Nusret YILMAZ, Esin AVŞAR, Gökhan TAZEGÜL, Alphan KÜPESİZ, Ramazan SARI, Hasan Ali ALTUNBAŞ, Mustafa Kemal BALCI

Endocrine and metabolic disorders in adult patients with thalassemia major

Aim: Iron overload in tissues, despite current chelation therapies, is a major cause of organ dysfunction and serious complicationsin thalassemia major. Similarly, iron accumulation in endocrine tissues pave the way for various endocrinopathies. Previous reportsregarding prevalence of endocrinopathies in thalassemia major varies significantly based on study population. In this study, weaimed to investigate the metabolic and endocrine disorders among the transfusion-dependent adult thalassemia major patients.Materials and Methods: Data from transfusion-dependent adult thalassemia major patients with regular follow-up were retrospectivelyevaluated. Former records of the patients were examined to evaluate endocrine disorders, on the basis of laboratory test results.Results: A total of 76 patients with a median age of 28 years, composed of 39 (51.3%) female and 37 (48.7%) male patients wereincluded. Out of the entire cohort, 36.8% (n=28) had hypogonadism, 30.3% (n=23) had thyroid dysfunction, 28.9% (n=22) had aglucose metabolism disorder and 7.9% (n=6) had hypoparathyroidism. Hypogonadism was encountered in 38.5% (n=15) of femalesand in 35.1% (n=13) of males. Only one patient from each gender had hypergonadotropic hypogonadism, possibly related to ironoverload, while the rest had hypogonadotropic hypogonadism. A positive history of delayed puberty was noted in 30.8% (n=12) offemales and 24.3% (n=9) of males. Of the patients, 30.3% (n=23) had one, 18.4% (n=14) had 2, 10.5% (n=8) had 3, and 1.3% (n=1)had 4 different endocrine dysfunctions. Accordingly, 61.5% of the patients had at least one endocrine dysfunction while only 39.5%(n=30) had no endocrine dysfunction at all.Conclusion: Survival time has been prolonged in patients with thalassemia major by virtue of effective transfusion and chelationtherapies. As a consequence of prolonged survival, endocrine dysfunctions commonly strike adult thalassemia major patients,therefore, endocrine functions need to be evaluated at regular intervals during follow-up.

PDF

___

1. Rachmilewitz EA and Giardina PJ. How I treat thalassemia. Blood 2011;118:3479-88.
2. Forni GL, Puntoni M, Boeri E, et al. The influence of treatment in specialized centers on survival of patients with thalassemia major. Am J Hematol 2009;84:317- 8.
3. Borgna-Pignatti C. Modern treatment of thalassaemia intermedia. Br J Haematol 2007;138:291-304.
4. Teawtrakul N, Jetsrisuparb A, Sirijerachai C, et al. Severe bacterial infections in patients with nontransfusion-dependent thalassemia: prevalence and clinical risk factors. Int J Infect Dis 2015;39:53-6.
5. Shamshirsaz AA, Bekheirnia MR, Kamgar M, et al. Metabolic and endocrinologic complications in betathalassemia major: a multicenter study in Tehran. BMC Endocr Disord 2003;3:4.
6. Toumba M, Sergis A, Kanaris C, et al. Endocrine complications in patients with Thalassaemia Major. Pediatr Endocrinol Rev 2007;5:642-8.
7. Shargian-Alon L, Pasvolsky O, Raanani P. Thalassemia Major and Intermedia in Patients Older than 35 Years: A Single Center Experience. Isr Med Assoc J 2017;19:767-71.
8. Sharma R, Seth A, Chandra J, et al. Endocrinopathies in adolescents with thalassaemia major receiving oral iron chelation therapy. Paediatr Int Child Health 2016;36:22-7.
9. American Diabetes Association. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2019. Diabetes Care 2019;42:13-28.
10. Bozzola M, Bozzola E, Montalbano C, et al. Delayed puberty versus hypogonadism: a challenge for the pediatrician. Ann Pediatr Endocrinol Metab 2018. 23:57-61.
11. Kazlauskaite, R, Evans AT, Villabona CV, et al. Corticotropin tests for hypothalamic-pituitary- adrenal insufficiency: a metaanalysis. J Clin Endocrinol Metab 2008;93:4245-53.
12. Lewiecki EM, Gordon CM, Baim S, et al. International Society for Clinical Densitometry 2007 Adult and Pediatric Official Positions Bone 2008;43:1115-21.
13. De Sanctis V, Elsedfy H, Soliman AT, et al. Endocrine profile of beta-thalassemia major patients followed from childhood to advanced adulthood in a tertiary care center. Indian J Endocrinol Metab 2016;20:451-9.
14. Belhoul KM, Bakir ML, Saned MS, et al. Serum ferritin levels and endocrinopathy in medically treated patients with beta thalassemia major. Ann Hematol 2012;91:1107-14.
15. Casale M, Citarella S, Filosa A, et al. Endocrine function and bone disease during long-term chelation therapy with deferasirox in patients with beta-thalassemia major. Am J Hematol 2014;89:1102-6.
16. Mula-Abed WA, Al Hashmi H, Al Muslahi M, et al. Prevalence of endocrinopathies in patients with Betathalassaemia major - a cross-sectional study in oman. Oman Med J 2008;23:257-62.
17. De Sanctis V, Elsedfy H, Soliman AT, et al. Clinical and Biochemical Data of Adult Thalassemia Major patients (TM) with Multiple Endocrine Complications (MEC) versus TM Patients with Normal Endocrine Functions: A long-term Retrospective Study (40 years) in a Tertiary Care Center in Italy. Mediterr J Hematol Infect Dis 2016;8:2016022.
18. Baldini M, Forti S, Marcon A, et al. Endocrine and bone disease in appropriately treated adult patients with beta-thalassemia major. Ann Hematol 2010;89:1207- 13.
19. Perera NJ, Lau NS, Mathews S, et al. Overview of endocrinopathies associated with beta-thalassaemia major. Intern Med J 2010;40:689-96.
20. Mehrvar A, Azarkeivan A, Faranoush M, et al. Endocrinopathies in patients with transfusiondependent beta-thalassemia. Pediatr Hematol Oncol 2008;25:187-94.
21. Wu HP, Lin CL, Chang YC, et al. Survival and complication rates in patients with thalassemia major in Taiwan. Pediatr Blood Cancer 2017;64:135-8.
22. Zervas A, Katopodi A, Protonotariou A, et al. Assessment of thyroid function in two hundred patients with betathalassemia major. Thyroid 2002;12:151-4.
23. Najafipour F, Aliasgarzadeh A, Aghamohamadzadeh N, et al. A cross-sectional study of metabolic and endocrine complications in beta-thalassemia major. Ann Saudi Med 2008;28: 361-6.
24. Angelopoulos NG, Goula A, Rombopoulos G, et al. Hypoparathyroidism in transfusion-dependent patients with beta-thalassemia. J Bone Miner Metab 2006;24:138-45.
25. Cunningham MJ, Macklin EA, Neufeld EJ, et al. Complications of beta-thalassemia major in North America. Blood 2004;104:34-9.
26. Jensen CE, Tuck SM, Agnew JE, et al. High prevalence of low bone mass in thalassaemia major. Br J Haematol 1998;103:911-5.
27. Gamberini MR, De Sanctis V, Gilli G. Hypogonadism, diabetes mellitus, hypothyroidism, hypoparathyroidism: incidence and prevalence related to iron overload and chelation therapy in patients with thalassaemia major followed from 1980 to 2007 in the Ferrara Centre. Pediatr Endocrinol Rev 2008;6:158-69.
28. Tavazzi D, Duca L, Graziadei G, et al. Membranebound iron contributes to oxidative damage of betathalassaemia intermedia erythrocytes. Br J Haematol 2001;112:48-50.
29. Ucar A, Oner N, Ozek G, et al. Evaluation of the glucocorticoid, mineralocorticoid, and adrenal androgen secretion dynamics in a large cohort of patients aged 6-18 years with transfusion-dependent beta-thalassemia major, with an emphasis on the impact of cardiac iron load. Endocrine 2016;53:240-8.
30. Altincik A and Akin M. Prevalence of Endocrinopathies in Turkish Children With beta-Thalassemia Major: A Single-Center Study. J Pediatr Hematol Oncol 2016 ;38:389-93.
31. Scacchi M, Danesi L, Cattaneo A, et al. The pituitaryadrenal axis in adult thalassaemic patients. Eur J Endocrinol 2010;162:43-8.
32. Scacchi M, Danesi L, Cattaneo A, et al. Growth hormone deficiency (GHD) in adult thalassaemic patients. Clin Endocrinol 2007;67:790-5.