Mona Ramadan NASR, Nermin Ali EBRAHİM, Manal Sayed RAMADAN, Omnia SALAHEDİN

Growth pattern in children with beta-thalassemia major and its relation with serum ferritin, IGF1 and IGFBP3

Amaç: Beta-talasemi majorlu (BTM) çocuklarda büyüme geriliği aşırı demir yükü ve endokrinolojik anormallikleri de içeren birçok muhtemel etyoloji nedeniyledir. Biz BTMli çocuklarda büyümeyi ve serum ferritin, tiroid hormonları, IGF1 ve IGFBP3 ile ilişkisini araştırmayı amaçladık. Gereç ve yöntem: Beta-talasemi majorlu 33 çocuk ve yaş, cinsiyet ve boy bakımından eşleştirilmiş 30 sağlıklı kontrol grubu çocuk için tam bir öykü ve fizik muayene ya- pılarak, antropometrik ölçümleri alındı. Her iki grupta açlık kan örnekleri alınarak tam kan sayımı, açlık kan şekeri, karaciğer fonksiyon testleri, serum ferritin, tiroid profile, IGF1 ve IGFP3 düzeyleri çalışıldı. Her iki grubun kemik yaşı radyolojik olarak belirlendi. Bulgular: Beta-talasemi major grubunda boy kısalığı %57.6 ve gecikmiş puberte % 45.5 oranında saptandı. Üst/Alt ekstremite oranı BTM grubunda kontrollere naza- ran anlamlı düşük bulundu (p=0.035). Talasemi grubunda açık hipotiroidi görülmedi ancak BTM grubunda IGF1 ve IGFBP3 düzeyleri kontrollerden anlamlı düşük bulundu (sırasıyla, p=0.022 ve p=0.037). T4 ile üst/alt ekstremi- te oranı arasında anlamlı bağıntı mevcuttu. IGF1, boy, transfüzyon süresi ve şelasyon süresi ile anlamlı ilişkili bulundu. Serum ferritin ile diğer değişkenler arasında an- lamlı bir korelasyon saptanmadı. Sonuç: Beta-talasemi majorlu çocuklarda düzenli trans- füzyonlar ve şelasyon tedavisine ragmen özellikle büyük çocuklarda büyüme geriliği belirgindir ve bunun nedeni asıl olarak büyüme hormone-IGF1 ve IGBP3 ekseninde- dir.

Beta-talasemi majorlu çocuklarda büyüme şekli ve serum ferritin, IGF1 ve IGFBP3 ile ilişkisi

Objectives: Growth impairment in children with Beta- thalassemia major (BTM) has several possible etiologies including excess iron overload and endocrinologic ab- normalities. We aimed to assess growth in children with BTM and its relation with serum ferritin, thyroid hormones, IGF1 and IGFBP3. Materials and methods: Thirty-three children with BTM and 30 healthy children (control group) matched in age, sex and height were subjected to full clinical history and examination, including anthropometric measurements. Fasting blood samples from both groups were taken for complete blood counts, fasting blood sugar, liver function tests, serum ferritin, thyroid profiles, IGF1 and IGFBP3. Bone ages for both groups were determined radiologi- cally. Results: A total of 57.6% of BTM group had retarded linear growth and 45.5% of them were with delayed pu- berty. There was statistical significant decrease in upper/ lower segment (U/L) ratio in the BTM group compared to the control group (p=0.035). No apparent hypothyroid- ism was found in the thalassemia group, but significant decreases were found in both IGF1 and IGFBP3 levels of the thalassemia group compared with the control group (p=0.022 and p=0.037, respectively). There was a signifi- cant correlation between T4 and U/L ratio (p

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1. Rund D. Beta-thalassemia. N Engl J Med 2005;353 (13):1135-46.
2. Loluis CK. Puberty and endocrine function in B- thalassemia major. J Pediatric Endocrinol Metab 1997;10(1):175-84.
3. Shalitin S, Carmi D, Weintrob N, et al. Serum feritin level as a predictor of impaired growth and puberty in thalassemia major patients. Eur J Haematol 2005; 74(1):93-100.
4. Wonke B. Clinical management of B-Thalassemia ma- jor. Semin Hematol 2001 38:450-359.
5. Raiola G, Galati MC, De Sanctis V, et al. Growth and puberty in thalassemia major. J Pediatr Endocrinol Metab 2003;Suppl 2:259-66.
6. Soliman AT, El Banna N, Ansari BM. GH response to provocation and circulating IGF-1 and IGFBP-3 con- centrations, the IGF-1 generation test and clinical response to GH therapy in children with beta thalas- semia. Eur J Endocrinol 1998; 138(3):384- 400.
7. White D, Kramer D, Johnson G, Dick F, Hamilton H. Prediction of bone marrow iron findings from tests performed on peripheral blood. Am J Clin Pathol 1986;72(3):346-51.
8. Gruhn JG, Barsano CP and Kumar Y. The develop- ment of tests of thyroid function. Arch Pathol Lab Med 1987;111(1):84- 100.
9. Gruelich WW, Pyle SI (1974): Radiographic Atlas of Skeletal Development of the Hand and Wrist. San Francisco, Stanford University Press. P.p.87-91.
10. Low LC. Growth of children with beta-thalassemia major. Indian J Pediatr 2005; 72(2): 159-64.
11. Aydinok Y, Darcan S, Polat A, et al. Endocrine com- plications in patients with beta-thalassemia major. J Trop Pediatr 2002; 48(1): 50-4.
12. Kattamis C, Liakopoulou T, Kattamis A. Growth and development in children with thalassemia major. Acta Paediatr Scand 1990; 366(Suppl 12):111-7.
13. Chrysis DC, Alexandrides TK, Koromantzou E, et al. Novel application of IGF-1 and IGFP-3 generation tests in the diagnosis of growth hormone axis distur- bances in children with beta-thalassaemia. Clin Endo- crinol (Oxf). 2001;54(2):253-9.
14. Bronspiegel-Weintrob N, Olivieri NF, Tyler B, Andrews DF, Freedman MH. Holland FJ. Effect of age at the start of iron chelation therapy on gonadal function in beta-thalassaemia major. New Eng J Med 1990;323, 713-9.
15. DeLuca G, Maggiolini M, Bria M, et al. GH secretion in thalassemia patients with short stature. Horm Res 1995;44(4):158-63.
16. Soliman AT, elzalabany MM, Mazlom Y, et al. Sponta- neous and provoked growth hormone (GH) secretion and insulin-like growth factor 1 (IGF-1) concentration in patients with beta thalassemia and delayed growth. J Trop Pediatr 1999; 45(6):327-37.
17. Yuksel B, M. Ozbek MN, Mungan NO, et al. Serum IGF-1 and IGFBP-3 Levels in healthy children be- tween 0 and 6 years of age. J Clin Res Pediatr Endo- crinol 2011;3(2):84-8.
18. Caliebe J, Martin DD, Ranke MB, Wit JM. The Auxo- logical and biochemical continuum of short children born small for gestational age (SGA) or with normal birth size (Idiopathic short stature). Int J Pediatr Endo- crinol 2010; 2010:852967.
19. Agular-Oliveira MH, Gill MS, de A Barretto ES, et al. Effect of severe growth hormone (GH) deficiency due to a mutation in the GH-releasing hormone receptor on insulin-like growth factors (IGFs), IGF-binding pro- tiens, and ternary complex formation throughout life. J Clin Endocrinol Metab 1999; 84(11):4118-26.
20. Gucev ZS, Oh Y, Kelley KM, Labarta JI, Vorwerk P, Rosenfeld RG. Evidence for insulin-like growth facror (IGF)-independent transcriptional regulation of IGF binding protein-3 by growth hormone in SKHEP-1 human hepatocarcinoma cells. Endocrinology 1997;138(4):1464-70.
21. Karydis I, Karagiorga-Lagna M, Nounopoulos C, To- lis G. Basal and stimulated levels of growth hormone, insulin-like growth factor-1(IGF-1), IGF-binding pro- teins in beta-thalassemia major. J Pediatr Endocrinol Metab 2004; 17(1):17-25.
22. Vidergor G, Goldfarb AW, Glaser B, Dresner-pollak R. Growth hormone reserve in adult beta-thalassemia patients. Endocrine 2007; 31(1):33-7.
23. William F Ganong. Review of Medical Physiology. 22nd edition 2005 Chapter 22 P 406.
24. Gapstur SM, Kopp P, Chiu BC, Gann PH, Colangelo LA, Liu K. Longitudinal associations of age, anthro- pometric and lifestyle factors with serum total insulin- like growth factor-I and IGF binding protein-3 levels in Black and White men: the CARDIA Male Hormone Study. Cancer Epidem Biomar 2004;13(12):2208-16.