Talasemi Majorlü Vakalarda Endokrin Komplikasyonların Değerlendirilmesi

Year 2008, Volume: 6 Issue: 3, 58 - 65, 01.12.2008

Birol Baytan Halil Sağlam Şahin Erdöl Aysun Nedime Beyazıt Taner Özgür Adalet Meral Güneş Ünsal Günay

Abstract

Amaç: Kan transfüzyonları beta talasemi major hastalarının dokularında demir birikimine yol açarak, endokrin sistem organları da dahil olmak üzere birçok organda çeşitli derecelerde fonksiyon kayıpları oluşturur. Bu çalışmanınamacı; hastanemiz Çocuk Hematoloji Polikliniğinde beta talasemi major tanısıyla izlenen hastalardaki endokrinolojik komplikasyonları saptamaktır.Gereç ve Yöntem: Uludağ Üniversitesi Tıp Fakültesi Çocuk Hematoloji BilimDalında Ocak 1976-Ağustos 2008 tarihleri arasında beta talasemi major tanısıyla takip edilen hastaların dosyaları retrospektif olarak incelenmiş ve tiroidbezi palpasyonu ile puberte değerlendirmesini de içeren ayrıntılı fizik muayeneleri yapılmıştır. Konsultasyon istenen hastalar Çocuk Endokrinoloji BilimDalında değerlendirilmiştir.Bulgular: Toplam 44 hastanın 20’si %45,5 kız, 24’ü %54,5 erkek olup hastaların ortalama kronolojik yaşı 13,54±7,32 2,75-35,2 yıl olarak hesaplanmıştır.“Osteoporoz” ve “büyüme hormonu eksikliği dışındaki büyüme geriliği olguları” hariç tutulduğunda toplam 12 %27,2 olguda, dahil edildiğinde ise 40 %90,9 olguda bir ya da birden fazla endokrin patoloji mevcuttu. Kırkdört olgunun 27’sinde %61,3 osteoporoz, 17’sinde %38,6 büyüme geriliği, 11’inde %25 osteopeni, 6’sında %13,6 hipogonadizm, 3’ünde %6,8 hipotiroidizm,2’sinde %4,5 hipoparatirodizm, 1’inde %2,3 büyüme hormonu eksikliği ve1’inde 2,3 tip I diabetes mellitus mevcuttu. Olguların ortalama ferritin düzeyi1976,15±1494,75 ng/ml, aylık ortalama transfüzyon sayısı ise 1,46±0,34 olaraksaptandı. Ferritin düzeyi ve aylık transfüzyon ihtiyacı ile endokrin komplikasyonlar arasında istatistiksel açıdan anlamlı birliktelik yoktu. Farklı şelasyontedavisi alan gruplardaki endokrin patolojiler farklılık göstermedi. Çalışmada0-9 yaş gurubu ile 10-19 yaş gurubu arasında büyüme geriliği açısından anlamlı fark bulunmuştur %8,3’e karşılık %30,6; p=0,049 . Sonuç: Talasemi majorlu hastalar endokrinolojik fonksiyon bozukluğu açısından risk altındadırlar ve kemik sağlıkları ciddi derecede bozulmuştur. On yaşından küçükler özellikle büyüme geriliği ve osteoporoz açısından, 10 yaş veüzerinde olanlar ise hipogonadizm, büyüme geriliği ve osteoporoz başta olmak üzere tüm endokrinolojik komplikasyonlar yönünden yakın izlenmelidirler

Keywords

Talasemi major, endokrinolojik komplikasyon, çocuklukçağı, ferritin, kan transfüzyonu

Evaluation of Endocrine Complications in Patients with Thalassemia Major

Abstract

Aim: Multiple blood transfusions in beta thalassemia patients causes iron overload in various tissues including endocrine glands thereby leading to multiple endocrine dysfunction. The aim of this study was to determine the endocrine complications seen in beta thalassemia patients followed-up in outpatient clinics of Pediatric Hematology Division of Uludag University Faculty of Medicine. Materials and Methods: The files of patients with thalassemia major followed-up in outpatient clinics of Pediatric Hematology Division of Uludag University Faculty of Medicine from January 1976 to August 2008 were retrospectively evaluated for endocrine disorders. All patients had a detailed physical examination including palpation of thyroid gland and pubertal staging. Endocrine evaluation was performed in the Division of Pediatric Endocrinology. Results: A total of 44 [20 female 45.5% ; 24 male 54.5% ; and mean chronological age 13.54±7.32 2.75-35.2 years] patients were evaluated. The ratios of patients with endocrine dysfunction were 27.2 % and 90.9%, respectively, when we exclude or include those with osteoporosis/osteopenia or growth failure other than growth hormone deficiency. Of all patients, 27 61.3% had osteoporosis, 17 38.6% had growth retardation, 11 25% had osteopenia, 6 13.6% had hypogonadism, 3 6.8% had hypothyroidism, 2 4.5% had hypoparathyroidism, 1 2.3 had growth hormone deficiency, and 1 2.3 had type 1 diabetes mellitus. Mean ferritin levels and monthly transfusion numbers were 1976.15±1494.75 ng/ml and 1.46±0.34, respectively. There were no significant association between ferritin levels, monthly transfusion needs, and endocrine dysfunctions studied. Endocrine dysfunctions did not differ significantly amongst those having different chelating agents. The ratio of patients with growth retardations in 10 to 19-age-group was significantly higher than those in 0 to 9-age-group 30.6% vs 8.3%; p=0.049 . Conclusion: Patients with thalassemia major are under increased risk of various endocrine dysfunction. Bone health is significantly compromised. Those younger than 10 years should be closely followed for especially growth retardation and osteoporosis/osteopenia and those who are 10 years of age or older should be followed for all endocrine pathologies, especially for hypogonadism, growth retardation, and osteoporosis. Journal of Current Pediatrics 2008; 6: 58-65

Keywords

Thalassemia major, endocrinologic complications, childhood, ferritin, blood transfusion

References

• 1. Nathan DG. Pioneers and modern ideas: prospective on thalassemia. Pediatrics 1998; 102: 281-3.
• 2. Olivieri NF. The beta-thalassemias. N Engl J Med1999; 341: 99-109.
• 3. Porter JB. A risk-benefit assessment of iron-chelation therapy. Drug Saf 1997; 17: 407-21.
• 4. Pld JM, Olivieri NF, Thein SL. Management and prognosis. In: Weatherall DJ, Clegg JB, eds. The Thalassaemia Syndromes. London: Blackwell Science 2001; 630-85.
• 5. Propper RD, Cooper B, Rufo RR, et al. Continuous subcutaneous administration of desferoxamine in patients with iron overload. N Engl J Med 1977; 297: 418-23.
• 6. Cavallo L, Licci D, Acquafredda A, et al. Endocrine involvement in children with beta-thalassemia major. Transverse and longitudinal functions. I. Pituitary-thyroidal axis function and its correlation with serum ferritin levels. Acta Endocrinol 1984; 107: 49-53.
• 7. Phenekos C, Karamerou A, Pipis P, et al. Thyroid function in patients with homozygous beta-thalassemia. Clin Endocrinol 1984; 20: 445-50.
• 8. Livadas DP, Sofroniadou K, Souvatzoglou A, Boukis M, Siafaka L, Koutras D. Functional insufficiency of thyroid and pituitary gland in beta-homozygous thalassemia with hemosiderosis. Acta Endocrinol 1984; 265S: 43-4.
• 9. Spitz IM, Hirsch HJ, Landau H, Zylber-Haran E, Gross V, Rachmilewitz EA. TSH secretion in thalassemia. J Endocrinol Invest 1984; 7: 495-9
• 10. Masala A, Meioni T, Gallisai D, et al. Endocrine functioning in multitransfused prepubertal patients with homozygous beta-thalassemia. J Clin Endocrinol Metab 1984; 58: 667-70.
• 11. Livadas DP, Sofroniadou K, Souvatzoglou A, Boukis M, Siafaka L, Koutras D. Pituitary and thyroid insufficiency in thalassemic hemosiderosis. Clin Endocrinol 1984; 20: 435-43.
• 12. De Sanctis V, Katz M, Wonke B, Tanas R, Bagni B. Gonadal function in patients with beta-thalassemia major. J Clin Pathol 1988; 41:133-7.
• 13. Borgna-Pignatti C, De Stefano P, Zonta L, et al. Growth and sexual maturation in thalassemia major. J Pediatr 1985;106: 150-5.
• 14. Landau H, Gross V, Dagan I, Palti Z, Rachmilewitz EA, Spitz MI. Growth and sexual development before and after sex steroid therapy in patients with thalassemia major. Arch Intern Med 1984; 144: 2341-6.
• 15. Pintor C, Loche S, Faedda A, et al. 1984 Sexual maturation and adrenal function in girls with thalassemia. J Endocrinol Invest 1984; 7: 181-4.
• 16. Saenger P, Schwartz E, Markenson AL, et al. Depressed serum somatomedin activity in beta-thalassemia. J Pediatr 1980; 6: 214- 8.
• 17. Pintor C, Cella SG, Manso P, et al. Impaired growth hormone response to GH-releasing hormone in thalassemia major. J Clin Endocrinol Metab 1986; 263-7.
• 18. Li A, Cheng M, Low W. Growth and development in patients with homozygous beta-thalassemia in Hong Kong. Birth Defects 1987; 23: 441-8.
• 19. Tolis G, Politis C, Kontopoulou I, et al. Pituitary somatotropic and corticotropic function in patients with beta-thalassemia on iron chelation therapy. Birth Defects 1987; 23: 449-52.
• 20. Torres FA, Bonduel M, Sciuccati G,et al. Beta thalassemia major in Argentina. Medicina 2002; 62: 124-34.
• 21. El-Hazmi M A, Al-Swailem A, Al-Fawaz I, Warsey A S, Al-Swailem A. Diabetes mellitus in children suffering from beta-thalassaemia. J Trop Pediatr 1994; 40: 26.
• 22. Khalifa A S, Salem M, Mounir E, et al. Abnormal glucose tolerance in Egyptian Beta thalassemic patients: Possible association in genotyping. Pediatr Diabetes 2004; 5: 126-32.
• 23. Flynn DM, Fairney A, Jackson D, Clayton BE. Hormonal changes in thalassaemia major. Arch Dis Child 1976; 51: 828-36.
• 24. Cario H, Holl RW, Debatin KM, Kohne E. Insulin sensitivity and beta-cell secretion in thalassaemia major with secondary hemochromatosis: assessment by oral glucose tolerance test. Eur J Pediatr 2003; 162: 139-46.
• 25. Italian Working Group on Endocrine Complications in Non-endocrine Diseases. Multicentre study on prevalence of endocrine complications in thalassaemia major. Clin Endocrinol 1995; 42: 581-86.
• 26. Chern J P S, Lin Kai-Hsin, Lu Meng-Yao, et al. Abnormal Glucose Tolerance in Transfusion- Dependent ß-Thalassemic Patients. Diabetes Care 2001; 24: 850-4.
• 27. Arrigo T, Crisafulli G, Meo A, et al. Glucose tolerance, insulin secretion and peripheral sensitivity in thalassaemia major. J Pediatr Endocrinol Metab 1998; 3: 863-6.
• 28. Rodriguez GC, Ortega AJJ, Alonso JL, et al. Evaluation of the efficacy of chelation therapy with deferoxamine in patients with thalassemia major. Med Clin 1994; 102: 721-4.
• 29. Merkel PA, Simonson DC, Amiel SA, et al. Insulin resistance and hyperinsulinemia in patients with thalassemia major treated by hypertransfusion. N Engl J Med 1988; 318: 809-14.
• 30. Ayd›nok Y, Darcan S, Polat A, et al. Endocrine complications in patients with beta thalassemia major. J Trop Peditr 2002; 48: 50-4.
• 31. Toumba M, Sergis A, Kanaris C, Skordis N. Endocrine complications in patients with Thalassaemia Major. Pediatr Endocrinol Rev 2007; 5: 642-8.
• 32. Firdevs B, Günöz H. Pediatrik endokrinolojide kullan›lan kaynak veriler. Kurto¤lu S. Pediatrik Endokrinoloji. 1. Bas›m. Akyseri. Pediatrik Endokrinoloji ve Oksoloji Derne¤i Yay›nlar›; 2003 p.747-807.
• 33. Update On Growth, Reproductive And Endocrine Complications In Thlassemia. Proceeding Of The 9th International Conference On Thalassemia And Hemoglobinopaties, Terrasini (Palermoi Italy) ,2003, Pediatric Endocrinology Rewiew, 2004; 2: 242-322.
• 34. De Sanctis V, Eleftheriou A, Malaventura C; Thalassaemia International Federation Study Group on Growth and Endocrine Complications in Thalassaemia. Prevalence of endocrine complications and short stature in patients with thalassaemia major: a multicenter study by the Thalassaemia International Federation (TIF). Pediatr Endocrinol Rev 2004; 2: 249-55.
• 35. Low LC. Growth, puberty and endocrine function in beta-thalassaemia major. J Pediatr Endocrinol Metab 1997; 10: 175-84.
• 36. Saka N, Sukur M, Bundak R, Anak S, Neyzi O, Gedikoglu G. Growth and puberty in thalassemia major J Pediatr Endocrinol Metab 1995; 8: 181-6.
• 37. Aydinok Y, Darcan S, Polat A,et al. Endocrine complications in patients with beta-thalassemia major.J Trop Pediatr 2002; 48: 50-4.
• 38. Mohammadian S, Bazrafshan HR, Sadeghi-Nejad A. Endocrine gland abnormalities in thalassemia major: a brief review. J Pediatr Endocrinol Metab 2003; 16: 957-64
• 39. Güler E, Pat›ro¤lu T and et al. Endocrinologic Complications of Thalassemia Major. Turkish Arcives of Pediatrics 1999; 34: 174-81.
• 40. S. Daar. A. V. Pathare. Combined therapy with desferrioxamine and deferiprone in beta thalassemia major patients with transfusional iron overload. Ann Hematol.2006; 85: 315-9
• 41. R. Origa et al. Combined therapy with deferiprone and desferrioxamine in thalassemia major. Haematologica 2005; 90: 1309-14.
• 42. Peng CT, Wu KH, Wu SF, et al. Deferiprone or deferoxamine vs. combination therapy in patients with beta-thalassemia major: a case study in Taiwan. Hemoglobin 2006; 30: 125-30.
• 43. Alymara V, Bourantas D, Chaidos A, et al. Effectiveness and safety of combined iron-chelation therapy with deferoxamine and deferiprone. Hematol J. 2004; 5: 475-9.
• 44. Miranda Athanassiou-Metaxa et al. Combined chelation therapy with deferiprone and desferrioxamine in ironoverloaded thalassemia patients. Haematologica. 2004; 89: 55-6.
• 45. Karen O, Gerdine K and et al. Multiple Hormone Deficiencies in Children with Hemochromatosis. Journal of Clinical Endocrinology and Metabolism 1993; 76: 357-61.
• 46. Melody C, Eric M, et al. Complications of Beta-thalassemia major in North America. Blood 2004; 104: 34-9.
• 47. Molyvda-Athanasopoulou E, Sioundas A, Karatzas N, Aggellaki M, Pazaitou K, Vainas I. Bone mineral density of patients with thalassemia major: four-year follow-up. Calcif Tissue Int. 1999; 64: 481-4.
• 48. Soliman AT, El Banna N, Abdel Fattah M, ElZalabani MM, Ansari BM. Bone mineral density in prepubertal children with beta-thalassemia: correlation with growth and hormonal data. Metabolism 1998; 47: 541-8.
• 49. Dresner Pollack R, Rachmilewitz E, Blumenfeld A, Idelson M, Goldfarb AW. Bone mineral metabolism in adults with beta-thalassaemia major and intermedia. Br J Haematol 2000; 111: 902-7.
• 50. Brändle M, Galeazzi RL, Morant R, Oesterle M. Osteopenia in beta-thalassemia major. Schweiz Med Wochenschr. 1996; 126: 1867-74.
• 51. Borgna-Pignatti C, De Stefano p, Zonta L et al. Growth and sexual maturation in thalassemia major. J Pediatr. 1985; 106: 150-55.
• 52. Zervas A, Katopodi A, Protonotariou A, et al. Assessment of thyroid function in two hundred patients with beta-thalassemia major.Thyroid 2002; 12: 151-4.
• 53. Zaino, E. C., Kuo, B., and Roginsky, M. S. Growth retardation in thalassemia major. Annals of the New York Academy of Sciences. 1969; 165.
• 54. Canale VC, Steinherz, P, New M, and Erlandson M. Endocrine function in thalassemia major. Annals of the New York Academy of Sciences 232-3.
• 55. Lassman MN, Genel M, Wise JK, Hendler R, and Felig P. Carbohydrate homeostasis and pancreatic islet cell function in thalassemia. Annals of Internal Medicine 80, 65.
• 56. Gabriele OF. Hypoparathyroidism associate with thalassemia. South Med J. 1971; 64: 115-6.
• 57. Chern JP, Lin KH. Hypoparathyroidism in transfusiondependent patients with beta-thalassemia. J Pediatr Hematol Oncol 2002; 24: 291-3.
• 58. Ellis, J. T., Schulman, I., and Smith, C. H. Generalized siderosis with fibrosis of liver and pancreas in Cooley's (Mediterranean) anemia with observations on the pathogenesis of the siderosis and fibrosis. American Journal of Pathology 1954; 30, 287.
• 59. Gulati R, Bhatia V, Agarwal SS. Early onset of endocrine abnormalities in beta-thalassemia major in a developing country. J Pediatr Endocrinol Metab 2000; 13: 651-6.