Endocrinological Problems in Adult Thalassemia Patients
AbstractThalassemia refers to a group of genetic disorders associated with defective synthesis of alpha or beta subunits of globin chain of HbA. Patients with thalassemia major are transfusion dependent for life and they suffer from numerous problems associated with chronic anemia; extramedullary hematopoiesis and an iron overload. Several endocrine organs are affected by the iron overload. Hypogonadism is the most common endocrine complication in thalassemia. Diabetes, osteoporosis, growth hormone deficiency are other endocrine disorders seen among thalassemic patients. This review begins with a case and mainly focusses on diagnosis and treatment of endocrinological problems in adult thalassemia major patients.
Giardina P, Forget B. Thalassemia syndromes. In: Hoffman R, Benz E, Shattil S, et al, eds. Hematology: Basic Principles and Practice (5th ed). Philadelphia, PA: Churchill Livingstone; 2008:535-563
Rachmilewitz EA, Giardina PJ. How I treat thalassemia. Blood. 2011;118:3479-88
Higgs DR, Engel JD, Stamatoyannopoulos G. Thalassaemia. Lancet 2012;379:373-83
Borgna-Pignatti C, Rogolotto S, De Stefano P, Zhao H, Cappellini MD, et al. Survival and complicaitions in patients with thalassemia major treated with transfusion and deferoxamine. Hematologica 2004;89:1187-93
Hershko C, Link G, Cabantchik I. Pathophysiology of iron overload. Ann N Y Acad Sci. 1998;30:191–201.
Andrews NC, Schmidt PJ. Iron homeostasis. Annual Review of Physiology, 2007;69:69–85.
Iancu TC: Biological and ultrastructural aspects of iron overload. An overview. New York, Hemisphere, 1990, pp 1–251.
Magro S, Puzzonia P, Consarino C, Galati MC, Morgione S, Porcelli D, et al. Hypothyroidism in patients with thalassaemia syndromes. Acta Haematol. 1990;84:72–6.
De Sanctis V. Growth and puberty and its management in thalassaemia. Horm Res. 2002;58:72–9
Soliman AT, Khalafallah H, Ashour R. Growth and factors affecting it in thalassemia major. Hemoglobin. 2009;33:S116–26.
De Sanctis V, Soliman AT, Elsedfy H, Skordis N, Kattamis C, Angastiniotis M,et al. Growth and endocrine disorders in thalassemia: The international network on endocrine complications in thalassemia (I-CET) position statement and guidelines. Indian J Endocrinol Metab. 2013;17:8-18
Salvatori R. Clinical management of growth hormone therapy in adults. Manag Care. 2009; 18(suppl 6):10-6
Skordis N. Endocrine investigation and follow up in thalassaemia. Time for specific guidelines. Thalassemia Reports. 2011;1(s2):e22.
Pincelli AI, Masera N, Tavecchia L, Perotti M, Perra S, Mariani R, et al. GH deficiency in adult B-thalassemia major patients and its relationship with IGF-1 production. Pediatr Endocrinol Rev. 2011;8 Suppl 2:284-9
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
Poggi M, Pascucci C, Monti S, Pugliese P, Lauri C, Amodeo G, et al. Prevalence of growth hormone deficiency in adult polytransfused β-thalassemia patients and correlation with transfusional and chelation parameters. J Endocrinol Invest. 2010;33:534-8
De Sanctis V, Soliman A, Candini G, Campisi S, Anastasi S, Iassin M. High prevalence of central hypothyroidism in adult patients with β-thalassemia major. Georgian Med News. 2013;222:88-94.
Filosa A, Di Maio S, Aloj G, Acampora C. Longitudinal study on thyroid function in patients with thalassemia major. J Pediatr Endocrinol Metab. 2006;19:1397-404
Mariotti S, Pigliaru F, Cocco MC, Spiga A, Vaquer S, Lai ME. β-thalassemia and thyroid failure: is there a role for thyroid autoimmunity? Pediatr Endocrinol Rev. 2011;8 Suppl 2:307-9.
Mariotti S, Loviselli A, Murenu S, Sau F, Valentino L, Mandas A, Vacquer S, Martino E, Balestrieri A, Lai ME. High prevalence of thyroid dysfunction in adult patients with beta-thalassemia major submitted to amiodarone treatment. J Endocrinol Invest. 1999;22:55-63.
Canatan D. The Thalassemia center of Antalya State Hospital: 15 years of experience (1994 to 2008). J Pediatr Hematol Oncol. 2013;35:24-7.
Aleem A, Al-Momen AK, Al-Harakati MS, Hassan A, Al-Fawaz I. Hypocalcemia due to hypoparathyroidism in beta-thalassemia major patients. Ann Saudi Med. 2000;20:364-6.
De Sanctis V, Vullo C, Bagni B, Chiccoli L. Hypoparathyroidism in beta-thalassemia major. Clinical and laboratory observations in 24 patients. Acta Haematol. 1992;88:105-8.
Karimi M, Rasekhi AR, Rasekh M, Nabavizadeh SA, Assadsangabi R, Amirhakimi GH. Hypoparathyroidism and intracerebral calcification in patients with beta-thalassemia major. Eur J Radiol. 2009;70:481-4.
Voskaridou E, Terpos E. New insights into the pathophysiologyand management of osteoporosis in patients with betathalassaemia. Br J Haematol 2004; 127:127–39.
Haidar R, Musallam KM, Taher AT. Bone disease and skeletal complications in patients with b thalassemia major. Bone 2011;48:425–32.
Skordis N, Toumba M. Bone disease in thalassaemia major: recent advances in pathogenesis and clinical aspects. Pediatr Endocrinol Rev. 2011;8 :300-6.
Wong P, Fuller PJ, Gillespie MT, Kartsogiannis V, Kerr PG, Doery JC, Paul E,Bowden DK, Strauss BJ, Milat F. Thalassemia Bone Disease: A 19 Year Longitudinal Analysis. J Bone Miner Res. 2014 April 25 J Bone Miner Res. 2014 Apr 25. doi: 10.1002/jbmr.2266.
Canatan D. The Thalassemia center of Antalya State Hospital: 15 years of experience (1994 to 2008). J Pediatr Hematol Oncol. 2013;35:24-27
Papapoulos SE. Bisphosphonates: how do they work? Best Pract Res Clin Endocrinol Metab 2008;22:831–47
Morabito N, Lasco A, Gaudio A et al.Bisphosphonates inthe treatment of thalassemia-induced osteoporosis. Osteoporos Int. 2002; 13: 644–9.
Voskaridou E, Anagnostopoulos A, Konstantopoulos K et al. Zoledronic acid for the treatment of osteoporosis in patients with beta-thalassemia: results from a single-center, randomized, placebo-controlled trial. Haematologica. 2006; 91: 1193–202.
Giusti A. Bisphosphonates in the management of thalassemia-associated osteoporosis: a systematic review of randomised controlled trials. J Bone Miner Metab. 2014 April 21.
Chatterjee R, Bajoria R. New concept in natural history and management of diabetes mellitus in thalassemia major. Hemoglobin 2009;33:S127–S130.
Argyropoulou MI, Kiortsis DN, Astrakas L, et al. Liver, bone marrow, pancreas and pituitary gland iron overload in young and adult thalassemic patients:AT2 relaxometry study. Eur Radiol 2007;17:3025-30.
Cario H, Holl RW, Debatin KM, et al. Insulin sensitivity and beta-cell secretion in thalassaemia major with secondary haemochromatosis: Assessment by oral glucose tolerance test. Eur J Pediatr 2003;162:139-146.
Suvarna J, Ingle H, Deshmukh CT. Insulin resistance and beta cell function in chronically transfused patients of thalassemia major. Indian Pediatr 2006;43:393–400.
Messina MF, Lombardo F, Meo A, Miceli M, Wasniewska M, Valenzise M, et al. Three-year prospective evaluation of glucose tolerance, beta-cell function and peripheral insulin sensitivity in non-diabetic patients with thalassemia major. J Endocrinol Invest. 2002;25:497-501.
Platis O, Anagnostopoulos G, Farmaki K, Posantzis M, Gotsis E, Tolis G. Glucose metabolism disorders improvement in patients with thalassaemia major after 24-36 months of intensive chelation therapy. Pediatr Endocrinol Rev. 2004;2 Suppl 2:279-81.
Wonke B, De Sanctis V. Clinical aspects of transfusional iron overload. Clin Exp Hematol. 2001;12:322–34.
Smaldone A. Glycemic control and hemoglobinopathy: When A1C may not be reliable. Diabetes Spectr. 2008;21:46–9
Ang AL, Tzoulis P, Prescott E, Davis BA, Barnard M, Shah FT. History of myocardial iron loading is a strong risk factor for diabetes mellitus and hypogonadism in adults with β thalassemia major. Eur J Haematol. 2014;92:229-36.
Perera NJ, Lau NS, Mathews S, Waite C, Ho PJ, Caterson ID. Overview of endocrinopathies associated with β-thalassaemia major. Intern Med J. 2010 ;40:689-96.
Noetzli LJ, Panigrahy A, Mittelman SD, Hyderi A, Dongelyan A, Coates TD, et al. Pituitary iron and volume predict hypogonadism in transfusional iron overload. Am J Hematol. 2012;87:167-71.
Au WY, Lam WW, Chu WW, Yuen HL, Ling AS, Li RC, et al. A cross-sectional magnetic resonance imaging assessment of organ specific hemosiderosis in 180 thalassaemia major patients in Hong Kong. Haematologica 2008;93:784–6.
Roussou P, Tsagarakis NJ, Kountouras D, Livadas S, Diamanti-Kandarakis E. Beta-thalassemia major and female fertility: the role of iron and iron-induced oxidative stress. Anemia. 2013;2013:617204.
Origa R, Piga A, Quarta G, Forni GL, Longo F, Melpignano A, et al. Pregnancy and beta-thalassemia: an Italian multicenter experience. Haematologica.2010;95:376-81.
Skordis N, Petrikkos L, Toumba M, Hadjigavriel M, Sitarou M, Kolnakou A, et al. Update on fertility in thalassaemia major. Pediatr Endocrinol Rev. 2004;2:296–302.
De Sanctis V, Vullo C, Katz M, Wonke B, Nannetti C, Bagni B. Induction of spermatogenesis in thalassaemia. Fertil Steril. 1998;50:969–75.
Poomthavorn P, Isaradisaikul B, Chuansumrit A, Khlairit P, Sriphrapradang A, Mahachoklertwattana P. High prevalence of “biochemical” adrenal insufficiency in thalassemics: Is it a matter of different testings or decreased cortisol binding globulin? J Clin Endocrinol Metab. 2010;95:4609–15.
Elsedfy HH, El Kholy M, Tarif R, Hamed A, Elalfy M. Adrenal function in thalassemia major adolescents. Pediatr Endocrinol Rev. 2011;8:295–9.
Jaruratanasirikul S, Tanchotikul S, Wongcharnchailert M, Laosombat V, Sangsupavanich P, Leetanaporn K. A low dose adrenocorticotropin test (1 microg ACTH) for the evaluation of adrenal function in children with beta-thalassemia receiving hypertransfusion with suboptimal iron-chelating therapy. J Pediatr Endocrinol Metab. 2007;20:1183- 8
Scacchi M, Danesi L, Cattaneo A, Valassi E, Pecori Giraldi F, et al. The pituitary-adrenal axis in adult thalassaemic patients. Eur J Endocrinol. 2010;162:43-8.
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