Cancer Risks in Patients Treated With Growth Hormone in Childhood: The SAGhE European Cohort Study

Swerdlow, Anthony; Cooke, Rosie; Beckers, Dominique; Borgström, Birgit; Butler, Gary; Carel, Jean Claude; Cianfarani, Stefano; Clayton, Peter E.; Coste, J; Deodati, Annalisa; Écosse, Emmanuel; Gausche, Ruth; Giacomozzi, Claudio; Hokken-Koelega, Anita C S; Khan, Aysha J.; Kieß, Wieland; Kuehni, Claudia E.; Mullis, Primus Ε.; Pfäffle, Roland; Sävendahl, Lars; Sommer, Grit; Thomas, Muriel; Tidblad, Anders; Tollerfield, Sally; Eycken, Liesbet Van; Zandwijken, Gladys R J

doi:10.1210/jc.2016-2046

Cited by 117 publications

(105 citation statements)

References 30 publications

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“…There was also no evidence to suggest that GH treatment raises the intrinsic risk of recurrence in childhood cancer survivors who have completed cancer therapy and have no signs of active neoplastic disease [8]. The data on neoplasia from the present analysis were included in assessments of the complete GeNeSIS cohort [41] and the findings were in line with results from reports on other large cohorts [9, 11]. In the total GeNeSIS population, 13 incident cancer cases were reported in the 19,054 patients with no reported history of malignancy, suggesting no increase in the risk of primary cancer [41].…”

Section: Discussionsupporting

confidence: 64%

“…There is no clear evidence supporting an association between GH treatment and either diabetes mellitus or neoplasia, except in patients with pre-existing risk factors [4-11]. Data from the National Cooperative Growth Study surveillance database revealed that serious adverse events were reported in only 2.4% of 54,996 patients treated with GH therapy for growth disorders in childhood [12].…”

Section: Introductionmentioning

confidence: 99%

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Growth Hormone Treatment for Short Stature in the USA, Germany and France: 15 Years of Surveillance in the Genetics and Neuroendocrinology of Short-Stature International Study (GeNeSIS)

et al. 2018

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Background/Aims: To describe characteristics, auxological outcomes and safety in paediatric patients with growth disorders treated with growth hormone (GH), for cohorts from the USA, Germany and France enrolled in GeNeSIS, a post-authorisation surveillance programme. Methods: Diagnosis and biochemical measurement data were based on reporting from, and GH treatment was initiated at the discretion of, treating physicians. Auxological outcomes during the first 4 years of GH treatment and at near-adult height (NAH) were analysed. Serious and treatment-emergent adverse events were described. Results: Children in the USA (n = 9,810), Germany (n = 2,682) and France (n = 1,667) received GH (dose varied between countries), most commonly for GH deficiency. Across diagnostic groups and countries, mean height velocity standard deviation score (SDS) was > 0 and height SDS increased from baseline during the first 4 years of treatment, with greatest improvements during year 1. Most children achieved NAH within the normal range (height SDS >−2). No new or unexpected safety concerns were noted. Conclusion: GH treatment improved growth indices to a similar extent for patients in all three countries despite variations in GH doses. Data from these three countries, which together contributed > 60% of patients to GeNeSIS, indicated no new safety signals and the benefit-risk profile of GH remains unchanged.

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Section: Discussionsupporting

confidence: 64%

Section: Introductionmentioning

confidence: 99%

Growth Hormone Treatment for Short Stature in the USA, Germany and France: 15 Years of Surveillance in the Genetics and Neuroendocrinology of Short-Stature International Study (GeNeSIS)

et al. 2018

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“…According to Pediatric Endocrine Society, while data are insufficient to suggest that GH causes tumorigenesis, children on GH treatment should be monitored closely if they have an increased risk of cancer (Allen et al, ; Grimberg & Allen, ; Raman et al, ). Unlike several other overgrowth syndromes, the risk of tumorigenesis in MCAP does not appear to be significantly elevated (Mirzaa, Conway, Graham Jr., & Dobyns, ; Mirzaa et al, , Swerdlow et al, ). Overall, given the risk for death and neurodevelopmental issues with untreated hypoglycemia that can be associated with GH deficiency, we recommend treatment with conservative doses of GH in children with MCAP confirmed to have GH deficiency and hypoglycemia.…”

Section: Discussionmentioning

confidence: 99%

Growth hormone deficiency in megalencephaly‐capillary malformation syndrome: An association with activating mutations in PIK3CA

Davis

Ware

Zeiger

et al. 2019

American J of Med Genetics Pt A

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Megalencephaly-capillary malformation syndrome (MCAP) is a brain overgrowth disorder characterized by cortical malformations (specifically polymicrogyria), vascular anomalies, and segmental overgrowth secondary to somatic activating mutations in the PI3K-AKT-MTOR pathway (PIK3CA). Cases of growth failure and hypoglycemia have been reported in patients with MCAP, raising the suspicion for unappreciated growth hormone (GH) deficiency. Here we report an observational multicenter study of children with MCAP and GH deficiency. Eleven participants were confirmed to have GH deficiency, all with very low or undetectable circulating concentrations of insulin-like growth factor-1 and insulin-like growth factor binding protein-3. Seven underwent GH stimulation testing and all had insufficient responses with a median GH peak of 3.7 ng/ml (range 1.1-8.6). Growth patterns revealed a drastic decline in length z-scores within the first year of life but then stabilized afterward. Five were treated with GH; one discontinued due to inconsolability. The other four participants

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“…The findings of decreased risk of breast cancer and the increased risk of meningioma and melanoma were reproduced in a Swedish registry study ( n = 1,409) (Ji et al, ). A large European study found no increased incidence of cancer in Turner syndrome women ( n = 3,189) treated with growth hormone (GH) (Swerdlow et al, ).…”

Section: Epidemiologymentioning

confidence: 99%

Recognition and management of adults with Turner syndrome: From the transition of adolescence through the senior years

Lin

Prakash

Andersen

et al. 2019

American J of Med Genetics Pt A

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Turner syndrome is recognized now as a syndrome familiar not only to pediatricians and pediatric specialists, medical geneticists, adult endocrinologists, and cardiologists, but also increasingly to primary care providers, internal medicine specialists, obstetricians, and reproductive medicine specialists. In addition, the care of women with Turner syndrome may involve social services, and various educational and neuropsychologic therapies. This article focuses on the recognition and management of Turner syndrome

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Cancer Risks in Patients Treated With Growth Hormone in Childhood: The SAGhE European Cohort Study

Abstract: Our results do not generally support a carcinogenic effect of r-hGH, but the unexplained trend in cancer mortality risk in relation to GH dose in patients with previous cancer, and the indication of possible effects on bone cancer, bladder cancer, and HL risks, need further investigation.

Cited by 117 publications

References 30 publications

Growth Hormone Treatment for Short Stature in the USA, Germany and France: 15 Years of Surveillance in the Genetics and Neuroendocrinology of Short-Stature International Study (GeNeSIS)

Growth Hormone Treatment for Short Stature in the USA, Germany and France: 15 Years of Surveillance in the Genetics and Neuroendocrinology of Short-Stature International Study (GeNeSIS)

Growth hormone deficiency in megalencephaly‐capillary malformation syndrome: An association with activating mutations in PIK3CA

Recognition and management of adults with Turner syndrome: From the transition of adolescence through the senior years

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