Abstract
Over the last three decades, short- and long-term observational studies, clinical trials, systematic reviews, and meta-analyses have provided relevant information on the efficacy and safety of growth hormone (GH) replacement therapy in adults with GH deficiency (AGHD). The knowledge acquired during this time has been compiled into different guidelines that offer clinicians an evidence-based, practical approach for the management of AGHD. There are, however, still open questions in some key areas in which recommendations are supported by only moderate or weak evidence. In the last recent years, the development of long-acting GH preparations has created new therapeutic possibilities by decreasing injection frequency, improving adherence and thereby potentially maximizing clinical outcomes. The aims of this review are to advance our understanding on the diagnosis and treatment of AGHD and to present an update and future perspectives on the use of long-acting GH preparations.
Highlights
In 1962, a 35-year-old woman with hypopituitarism was the first adult treated with pituitary growth hormone (GH)
At that time limited availability of pituitary GH restricted its therapeutic use to those few children with more severe forms of growth retardation. This problem was solved in 1985 with the introduction in the clinical practice of unrestricted amounts of recombinant human GH, which created several novel therapeutic opportunities. It was in this context that a new entity in hypopituitary patients receiving replacement therapy for thyroid-stimulating hormone (TSH), follicle-stimulating hormone/luteinizing hormone (FSH/ LH) and/or adrenocorticotropic hormone (ACTH) deficiencies, but not for GH deficiency (GHD), started to be defined as: “adult GH deficiency” (AGHD)[2]
This pioneer study was followed by others confirming this finding, and a recent meta-analysis concluded that the risk of premature mortality in hypopituitarism is high in women and in patients diagnosed at a younger age[4,5,6,7]
Summary
In 1962, a 35-year-old woman with hypopituitarism was the first adult treated with pituitary growth hormone (GH). In a placebo-controlled trial, Biller et al.[79] observed a significant reduction of fat mass (mainly due to decreased trunk fat) and increase in lean body mass in AGHD patients after 6 months of treatment with a sustained-release GH formulation This trial continued in an open-label extension phase up to 52 weeks, which confirmed a prolonged and sustained effect of the LAGH preparation in. Reducing fat mass and increasing lean body mass, serum IGF-I, and IGF-binding protein 3 (IGFBP-3) level[80] While these preliminary data reassure the non-inferiority of LAGH preparations in relation to daily GH injections, their efficacy and safety over years and their implication for costs and compliance remain to be elucidated in ongoing and future clinical trials. Grant information The author(s) declared that no grants were involved in supporting this work
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