Long-Term Safety of Recombinant Human Growth Hormone in Children

被引:221
作者
Bell, J. [1 ]
Parker, K. L. [2 ]
Swinford, R. D. [3 ]
Hoffman, A. R. [4 ,5 ]
Maneatis, T. [6 ]
Lippe, B. [6 ]
机构
[1] Columbia Univ, Med Ctr, New York, NY 10032 USA
[2] Univ Texas Med Branch, Galveston, TX 77555 USA
[3] Univ Texas Houston, Hlth Sci Ctr, Houston, TX 77030 USA
[4] VA Palo Alto Hlth Care Syst, Palo Alto, CA 94305 USA
[5] Stanford Univ, Palo Alto, CA 94305 USA
[6] Genentech Inc, San Francisco, CA 94080 USA
关键词
PRADER-WILLI-SYNDROME; NATIONAL COOPERATIVE GROWTH; CAPITAL FEMORAL EPIPHYSIS; POSTTRANSPLANT LYMPHOPROLIFERATIVE DISORDER; CHILDHOOD-CANCER SURVIVOR; TURNER-SYNDROME; PSEUDOTUMOR CEREBRI; ACUTE-PANCREATITIS; DIABETES-MELLITUS; UNITED-STATES;
D O I
10.1210/jc.2009-0178
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: Between 1985 and 2006, the National Cooperative Growth Study (NCGS) monitored the safety and efficacy of recombinant human growth hormone (rhGH) in 54,996 children. Methods: Enrolled patients were followed until rhGH discontinuation. Investigators submitted adverse event reports for targeted events or those potentially rhGH-related. Results: Early concerns about de novo leukemia in patients without risk factors have not been substantiated-three observed vs. 5.6 expected in age-matched general population based on years at risk [standard incidence ratio (SIR), 0.54; 95% confidence interval (CI), 0.11-1.58]. De novo malignancies (intracranial and extracranial) were not significantly increased in patients without risk factors (29 confirmed vs. 26 expected; SIR, 1.12; 95% CI, 0.75-1.61). Second neoplasms occurred in 49 patients, of whom 37 had irradiation for their initial tumors (including five of 16 retinoblastoma patients, three of whom had bilateral retinoblastoma) consistent with an increased risk with rhGH. Thirty-three patients developed type 1 diabetes mellitus (DM) (37 expected; SIR, 0.90; 95% CI, 0.62-1.26). Type 2 DM and nonspecified DM were reported in 20 and eight patients, respectively. Two deaths were reported in patients with Prader-Willi syndrome and five deaths from aortic dissection in patients with Turner syndrome. In patients with organic GH deficiency and idiopathic panhypopituitarism, 11 events of acute adrenal insufficiency occurred, including four deaths, consistent with a reported increased risk for adrenal insufficiency in hypopituitary patients with or without rhGH treatment. Conclusion: After more than 20 yr, leukemia, a major safety issue initially believed associated with GH, has not been confirmed, but other signals, including risk of second malignancies in patients previously treated with irradiation, have been detected or confirmed through the NCGS. These data further clarify the events associated with rhGH and, although confirming a favorable overall safety profile, they also highlight specific populations at potential risk. (J Clin Endocrinol Metab 95: 167-177, 2010)
引用
收藏
页码:167 / 177
页数:11
相关论文
共 52 条
[1]   Safety of human growth hormone therapy: Current topics [J].
Allen, DB .
JOURNAL OF PEDIATRICS, 1996, 128 (05) :S8-S13
[2]   GROWTH-HORMONE TREATMENT IN THE UNITED-STATES - DEMOGRAPHIC AND DIAGNOSTIC FEATURES OF 2331 CHILDREN [J].
AUGUST, GP ;
LIPPE, BM ;
BLETHEN, SL ;
ROSENFELD, RG ;
SEELIG, SA ;
JOHANSON, AJ ;
COMPTON, PG ;
FRANE, JW ;
MCCLELLAN, BH ;
SHERMAN, BM .
JOURNAL OF PEDIATRICS, 1990, 116 (06) :899-903
[3]   Sudden death in Prader-Willi syndrome:: Brief review of five additional cases -: Concerning the article by U.!Eiholzer et al.:: Deaths in children with Prader-Willi syndrome.: A contribution to the debate about the safety of growth hormone treatment in children with PWS (Horm Res 2005; 63: 33-39) [J].
Bakker, Bert ;
Maneatis, Thomas ;
Lippe, Barbara .
HORMONE RESEARCH, 2007, 67 (04) :203-204
[4]   Safety of recombinant deoxyribonucleic acid-derived growth hormone: The national cooperative growth study experience [J].
Blethen, SL ;
Allen, DB ;
Graves, D ;
August, G ;
Moshang, T ;
Rosenfeld, R .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1996, 81 (05) :1704-1710
[5]   Slipped capital femoral epiphysis in children treated with growth hormone - A summary of the National Cooperative Growth Study Experience [J].
Blethen, SL ;
Rundle, AC .
HORMONE RESEARCH, 1996, 46 (03) :113-116
[6]   Long-term safety of recombinant human growth hormone in Turner syndrome [J].
Bolar, Katrina ;
Hoffman, Andrew R. ;
Maneatis, Thomas ;
Lippe, Barbara .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2008, 93 (02) :344-351
[7]   Incidence of diabetes mellitus and impaired glucose tolerance in children and adolescents receiving growth-hormone treatment [J].
Cutfield, WS ;
Wilton, P ;
Bennmarker, H ;
Albertsson-Wikland, K ;
Chatelain, P ;
Ranke, MB ;
Price, DA .
LANCET, 2000, 355 (9204) :610-613
[8]  
Dabelea D, 2007, JAMA-J AM MED ASSOC, V297, P2716, DOI 10.1001/jama.297.24.2716
[9]   Recombinant growth hormone use pretransplant and risk for post-transplant lymphoproliferative disease - A report of the NAPRTCS [J].
Dharnidharka, Vikas R. ;
Talley, Lynya I. ;
Martz, Karen L. ;
Stablein, Donald M. ;
Fine, Richard N. .
PEDIATRIC TRANSPLANTATION, 2008, 12 (06) :689-695
[10]   Risk factors for posttransplant lymphoproliferative disorder (PTLD) in pediatric kidney transplantation: A report of the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS) [J].
Dharnidharka, VR ;
Sullivan, EK ;
Stablein, DM ;
Tejani, AH ;
Harmon, WE .
TRANSPLANTATION, 2001, 71 (08) :1065-1068