ESPE Yearbook of Paediatric Endocrinology

The Journal of Clinical Endocrinology & Metabolism, 2021, Vol. 106, No. 9, e3634–e3643PMID: 33950234

Brief Summary: This trial explored the effects of rhGH treatment in patients with Prader-Willi syndrome (PWS) on respiratory and sleep parameters. The trial was randomized and placebo-controlled for 1 year, followed by a 2-year, open-phase GH treatment period. Polysomnography performed every 6 months revealed no adverse effects of rhGH treatment on respiratory parameters such as apnea-hypopnea index and tonsillar hypertrophy. Sleep efficiency improved after rhGH treatment. These findings support the use of rhGH treatment in adults with PWS.

PWS is considered the most frequent genetic cause of obesity, occurring in approximately 1:10,000-1:30,000 live births and is a complex multisystem disorder, characterized by neonatal hypotonia and feeding difficulties in early infancy, short stature, behavioral problems, cognitive impairment, psychiatric illness, dysmorphic features, multiple endocrine abnormalities, early development of hyperphagia with food-seeking behavior and progressive development of severe obesity, unless eating is not promptly restricted (1). Sleep-related breathing disorders (SRBDs) are frequent in PWS with a high prevalence of obstructive sleep apnea (OSA), up to 80% in children and 22% in adults (2). There are speculations about potential associations between GH therapy and unexpected death in children and for this reason a close monitoring of sleep apneas during GH treatment is needed. Recent data have shown that GH can be safely administered in children with PWS, provided that SRBDs are monitored and treated appropriately (3). In adult PWS patients data were still conflicting.

This study describes the effect of short- and long-term GH treatment on respiratory and sleep parameters in 37 adult PWS patients (15 males and 22 females; mean age 29.5 years). They were randomly assigned to 1 year of GH treatment (n = 19) or placebo (n = 18), followed by 2 years of GH treatment to all. Polysomnography was performed every six months. At year 1, IGF-1 increased in the GH-treated group, whereas it was unchanged in the placebo group. No differences were seen between GH and placebo on respiratory or sleep parameters. Sleep efficiency increased during 3 years of continuous GH treatment, even after adjustment for BMI. Apnea-hypopnea index was normal at baseline and did not increase during treatment. Ear-nose-throat examination did not find any tonsillar enlargement. The authors concluded that GH treatment of adults with PWS was associated with improved sleep efficiency and no adverse impact on respiratory function.

This study confirms in adults what is already recognized in children with PWS, GH therapy has no negative impact on respiration and sleep parameters. However, due to the high frequency of SRBDs, repeated sleep analysis should be performed in any child and adult with PWS, regardless of GH treatment. A weakness is the small number of patients enrolled in the trial but this limitation is partly compensated by the prospective longitudinal long-term placebo-controlled design.

References: 1. Angulo MA, Butler MG, Cataletto ME. Prader-Willi syndrome: a review of clinical, genetic and endocrine finding. J Endocrinol Invest. 2015;38(12):1249–1263. 2. Miller J, Wagner M. Prader-Willi syndrome and sleep-disordered breathing. Pediatr Ann. 2013;42(10):200–204. 3. Festen DA, de Weerd AW, van den Bossche RA, Joosten K, Hoeve H, Hokken-Koelega AC. Sleep-related breathing disorders in prepubertal children with Prader-Willi syndrome and effects of growth hormone treatment. J Clin Endocrinol Metab. 2006;91(12):4911–4915.