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J Clin Endocrinol Metab. 2019 Feb 1;104(2):379-389. doi: 10.1210/jc.2018-01189.

Safety Outcomes During Pediatric GH Therapy: Final Results From the Prospective GeNeSIS Observational Program.

Author information

1
Eli Lilly and Company, Windlesham, Surrey, United Kingdom.
2
Eli Lilly and Company, Indianapolis, Indiana.
3
National and Kapodistrian University of Athens, School of Medicine, Athens, Greece.
4
Dalhousie University/IWK Health Centre, Halifax, Nova Scotia, Canada.
5
University of Montreal and CHU Ste-Justine, Montreal, Quebec, Canada.
6
Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
7
Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada.
8
Hôpital Bicêtre Paris Sud, Paris, France.
9
Ospedale Pediatrico Microcitemico "A. Cao," AO Brotzu, Cagliari, Italy.
10
Istituto Giannina Gaslini, University of Genova, Genoa, Italy.
11
Corporació Sanitària Parc Taulí, Sabadell, Spain.
12
Hôpital Universitaire Necker Enfants Malades and Université Paris Descartes, Centre des Maladies Endocrines Rares de la Croissance, Paris, France.
13
University of Modena and Reggio Emilia, Modena, Italy.
14
University Children's Hospital, Bochum, Germany.
15
Oregon Health and Science University, Portland, Oregon.
16
Hospital Vall d'Hebron, Universidad Autónoma de Barcelona, Barcelona, Spain.
17
Osaka City General Hospital, Miyakojima-ku, Osaka, Japan.
18
University of Giessen, Giessen, Germany.

Abstract

Context:

Safety concerns have been raised regarding premature mortality, diabetes, neoplasia, and cerebrovascular disease in association with GH therapy.

Objective:

To assess incidence of key safety outcomes.

Design:

Prospective, multinational, observational study (1999 to 2015).

Setting:

A total of 22,311 GH-treated children from 827 investigative sites in 30 countries.

Patients:

Children with growth disorders.

Interventions:

GH treatment.

Main outcome measures:

Standardized mortality ratio (SMR) and standardized incidence ratio (SIR) with 95% CIs for mortality, diabetes, and primary cancer using general population registries.

Results:

Predominant short stature diagnoses were GH deficiency (63%), idiopathic short stature (13%), and Turner syndrome (8%), with mean ± SD follow-up of 4.2 ± 3.2 years (∼92,000 person-years [PY]). Forty-two deaths occurred in patients with follow-up, with an SMR (95% CI) of 0.61 (0.44, 0.82); the SMR was elevated for patients with cancer-related organic GH deficiency [5.87 (3.21, 9.85)]. Based on 18 cases, type 2 diabetes mellitus (T2DM) risk was elevated [SIR: 3.77 (2.24, 5.96)], but 72% had risk factors. In patients without cancer history, 14 primary cancers were observed [SIR: 0.71 (0.39, 1.20)]. Second neoplasms occurred in 31 of 622 cancer survivors [5.0%; 10.7 (7.5, 15.2) cases/1000 PY] and intracranial tumor recurrences in 67 of 823 tumor survivors [8.1%; 16.9 (13.3, 21.5) cases/1000 PY]. All three hemorrhagic stroke cases had risk factors.

Conclusions:

GeNeSIS (Genetics and Neuroendocrinology of Short Stature International Study) data support the favorable safety profile of pediatric GH treatment. Overall risk of death or primary cancer was not elevated in GH-treated children, and no hemorrhagic strokes occurred in patients without risk factors. T2DM incidence was elevated compared with the general population, but most cases had diabetes risk factors.

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