Adult height; Body mass index; Growth hormone; Noonan syndrome; Pediatrics, Perinatology and Child Health; Endocrinology, Diabetes and Metabolism; Endocrinology
Abstract :
[en] Introduction A variable near adult height (NAH) outcome after growth hormone (GH) therapy in Noonan syndrome (NS) patients with short stature has been reported. The main objective of this study was to evaluate NAH and body mass index (BMI) evolution in a large Belgian cohort of NS patients treated for short stature. The secondary objectives were to investigate whether sex, genotype, the presence of a thoracic deformity and/or a heart anomaly might affect NAH and to validate the recently developed NAH prediction model by Ranke et al. Methods Clinical and auxological data of GH treated short NS patients born before 2001 were extracted from the national Belgrow registry. NAH was available in 54 (35 male) genotyped NS using a gene panel of 9 genes, showing pathogenic variants in PTPN11 in 32 and in SOS1 in 5 patients, while in 17 patients gene panel analysis was inconclusive (no mutation group). Results After a median (P10; P90) duration of 5.4 (2.2-10.3) years of GH therapy with a median dose of 0.05 mg/kg/day NS patients reached a median NAH of -1.7 (-3.4; -0.8) SDS. Median total height gain was 1.1 (0.1; 2.3) SDS. Sex, genotype and the presence of a thoracic or cardiac malformation did not correlate with NAH or total height gain. Linear regression modelling revealed that height SDS at start (beta=0.90, p<0.001), mid-parental height SDS (beta =0.27; p=0.005), birth weight SDS (beta=0.15; p=0.051), age at start (beta=0.07; p=0032) were independently associated with NAH SDS. Median BMI SDS increased significantly (p<0.001) from -1.0 (-2.5; 0.0) at start to -0.2 (-1.5; 0.9) at NAH. The observed NAH in a subgroup of 44 patients with more than 3 years of GH treatment was not statistically different from the predicted NAH by the Noonan NAH prediction model of Ranke. Conclusion Long-term GH therapy at a dose of 0.05 mg/kg/day in short NS patients is effective in improving adult height and BMI, irrespective of the genotype and presence or absence of cardiac and or thoracic anomalies.
Disciplines :
Pediatrics Endocrinology, metabolism & nutrition
Author, co-author :
De Schepper, Jean; Division of Pediatric Endocrinology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium ; Research Unit GRON, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium
Thomas, Muriel; The BElgian and Luxembourg Society for PEdiatric Endocrinology and Diabetology (BELSPEED), Brussels, Belgium
Huysentruyt, Koen; Research Unit GRON, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium ; Division of Pediatric Gastroenterology and Nutrition, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium
Becker, Marianne; Department of Pediatric Endocrinology and Diabetology, Centre Hospitalier de Luxembourg, Luxembourg, Luxembourg
Boros, Emese; Pediatric Endocrinology Unit, Hôpital Universitaire de Bruxelles (HUB), Hôpital Universitaire des Enfants Reine Fabiola (HUDERF), Université libre de Bruxelles (ULB), Brussels, Belgium
Casteels, Kristina; Department of Pediatrics, Universitair Ziekenhuis Leuven, Leuven, Belgium ; Department of Development and Regeneration, KU Leuven, Leuven, Belgium
Chivu, Olimpia; Department of Pediatrics, Clinique CHC MontLégia, Liège, Belgium
De Waele, Kathleen; Department of Pediatrics, Universitair Ziekenhuis Gent, Gent, Belgium
Dotremont, Hilde; Department of Pediatric Endocrinology and Diabetology, Universitair Ziekenhuis Antwerpen, Edegem, Belgium
Lysy, Philippe A; Service of Specialized Pediatrics, Pediatric Endocrinology Unit, Cliniques Universitaires Saint-Luc, Brussels, Belgium
Massa, Guy; Department of Pediatrics, Jessa Ziekenhuis, Hasselt, Belgium
Parent, Anne-Simone ; Université de Liège - ULiège > Département des sciences cliniques > Pédiatrie
Rochtus, Anne; Department of Pediatrics, Universitair Ziekenhuis Leuven, Leuven, Belgium ; Department of Development and Regeneration, KU Leuven, Leuven, Belgium
Gies, Inge; Division of Pediatric Endocrinology, Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium ; Research Unit GRON, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Brussels, Belgium
The study was funded by the Belgian and Luxembourg Society for Pediatric Endocrinology and Diabetology (BELSPEED). AR is supported by a post doc research fellowship funded by University Hospitals Leuven (KOOR-UZ Leuven).
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