Long-Term Mortality after Recombinant Growth Hormone Treatment for Isolated Growth Hormone Deficiency or Childhood Short Stature: Preliminary Report of the French SAGhE Study

Abstract

Mortality rates were increased in this population of adults treated as children with recombinant GH, particularly in those who had received the highest doses. Specific effects were detected in terms of death due to bone tumors or cerebral hemorrhage but not for all cancers. These results highlight the need for additional studies of long-term mortality and morbidity after GH treatment in childhood.

Seeds of neuroendocrine doubt

“…However, large long-term follow up studies of children who received recombinant GH from 1985 onwards (i.e. no risk of human-human transmission) were found to have a 5-7 fold increased risk of cerebrovascular disease and, in particular, subarachnoid haemorhage, suggesting that this cohort have predisposing factors leading to increased risk of intracranial haemorrhage, irrespective of having received c-hGH 13,14 .…”

Is safety of childhood growth hormone therapy related to dose? Data from a large observational study

“…Accumulated experience of GH treatment captured in these large observational databases supports a favorable safety profile (10,11). However, in 2012, preliminary data from the French cohort of the Safety and Appropriateness of Growth Hormone Treatments in Europe (SAGhE) study, a retrospective evaluation of 6928 patients diagnosed with GHD, ISS, or born SGA and treated as children with GH, raised concerns regarding the long-term safety of GH therapy and suggested a link between GH use during childhood and premature death (12). In these patients, considered to be at low risk of mortality, the standardized mortality ratio (SMR) was 1.33, with an increased risk of death among patients who had received GH doses >50 μg/kg/ day (P < 0.04).…”

Growth hormone, insulin-like growth factor system and carcinogenesis

“…Recently, the French Safety and Appropriateness of Growth Hormone treatments in Europe (SAGhE), a study carried out to evaluate the long-term mortality of a population-based cohort of patients treated with rhGH in childhood in France, found increased mortality rates in adults treated as children with rhGH, particularly in those who received the highest doses. In relation to neoplasia, all type cancer-related mortality was not increased, but a specific effect was detected for bone tumours [85]. However, this was represented by 3 cases of bone neoplasms vs. 0.6 expected in more than 6500 individuals with a 95% confidence interval ranging from 1.01-14.61.…”