CONTEXT: Safety concerns regarding premature mortality, diabetes, neoplasia and cerebrovascular disease in association with growth hormone (GH) therapy have been raised. OBJECTIVE: To assess incidence of key safety outcomes. DESIGN: Prospective, multinational, observational study (1999-2015). SETTING: 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 (SMR) and incidence (SIR) ratios with 95% confidence intervals (CI) 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 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 (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 31/622 (5.0%) cancer survivors (10.7 [7.5-15.2] cases/1000 PY), and intracranial tumor recurrences in 67/823 (8.1%) tumor survivors (16.9 [13.3-21.5] cases/1000 PY). All 3 hemorrhagic stroke cases had risk factors. CONCLUSIONS: GeNeSIS data support the favourable safety profile of pediatric GH treatment. Overall risk for 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 to the general population, but most cases had diabetes risk factors.

Safety outcomes during pediatric GH therapy: final results from the prospective GeNeSIS observational program / Child, Cj; Zimmermann, Ag; Chrousos, Gp; Cummings, E; Deal, Cl; Hasegawa, T; Jia, N; Lawrence, S; Linglart, A; Loche, S; Maghnie, M; Pérez Sánchez, J; Polak, M; Predieri, B; Richter-Unruh, A; Rosenfeld, Rg; Yeste, D; Yorifuji, T; Blum, Wf. - In: THE JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM. - ISSN 0021-972X. - 104:2(2019), pp. 379-389. [10.1210/jc.2018-01189]

Safety outcomes during pediatric GH therapy: final results from the prospective GeNeSIS observational program

Predieri B;
2019

Abstract

CONTEXT: Safety concerns regarding premature mortality, diabetes, neoplasia and cerebrovascular disease in association with growth hormone (GH) therapy have been raised. OBJECTIVE: To assess incidence of key safety outcomes. DESIGN: Prospective, multinational, observational study (1999-2015). SETTING: 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 (SMR) and incidence (SIR) ratios with 95% confidence intervals (CI) 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 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 (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 31/622 (5.0%) cancer survivors (10.7 [7.5-15.2] cases/1000 PY), and intracranial tumor recurrences in 67/823 (8.1%) tumor survivors (16.9 [13.3-21.5] cases/1000 PY). All 3 hemorrhagic stroke cases had risk factors. CONCLUSIONS: GeNeSIS data support the favourable safety profile of pediatric GH treatment. Overall risk for 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 to the general population, but most cases had diabetes risk factors.
13-set-2018
104
2
379
389
Safety outcomes during pediatric GH therapy: final results from the prospective GeNeSIS observational program / Child, Cj; Zimmermann, Ag; Chrousos, Gp; Cummings, E; Deal, Cl; Hasegawa, T; Jia, N; Lawrence, S; Linglart, A; Loche, S; Maghnie, M; Pérez Sánchez, J; Polak, M; Predieri, B; Richter-Unruh, A; Rosenfeld, Rg; Yeste, D; Yorifuji, T; Blum, Wf. - In: THE JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM. - ISSN 0021-972X. - 104:2(2019), pp. 379-389. [10.1210/jc.2018-01189]
Child, Cj; Zimmermann, Ag; Chrousos, Gp; Cummings, E; Deal, Cl; Hasegawa, T; Jia, N; Lawrence, S; Linglart, A; Loche, S; Maghnie, M; Pérez Sánchez, J; Polak, M; Predieri, B; Richter-Unruh, A; Rosenfeld, Rg; Yeste, D; Yorifuji, T; Blum, Wf
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1169036
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