Investigation of Pituitary-Thyroid Axis and Thyroid Functions in Adolescent Patients with Thalassemia Major

Abstract

With modern treatment approaches in patients with thalassemia major, the life expectancy and quality of life of patients have increased, but chronic hypoxia, anemia and endocrine dysfunction related to iron accumulation continue to be seen. In various studies, thyroid dysfunction has been reported between 4% and 29% in patients with TM. In this study; Examination of thyroid gland and pituitary-thyroid axis functions in patients with a diagnosis of beta thalassemia major (β-TM) and its relationship with ferritin values, which is an indicator of body iron accumulation, were investigated.
Materials and Methods: Our study was designed as a prospective and single center. Twenty-two patients aged 10 years and older who were followed up with a diagnosis of-TM and received regular blood transfusion were included in the study. TSH response to basal thyroid hormones, Thyroid-Stimulating Hormone (TSH) and simultaneous Thyrotropine Releasing Hormone (TRH) stimulation were evaluated in order to examine the demographic structure, clinical characteristics, thyroid gland and pituitary-thyroid axis functions of the patients. Results were compared with serum ferritin values and healthy controls.
Results: Eight (36.3%) of the patients were female, the mean age was 14.03 ± 2.19 years. Total transfusion time was on average 149.9 ± 38.3 months. There was a significant positive correlation between basal TSH values and peak TSH values (r = 0.38, p <0.05) and between basal TSH and 60th minute TSH. Thyroid dysfunction was present in 27.2% of the cases. Three patients had primary hypothyroidism, two patients had subclinical hypothyroidism, and one patient had hypothalamic hypothyroidism. Secondary hypothyroidism and low T3 syndrome were not found. The average ferritin levels were 4557.18 ± 4141.31 ng / mL. There was a significant positive correlation between ferritin values and 20th minute TSH (r = 0.44, p <0.05) and 60th minute TSH (r = 0.45, p <0.05), ΔTSH (r = 0.47, p <0.05).
Discussion and Conclusion: Detecting thyroid dysfunction when hormonal examination is performed in patients with TM who do not have clinical symptoms and symptoms of hypothyroidism, especially in patients over 10 years of age, regular monitoring of thyroid hormones in terms of early diagnosis and treatment reveals its importance.

Keywords

• Thalassemia Major
• Pituitary-Thyroid Axis
• Thyroid functions

Talasemi Majorlu Adolesan Hastalarda Hipofiz-Tiroid Aksı ve Tiroid Fonksiyonlarının İncelenmesi

Öz

Giriş: Talasemi majorlu hastalarda modern tedavi yaklaşımları ile hastaların yaşam süresi uzamış, yaşam kalitesi artmıştır, ancak kronik hipoksi, anemi ve demir birikimine bağlı gelişen endokrin fonksiyon bozuklukları görülmeye devam etmektedir. Çeşitli araştırmalarda TM’lu hastalarda % 4 ila % 29 arasında tiroid fonksiyon bozukluğu bildirilmektedir. Bu çalışmada; beta talasemi major ( β-TM) tanısı ile izlenen hastalarda tiroid bezi ve hipofiz-tiroid aksı fonksiyonlarının incelenmesi ve vücut demir birikiminin bir göstergesi olan ferritin değerleri ile ilişkisi araştırılmıştır. Gereç ve Yöntem: Çalışmamız prospektif ve tek merkezli olarak tasarlandı. β-TM tanısı ile izlenen ve düzenli kan transfüzyonu alan 10 yaş ve üzeri 22 olgu çalışmaya dahil edildi. Hastaların demografik yapıları, klinik özellikleri, tiroid bezi ve hipofiz-tiroid aksı fonksiyonlarının incelenmesi amacıyla, bazal tiroid hormonları, Thyroid-Stimulating Hormone (TSH) ve eş zamanlı Thyrotropine Releasing Hormone (TRH) uyarısına TSH yanıtı değerlendirildi. Sonuçlar, serum ferritin değerleri ve sağlıklı kontrollerle karşılaştırıldı. Bulgular: Hastaların 8 (%36.3)’i kız, yaş ortalaması 14.03±2.19 yıldı. Total transfüzyon süresi ortalama 149.9±38.3 aydı. Bazal TSH değerleri ile pik TSH değerleri arasında (r=0.38, p<0.05) ve bazal TSH ile 60. dk TSH arasında anlamlı pozitif korelasyon vardı. Olguların % 27,2’sinde tiroid disfonksiyonu vardı. Üç hastada primer hipotiroidi, iki hastada subklinik düzeyde hipotiroidi, bir hastada hipotalamik hipotiroidi tespit edildi. Sekonder hipotiroidi ve düşük T3 sendromuna rastlanmadı. Ferritin düzeyleri ortalaması 4557.18 ± 4141.31 ng/mL idi. Ferritin değerleri ile 20. dk TSH ( r=0.44, p<0.05) ve 60. dk TSH (r=0.45, p<0.05), ΔTSH ( r=0.47, p<0.05 ) arasında anlamlı pozitif korelasyon vardı. Tartışma ve Sonuç: Klinik olarak hipotiroidiye ait semptom ve bulgu vermeyen TM’lu hastalarda hormonal inceleme yapıldığında tiroid disfonksiyonu tespit edilmesi özellikle 10 yaş üzeri TM’lu hastalarda tiroid hormonlarının düzenli aralıklarla takibinin erken tanı ve tedavi açısından önemini ortaya koymaktadır.

Anahtar Kelimeler

• Talasemi major
• Hipofiz-tiroid aksı
• Tiroid fonksiyonları

References

1. Origa R. (2017). β-Thalassemia. Genetics in medicine : official journal of the American College of Medical Genetics, 19(6), 609–619.
2. Soliman, A. T., Al Yafei, F., Al-Naimi, L., Almarri, N., Sabt, A., Yassin, M., & De Sanctis, V. (2013). Longitudinal study on thyroid function in patients with thalassemia major: High incidence of central hypothyroidism by 18 years. Indian journal of endocrinology and metabolism, 17(6), 1090–1095.
3. 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 : official journal of the American Thyroid Association, 12(2), 151–154.
4. Chirico, V., Lacquaniti, A., Salpietro, V., Luca, N., Ferraù, V., Piraino, B., Rigoli, L., Salpietro, C., & Arrigo, T. (2013). Thyroid dysfunction in thalassaemic patients: ferritin as a prognostic marker and combined iron chelators as an ideal therapy. European journal of endocrinology, 169(6), 785–793.
5. Upadya, S. H., Rukmini, M. S., Sundararajan, S., Baliga, B. S., & Kamath, N. (2018). Thyroid Function in Chronically Transfused Children with Beta Thalassemia Major: A Cross-Sectional Hospital Based Study. International journal of pediatrics, 2018, 9071213.
6. De Sanctis, V., Soliman, A. T., Canatan, D., Yassin, M. A., Daar, S., Elsedfy, H., Di Maio, S., Raiola, G., Corrons, J. V., & Kattamis, C. (2019). Thyroid Disorders in Homozygous β-Thalassemia: Current Knowledge, Emerging Issues and Open Problems. Mediterranean journal of hematology and infectious diseases, 11(1), e2019029.
7. Belhoul, K. M., Bakir, M. L., Saned, M. S., Kadhim, A. M., Musallam, K. M., & Taher, A. T. (2012). Serum ferritin levels and endocrinopathy in medically treated patients with β thalassemia major. Annals of hematology, 91(7), 1107–1114.
8. Richardson, M. E., Matthews, R. N., Alison, J. F., Menahem, S., Mitvalsky, J., Byrt, E., & Harper, R. W. (1993). Prevention of heart disease by subcutaneous desferrioxamine in patients with thalassaemia major. Australian and New Zealand journal of medicine, 23(6), 656–661.

9. DeGroot LJ. Endocrinology. In: DeGroot LJ, editor. Endocrinology. Toronto: Saunders; 1989. pp. 583–601.
10. Magro, S., Puzzonia, P., Consarino, C., Galati, M. C., Morgione, S., Porcelli, D., Grimaldi, S., Tancrè, D., Arcuri, V., & De Santis, V. (1990). Hypothyroidism in patients with thalassemia syndromes. Acta haematologica, 84(2), 72–76.
11. Sabato, A. R., de Sanctis, V., Atti, G., Capra, L., Bagni, B., & Vullo, C. (1983). Primary hypothyroidism and the low T3 syndrome in thalassaemia major. Archives of disease in childhood, 58(2), 120–127.
12. Neyzi, O., Furman, A., Bundak, R., Gunoz, H., Darendeliler, F., & Bas, F. (2006). Growth references for Turkish children aged 6 to 18 years. Acta paediatrica (Oslo, Norway : 1992), 95(12), 1635–1641.
13. Perez C, Scrimshaw S, Munoz A. Technique of endemic goiter surveys. In Endemic Goiter. Geneva: WHO; 1960. pp. 369–383
14. Tanner, J. M., & Whitehouse, R. H. (1976). Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty. Archives of disease in childhood, 51(3), 170–179.
15. Greulich WW, Pyle SI, Radiographic Atlas of Skeletal Development of the Hand and the Wrist (2nd Ed). Stanford University Press, Stanford, CA; 1959.
16. Canale, V. C., Steinherz, P., New, M., & Erlandson, M. (1974). Endocrine function in thalassemia major. Annals of the New York Academy of Sciences, 232(0), 333–345.
17. de Luca, F., Melluso, R., Sobbrio, G., Canfora, G., & Trimarchi, F. (1980). Thyroid function in thalassaemia major. Archives of disease in childhood, 55(5), 389–392.
18. Landau, H., Matoth, I., Landau-Cordova, Z., Goldfarb, A., Rachmilewitz, E. A., & Glaser, B. (1993). Cross-sectional and longitudinal study of the pituitary-thyroid axis in patients with thalassaemia major. Clinical endocrinology, 38(1), 55–61.
19. De Sanctis, V., Tanas, R., Gamberini, M. R., Sprocati, M., Govoni, M. R., & Marsella, M. (2008). Exaggerated TSH response to TRH ("sub-biochemical" hypothyroidism) in prepubertal and adolescent thalassaemic patients with iron overload: prevalence and 20-year natural history. Pediatric endocrinology reviews : PER, 6 Suppl 1, 170–173.
20. Livadas, D. P., Sofroniadou, K., Souvatzoglou, A., Boukis, M., Siafaka, L., & Koutras, D. A. (1984). Pituitary and thyroid insufficiency in thalassaemic haemosiderosis. Clinical endocrinology, 20(4), 435–443.
21. De Sanctis, V., Soliman, A., Candini, G., Campisi, S., Anastasi, S., & Iassin, M. (2013). High prevalence of central hypothyroidism in adult patients with β-thalassemia major. Georgian medical news, (222), 88–94.
22. De Sanctis, V., Soliman, A. T., Canatan, D., Tzoulis, P., Daar, S., Di Maio, S., Elsedfy, H., Yassin, M. A., Filosa, A., Soliman, N., Mehran, K., Saki, F., Sobti, P., Kakkar, S., Christou, S., Albu, A., Christodoulides, C., Kilinc, Y., Al Jaouni, S., Khater, D., … Kattamis, C. (2019). An ICET-A survey on occult and emerging endocrine complications in patients with β-thalassemia major: Conclusions and recommendations. Acta bio-medica : Atenei Parmensis, 89(4), 481–489.
23. Flynn, D. M., Fairney, A., Jackson, D., & Clayton, B. E. (1976). Hormonal changes in thalassaemia major. Archives of disease in childhood, 51(11), 828–836.
24. De Sanctis, V., Soliman, A., & Yassin, M. (2013). Iron overload and glucose metabolism in subjects with β-thalassaemia major: an overview. Current diabetes reviews, 9(4), 332–341.
25. Masala, A., Meloni, T., Gallisai, D., Alagna, S., Rovasio, P. P., Rassu, S., & Milia, A. F. (1984). Endocrine functioning in multitransfused prepubertal patients with homozygous beta-thalassemia. The Journal of clinical endocrinology and metabolism, 58(4), 667–670.
26. al-Hader, A., Bashir, N., Hasan, Z., & Khatib, S. (1993). Thyroid function in children with beta-thalassemia major in north Jordan. Journal of tropical pediatrics, 39(2), 107–110.
27. Gamberini, M. R., 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. Pediatric endocrinology reviews : PER, 6 Suppl 1, 158–169.
28. Soliman AT, Sanctis VD, Elalaily R, Yassin M. Insulin-like growth factor-I and factors affecting it in thalassemia major. Indian J Endocr Metab 2015; 19: 245-51.
29. Borgna-Pignatti, C., De Stefano, P., Zonta, L., Vullo, C., De Sanctis, V., Melevendi, C., Naselli, A., Masera, G., Terzoli, S., & Gabutti, V. (1985). Growth and sexual maturation in thalassemia major. The Journal of pediatrics, 106(1), 150–155.