Growth hormone (GH) secretion in children with Noonan syndrome: frequently abnormal without consequences for growth or response to GH treatment.
The role of GH insufficiency in the pathogenesis of short stature in Noonan syndrome is unclear. Cross-sectional study. Seventeen patients with Noonan syndrome (13 boys, 4 girls; aged 4.8-13.3 (mean 9.2) years) and short stature before start of GH treatment. Spontaneous 12-h overnight GH secretion by continuous sampling analysed using Pulsar, plasma IGF-I and IGFBP-3 levels, and 24-h urinary GH excretion were measured at start of GH treatment. A glucagon stimulation test was performed. Height and height velocity were monitored before and after 1 year of GH treatment. IGF-I and IGFBP-3 were remeasured after 1 year of GH treatment. Nine of the 17 children had a mean overnight GH concentration below the lower limit of the normal range. In six of the 17 patients, overnight GH profiles showed high trough GH concentrations. Glucagon stimulation tests were normal in 16 of the 17 patients. Mean IGF-I level was below normal (-0.4 SD). None of the parameters regarding GH secretion obtained from the overnight profile or provocative test was related to height or height velocity, nor to first year response to GH treatment. IGF-I and IGFBP-3 did not correlate with any of the GH secretion data. IGF-I and IGFBP-3 were related to height and height velocity at the start of GH treatment (r = 0.53 (P < 0.01) and r = 0.61 (P < 0.03) respectively). Rises in IGF-I and IGFBP-3 under GH treatment were related to the increment in height velocity (r = 0.70 (P < 0.01) and r = 0.71 (P < 0.02) respectively). Abnormalities in GH secretion are frequent in patients with Noonan syndrome and short stature. These abnormalities were not related to auxology at start of or response to GH treatment. Clinically GH insufficiency is not important in Noonan syndrome and monitoring spontaneous GH secretion is not necessary before the start of GH treatment.
Noordam
C
C
Departments of Paediatric Endocrinology, 435, University Medical Centre St. Radboud, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. C.Noordam@ckskg.azn.nl
van der Burgt
I
I
Sweep
C G
CG
Delemarre-van de Waal
H A
HA
Sengers
R C
RC
Otten
B J
BJ
D000293:Adolescent; D001827:Body Height; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D005260:Female; D005934:Glucagon; D006130:Growth Disorders / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism; D013006:Growth Hormone / Q000097:blood* / Q000627:therapeutic use / Q000652:urine; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D008991:Monitoring, Physiologic / Q000379:methods; D009634:Noonan Syndrome / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D012044:Regression Analysis; D013268:Stimulation, Chemical
D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D005934:Glucagon