GH/IGF-I axis in Prader-Willi syndrome: evaluation of IGF-I levels and of the somatotroph responsiveness to various provocative stimuli. Genetic Obesity Study Group of Italian Society of Pediatric Endocrinology and Diabetology.
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.
Corrias
A
A
Division of Pediatric Endocrinology, Regina Margherita Hospital, Turin, Italy.
Bellone
J
J
Beccaria
L
L
Bosio
L
L
Trifirò
G
G
Livieri
C
C
Ragusa
L
L
Salvatoni
A
A
Andreo
M
M
Ciampalini
P
P
Tonini
G
G
Crinò
A
A
D000293:Adolescent; D000316:Adrenergic alpha-Agonists / Q000009:adverse effects; D000328:Adult; D001120:Arginine / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D003000:Clonidine / Q000009:adverse effects; D005260:Female; D019382:Human Growth Hormone / Q000378:metabolism*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000378:metabolism; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D011218:Prader-Willi Syndrome / Q000378:metabolism*; D011863:Radioimmunoassay
D000316:Adrenergic alpha-Agonists; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D001120:Arginine; D003000:Clonidine