Long-Term Mortality and Causes of Death in Isolated GHD, ISS, and SGA Patients Treated with Recombinant Growth Hormone during Childhood in Belgium, The Netherlands, and Sweden: Preliminary Report of 3 Countries Participating in the EU SAGhE Study

Paris Diderot University, Lutetia Parisorum, Île-de-France, France
The Journal of Clinical Endocrinology and Metabolism (Impact Factor: 6.21). 02/2012; 97(2):E213-7. DOI: 10.1210/jc.2011-2882
Source: PubMed

ABSTRACT The long-term mortality in adults treated with recombinant GH during childhood has been poorly investigated. Recently released data from the French part of the European Union Safety and Appropriateness of GH treatments in Europe (EU SAGhE) study have raised concerns on the long-term safety of GH treatment.
To report preliminary data on long-term vital status and causes of death in patients with isolated GH deficiency or idiopathic short stature or born small for gestational age treated with GH during childhood, in Belgium, The Netherlands, and Sweden.
Data were retrieved from national registries of GH-treated patients and vital status from National Population Registries. Causes of death were retrieved from a National Cause of Death Register (Sweden), Federal and Regional Death Registries (Belgium), or individual patient records (The Netherlands).
All patients diagnosed with isolated GH deficiency or idiopathic short stature or born small for gestational age started on recombinant GH during childhood from 1985-1997 and who had attained 18 yr of age by the end of 2010 were included. Vital status was available for approximately 98% of these 2,543 patients, corresponding to 46,556 person-years of observation.
Vital status, causes of death, age at death, year of death, duration of GH treatment, and mean GH dose during treatment were assessed.
Among 21 deaths identified, 12 were due to accidents, four were suicides, and one patient each died from pneumonia, endocrine dysfunction, primary cardiomyopathy, deficiency of humoral immunity, and coagulation defect.
In these cohorts, the majority of deaths (76%) were caused by accidents or suicides. Importantly, none of the patients died from cancer or from a cardiovascular disease.

24 Reads
  • Source
    • "The only death in the ICOGHD group was due to Creutzfeldt-Jakob disease related to prior use of human cadaveric derived GH product [21]. Furthermore, the observation of no mortality increase for ICOGHD patients in HypoCCS is consistent with the observations in the SAGhE cohorts from Sweden, Belgium, and the Netherlands [2] and that in idiopathic GHD patients from a Danish cohort [22]. Therefore, the result of the mortality analysis does not indicate that recombinant GH during childhood is related to increased mortality in either the COGHD or ICOGHD groups. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The French Safety and Appropriateness of Growth Hormone treatments in Europe (SAGhE) cohort has raised concern of increased mortality risk during follow-up into adulthood in certain patients who had received growth hormone (GH) treatment during childhood. The Hypopituitary Control and Complications Study monitored mortality and morbidity of adult GH-deficient patients including those with childhood-onset GH deficiency (COGHD) who received GH treatment as children. Evaluate risk of mortality, cancer, myocardial infarction (MI) and stroke in a prospective observational study. COGHD patients [n = 1,204, including 389 diagnosed with idiopathic COGHD (ICOGHD)] had received pediatric GH treatment. Standardized mortality ratios (SMRs), and cancer standardized incidence ratios (SIRs) in patients without a prior cancer were estimated relative to reference populations. Crude incidence rates were estimated for MI and stroke. No increased mortality or cancer incidence was observed, as compared with reference populations, during a follow-up of 3.7 ± 3.3 years (mean ± SD). The overall SMR for COGHD was 1.14 [95 % confidence interval (CI) 0.55-2.10], and for ICOGHD, 0.33 (0.01-1.84). The overall cancer SIR for COGHD was 0.27 (0.01-1.50), and for ICOGHD, 0.00 (0.00-2.45). No incident case of MI was reported. The crude stroke incidence rate [181.3 per 100,000 person-years] in COGHD patients was consistent with the rates reported in reference populations. No incident case of stroke was identified in ICOGHD patients who are presumed to have no increased stroke risk factors. The results indicate no increased risk of mortality or incidence of cancer, stroke, or MI in adult GH-deficient patients who had previously received pediatric GH treatment.
    Pituitary 10/2013; 17(5). DOI:10.1007/s11102-013-0529-6 · 3.20 Impact Factor
  • Source
    • "The long-term safety of GH treatment in childhood has been under intense recent discussion due to the Safety and Appropriateness of Growth hormone treatments in Europe (SAGhE) mortality data from France suggesting increased all-cause, bone tumor-related, and circulatory system disease-related mortality over the mean 17.3-year follow-up period among adults who had received GH treatment as children (N = 6928) for the diagnoses of idiopathic isolated GHD, neurosecretory dysfunction, idiopathic short stature or born SGA [52]. However, the preliminary data from Belgium, The Netherlands, and Sweden (N = 2543) contrasted with the report from France in that the majority of the 21 deaths that occurred over the follow-up period were due to accidents or suicide and not a single case of death was related to cancer or cardiovascular disease [53]. Questions have been raised about the SAGhE data from France due to methodological limitations of the study, including the lack of an ideal control group of untreated patients, and in August 2011, the FDA stated the evidence of increased risk of death is inconclusive [54,55]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Approximately 10% of children born small for their gestational age (SGA) fail to show catch-up growth and may remain short-statured as adults. Despite treatment guidelines for children born SGA that recommend referral for growth hormone (GH) therapy evaluation and initiation by ages 2 to 4 years, the average age of GH treatment initiation is typically much later, at ages 7 to 9 years. Delayed referral for GH treatment is problematic as studies show younger age at GH treatment initiation in children born SGA is an independent predictor for responses such as optimal growth acceleration, normalization of prepubertal height, and most importantly, adult height (AH). This review discusses the importance and associated challenges of early diagnosis of children born SGA who fail to show catch-up growth, contrasts the recommended age of referral for these patients and the average age of GH treatment initiation, and discusses studies showing the significant positive effects of early referral and treatment with GH on AHs in short-statured children born SGA. To optimize the eventual height in short-statured SGA children who fail to manifest catch-up growth, a lowering of the average age of referral for GH therapy evaluation is needed to better align with consensus recommendations for SGA management. The importance of increasing parental and physician awareness that most children born SGA will do well developmentally and will optimally benefit from early initiation of GH treatment when short-statured is addressed, as is the need to shift the age of referral to better align with consensus recommendations.
    International Journal of Pediatric Endocrinology 05/2012; 2012(1):11. DOI:10.1186/1687-9856-2012-11
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Growth hormone (GH) is widely prescribed for children with short stature across a range of growth disorders. Recombinant human (rh) insulin-like growth factor-1 (rhIGF-1) therapy is approved for severe primary IGF-I deficiency - a state of severe GH resistance. Evidence is increasing for an unacceptably high rate of poor or unsatisfactory response to growth-promoting therapy (i.e. not leading to significant catch up growth) in terms of change in height standard deviation score (SDS) and height velocity (HV) in many approved indications. Consequently, there is a need to define poor response and to prevent or correct it by optimizing treatment regimens within accepted guidelines. Recognition of a poor response is an indication for action by the treating physician, either to modify the therapy or to review the primary diagnosis leading either to discontinuation or change of therapy. This review discusses the optimal investigation of the child who is a candidate for GH or IGF-1 therapy so that a diagnosis-based choice of therapy and dosage can be made. The relevant parameters in the evaluation of growth response are described together with the definitions of poor response. Prevention of poor response is addressed by discussion of strategy for first-year management with GH and IGF-1. Adherence to therapy is reviewed as is the recommended action following the identification of the poorly responding patient. The awareness, recognition and management of poor response to growth-promoting therapy will lead to better patient care, greater cost-effectiveness and increased opportunities for clinical benefit.
    Clinical Endocrinology 04/2012; 77(2):169-81. DOI:10.1111/j.1365-2265.2012.04420.x · 3.46 Impact Factor
Show more