Background: A reduced GH response to different stimulation tests have been documented in both children and adults with PraderWilli syndrome (PWS), independently from obesity. Previous reports suggested the hypothesis of an age dependent derangement of the hypothalamuspituitary axis occurring in PWS subjects.
Objective and hypotheses: In this longitudinal study we re-evaluated the GH responsiveness to a combined test after long-term GH therapy in children with PWS, analyzing the possible impact of sex, BMI and genetic subtypes.
Method: GH peak (GHp) after GHRH+arginine or GHRH+pyridostigmine and IGF1 levels in 28 genetically confirmed PWS children were evaluated at baseline (16 males; age 4.7±2.7 years; heightSDS −1.0±1.1; BMISDS 2.9±3.2; 16 obese, 16 with del15) and after a median period of 9.4 years (age 14.3±2.4 years; heightSDS −1.1±1.2; BMISDS 3.0±2.0; 20 obese). All subjects underwent GH treatment after the first evaluation, withdrawn in all cases at least 6 months before the retesting.
Results: A decrease in GHp at retesting was observed (baseline: 20.5±12.3; at retesting: 13.5±11.1; P=0.031), while IGF1 levels were similar. PWS with del15 showed a higher IGF1 at baseline compared to UPD15 subjects (119.3±63.2 vs 63.9±47.7 ng/ml respectively; P=0.023) but not at retesting. Obese subjects compared to non obese patients showed lower GHp either at baseline (15.8±10.6 vs 26.8±11.9 ng/ml; P=0.016) and at retesting (10.2±7.7 vs 22.8±14.4 ng/ml; P=0.007). At baseline we did not find any correlation between GHp, IGF1 and other parameters considered, while at retesting we found a negative correlation between GHp (r=−531) and IGF1 (r=−0.422) and BMISDS. These negative correlations were confirmed in the multivariate model when age, sex, genetic subtypes and pubertal stage were considered (β=−0.531 and −0.422 respectively).
Conclusion: Our data suggest that PWS children have a normal GH pituitary reserve that gradually declines with age. Obesity seems to be the only factor influencing this impairment over time.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology