GH/IGF-I axis in Prader-Willi syndrome: Evaluation of IGF-I levels and of the somatotroph responsiveness to various provocative stimuli

Abstract

Basal IGF-I levels and the GH response to at least two among provocative stimuli such as clonidine (CLO, Catapresan, 150 mcg/m2 p.o.), GHRH (1 mcg/kg i.v.)+arginine (ARG, 0.5 g/kg i.v. infusion during 30 min) and GHRH+pyridostigmine (PD, Mestinon cpr 60 mg p.o.) have been evaluated in 43 children with Prader-Willi syndrome (PWS, 17 males and 26 females, age 3-22 yr, 7 normal weight and 36 obese PWS), in 25 normal short children (NC, 17 males and 8 females, 7.7-18.5 yr) and in 24 children with simple obesity (OB, 14 males, 10 females, 7.7-21.5 yr). Both normal weight and obese PWS had mean IGF-I levels lower than those recorded in NC (p<0.001) and OB (p<0.001). The GH responses to GHRH+ARG and GHRH+PD in NC were similar and higher than that to CLO (p<0.001). In PWS the GH response to GHRH+ARG was higher than that to GHRH+PD (p<0.001) which, in turn, was higher than that to CLO (p<0.001); these responses in PWS were lower than those in normal children (p<0.02) and similar to those in OB. In normal weight PWS the GH responses to GHRH+ARG and to GHRH+PD were similar and higher than to CLO (p<0.05); however, each provocative stimulus elicited a GH rise lower than that in NC (p<0.05). In obese PWS as well as in OB the GH response to GHRH+ARG was higher than that to GHRH+PD (p<0.02) which, in turn, was higher than that to CLO (p<0.001); all GH responses in obese PWS and OB were lower than those in NC (p<0.001) but similar to those in normal weight PWS. In conclusion, patients with PWS show clear reduction of IGF-I levels as well as of the somatotroph responsiveness to provocative stimuli independently of body weight excess. These results strengthen the hypothesis that PWS syndrome is frequently connotated by GH insufficiency.

Prader&ndash;Willi syndrome: clinical problems in transition from pediatric to adult care

“…22,28 In addition, previous reports support the hypothesis of an age-dependent derangement of the hypothalamus-pituitary axis occurring in PWS subjects, also regarding GH secretion. In fact, there is evidence of GH insufficiency after reaching final height, although study findings differ largely on the prevalence of this clinical feature in the adult.…”

Effects of Growth Hormone Therapy on Glucose Metabolism and Insulin Sensitivity Indices in Prepubertal Children with Prader-Willi Syndrome

“…Many studies found that a large percentage of PWS patients had a blunted GH response to standard provocative tests [6,7,8,9,10]. Nevertheless, the majority of these subjects are overweight or obese, a condition which is itself known to reduce the response of GH secretion to pharmacological stimulation tests [11].…”

Síndrome de Prader-Willi: aspectos metabólicos associados ao tratamento com hormônio de crescimento

“…Considerando o valor de corte de 5 ng/ml, três pacientes foram não responsivos. Vários autores descrevem a secreção diminuída de GH na SPW como uma irregularidade neurossecretória (16,27).…”