Early GH treatment is effective and well tolerated in children with Turner syndrome: NordiNet® IOS and ANSWER program
Open accessAbstract
CONTEXT: Despite having normal growth hormone (GH) secretion, individuals with Turner syndrome (TS) have short stature. Treatment with recombinant human GH is recommended for TS girls with short stature. OBJECTIVE: This work aimed to evaluate the effectiveness and safety of Norditropin (somatropin, Novo Nordisk) with up to 10 years of follow-up in children with TS. METHODS: Secondary analysis was conducted of Norditropin data from 2 non-interventional studies: NordiNet® IOS (NCT00960128) and the ANSWER program (NCT01009905). RESULTS: A total of 2377 girls with TS were included in the safety analysis set (SAS), with 1513 in the treatment-naive effectiveness analysis set (EAS). At the start of treatment, 1273 (84%) participants were prepubertal (EAS); mean (SD) age was 8.8 (3.9) years. Mean (SD) dose received at the start of GH treatment was 0.045 (0.011) mg/kg/day (EAS). Mean (SD) baseline insulin-like growth factor-1 (IGF-I) SD score (SDS) was -0.86 (1.52), and mean (SD) duration of GH treatment (SAS) was 3.8 (2.8) years.Height SDS (HSDS) increased throughout follow-up, with near-adult HSDS reached by 264 (17%) participants (mean [SD] -1.99 [0.94]; change from baseline +0.90 [0.85]). During the study, 695 (46%) participants (EAS) entered puberty at a mean (SD) age of 12.7 (1.9) years (whether puberty was spontaneous or induced was unknown). Within the SAS, mean IGF-I SDS (SD) at year 10 was 0.91 (1.69); change from baseline +1.48 (1.70). Serious adverse reactions were reported in 10 participants (epiphysiolysis [n = 3]). CONCLUSION: GH-treated participants with TS responded well, without new safety concerns. Our real-world data are in agreement with previous studies.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Data from GH registries provide no evidence of an increase in risk of neoplasia with treatment.
“data from GH registries provide no evidence of an increase in risk of neoplasia with treatment.173,208,222-224”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [224]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Usher, R. H., & McLean, F. H. (1969) · The Journal of Pediatrics · doi:10.1016/s0022-3476(69)80224-6 · Cited by 1,260 · see citing works
Nielsen, J., & Wohlert, M. (1991) · Human Genetics · doi:10.1007/bf01213097 · Cited by 1,193 · see citing works
Gravholt, C. H., Andersen, N. H., Conway, G. S., Dekkers, O. M., Geffner, M. E., Klein, K. O., Lin, A. E., Mauras, N., Quigley, C. A., Rubin, K., et al. (2017) · European Journal of Endocrinology · doi:10.1530/eje-17-0430 · Cited by 1,101 · see citing works
Self-citationCare of girls and women with Turner syndrome: a guideline of the Turner syndrome study group
Bondy, C. A. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-1374 · Cited by 1,005 · see citing works
Prevalence, incidence, diagnostic delay, and mortality in Turner syndrome
Stochholm, K., Juul, S., Juel, K., Naeraa, R. W., & Højbjerg Gravholt, C. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-0558 · Cited by 652 · see citing works
Juul, A., Dalgaard, P., Blum, W. F., Bang, P., Hall, K. E., Michaelsen, K. F., Müller, J., & Skakkebæk, N. E. (1995) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.80.8.7543116 · Cited by 463 · see citing works
Brabant, G. E., Mühlen, A. V. Z., Wüster, C. C., Ranke, M. B., Kratzsch, J., Kieß, W., Ketelslegers, J., Wilhelmsen, L., Hulthén, L., Saller, B., et al. (2003) · Hormone Research in Paediatrics · doi:10.1159/000071871 · Cited by 360 · see citing works
Long-term safety of recombinant human growth hormone in children
Bell, J., Parker, K. L., Swinford, R. D., Hoffman, A. R., Maneatis, T., & Lippe, B. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-0178 · Cited by 301 · see citing works
(2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2004-2187 · Cited by 256 · see citing works
Non-Compliance with Growth Hormone Treatment in Children Is Common and Impairs Linear Growth
Cutfield, W. S., Derraik, J. G. B., Gunn, A. J., Reid, K., Delany, T., Robinson, E., & Hofman, P. L. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016223 · Cited by 251 · see citing works
Growth hormone plus childhood low-dose estrogen in Turner's syndrome
Ross, J. L., Quigley, C. A., Cao, D., Feuillan, P., Kowal, K., Chipman, J. J., & Cutler, G. B. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1005669 · Cited by 212 · see citing works
Ranke, M. B., Lindberg, A., Chatelain, P., Wilton, P., Cutfield, W. S., Albertsson-Wikland, K. G., & Price, D. A. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.11.6976 · Cited by 148 · see citing works
Davenport, M. L., Crowe, B. J., Travers, S. H., Rubin, K., Ross, J. L., Fechner, P. Y., Gunther, D. F., Liu, C., Geffner, M. E., Thrailkill, K., et al. (2007) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-2874 · Cited by 147 · see citing works
Reference values for height, height velocity and weight in Turner's Syndrome
Rongen‐Westerlaken, C., Corel, L. J. A., den Broeck, J. V., Massa, G., KARLBERG, J. P. E., Albertsson-Wikland, K. G., Næraa, R. W., & Wit, J. M. (1997) · Acta Paediatrica · doi:10.1111/j.1651-2227.1997.tb15174.x · Cited by 131 · see citing works
Recombinant growth hormone for children and adolescents with Turner syndrome
Baxter, L., Bryant, J., Cave, C. B., & Milne, R. (2007) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd003887.pub2 · Cited by 122 · see citing works
Long-term safety of recombinant human growth hormone in Turner syndrome
Bolar, K., Hoffman, A. R., Maneatis, T., & Lippe, B. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2007-1723 · Cited by 116 · see citing works
Darendelıler, F., Karagiannis, G., & Wilton, P. (2007) · Hormone Research in Paediatrics · doi:10.1159/000110474 · Cited by 115 · see citing works
Spontaneous Growth in Turner's Syndrome
Ranke, M. B., Stubbe, P., Majewski, F., & Bierich, J. R. (1988) · Acta Paediatrica · doi:10.1111/j.1651-2227.1988.tb10796.x · Cited by 113 · see citing works
Romano, A. A., Dana, K., Bakker, E., Davis, D. A., Hunold, J. J., Jacobs, J. R., & Lippe, B. M. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-2094 · Cited by 112 · see citing works
Current Indications for Growth Hormone Therapy for Children and Adolescents
Richmond, E. J., & Rogol, A. D. (2010) · Endocrine development · doi:10.1159/000316130 · Cited by 103 · see citing works
Efficacy and safety of oxandrolone in growth hormone-treated girls with Turner syndrome
Menke, L. A., Sas, T. C. J., de Muinck Keizer-Schrama, S. M. P. F., Zandwijken, G. R. J., de Ridder, M. A. J., Odink, R. J., Jansen, M., Delemarre-van de Waal, H. A., Stokvis-Brantsma, W. H., Waelkens, J. J., et al. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-1821 · Cited by 94 · see citing works
Child, C. J., Zimmermann, A. G., Chrousos, G. P., Cummings, E., Deal, C. L., Hasegawa, T., Jia, N., Lawrence, S., Linglart, A., Loche, S., et al. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2018-01189 · Cited by 80 · see citing works
Self-citationLong‐term safety of growth hormone—A combined registry analysis
Stochholm, K., & Kieß, W. (2017) · Clinical Endocrinology · doi:10.1111/cen.13502 · Cited by 74 · see citing works
Gault, E. J., Perry, R. J., Cole, T. J., Casey, S., Paterson, W. F., Hindmarsh, P. C., Betts, P., Dunger, D. B., Donaldson, M. D. C., & on behalf of the British Society for Paediatric Endocrinology and Diabetes (2011) · BMJ · doi:10.1136/bmj.d1980 · Cited by 71 · see citing works
Swerdlow, A. J., Cooke, R., Albertsson-Wikland, K. G., Borgström, B., Butler, G. E., Cianfarani, S., Clayton, P., Coste, J., Deodati, A., Écosse, E., et al. (2015) · Hormone Research in Paediatrics · doi:10.1159/000435856 · Cited by 62 · see citing works
Lessons from the national cooperative growth study
Wyatt, D. (2004) · European Journal of Endocrinology · doi:10.1530/eje.0.151s055 · Cited by 57 · see citing works
Quigley, C. A., Wan, X., Garg, S., Kowal, K., Cutler, G. B., & Ross, J. L. (2014) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2013-4518 · Cited by 56 · see citing works
Plotnick, L., Attie, K. M., Blethen, S. L., & Sy, J. P. (1998) · PEDIATRICS · doi:10.1542/peds.102.s3.479 · Cited by 54 · see citing works
Savendahl, L. S., Polak, M., Backeljauw, P. F., Blair, J., Miller, B. S., Rohrer, T. R., Pietropoli, A., Ostrow, V., & ROSS, J. L. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2019-00775 · Cited by 54 · see citing works
Self-citationPasquino, A. M., Pucarelli, I., Segni, M., Tarani, L., Calcaterra, V., & Larizza, D. (2005) · Journal of Endocrinological Investigation · doi:10.1007/bf03347202 · Cited by 53 · see citing works
Höybye, C., Savendahl, L. S., Christesen, H. T., Lee, Pedersen, Schlumpf, Germak, & ROSS, J. L. (2013) · Clinical Epidemiology · doi:10.2147/clep.s42602 · Cited by 47 · see citing works
GeNeSIS National Board on behalf of the GeNeSIS Italian Investigators, Cappa, M., Iughetti, L., Loche, S., Maghnie, M., & Vottero, A. (2015) · Journal of Endocrinological Investigation · doi:10.1007/s40618-015-0418-0 · Cited by 40 · see citing works
Body mass index (BMI) in Turner syndrome before and during growth hormone (GH) therapy
Blackett, P. R., Rundle, A. C., Frane, J. W., & Blethen, S. L. (2000) · International Journal of Obesity · doi:10.1038/sj.ijo.0801119 · Cited by 33 · see citing works
Sheanon, N. M., & Backeljauw, P. F. (2015) · International Journal of Pediatric Endocrinology · doi:10.1186/s13633-015-0013-3 · Cited by 31 · see citing works
Self-citationImpact of Age and Duration of Growth Hormone Therapy in Children with Turner Syndrome
ROSS, J. L., Lee, P. A., Gut, R., & Germak, J. A. (2011) · Hormone Research in Paediatrics · doi:10.1159/000333073 · Cited by 29 · see citing works
Lee, P. A., ROSS, J. L., Pedersen, B. T., Kotnik, P., Germak, J. A., & Christesen, H. T. (2015) · International Journal of Pediatric Endocrinology · doi:10.1186/s13633-015-0015-1 · Cited by 26 · see citing works
Syndrome de Turner: croissance staturopondérale et maturation osseuse spontanées
Cabrol, S., Saab, C., Gourmelen, M., et al. (1996) · Archives de Pédiatrie · doi:10.1016/0929-693x(96)84683-5 · Cited by 26 · see citing works
Update on Turner and Noonan Syndromes
Chacko, E., Graber, E., Regelmann, M. O., Wallach, E., Costin, G., & Rapaport, R. (2012) · Endocrinology and Metabolism Clinics of North America · doi:10.1016/j.ecl.2012.08.007 · Cited by 26 · see citing works
Growth Hormone and Treatment Controversy; Long-Term Safety of rGH
DiVall, S. A., & Radovick, S. (2013) · Current Pediatrics Reports · doi:10.1007/s40124-013-0009-5 · Cited by 23 · see citing works
Final Adult Height after Growth Hormone Treatment in Patients with Turner Syndrome
Ahn, J. M., Suh, J., Kwon, A., Chae, H. W., & Kim, H.-S. (2019) · Hormone Research in Paediatrics · doi:10.1159/000500780 · Cited by 23 · see citing works
Weight gain in Turner syndrome: association to puberty induction?—longitudinal analysis of KIGS data
Reinehr, T., Lindberg, A., Toschke, C., Cara, J., Chrysis, D., & Camacho‐Hübner, C. (2016) · Clinical Endocrinology · doi:10.1111/cen.13044 · Cited by 21 · see citing works
Circulating growth hormone isoforms in girls with Turner's syndrome
Blethen, S. L., Albertsson-Wikland, K. G., Faklis, E., & Chasalow, F. I. (1994) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.78.6.8200948 · Cited by 21 · see citing works
Backeljauw, P., Kanumakala, S., Loche, S., Schwab, K. O., Pfäffle, R. W., Höybye, C., Lundberg, E., Battelino, T., Kriström, B., Giemza, T., et al. (2021) · Hormone Research in Paediatrics · doi:10.1159/000515875 · Cited by 19 · see citing works
Self-citationDeal, C., Kirsch, S. E., Chanoine, J., Lawrence, S. L., Cummings, E. A., Rosolowsky, E. T., Marks, S. D., Jia, N., & Child, C. J. (2018) · CMAJ Open · doi:10.9778/cmajo.20180020 · Cited by 18 · see citing works
Job, J. C., & Landier, F. (2008) · Hormone Research · doi:10.1159/000181910 · Cited by 17 · see citing works
Tai, S., Tanaka, T., Hasegawa, T., Ozono, K., Tanaka, H., Kanzaki, S., Yokoya, S., Fujieda, K., Chihara, K., & Seino, Y. (2012) · Endocrine Journal · doi:10.1507/endocrj.ej11-0386 · Cited by 14 · see citing works
GH Responsiveness in Children With Noonan Syndrome Compared to Turner Syndrome
Dahlgren, J., & Albertsson-Wikland, K. G. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.737893 · Cited by 10 · see citing works
Rose, S. R., Reeves, G., Gut, R., & Germak, J. A. (2015) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2015.08.036 · Cited by 9 · see citing works
Miller, B. S., Aydin, F., Lundgren, F., Lindberg, A., & Geffner, M. E. (2014) · Hormone Research in Paediatrics · doi:10.1159/000360005 · Cited by 7 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- [20]Backeljauw P, Blair JC, Ferran J-M, et al Supplementary material for “Early GH treatment is effective and well tolerated in children with Turner syndrome: NordiNet IOS and ANSWER program.” Date of deposit: 27 March 2023. https://figshare.com/articles/journal_contribution/Supplementary_materials_for_Early_GH_Treatment_is_Effective_and_Well_Tolerated_in_Children_with_Turner_Syndrome_NordiNet_IOS_and_ANSWER_Program_/22341088 PMC10505549 36947589
Cited by
Sorted by citations
Clinical practice guidelines for the care of girls and women with Turner syndrome.
Gravholt, C. H., Andersen, N. H., Christin-Maitre, S., Davis, S. M., Duijnhouwer, A., Gawlik, A., Maciel-Guerra, A. T., Gutmark-Little, I., Fleischer, K., Hong, D., et al. (2024) · European Journal of Endocrinology · doi:10.1093/ejendo/lvae050 · Cited by 224 · see citing works
- Authors
- Backeljauw, P., Blair, J. C., Ferran, J.-M., Kelepouris, N., Miller, B. S., Pietropoli, A., Polak, M., Sävendahl, L., Verlinde, F., & Rohrer, T. R.
- Affiliations
- Cincinnati Children's Hospital Medical Center (US)
- Alder Hey Children's NHS Foundation Trust (GB)
- Pharmacologie et évaluation thérapeutiques chez l'enfant et la femme enceinte (FR)
- Novo Nordisk (India) (IN)
- Fairview Health Services (US)
- Novo Nordisk (Switzerland) (CH)
- Hôpital Necker-Enfants Malades (FR)
- Karolinska Institutet, Karolinska University Hospital , 171 64 Solna , Sweden
- Belgian Society for Pediatric Endocrinology and Diabetology , 1090 Brussels , Belgium
- Universitätsklinikum des Saarlandes (DE)
- Corresponding author
- Backeljauw, Philippe
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2023-03-22
- Volume
- 108
- Issue
- 10
- Pages
- 2653-2665
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- PMC
- PMC10505549
- OpenAlex
- W4353043754
- Cited by
- 12
- References
- 49
- Citations by year
- 2026: 4 · 2025: 3 · 2024: 4 · 2023: 1
- FWCI
- 2.46
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Novo Nordisk
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- Turner syndrome, growth hormone therapy, recombinant human growth hormone, short stature, children, long-term safety, effectiveness, insulin-like growth factor I, height SDS, puberty, epiphysiolysis, adverse effects
- MeSH terms
- Adult, Body Height, Child, Child, Preschool, Dwarfism, Pituitary, Female, Growth Disorders, Humans, Insulin-Like Growth Factor I, Turner Syndrome, Human Growth Hormone
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
