sermorelin and Prader-Willi-Syndrome

It is unclear if poor health outcomes of adult patients with Prader-Willi syndrome (PWS) are influenced by GH deficiency (GHD). Few studies have been focused on PWS adults, but further information on the concomitant role of obesity on GH/IGF-I axis function is needed. The aim of our study was to investigate the prevalence of GHD in a large group of adult subjects with genetically confirmed PWS.. We studied the GH response to a combined administration of GHRH (1 microg/kg i.v. at 0 minutes) and arginine (ARG) (30 g i.v., infused from 0 to 30 minutes) as well as the baseline IGF-I levels, in a group of 44 PWS adults (18 males, 26 females) aged 18-41.1 years. The same protocol was carried out in a control group of 17 obese subjects (7 males, 10 females) aged 21.8-45.8 years.. Blood samples were taken at -15 and 0 minutes and then 30, 45, 60, 90 and 120 minutes after GHRH administration. Serum GH and total IGF-I concentrations were measured by chemioluminescence. Statistical analysis was performed by Student's t-test for unpaired data, and using analysis of variance for parametric and nonparametric (Mann-Whitney test) data, where appropriate. The relationship between pairs of variables was assessed by Pearson's correlation. Independent variables influencing GH secretion were tested by multiple linear regression analysis.. The GH response to GHRH + ARG was significantly lower in PWS patients (GH peak (mean +/- SE) 8.4 +/- 1.2 microg/l; AUC: 471.4 +/- 77.8 microg/l/h) than obese subjects (GH peak 15.7 +/- 2.9 microg/l, P < 0.02; AUC 956 +/- 182.9 microg/l/h, P < 0.005). When considered individually, 17 of 44 PWS individuals (38.6%) were severely GHD, according to the cut-off limit of 4.1 microg/l for obese individuals, and low IGF-I-values were present in 33 PWS patients. Moreover, impaired GH response was combined with subnormal IGF-I levels in all PWS patients with GHD.. Adult subjects with PWS had a reduced responsiveness to GHRH + ARG administration associated with reduced IGF-I levels. In addition, a severe GHD for age was demonstrated in a significant percentage of PWS subjects. These findings are in agreement with the hypothesis that a complex derangement of hypothalamus-pituitary axis occurred in PWS, and suggested that impaired GH secretion is not an artefact of obesity.

Topics: Adolescent; Adult; Arginine; Case-Control Studies; Female; Growth Hormone; Humans; Insulin-Like Growth Factor I; Linear Models; Luminescent Measurements; Male; Middle Aged; Obesity; Prader-Willi Syndrome; Secretory Rate; Sermorelin; Statistics, Nonparametric

In order to evaluate the impairment of GH response in patients affected by Prader-Labhardt-Willi (PLW) syndrome, in 18 patients we studied GH response to clonidine and to GHRH + pyridostigmine, a cholinergic drug which enhances GHRH induced GH responsiveness in obese patients. After clonidine GH response was abnormal in 14/18 subjects (mean GH peak: 4.1 +/- 1.3 micrograms/l; area under curve: 208.1 +/- 74.2 micrograms/l.h) while all but 5 patients showed an inadequate GH response to GHRH + pyridostigmine (mean GH peak: 13.4 +/- 2.5 micrograms/l; area under curve: 903.4 +/- 171.0 micrograms/l.h). However, in the three patients with low adiposity index, GH response to GHRH + pyridostigmine was significantly higher than that observed in fatter subjects. In addition, GH response to GHRH + pyridostigmine was negatively correlated to age and adiposity index. In conclusion, our data are consistent with the hypothesis of the existence of a complex derangement of GH neuroendocrine regulation in these subjects.

Topics: Adolescent; Adrenergic alpha-Agonists; Adult; Child; Cholinesterase Inhibitors; Clonidine; Female; Human Growth Hormone; Humans; Insulin-Like Growth Factor I; Male; Prader-Willi Syndrome; Pyridostigmine Bromide; Sermorelin