Clinical and Experimental Pediatrics

The Korean Pediatric Society (대한소아청소년과학회)
권호 표지
DOI QR코드

DOI QR Code

Endocrine dysfunction after bone marrow transplantation during childhood and adolescence

소아 및 청소년기에서 골수이식 후에 발생할 수 있는 내분비 기능 부전

  • Jin, Hye Young (Department of Pediatrics, Asan Medical Center Children's Hospital University of Ulsan College of Medicine) ;
  • Choi, Jin-Ho (Department of Pediatrics, Asan Medical Center Children's Hospital University of Ulsan College of Medicine) ;
  • Im, Ho-Joon (Department of Pediatrics, Asan Medical Center Children's Hospital University of Ulsan College of Medicine) ;
  • Seo, Jong-Jin (Department of Pediatrics, Asan Medical Center Children's Hospital University of Ulsan College of Medicine) ;
  • Moon, Hyung-Nam (Department of Pediatrics, Asan Medical Center Children's Hospital University of Ulsan College of Medicine) ;
  • Yoo, Han-Wook (Department of Pediatrics, Asan Medical Center Children's Hospital University of Ulsan College of Medicine)
  • 진혜영 (울산의대 서울아산병원 소아청소년병원 소아청소년과) ;
  • 최진호 (울산의대 서울아산병원 소아청소년병원 소아청소년과) ;
  • 임호준 (울산의대 서울아산병원 소아청소년병원 소아청소년과) ;
  • 서종진 (울산의대 서울아산병원 소아청소년병원 소아청소년과) ;
  • 문형남 (울산의대 서울아산병원 소아청소년병원 소아청소년과) ;
  • 유한욱 (울산의대 서울아산병원 소아청소년병원 소아청소년과)
  • Received : 2010.01.13
  • Accepted : 2010.03.02
  • Published : 2010.03.15
Download PDF
⟨ Previous Next ⟩

Abstract

Purpose : Several complications can occur in patients who received bone marrow transplantation (BMT) during childhood and adolescence. This study aims to investigate endocrine dysfunctions after BMT so that better care can be provided to care for long-term survivors of BMT. Methods : One hundred patients (61 males, 39 females) were included in this study. Clinical parameters such as initial diagnosis, age at BMT, conditioning regimen, presence of graft-versus-host disease (GVHD), growth pattern, thyroid function, and pubertal status were retrospectively reviewed to evaluate risk factors associated with endocrine dysfunction. Results : Height standard deviation score (SDS) at BMT, after 1 year of BMT, and at the last visit were $0.08{\pm}1.04$, $-0.09{\pm}1.02$, and $-0.27{\pm}1.18$, respectively (P =0.001). Height SDS significantly decreased in patients who received total body irradiation (TBI) (P =0.017). One of the patients who received TBI demonstrated growth hormone deficiency. Thirty (31.9%) of 94 patients had compensated hypothyroidism. Incidence of compensated hypothyroidism was higher among those who had GVHD (odds ratio 2.82, P =0.025). Of the 32 patients (17 males, 15 females) who were over 14 years in male and 13 years in female at the last visit, 16 (3 males, 13 females) had increased luteinizing hormone (LH) or follicle-stimulating hormone (FSH). Abnormal elevation of LH or FSH was more common in females (odds ratio 30.3, P =0.001). Conclusion : The most common endocrine dysfunction was ovarian insufficiency. Regular check-up for endocrine function needs to be required due to high incidence of endocrine dysfunction in patients with BMT.

목 적 : 소아와 청소년기에 골수이식을 받은 환자들은 여러 가지 조기 또는 후기 합병증이 발생할 수 있다. 본 연구에서는 이식 후 발생할 수 있는 내분비 기능 부전에 대해 분석하여 이식 후 추적 관리에 도움이 되고자 하였다. 방 법 : 골수이식을 받은 100명(남자 61명, 여자 39명)의 환자들을 대상으로 진단명, 이식 당시 연령, 전처치 방법, 만성 이식편대 숙주병 유무, 성장 패턴, 갑상샘 기능, 사춘기 발달 상태 등을 후향적으로 조사하여 내분비 기능 부전과 관련이 있는 위험 인자가 있는지 분석하였다. 결 과 : 이식 당시, 이식 1년후, 최종 내원시의 신장 표준편차 점수는 각각 $0.08{\pm}1.04$, $-0.09{\pm}1.02$, $-0.27{\pm}1.18$로 의미있게 감소하였다(P =0.001). 전처치로 TBI를 받은 경우 TBI를 받지 않은 군에 비하여 이식 전보다 신장 표준편차 점수가 더 많이 감소하였다(P =0.017). TBI를 시행한 환자 중 1명에서 성장 호르몬 결핍을 보였다. 갑상샘 기능 검사를 시행한 94명 중 30명(31.9%)이 보상성 갑상샘저하증이었고 만성 이식편대 숙주병이 있었던 환자에서 보상성 갑상샘저하증의 빈도가 높았다(odds ratio=2.82, P =0.025). 최종 내원 시 만 14세 이상 남자 17명, 만 13세 이상 여자 15명 중에서 비정상적인 LH 또는 FSH의 상승을 보인 경우는 남자 3명, 여자 13명으로 여아가 의미 있게 많았다(odds ratio=30.3, P =0.001). 결 론 : 소아나 청소년기에 골수이식을 받은 환자에서 가장 흔한 내분비 기능 이상은 난소 기능 부전이며 그 외 높은 빈도의 내분비 기능 이상을 보이므로 정기적인 내분비 기능 검사가 필요하다.

Keywords

References

  1. Shalet SM. Endocrine consequences of treatment of malignant disease. Arch Dis Child 1989;64:1635-41 https://doi.org/10.1136/adc.64.11.1635
  2. Tauchmanov$\'{a}$ L, Selleri C, Rosa GD, Pagano L, Orio F, Lombardi G, et al. High prevalence of endocrine dysfunction in long-term survivors after allogeneic bone marrow transplantation for hematologic diseases. Cancer 2002;95:1076–84 https://doi.org/10.1002/cncr.10773
  3. Shalet SM, Didi M, Oglivy-Stuart AL, Schulga J, Donaldson MD. Growth and endocrine function after bone marrow transplantation. Clin Endocrinol 1995;42:333-9 https://doi.org/10.1111/j.1365-2265.1995.tb02640.x
  4. Legault L, Bonny Y. Endocrine complications of bone marrow transplantation in children. Pediatr Transplant 1999;3:60-6 https://doi.org/10.1034/j.1399-3046.1999.00009.x
  5. Bakker B, Massa GG, Oostdijk W, Van Weel-Sipman MH, Vossen JM, Wit JM. Pubertal development and growth after total-body irradiation and bone marrow transplantation for haematological malignancies. Eur J Pediatr 2000;159:31-7 https://doi.org/10.1007/s004310050006
  6. Lee DH, Lee JY, Kwon YJ, Jung MH, Cho B, Kim HK, et al. Final adult height of children with normal endocrine function after hematopoietic stem cell transplantation. J Korean Soc Pediatr Endocrinol 2007;12:15-20
  7. Jo HH, Kim MR, Kwon DJ, Kim JH, Sung IK, Kim JH. Factors affecting normal pubertal development after bone marrow transplantation in girls. Korean J Obstet Gynecol 2004;47:320-5
  8. Ha KH, Jung MH, Chung NG, Cho B, Suh BK, Kim HK, et al. Puberty and gonadal function after bone marrow transplantation during childhood. J Korean Soc Pediatr Endocrinol 2006;11:148-54
  9. Fisher DA. The Quest Diagnostics Manual: Pediatric Endocrinology. 3rd ed. San Juan Capistrano : Quest Diagnostics Incorporated, 2004;72-3, 118-9
  10. Faraci M, B$\'{e}$k$\'{a}$ssy AN, De Fazio V, Tichelli A, Dini G. Nonendocrine late complications in children after allogeneic haematopoietic SCT. Bone Marrow Transplantation 2008;41:49-57 https://doi.org/10.1038/bmt.2008.55
  11. Cohen A, Rovelli A, Bakker B, Uderzo C, van Lint MT, Esperou H, et al. Final height of patients who underwent bone marrow transplantation for hematological disorders during childhood: a study by the working party for late effects-EBMT. Blood 1999;93:4109-15
  12. Huma Z, Boulad F, Black P, Heller G, Sklar C. Growth in children after bone marrow transplantation for acute leukemia. Blood 1995;86:819-24
  13. Frisk P, Arvidson J, Gustafsson J, L$\"{o}$nnerholm G . Pubertal development and final height after autologous bone marrow transplantation for acute lymphoblastic leukemia. Bone Marrow Transplant 2004;33:205-10 https://doi.org/10.1038/sj.bmt.1704324
  14. Clement-De Boers A, Oostdijk W, Van Weel-Sipman MH, Van den Broeck J, Wit JM, Vossen JM. Final height and hormonal function after bone marrow transplantation in children. J Pediatr 1996;129:544-50 https://doi.org/10.1016/S0022-3476(96)70119-1
  15. Bakker B, Oostdijk W, Bresters D, Walenkamp MJ, Vossen JM, Wit JM. Disturbances of growth and endocrine function after busulphan-based conditioning for haematopoietic stem cell transplantation during infancy and childhood. Bone Marrow Transplantat 2004;33:1049-56 https://doi.org/10.1038/sj.bmt.1704481
  16. Afify Z, Shaw PJ, Clavano-Harding A, Cowell CT. Growth and endocrine function in children with acute myeloid leukaemia after bone marrow transplantation using busulfan/cyclophosphamide. Bone Marrow Transplant 2000;25:1087–92 https://doi.org/10.1038/sj.bmt.1702384
  17. Shalitin S, Phillip M, Stein J, Goshen Y, Carmi D, Yaniv I. Endocrine dysfunction and parameters of the metabolic syndrome after bone marrow transplantation during childhood and adolescence. Bone Marrow Transplant 2006;37:1109-17 https://doi.org/10.1038/sj.bmt.1705374
  18. Matsumoto M, Ishiguro H, Tomita Y, Inoue H, Yasuda Y, Shimizu T, et al. Changes in thyroid function after bone marrow transplant in young patients. Pediatr Int 2004;46:291-5 https://doi.org/10.1111/j.1442-200x.2004.01894.x
  19. Ishiguro H, Yasuda Y, Tomita Y, Shinagawa T, Shimizu T, Morimoto T, et al. Long-term follow-up of thyroid function in patients who received bone marrow transplantation during childhood and adolescence. J Clin Endocrinol Metab 2004;89:5981-6 https://doi.org/10.1210/jc.2004-0836
  20. Barnes ND. Effects of external irradiation on the thyroid gland in childhood. Horm Res 1988;30:84-9 https://doi.org/10.1159/000181034
  21. Bailey HK, Kappy MS, Giller RH, Gralla J. Time-course and risk factors of hypothyroidism following allogeneic hematopoietic stem cell transplantation (HSCT) in children conditioned with fractionated total body irradiation. Pediatr Blood Cancer 2008;51:405-9 https://doi.org/10.1002/pbc.21634
  22. Couto-Silva AC, Trivin C, Thibaud E, Esperou H, Michon J, Brauner R. Factors affecting gonadal function after bone marrow transplantation during childhood. Bone Marrow Transplant 2001;28:67-75 https://doi.org/10.1038/sj.bmt.1703089
  23. Ishiguro H, Yasuda Y, Tomita Y, Shinagawa T, Shimizu T, Morimoto T, et al. Gonadal shielding to irradiation is effective in protecting testicular growth and function in long-term survivors of bone marrow transplantation during childhood or adolescence. Bone Marrow Transplant 2007;39:483-90 https://doi.org/10.1038/sj.bmt.1705612
  24. Andersson AM, Juul A, Petersen JH, Muller J, Groome NP, Skakkebaek NE. Serum inhibin B in healthy pubertal and adolescent boy: relation to age, stage of puberty, and folliclestimulating hormone, luteinizing hormone, testosterone and estradiol levels. J Clin Endocrinol Metab 1997;82:3976-82 https://doi.org/10.1210/jc.82.12.3976
  25. Thibaud E, Rodriguez-Macias K, Trivin C, Esp$\'{e}$rou H, Michon J, Brauner R. Ovarian function after bone marrow transplantation during childhood. Bone Marrow Transplant 1998;21:287-90 https://doi.org/10.1038/sj.bmt.1701075
  26. Sanders JE, Buckner CD, Amos D, Levy W, Appelbaum FR, Doney K, et al. Ovarian function following marrow transplantation for aplastic anemia or leukemia. J Clin Oncol 1988;6:813-8
  27. Spinelli S, Chiodi S, Bacigalupo A, Brasca A, Menada MV, Petti AR, et al. Ovarian recovery after total body irradiation and allogeneic bone marrow transplantation: long-term follow up of 79 females. Bone Marrow Transplant 1994;14:373-80 https://doi.org/10.1038/jcbfm.1994.48
  28. Matsumoto M, Shinohara O, Ishiguro H, Shimizu T, Hattori K, Ichikawa M, et al. Ovarian function after bone marrow transplantation performed before menarche. Arch Dis Child 1999;80:452-4 https://doi.org/10.1136/adc.80.5.452
  29. Kerschan-Schindl K, Mitterbauer M, Füreder W, Kudlacek S, Grampp S, Bieglmayer C, et al. Bone metabolism in patients more than five years after bone marrow transplantation. Bone Marrow Transplant 2004;34:491-6 https://doi.org/10.1038/sj.bmt.1704618
  30. Taskinen M, Saarinen-Pinkala UM, Hovi L, Lipsanen-Nyman M. Impaired glucose tolerance and dyslipidaemia as late effects after bone-marrow transplantation in childhood. Lancet 2000;16:993-7