyanti
Aditiawati Aditiawati
Dian Puspita Sari

Abstract

Background Endocrine disorders in thalassemia major children patients occur due to iron overload and hemosiderosis in endocrine organs. Early detection is needed to prevent complications and improve the quality of life. An association between serum ferritin and endocrine disorders in thalassemia patients has been inconclusive to date.


Objective To analyze for possible associations between serum ferritin and endocrine disorders (short stature, delayed puberty, delayed bone age, hypothyroidism, impaired glucose tolerance, and diabetes mellitus) and the incidence of each disorder  in thalassemia major.


Methods There were 115 thalassemia major patients aged 10-18 years involved in our cross-sectional study from June 2019 - June 2020 in the Pediatrics Department, DR. M Hosein Hospital, Palembang, South Sumatera. Anthropometry and socioeconomic status informations  were collected from physical examination and interview. Ferritin, FT4, TSH, Hb and glucose levels measured by using standard methods for each item in the laboratory, mean while the skeletal age assessment  was determined by using  FELS method.


Results This study included 83 (72.2%) girls and 32 (27.8%) boys. There were 89 (77.4%) subjects with short stature, 74 (64.4%) with delayed bone age, 30 (26.1%) with impaired glucose tolerance, 25 (21.7%) with delayed puberty, 4 (3.5%) with diabetes mellitus (DM), and none with hypothyroidism. Bivariate and multivariate analyses revealed no associations between serum ferritin and short stature, delayed bone age, impaired glucose tolerance, delayed puberty, and DM.


Conclusion There is a high prevalence of endocrine disorders in pediatric thalassemia patients, especially short stature and delayed bone age. However, there are no associations between serum ferritin and endocrine disorders in these patients.

Article Details

How to Cite
1.
Dewiyanti E, Aditiawati A, Sari D. Serum ferritin levels and endocrine disorders in children with thalassemia major. PI [Internet]. 28May2021 [cited 25Jul.2021];61(3):125-. Available from: https://paediatricaindonesiana.org/index.php/paediatrica-indonesiana/article/view/2547
Section
Pediatric Endocrinology
Received 2020-11-30
Accepted 2021-05-28
Published 2021-05-28

References

1. Eijkman Institute. Thalassemia. [cited 2020 November 3]. Avilable from: http://www.eijkman.go.id/units/red-blood-cell-disorders/activities/thalassemia/
2. De Sanctis Vincenzo,Kattamis C,Canatan D,Soliman A,Yassin M, Wali Y. Beta Thalassemia distribution in the old world: an ancient disease seen from a historical standpoint. Medit J Hematol Infect Dis.. 2017;9:e2017018. DOI:10.4084/mjhid.2017.018
3. Divisi Hemato-onkologi anak RSMH. Register pasien talasemia. Palembang: RSMH; 2018.
4. Gupta R, Musallam KM, Taher AT, Rivella S. Ineffective Erythropoiesis: Anemia and Iron Overload. Hematol Oncol Clin North Am. 2018;32:213-221. DOI: 10.1016/j.hoc.2017.11.009
5. Al-Hakeim H, Abdulzahra M, Ridha M. Study of the effect of iron overload on the function of endocrine glands in male thalassemia patients. Asian J Transfus Sci. 2011;5:127. DOI: 10.4103/0973-6247.83236
6. Taher AT, Musallam KM, Inati A. Iron overload: consequences, assessment, and monitoring. Hemoglobin. 2009;33(sup1):S46-S57. DOI: 10.3109/03630260903346676
7. Taher AT, Saliba AN. Iron overload in thalassemia: different organs at different rates. Hematology. 2017;2017:265-271. DOI: 10.1182/asheducation-2017.1.265
8. Al-Akhras A, Badr M, El-Safy U, Kohne E, Hassan T, Abdelrahman H, et al. Impact of genotype on endocrinal complications in β-thalassemia patients. Biomed.Rep. 2016;4:728-736. doi: 10.3892/br.2016.646
9. De Sanctis V, Soliman A, Elsedfy H, Skordis N, Kattamis C, Angastiniotis M, et al. Growth and endocrine disorders in thalassemia: The international network on endocrine complications in thalassemia (I-CET) position statement and guidelines. Indian J Endocr Metab. 2013;17:8. DOI: 10.4103/2230-8210.107808
10. Azami M, Parizad N, Sayehmiri K. Prevalence of hypothyroidism, hypoparathyroidism and the frequency of regular chelation therapy in patients with thalassemia major in Iran: A Systematic review and meta-analysis study. Iran J Ped Hematol Oncol. 2016;6:261-76.
11. Elalfy MS, Esmat G, Matter RM, Abdel Aziz HE, Massoud WA. Liver fibrosis in young Egyptian beta-thalassemia major patients: relation to hepatitis C virus and compliance with chelation. Ann. Hepatol. 2013;12:54-61. DOI: 10.1016/S1665-2681(19)31385-7.
12. Ferdian BA, Rosdiana N, Lubis B. Impact of iron therapy on Mentzer index and red cell distribution width index in primary school children with iron deficiency anemia. Paediatr. Indones. 2009;49:195-9. DOI: 10.14238/pi49.4.2009.195-9.
13. Badfar DG, Nasirkandy DMP, Shohani DM, Mansouri A, Shabani E, Rahmati S, et al. Prevalence of short stature, underweight and delayed puberty in Iranian patients with thalassemia major: A systematic review and meta-analysis. Iran J Ped Hematol Oncol. 2017;7:15. Iran J Ped Hematol Oncol. 2017;7:245-259.
14. Al-Agha A, Shabakah SA, Ocheltree A, Abdullatif DEM, Jaouni KA. Endocrinopathies in children and adolescents with b-thalassemia major. J Appl Hematol 2011;2:20-4.
15. Chahkandi T, Norouziasl S, Farzad M, Ghanad F. Endocrine disorders in β-thalassemia major. ijp ; Int J Pediatr. 2017;5:5531-8. DOI: 10.22038/ijp.2017.21937.1834
16. Elizabeth J. Mayer-Davis, Anna R. Kahkoska, Craig, Jefferies 
Dana Dabelea, Naby Balde, Chun X. Gong, Pablo Aschner, Maria E. Craig. ISPAD Clinical Practice Consensus Guidelines 2018: Definition, epidemiology, and classification of diabetes in children and adolescents . Pediatr Diabetes. 2018;19 (Suppl. 27):7–19. https://doi.org/10.1111/pedi.12773
17. Galanello R, Origa R. Beta-thalassemia. Orphanet J Rare Dis. 2010;5:11. DOI: 10.1186/1750-1172-5-11
18. Angastiniotis M, Lobitz S. Thalassemias: An Overview. IJNS. 2019;5:16. DOI: 10.3390/ijns5010016.
19. Jaya IK, Sari DP, Zen NF. Gambaran usia tulang pada pasien talasemia dengan perawakan pendek di bagian ilmu kesehatan anak RSUP Dr. Moh Hoesin Palembang. Jurnal Kedokteran dan Kesehatan FK UNSRI. 2015:2:217-22.
20. Putri DM, Oenzil F, Efrida E. Gambaran status gizi anak talasemia β mayor di RSUP Dr. M. Djamil Padang. Jurnal Kesehatan Andalas. 2015;4. DOI: 10.25077/jka.v4i3.367.
21. Ayudhia S, Rini EA. Gangguan Endokrin pada Pasien Thalassemia β Mayor di RSUP M Djamil Padang. Human Care. 2020;5:554. DOI: 10.32883/hcj.v5i2.708
22. Sherief LM, Abd El-Salam SM, Kamal NM, El Safy O, Almalky MAA, Azab SF, et al. Nutritional Biomarkers in Children and Adolescents with Beta-Thalassemia-Major: An Egyptian Center Experience. Biomed Res. Int. 2014;2014:1-7. DOI: 10.1155/2014/261761.
23. Mahachoklertwattana P, Sirikulchayanonta V, Chuansumrit A, Karnsombat P, Choubtum L, Sriphrapradang A, et al. Bone histomorphometry in children and adolescents with β-Thalassemia disease: iron-associated focal osteomalacia. J. Clin. Endocrinol. Metab. 2003;88:3966-72. DOI: 10.1210/jc.2002-021548.
24. Elalfy MS, Saber MM, Adly AAM, Ismail EA, Tarif M, Ibrahim F, et al. Role of vitamin C as an adjuvant therapy to different iron chelators in young β-thalassemia major patients: efficacy and safety in relation to tissue iron overload. Eur J Haematol. 2016;96:318-26. DOI: 10.1111/ejh.12594.
25. Indrasari ND, Timan IS, Wahidiyat PA. Difference of collagen IV in liver damage and hepatitis C infection in iron overload thalassemia patients. Indonesian J Clin Pathol Med Lab. 2015;22:1-8.
26. Suvarna J, Ingle H, Deshmukh CT. Insulin resistance and beta cell function in chronically transfused patients of thalassemia Major. Indian Pediatr. 2006;43:8. PMID: 16735760.
27. Erdoğan E, Canatan D, Örmeci AR, Vural H, Aylak F. The effects of chelators on zinc levels in patients with thalassemia major. J. Trace Elem. Med. Biol. 2013;27:109-11. DOI:10.1016/j.jtemb.2012.10.002
28. Mojtahedzadeh F, Kosaryan M, Mahdavi M-R, Akbari J. The effect of folic acid supplementation in beta thalassemia major: a randomized placebo-controlled clinical trial. Arch Iranian Med. 2006;9:266-8. PMID: 16859064.
29. Andayani SH, Sekarwana N, Fadil R. Association between age and serum ferritin level with bone age deficit in children with thalassemia major. Paediatr Indones. 2008;48:33-6. DOI:10.14238/pi48.1.2008.33-6.
30. Chern JPS, Lin KH, Lu MY, Lin DT, Lin KS, Chen JD, et al. Abnormal Glucose Tolerance in Transfusion-Dependent -Thalassemic Patients. Diabetes Care. 2001;24:850-4. DOI: 10.2337/diacare.24.5.850.
31. Shalitin S, Carmi D, Weintorb N, Phillip M. Serum ferritin level as a predictor of impaired growth and puberty in thalassemia major patients. Eur J Haematol. 2005;74:93-100. DOI: 10.1111/j.1600-0609.2004.00371.x.
32. Anderson CP, Shen L, Einstein R, Leibold E. Mammalian iron metabolism and its control by iron regulatory proteins. Biochim Biophys Acta. 2012;1823:1468-83. DOI: 10.1016/j.bbamcr.2012.05.010.
33. Batubara JR, Akib A, Pramita D. Delayed puberty in thalassemia major patients. Paediatr Indones. 2016;44:143-7. DOI: 10.14238/pi44.4.2004.143-7.
34. Tesorierie L, D’Arpa D, Butera D, Allegra M, Renda D, Maggio A, et al. Oral supplements of vitamin E improve measures of oxidative stress in plasma and reduce oxidative damage to LDL and erythrocytes in 𝛽-thalassemia intermedia patients. Free Radic. Res. 2001;34:529-40. DOI: 10.1080/10715760100300461.
35. Seyed Eshaqh-Hoseini SK, Jafari-Koshki T, Arsang-Jang Shapouri J. Endocrinopathy complications and the role of serum ferritin as a marker of endocrinopathy prediction in patients with beta-thalassemia major. Adv Hum Biol 2018;8:169-74. DOI: 0.4103/AIHB.AIHB_18_18.