ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: J Clin Endocrinol Metab 2017; 102:1702-1711

Short stature is a common feature of children with Prader-Willi syndrome (PWS) as well as hypotonia, hyperphagia, obesity, hypogonadism, behavioral disturbances and hypothalamic dysfunction. Alterations in the GH/IGF1 axis are common in patients with PWS, GH deficiency occurring in approximately 74% and IGF-1 deficiency in nearly 100% [1]. These patients show reduced spontaneous 24-hour GH secretion, insufficient response to GH stimulation testing, sub-normal levels of IGF-1 and reduced pubertal spurt. GH treatment increases height in PWS children and, besides its positive effects on growth, improves body composition, motor development, energy expenditure, bone mineralization and cardiovascular health. Although GH is widely used in PWS patients, the available evidence on long-term efficacy and safety on a large cohort of GH-treated PWS children are limited.

This study sheds light on the long-term efficacy of GH treatment in PWS children by analysing data collected in the largest available international database. Although GH therapy was far less effective in stimulating growth than in non-PWS GHD subjects, these results confirm the effectiveness of this treatment in children with PWS leading to an average final height of −1.2 SDS, corresponding to 170 cm in males and 156 cm in girls, consistent with previous studies performed in smaller numbers [2-4]. GH was effective not only in increasing height but also in controlling the progression of obesity. BMI increased during GH treatment, but remained within the normal range, in contrast to the natural tendency of progressive worsening of obesity in children with PWS. Consistent with this finding are previous reports showing an improvement of body composition [5-8].

The overall safety of GH therapy was satisfactory with a mortality rate less than the reported 3% annual mortality rate in patients with PWS younger than 30 years [9]. Nevertheless, the high number of patients with scoliosis and sleep apnea as well as the occurrence of diabetes mellitus (10 cases) and leukemia (2 cases) suggest the need of close monitoring of patients with PWS in general and particularly in those undergoing GH therapy [10].

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3. Lindgren AC, Hagenas L, Muller J, Blichfeldt S, Rosenborg M, Brismar T, et al. Effects of growth hormone treatment on growth and body composition in Prader-Willi syndrome: a preliminary report. The Swedish National Growth Hormone Advisory Group. Acta Paediatr Suppl. 1997;423:60-2.

4. Eiholzer U, l’Allemand D. Growth hormone normalises height, prediction of final height and hand length in children with Prader-Willi syndrome after 4 years of therapy. Horm Res. 2000;53:185-92.

5. Carrel AL, Myers SE, Whitman BY, Allen DB. Benefits of long-term GH therapy in Prader-Willi syndrome: a 4-year study. J Clin Endocrinol Metab. 2002;87:1581-5.

6. Lindgren AC, Hagenas L, Muller J, Blichfeldt S, Rosenborg M, Brismar T, et al. Growth hormone treatment of children with Prader-Willi syndrome affects linear growth and body composition favourably. Acta Paediatr. 1998;87:28-31.

7. Bakker NE, Siemensma EP, Koopman C, Hokken-Koelega AC. Dietary Energy Intake, Body Composition and Resting Energy Expenditure in Prepubertal Children with Prader-Willi Syndrome before and during Growth Hormone Treatment: A Randomized Controlled Trial. Horm Res Paediatr. 2015;83:321-31.

8. Deal CL, Tony M, Hoybye C, Allen DB, Tauber M, Christiansen JS, et al. GrowthHormone Research Society workshop summary: consensus guidelines for recombinant human growth hormone therapy in Prader-Willi syndrome. J Clin Endocrinol Metab. 2013;98:E1072-87.

9. Whittington JE, Holland AJ, Webb T, Butler J, Clarke D, Boer H. Population prevalence and estimated birth incidence and mortality rate for people with Prader-Willi syndrome in one UK Health Region. J Med Genet. 2001;38:792-8.

10. Deal CL, Tony M, Höybye C, Allen DB, Tauber M, Christiansen JS, et al. GrowthHormone Research Society workshop summary: consensus guidelines for recombinant human growth hormone therapy in Prader-Willi syndrome. J Clin Endocrinol Metab. 2013;98:E1072-87.