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      The KIGS Experience with the Addition of Gonadotropin-Releasing Hormone Agonists to Growth Hormone (GH) Treatment of Children with Idiopathic GH Deficiency

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          Although recombinant techniques have enabled the production of limitless amounts of human growth hormone (GH), and clinical methods for diagnosis and treatment have been greatly enhanced, the mean final heights of children with idiopathic GH deficiency (IGHD) treated with GH remain in the range of –1.3 standard deviation scores (SDS) below normal height. One of the methods used to increase height outcomes is to delay the onset and progression of puberty to allow for a longer ‘pre-pubertal’ growth phase. We reviewed the KIGS (Pharmacia International Growth Database) data of patients with IGHD who had been treated with gonadotropin-releasing hormone agonists (GnRHa) in order to see if a greater gain in height could be achieved by altering the tempo of pubertal maturation. Near-final height data were analysed in 39 adolescents (out of a total of 249) who had received GH + GnRHa therapy and were compared with similar data from 1,893 patients with IGHD treated with GH alone. The total change in height SDS in boys who received GH alone was +1.6, in contrast to +1.1 in GH + GnRHa-treated boys; the total change in height SDS in girls who received GH alone was +1.4 in contrast to +1.1 in girls treated with GH + GnRHa. The near final height SDS in girls treated with GH + GnRHa was 1.0 below the mid-parental target height (MPH), whereas there was only a –0.5 SDS difference in girls treated with GH. Approximation to the MPH did not differ in boys between the two treatment groups. These data suggest that the attainment of a substantial height SDS by manipulating the tempo of puberty is limited, but that optimizing growth during the pre-pubertal phase is a more important factor.

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          Most cited references 9

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          Gonadotropin-releasing hormone and its analogs.

          GnRH and its analogues have led to exciting new avenues of therapy in virtually every subspecialty of internal medicine as well as in gynecology, pediatrics, and urology. Since their discovery in 1971, it has been demonstrated that GnRH and its analogues enable medical professionals to influence the hypothalamic-pituitary-gonadal axis in two distinct classes of therapeutic applications. The first provides natural sequence GnRH in a pulsatile fashion via portable infusion pumps to mimic the normal physiology of hypothalamic GnRH secretion and restores reproductive potential to infertile men and women with disorders of endogenous GnRH secretion. The second mode uses long-acting GnRH agonists administered in a depot delivery to produce a paradoxical desensitization of pituitary gonadotropin secretion which, in turn, results in a complete ablation of the reproductive axis. This biochemical castration induced by GnRH agonist administration is a safe, effective, complete, and reversible method of removing the overlay of gonadal steroids from a variety of diseases which they are known to exacerbate. These diseases include endometriosis and uterine fibroids in women, prostate cancer in men, and precocious puberty in both sexes. This review examines the physiologic and pharmacologic principles underlying the advances produced by these agents, the mechanism of action of GnRH and its analogues at the cellular level, and the individual therapeutic applications to which these analogues have been applied. Because virtually every subspecialty of medicine will be touched by the GnRH analogues, this review provides an overview and background of their use.
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            High Dose Recombinant Human Growth Hormone (GH) Treatment of GH-Deficient Patients in Puberty Increases Near-Final Height: A Randomized, Multicenter Trial

             N Mauras (2000)
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              Long-Term Outcome after Depot Gonadotropin-Releasing Hormone Agonist Treatment of Central Precocious Puberty: Final Height, Body Proportions, Body Composition, Bone Mineral Density, and Reproductive Function

               S Heger (1999)

                Author and article information

                Horm Res Paediatr
                Hormone Research in Paediatrics
                S. Karger AG
                July 2003
                17 November 2004
                : 60
                : Suppl 1
                : 68-73
                aBaystate Medical Center Children’s Hospital, Tufts University School of Medicine Springfield, Mass., USA; bPharmacia Corporation, KIGS/KIMS Outcomes Research, Stockholm, Sweden; cPaediatric Endocrinology Section, University Children’s Hospital, Tübingen, Germany; dRoyal Manchester Children’s Hospital, Manchester, UK; ePediatric Growth Research Centre, University of Göteborg, Göteborg, Sweden; fInstitute of Endocrinology, Parramatta, Australia
                71229 Horm Res 2003;60(suppl 1):68–73
                © 2003 S. Karger AG, Basel

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                Page count
                Figures: 1, Tables: 4, References: 36, Pages: 6


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