Status of Thyroid Function and Iron Overload in Adolescents and Young Adults with Beta- Thalassemia Major Treated with Deferoxamine in Jordan
Thyroid dysfunction is one of the most frequently
reported complications of chronic blood transfusion therapy in patients with beta-thalassemia major (BTM). However, the occurrence of thyroid dysfunction and its possible association with
iron overload in BTM patients is still under debate. Therefore, this
study aimed to investigate the status of thyroid functions and iron overload in adolescent and young adult patients with BTM in Jordan population. Thirty six BTM patients aged 12-28 years and matched controls were included in this study. All patients have been receiving frequent blood transfusion to maintain pretransfusion hemoglobin
concentration above 10 g dl-1 and deferoxamine at a dose of 45 mg kg-1 day-1 (8 h, 5-7 days/week) by subcutaneous infusion. Blood
samples were drawn from patients and controls. The status of thyroid functions and iron overload was evaluated by measurements of serum
free thyroxine (FT4), triiodothyronine (FT3), thyrotropin (TSH) and
serum ferritin level. A number of some hematological and
biochemical parameters were also measured. It was found that hematocrit, serum ferritin, hemoglobin, FT3 and zinc, copper mean values were significantly higher in the patients than in the controls (P< 0.05). On other hand, leukocyte, FT4 and TSH mean values were
similar to that of the controls. In addition, our data also indicated that
all of the above examined parameters were not significantly affected
by the patient-s age and gender. Deferoxamine approach for removing excess iron from our BTM patient did not normalize the
values of serum ferritin, copper and zinc, suggesting poor compliance
with deferoxamine chelation therapy. Thus, we recommend the use
of a combination of deferoxamine and deferiprone to reduce the risk
of excess of iron in our patients. Furthermore, thyroid dysfunction
appears to be a rare complication, because our patients showed
normal mean levels for serum TSH and FT4. However, high mean
levels of serum ferritin, zinc, copper might be seen as potential risk
factors for initiation and development of thyroid dysfunctions and
other diseases. Therefore, further studies must be carried out at
yearly intervals with large sample number, to detect subclinical
thyroid dysfunction cases.
[1] Modell B, Khan M, Darlison M, King A, Layton M, Old J, Petrou M,
Varnavides L 2001 A national register for surveillance of inherited disorders: beta thalassaemia in the United Kingdom. Bulletin of the
WHO 79:1006-1013.
[2] Rund D, Rachmilewitz E 2005 Beta-thalassemia. N Engl J Med 353:1135-1146.
[3] Olivieri NF 1999 The beta-thalassemias. N Engl J Med 341:99-109.
[4] Andrews NC 1999 Disorders of iron metabolism. N Engl J Med 341:1986-1995.
[5] Cunningham MJ, Macklin EA, Neufeld EJ, Cohen AR 2004
Complications of beta-thalassemia major in North America. Blood
104:34-9.
[6] Farmaki K, Tzoumari I and Pappa C 2008 Reversal of hypothyroidism in
well chelated β-thalassemia major patients. Presented at: 50th Annual Meeting of ASH; December 6-8; San Francisco, Calif.
[7] Toumba M, Sergis A, Kanaris C, Skordis N 2007 Endocrine
complications in patients with Thalassaemia Major. Pediatr Endocrinol Rev 5:642-648.
[8] Gamberini MR, De Sanctis V, Gilli G 2008 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 1:158-169
[9] Arthur JR, Beckett GJ 1999 Thyroid function. Br Med Bull 55:658-668.
[10] Brittenham G, Griffith PM, Nienhuis AW, McLaren CE, Young NS, Tucker EE, Allen CJ, Farrell DE, Harris JW 1994 Efficacy of deferoxamine in preventing complications of iron overload in patients
with thalassemia major. N Engl J Med 331:567-573.
[11] Borgna-Pignatti C, Rugolotto S, De Stefano P, Zhao H, Cappellini MD,
Del Vecchio GC, Romeo MA, Forni GL, Gambirini MR, Ghilardi R, Piga A, Cnaan A 2004. Survival and complications in patients with
thalassemia major treated with transfusion and deferoxamine.
Haematologica 89:1187-1193.
[12] Cappellini N, Cohen A, Eleftheriou A, Piga A, Porter JB (Eds).
Guidelines for the Clinical Management of Thalassaemia. Thalassaemia
International Federation Publications 2000.
[13] Bunker VW 1992 Free radicals, antioxidants and ageing. Med Lab Sci
49:299-312.
[14] Kietzmann M 2000 Immunotoxicology of environmental and
occupational metals. Toxicon 38:735-741.
[15] Kralik A, Eder K, Kirchgessner M 1996 Influence of zinc and selenium
deficiency on parameters relating to thyroid hormone metabolism. Horm
Metab Res 28:223-226.
[16] Nishiyama S, Futagoishi-Suginohara Y, Matsukura M, Nakamura T, Higashi A, Shinohara M, Matsuda I 1994 Zinc supplementation alters
thyroid hormone metabolism in disabled patients with zinc deficiency. J
Am Coll Nutr 13: 62-67.
[17] Olivieri NF, Brittenham GM 1997 Iron chelating therapy and the
treatment of thalassaemia. Blood 89: 739-761.
[18] Cohen AR, Galanello R, Piga A, Dipalma A, Vullo C, Tricta F 2002
Safety profile of the oral iron chelator deferiprone: A multicenter study.
Br J Haematol 108:305-312.
[19] Galanello 2007 Deferiprone in the treatment of transfusion dependent
thalassemia: a review and perspective. Therapeutics and Clinical Risk
Management 3:795-805.
[20] Payne KA, Rofail D, Baladi JF, Viala M, Abetz L, Desrosiers MP,
Lordan N, Ishak K, Proskorovsky I 2008 Iron chelation therapy: clinical
effectiveness, economic burden and quality of life in patients with iron
overload. Adv Ther 25:725-42.
[21] El-Beshlawy A, Manz C, Naja M, Eltagui M, Tarabishi C, Youssry I, Sobh H, Hamdy M, Sharaf I, Mostafa A, Shaker O, Hoffbrand AV,
Taher A 2008 Iron chelation in thalassemia: combined or monotherapy?
The Egyptian experience. Ann Hematol 87:545-550.
[22] Gupta RP, Verma PC, Garg SL 1997 Effect of experimental zinc
deficiency on thyroid gland in guinea-pigs. Ann Nutr Metab 41:376-
381.
[23] Porter JB, Davis BA 2002 Monitoring chelation therapy to achieve
optimal outcome in the treatment of thalassaemia. Best Pract Res Clin
Haematol 15:329-368.
[24] Kassab CA, Laradi S, Ferchichi S, Khelil AH, Feki M, Amri F 2003
Oxidant, antioxidant status and metabolic data in patients with betathalassaemia.
Clin Chim Acta 338: 79-86.
[25] Zervas A, Katopodi A, Protonotariou A, Livadas S, Karagiorga M,
Politis C, Tolis G 2002 Assessment of thyroid function in two hundred
patients with beta-thalassemia major. Thyroid 12:151-154.
[26] Jaruratanasirikul S, Wongcharnchailert M, Laosombat V,
Sangsupavanich P, Leetanaporn K 2007 Thyroid function in betathalassemic
children receiving hypertransfusions with suboptimal ironchelating
therapy. J Med Assoc Thai 90:1798-1802.
[27] Landau H, Matoth I, Landau-Cordova Z, Goldfarb A, Rachmilewitz EA,
Glaser B 1993 Cross-sectional and longitudinal study of the pituitarythyroid
axis in patients with thalassaemia major. Clin Endocrinol (Oxf)
38:55-61.
[28] De Sanctis V, De Sanctis E, Ricchieri P, Gubellini E, Gilli G, Gamberini
MR 2008 Mild subclinical hypothyroidism in thalassaemia major:
prevalence, multigated radionuclide test, clinical and laboratory longterm
follow-up study. Pediatr Endocrinol Rev 6:174-180.
[29] Zheng Y, Li XK, Wang Y, Cai L 2008 The Role of zinc, copper and iron
in the pathogenesis of diabetes and diabetic complications: therapeutic
effects by chelators. Hemoglobin 32:135 - 145.
[30] Bashir NA 1995 Serum zinc and copper levels in sickle cell anaemia and
beta-thalassaemia in northern Jordan. Ann Trop Paediat 15:291-293.
[31] Oktekin R, Gokmen G 2000 Iron, Zinc, Copper levels of thalassemia
patients of northern Cyprus. Trace Elem Man Anim 3:627-628.
[32] Mehdizadeh M, Zamani G, Tabatabasee S 2008 Zinc status in patients
with major beta-thalassemia. Pediatric Hematol Oncol 25:49-54.
[33] Klevay LM 2001 Iron overload can induce mild copper deficiency. J
Trace Elem Med Biol 14:237-240.
[34] Nasr R, Ali S, Shaker M, Elgabry E 2002 Antioxidant micronutrients in
children with thalassaemia in Egypt. East Mediterr Health J 8:4-5.
[35] Maret W, Sandstead H 2006 Zinc requirements and the risks and
benefits of zinc supplementation. J Trace Elem Med Biol 20:3-18.
[36] Kontoghiorghes GJ, Neocleous K, Kolnagou 2003 A Benefits and risks
of deferiprone in iron overload in Thalassaemia and other conditions:
comparison of epidemiological and therapeutic aspects with
deferoxamine. Drug Saf 26:553-584.
[37] Argyropoulou MI, Astrakas L 2007 MRI evaluation of tissue iron
burden in patients with β-thalassaemia major. Pediatr Radiol 37:1191-1200.
[38] Chou ST, Weiss MJ 2007 Diseased red blood cells topple iron balance.
Nature Medicine 13:1020 - 1021.
[1] Modell B, Khan M, Darlison M, King A, Layton M, Old J, Petrou M,
Varnavides L 2001 A national register for surveillance of inherited disorders: beta thalassaemia in the United Kingdom. Bulletin of the
WHO 79:1006-1013.
[2] Rund D, Rachmilewitz E 2005 Beta-thalassemia. N Engl J Med 353:1135-1146.
[3] Olivieri NF 1999 The beta-thalassemias. N Engl J Med 341:99-109.
[4] Andrews NC 1999 Disorders of iron metabolism. N Engl J Med 341:1986-1995.
[5] Cunningham MJ, Macklin EA, Neufeld EJ, Cohen AR 2004
Complications of beta-thalassemia major in North America. Blood
104:34-9.
[6] Farmaki K, Tzoumari I and Pappa C 2008 Reversal of hypothyroidism in
well chelated β-thalassemia major patients. Presented at: 50th Annual Meeting of ASH; December 6-8; San Francisco, Calif.
[7] Toumba M, Sergis A, Kanaris C, Skordis N 2007 Endocrine
complications in patients with Thalassaemia Major. Pediatr Endocrinol Rev 5:642-648.
[8] Gamberini MR, De Sanctis V, Gilli G 2008 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 1:158-169
[9] Arthur JR, Beckett GJ 1999 Thyroid function. Br Med Bull 55:658-668.
[10] Brittenham G, Griffith PM, Nienhuis AW, McLaren CE, Young NS, Tucker EE, Allen CJ, Farrell DE, Harris JW 1994 Efficacy of deferoxamine in preventing complications of iron overload in patients
with thalassemia major. N Engl J Med 331:567-573.
[11] Borgna-Pignatti C, Rugolotto S, De Stefano P, Zhao H, Cappellini MD,
Del Vecchio GC, Romeo MA, Forni GL, Gambirini MR, Ghilardi R, Piga A, Cnaan A 2004. Survival and complications in patients with
thalassemia major treated with transfusion and deferoxamine.
Haematologica 89:1187-1193.
[12] Cappellini N, Cohen A, Eleftheriou A, Piga A, Porter JB (Eds).
Guidelines for the Clinical Management of Thalassaemia. Thalassaemia
International Federation Publications 2000.
[13] Bunker VW 1992 Free radicals, antioxidants and ageing. Med Lab Sci
49:299-312.
[14] Kietzmann M 2000 Immunotoxicology of environmental and
occupational metals. Toxicon 38:735-741.
[15] Kralik A, Eder K, Kirchgessner M 1996 Influence of zinc and selenium
deficiency on parameters relating to thyroid hormone metabolism. Horm
Metab Res 28:223-226.
[16] Nishiyama S, Futagoishi-Suginohara Y, Matsukura M, Nakamura T, Higashi A, Shinohara M, Matsuda I 1994 Zinc supplementation alters
thyroid hormone metabolism in disabled patients with zinc deficiency. J
Am Coll Nutr 13: 62-67.
[17] Olivieri NF, Brittenham GM 1997 Iron chelating therapy and the
treatment of thalassaemia. Blood 89: 739-761.
[18] Cohen AR, Galanello R, Piga A, Dipalma A, Vullo C, Tricta F 2002
Safety profile of the oral iron chelator deferiprone: A multicenter study.
Br J Haematol 108:305-312.
[19] Galanello 2007 Deferiprone in the treatment of transfusion dependent
thalassemia: a review and perspective. Therapeutics and Clinical Risk
Management 3:795-805.
[20] Payne KA, Rofail D, Baladi JF, Viala M, Abetz L, Desrosiers MP,
Lordan N, Ishak K, Proskorovsky I 2008 Iron chelation therapy: clinical
effectiveness, economic burden and quality of life in patients with iron
overload. Adv Ther 25:725-42.
[21] El-Beshlawy A, Manz C, Naja M, Eltagui M, Tarabishi C, Youssry I, Sobh H, Hamdy M, Sharaf I, Mostafa A, Shaker O, Hoffbrand AV,
Taher A 2008 Iron chelation in thalassemia: combined or monotherapy?
The Egyptian experience. Ann Hematol 87:545-550.
[22] Gupta RP, Verma PC, Garg SL 1997 Effect of experimental zinc
deficiency on thyroid gland in guinea-pigs. Ann Nutr Metab 41:376-
381.
[23] Porter JB, Davis BA 2002 Monitoring chelation therapy to achieve
optimal outcome in the treatment of thalassaemia. Best Pract Res Clin
Haematol 15:329-368.
[24] Kassab CA, Laradi S, Ferchichi S, Khelil AH, Feki M, Amri F 2003
Oxidant, antioxidant status and metabolic data in patients with betathalassaemia.
Clin Chim Acta 338: 79-86.
[25] Zervas A, Katopodi A, Protonotariou A, Livadas S, Karagiorga M,
Politis C, Tolis G 2002 Assessment of thyroid function in two hundred
patients with beta-thalassemia major. Thyroid 12:151-154.
[26] Jaruratanasirikul S, Wongcharnchailert M, Laosombat V,
Sangsupavanich P, Leetanaporn K 2007 Thyroid function in betathalassemic
children receiving hypertransfusions with suboptimal ironchelating
therapy. J Med Assoc Thai 90:1798-1802.
[27] Landau H, Matoth I, Landau-Cordova Z, Goldfarb A, Rachmilewitz EA,
Glaser B 1993 Cross-sectional and longitudinal study of the pituitarythyroid
axis in patients with thalassaemia major. Clin Endocrinol (Oxf)
38:55-61.
[28] De Sanctis V, De Sanctis E, Ricchieri P, Gubellini E, Gilli G, Gamberini
MR 2008 Mild subclinical hypothyroidism in thalassaemia major:
prevalence, multigated radionuclide test, clinical and laboratory longterm
follow-up study. Pediatr Endocrinol Rev 6:174-180.
[29] Zheng Y, Li XK, Wang Y, Cai L 2008 The Role of zinc, copper and iron
in the pathogenesis of diabetes and diabetic complications: therapeutic
effects by chelators. Hemoglobin 32:135 - 145.
[30] Bashir NA 1995 Serum zinc and copper levels in sickle cell anaemia and
beta-thalassaemia in northern Jordan. Ann Trop Paediat 15:291-293.
[31] Oktekin R, Gokmen G 2000 Iron, Zinc, Copper levels of thalassemia
patients of northern Cyprus. Trace Elem Man Anim 3:627-628.
[32] Mehdizadeh M, Zamani G, Tabatabasee S 2008 Zinc status in patients
with major beta-thalassemia. Pediatric Hematol Oncol 25:49-54.
[33] Klevay LM 2001 Iron overload can induce mild copper deficiency. J
Trace Elem Med Biol 14:237-240.
[34] Nasr R, Ali S, Shaker M, Elgabry E 2002 Antioxidant micronutrients in
children with thalassaemia in Egypt. East Mediterr Health J 8:4-5.
[35] Maret W, Sandstead H 2006 Zinc requirements and the risks and
benefits of zinc supplementation. J Trace Elem Med Biol 20:3-18.
[36] Kontoghiorghes GJ, Neocleous K, Kolnagou 2003 A Benefits and risks
of deferiprone in iron overload in Thalassaemia and other conditions:
comparison of epidemiological and therapeutic aspects with
deferoxamine. Drug Saf 26:553-584.
[37] Argyropoulou MI, Astrakas L 2007 MRI evaluation of tissue iron
burden in patients with β-thalassaemia major. Pediatr Radiol 37:1191-1200.
[38] Chou ST, Weiss MJ 2007 Diseased red blood cells topple iron balance.
Nature Medicine 13:1020 - 1021.
@article{"International Journal of Medical, Medicine and Health Sciences:62031", author = "Fawzi Irshaid and Kamal Mansi", title = "Status of Thyroid Function and Iron Overload in Adolescents and Young Adults with Beta- Thalassemia Major Treated with Deferoxamine in Jordan", abstract = "Thyroid dysfunction is one of the most frequently
reported complications of chronic blood transfusion therapy in patients with beta-thalassemia major (BTM). However, the occurrence of thyroid dysfunction and its possible association with
iron overload in BTM patients is still under debate. Therefore, this
study aimed to investigate the status of thyroid functions and iron overload in adolescent and young adult patients with BTM in Jordan population. Thirty six BTM patients aged 12-28 years and matched controls were included in this study. All patients have been receiving frequent blood transfusion to maintain pretransfusion hemoglobin
concentration above 10 g dl-1 and deferoxamine at a dose of 45 mg kg-1 day-1 (8 h, 5-7 days/week) by subcutaneous infusion. Blood
samples were drawn from patients and controls. The status of thyroid functions and iron overload was evaluated by measurements of serum
free thyroxine (FT4), triiodothyronine (FT3), thyrotropin (TSH) and
serum ferritin level. A number of some hematological and
biochemical parameters were also measured. It was found that hematocrit, serum ferritin, hemoglobin, FT3 and zinc, copper mean values were significantly higher in the patients than in the controls (P< 0.05). On other hand, leukocyte, FT4 and TSH mean values were
similar to that of the controls. In addition, our data also indicated that
all of the above examined parameters were not significantly affected
by the patient-s age and gender. Deferoxamine approach for removing excess iron from our BTM patient did not normalize the
values of serum ferritin, copper and zinc, suggesting poor compliance
with deferoxamine chelation therapy. Thus, we recommend the use
of a combination of deferoxamine and deferiprone to reduce the risk
of excess of iron in our patients. Furthermore, thyroid dysfunction
appears to be a rare complication, because our patients showed
normal mean levels for serum TSH and FT4. However, high mean
levels of serum ferritin, zinc, copper might be seen as potential risk
factors for initiation and development of thyroid dysfunctions and
other diseases. Therefore, further studies must be carried out at
yearly intervals with large sample number, to detect subclinical
thyroid dysfunction cases.", keywords = "beta-thalassemia major, deferoxamine, iron overload, triiodothyronine, zinc.", volume = "3", number = "10", pages = "314-6", }
