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. Yaz›flma Adresi/Address for Correspondence: Dr. Halil Sa¤lam, Uluda¤ Üniversitesi T›p Fakültesi Çocuk Sa¤l›¤› ve Hastal›klar› Anabilim Dal›, Çocuk Endokrinoloji Bilim Dal›, Görükle, Bursa, Türkiye Tel: +90 224 295 04 24 Faks: +90 224 442 81 43 E-posta: drhalil@uludag.edu.tr Al›nd›¤› Tarih: 09.07.2008 Kabul Tarihi: 11.08.2008 GüncelPediatri 58 Özgün Araflt›rma/Original Article Girifl Beta talasemi major hemoglobin sentezindeki bozukluk sonucu ciddi anemiye neden olan kal›tsal bir bozukluktur. Bu hastalarda uzun dönem kan transfüzyonlar›na ba¤l› geliflen sekonder hemokromatozis sonucu de¤iflik endokrin komplikasyonlar ortaya ç›kmaktad›r (1-7). Büyüme gerili¤i, hipotiroidizm, hipoparatiroidizm, gonadal yetersizlik ve puberte gecikmesi, diabetes mellitus, adrenal yetmezlik, osteoporoz, kardiyak fonksiyon bozuklu¤u geliflebilmektedir (1-15,20-26). Hipotiroidizm ve diyabet gibi endokrin bozukluklar endokrin bezlerde demir birikimine ba¤l›d›r (6-11). Puberte gecikmesi primer veya sekonder gonadal yetmezli¤e ba¤l›d›r (10-15). Büyüme gerili¤i, kronik hastal›kla birlikte bozulmufl insülin benzeri büyüme faktörü-1 (IGF-1) ve bozulmufl büyüme hormonu aktivitesine ba¤l›d›r (16-19). Yap›lan baz› çal›flmalarda talasemi majörlü hastalarda %4-24 oran›nda glukoz tolerans› bozulmufl (20-24,26) ve %0-26’s›nda diabetes mellitus geliflmifltir (20-28). ‹nsülin yetersizli¤i pankreas adac›k hücrelerinde demir depolanmas›na ba¤l›d›r (24,29). Yaklafl›k %60 hastada bir veya daha fazla endokrin bez disfonksiyonu bulunmaktad›r (30). Bu komplikasyonlar› önlemek için de¤iflik demir flelatörleri kullan›lmaktad›r. Bir derlemede deferipron ile gerçeklefltirilen oral demir flelasyon tedavisi beta talasemi majörlü hastalarda endokrinopatileri önlemede subkutan demir flelasyon tedavisi kadar etkili bulunmufltur (31). Bu çal›flman›n amac› merkezimizde beta talasemi major tan›s›yla izlenen hastalardaki endokrin komplikasyon s›kl›¤›n› ve uygulanan flelasyon tedavileri aç›s›ndan farkl›l›k olup olmad›¤›n› saptamakt›r. Gereç ve Yöntem Çal›flma verileri Uluda¤ Üniversitesi T›p Fakültesi Çocuk Hematoloji Poliklini¤inde Ocak 1976-A¤ustos 2008 tarihleri aras›nda beta talasemi major tan›s›yla takip edilen 44 olgunun dosyalar›ndan elde edilmifltir. Hastalar yafl da¤›l›m› aç›s›ndan 0-9 yafl, 10-19 yafl ve 20 yafl üstünde olmak üzere 3 gruba ayr›lm›flt›r. Olgular ald›klar› flelasyon tedavileri aç›s›ndan 4 gruba ayr›lm›flt›r; 1) deferoksamin, 2) deferipron, 3) deferasiroks, 4) deferoksamin ve deferipronu birlikte kullananlar. Bu olgular en az bir y›ld›r bu tedavileri düzenli kullanmaktayd›. Hastalar›n dosya kay›tlar›ndan; ad›, soyad›, yafl›, cinsiyeti, boyu, a¤›rl›¤›, do¤um tarihi, tan› tarihi, tedavisi, ayl›k transfüzyon say›s›, puberte ve guatr evresi, açl›k kan flekeri (AKfi), serum kalsiyum (Ca), fosfor (P), alkalen fosfataz (ALP) ve demir (Fe) düzeyleri, serum demir ba¤lama kapasitesi (FeBK), ferritin, parathormon (PTH), TSH, TT4, ACTH, kortizol, FSH, LH, östrojen ya da testosteron düzeyleri, talasemi gen mutasyon analizi ve kemik mineral yo¤unlu¤u (KMY) (z-skorlar›) de¤erleri elde edildi. Hasta yafllar› desimal y›l olarak belirtildi. 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) Key words: Thalassemia major, endocrinologic complications, childhood, ferritin, blood transfusion