Safety of Growth Hormone for Children with Turner Syndrome

Source: Bolar K, Hoffman AR, Maneatis T, et al. Long-term safety of recombinant human growth hormone in Turner syndrome. J Clin Endocrinol Metab. 2008;93(2):344–351; doi:10.1210/ jc.2007-1723.To assess the safety of treating children with Turner Syndrome (TS) with recombinant human growth hormone (rhGH), researchers from the University of Texas-Galveston, Stanford, and Genentech, Inc. reviewed data collected as part of the National Cooperative Growth Study (NCGS). The NCGS is an ongoing project of Genentech. Investigators beginning patients on a Genentech rhGH product are required to provide reports of serious adverse events (AEs) and targeted AEs, irrespective of relationship to rhGH, including malignancy, diabetes mellitus, intracranial hypertension (IH), scoliosis, slipped femoral epiphysis (SCFE), and pancreatitis.For the current study, safety data for 5,220 children with TS and almost 50,000 non-TS patients treated with rhGH from 1985 until 2006 were compared. Age at enrollment was 0.1–21.2 years for TS patients with a mean age of 9.8 years. Safety data were presented in four categories: overall safety including deaths; targeted events associated with rhGH; events associated with TS; and other serious AEs.The incidence of reported serious AEs among patients with TS was 2.2% compared to 2.9% for the non-TS population. The incidence of targeted AEs among the 5,220 TS patients was 8.5% (442) compared with 7.3% in the non-TS population. Seven TS patients died, five from aortic dissection or rupture, a known complication of TS.1–3 The incidence of events known to be associated with rhGH including IH, SCFE, scoliosis, diabetes, and pancreatitis were all higher in TS patients than in those without TS. The incidence of new-onset malignancies in patients without other risk factors was 0.11% for TS patients compared with 0.06% for non-TS patients.The authors conclude that patients with TS who were treated with rhGH had an increased risk for selected AEs. However, the rate of death from aortic dissection/rupture in TS patients in this study is similar to that found in previous studies of TS patients not receiving growth hormone;1–3 thus, it is unlikely that rhGH contributed to these patients’ deaths. It is uncertain whether the reported malignancies represent an inherited increased risk in TS patients. The NCGS and similar registries, although focused in the years during rhGH treatment, may provide valuable information regarding the natural history of TS in childhood.Dr. Varma has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.This study, which was organized and supported by Genentech, drew on the largest database of TS individuals in the US. TS is a common chromosomal anomaly which is seen in about 1:2,500 live female births.4 At any given time in the US there are about 50,000 girls and women who are affected by this disorder. Patients with TS are at increased risk for a variety of problems including coarctation of aorta, bicuspid aortic valve, aortic dilation, dissection, and rupture. Features of TS include short stature, gonadal dysgenesis, hearing loss, renal anomalies, hypothyroidism, glucose intolerance, and webbing of the neck with low posterior hair line.5Without any treatment, the average adult height of TS patients is 56–58 inches. By initiating rhGh treatment at appropriate times in these girls, their adult height on average is increased by 2–3 inches. The results of the current study suggest that the complications and AEs seen in TS patients treated with rhGH are slightly higher than in non-TS populations. In addition, complications like aortic dissection and dissection/ruptures were not seen in non-TS patients. It is quite possible that some of the increased rate in observed AEs among TS patients may be inherently related to the condition rather than a result of rhGH treatment.The results provide a caution that one should monitor for these AEs and complications when treating TS patients with rhGH. These recognized complications must be discussed with the parents and the patient before the start of rhGH treatment so that their consent for the treatment is informed. Parents should also be assured that if at any time the patient feels uncomfortable with rhGH treatment, it can be easily discontinued.