Endocrine Abstracts

Growth hormone (GH) deficient adults present with a wide spectrum of clinical presentations commonly called GHD syndrome. Detection of GHD is important especially as successful GH replacement therapy ameliorates many symptoms of the GHD syndrome and is accompanied by a significant improvement in quality of life (QoL) in GHD patients. GH therapy has been available for adults in the last twenty years and the results from large pharmaco-epidemiological follow ups under GH treatment, show a decrease in morbidity and mortality.

One of the future issues for GH replacement is changing the administration schedule from daily to weekly or monthly. GH is replaced by daily injections which in the long term may compromise patient’s compliance (assessment of frequency of missed GH doses) and persistence (continuing GH therapy without interruption). Many factors may be associated with low compliance estimated by low insulin- like growth factor 1 (IGF1 levels) at the end of each year of follow up. A few studies have evaluated patient’s relationship to compliance and the need for improvement was realized. Several approaches have been taken to develop long acting forms of GH. The long acting GH molecule has been obtained by different approaches (binding of polyethylene glycol (PEG) with rhGH or rhGH is embedded in a matrix of sodium hyaluronate and lecithin). Each of the preparations has been tested in experimental model and clinical trials are ongoing. The extended GH half life resulted in increases in IGF1 and the extended duration if the IGF1 increase which allowed less frequent GH administration (weekly, every 14 days or monthly). During clinical trial with pegylated GH molecules, lipoatrophy occurred at the injection-site and the study had to be terminated. On the other hand phase III, double blind, randomized, placebo controlled multicenter study with rhGH embedded in sodium hyaluronate and lecithin was successfully completed.

Another future issue is the use of EMEA approved biosimilars of GH which still do not have enough data providing safety and efficacy, including immunogenicity studies and clinical trials. In some European countries biosimilar GH is already widely used and reimbursed.