Factors associated with insulin-like growth factor-1 in children with thalassemia major

Main Article Content

Muhammad Riza
Sri Mulatsih
Rina Triasih


Background Insulin-like growth factor-1 (IGF-1) deficiency is the major cause of growth disorders and delayed puberty in children with thalassemia. Hence, identifying factors contributing to IGF-1 deficiency in thalassemia is of importance.

Objectives To evaluate the correlation between IGF-1 level and nutritional status, ferritin level, pre-transfusion hemoglobin, thyroid, as well as alanine transaminase level.

Methods We conducted a study in children aged 2 to 18 years with thalassemia major who visited outpatient clinics at two hospitals in Indonesia, Dr. Sardjito Hospital, Yogyakarta and Dr. Moewardi Hospital, Surakarta, Central Java, from July to December 2015. Clinical, laboratory, and demographic data were reviewed from medical records. IGF-1 levels were measured using an immunochemiluminiscent method.

Results A total of 48 children were recruited into the study. Subjects mean IGF-1 level was 109.28 ng/mL (SD 90.26) ng/mL. Seventy-five percent of the children had IGF-1 level < -2SD. Subjects mean ferritin, pre-transfusion hemoglobin and ALT  levels were 3.568 (SD 2131.31) ng/mL; 7.97 (SD 0.85) g/dL and 49.7 (SD 43.1), respectively. Most of the children (91.7%) was eutyroid, with a mean of TSH and FT4 level was 2.7 (SD 1.5) nmol/L and 12.3 (SD 7.1) μIU/ml, respectively.

 Ferritin level had no significant correlation with IGF-1 level
(r=-0.794; P=0.431). However, a strong, positive correlation was documented between pre-transfusion hemoglobin level and IGF-1 level (r=2.380; P=0.022). Multivariate linear regression analysis revealed that factors with significant correlations to IGF-1 level were pre-transfusion hemoglobin level <8 g/dL (β=-0.090; 95%CI -0.002 to 0.182; P=0.056) and undernutrition (β=0.077; 95%CI 0.045 to 0.109; P<0.001).

Conclusion Low pre-transfusion hemoglobin level and undernutrition are significantly correlated to low IGF-1 level in children with thalassemia major.

Article Details

How to Cite
Riza M, Mulatsih S, Triasih R. Factors associated with insulin-like growth factor-1 in children with thalassemia major. PI [Internet]. 11Apr.2019 [cited 24Apr.2019];59(2). Available from: https://paediatricaindonesiana.org/index.php/paediatrica-indonesiana/article/view/2074
Pediatric Hemato-Oncology


1. Lanzkowsky P. Manual of pediatric hematology and oncology. 4th ed. Burlington: Elsevier Academic Press; 2005; p. 181-91.
2. WHO guidelines for the control of haemoglobin disorders; Report of the VI Annual Meeting of the WHO Working Group on Haemoglobinopathies, Cagliari, Sardinia, 8-9 April, 1989; Geneva: World Health Organization; 1994.
3. Wahidiyat PA. Complication of thalassemia major. In: Subanada IB, Kumara Wati KD, Sidiartha IGL, Lingga Utama IMGD, Supartha M, Setyorini A, editors. The 10th Continuing Medical Education Departemen Ilmu Kesehatan Anak FK UNUD/RSUP Sanglah. Bali: Department of Child Health, Universitas Udayana; 2010.
p. 119-32.
4. Alatzoglou KS, Dattani MT. Acquired disorders of the hypothalamo-pituitary axis. In: Brook C, Clayton P, Brown R, editors. Brook’s clinical pediatric endocrinology. 6th ed. West Sussex UK: Wiley-Backwell Publishing; 2009. p. 106-23.
5. Soliman A, De Sanctis V, Yassin M, Abdelrahman MO. Growth hormone - insulin-like growth factor-I axis and bone mineral density in adults with thalassemia major. Indian J Endocrinol Metab. 2014;18:32-8.
6. Karamifar H, Karimi M, Sobhani N. Insulin-like growth factor-1 levels in children with beta-thalassemia minor. Turk J Haematol. 2008;25:136–9.
7. Soliman AT, De Sanctis V, Elalaily R, Yassin M. 2015. Insulin-like growth factor-I and factors affecting it in thalassemia major. Indian J Endocrinol Metab. 2015;19:245–51.
8. Tsunawaki T, Sakai K, Momomura M, Wachi Y, Matsuzawa Y, Iwashita M. Hypoxia alters phosphorylation status of insulin-like growth factor (IGF)-binding protein-1 and attenuates biological activities of IGF-I in HepG2 cell cultures. J Obstet Gynaecol Res. 2013;39:1367-73.
9. World Health Organization. Growth reference data for 5-19 years. [cited 2016 July 12]; Available from: http://www.who. int/growthref/en/.
10. Kajimura S, Aida K, Duan C. Insulin-like growth factor-binding protein-1 (IGFBP-1) mediates hypoxia-induced embryonic growth and developmental retardation. Proc Natl Acad Sci USA. 2005;102:1240-5.
11. Rachmilewitz E, Weizer-Stern O, Adamsky K, Amariglio N, Rechavi G, Breda L, et al. Role of iron inducing oxidative stress in thalassemia: can it be prevented by inhibition of absorption and by antioxidants?. Ann N Y Acad Sci. 2005;1054:118-23.
12. Papaconstantinou J. Insulin/IGF-1 and ROS signaling pathway cross-talk in aging and longevity determination. Mol Cell Endocrinol. 2009;299:89-100.
13. Hashemi A, Ordooei M, Golestan M, Ghalibaf AM, Mahmoudabadi F, Arefinia M, et al. Hypothyroidism and serum ferritin level in patients with major ß thalassemia. Iran J Pediatr Hematol Oncol. 2011;1:53-6.
14. Hamidah A, Rahmah R, Azmi T, Aziz J, Jamal R. Short stature and truncal shortening in transfusion dependent thalassemia patients: results from a thalassemia center in Malaysia. Southeast Asian J Trop Med Public Health. 2001;32:625-30.
15. Gomber S, Dewan P. Physical growth patterns and dental caries in thalassemia. Indian Pediatr. 2006;43:1064-9.
16. Weatherall DJ, Clegg JB. The thalassaemia syndrome. 4th ed. Hoboken: Blackwell Science. 2001; p. 287-95.
17. Maggio M, De Vita F, Lauretani F, Butto V, Bondi G, Cattabiani C, et al. IGF-1, the cross road of the nutritional, inflammatory and hormonal pathways to frailty. Nutrients. 2013;5:4184-205.
18. Mirhosseini NZ, Shahar S, Ghayour-Mobarhan M, Kamarudin NA, Banihashem A, Yusoof NAM, et al. Factors affecting nutritional status among pediatric patients with transfusion-dependent β-thalassemia. Mediterr J Nutr Metab. 2013;6:45–51.
19. Bulan S. 2009. Factors associated with quality of life among thalassemia beta major. [master’s thesis] [Semarang]: Diponegoro University; 2009.
20. Ratih P D, Susanto R, Sudarmanto B. Pengaruh deferasirox terhadap kadar T4 dan TSH pada β-thalassemia major dengan kadar ferritin tinggi. Sari Pediatri. 2011;12:433-9.
21. Eshragi P, Tamaddoni A, Zarifi K, Mohannadhasani A, Aminzadeh M. Thyroid function in major thalassemia patients: is it related to height and chelation therapy? Caspian J Intern Med. 2011;2:189-93.
22. Kurtoglu A, Kurtoglu E, Temizkan AK. Effect of iron overload on endocrinopathies in patients with β-thalassaemia major and intermedia. Endokrynol Pol. 2012;63:260–3.
23. De Sanctis V, Soliman AT, Candini G, Yassin M, Raiola G, Galati MC, et al. Insulin-like growth factor-1 (IGF-1): demographic, clinical and laboratory data in 120 consecutive adult patients with thalassaemia major. Mediterr J Hematol Infect Dis. 2014;6:e2014074.