Effects of Growth Hormone Treatment on Sleep-Related Parameters in Adults With Prader-Willi Syndrome

Author:

Shukur Hasanain Hamid1ORCID,Hussain-Alkhateeb Laith2ORCID,Farholt Stense3,Nørregaard Ole4,Jørgensen Anders Palmstrøm5ORCID,Hoybye Charlotte16ORCID

Affiliation:

1. Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Solna SE-171 76, Sweden

2. Global Health, School of Public Health and Community Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden

3. Center for Rare Diseases, Department of Pediatric and Adolescent Medicine, Aarhus University Hospital, DK-8200 Aarhus N, Denmark

4. Danish Respiratory Center West, Department of Anaesthesiology and Intensive Care, Aarhus University Hospital, DK-8200 Aarhus N, Denmark

5. Section of Specialized Endocrinology, Department of Endocrinology, Oslo University Hospital, Rikshospitalet, 0424 Oslo, Norway

6. Department of Endocrinology, Karolinska University Hospital, SE-171 76 Stockholm, Sweden

Abstract

Abstract Context Prader-Willi syndrome (PWS) is a rare, genetic, multisymptom, neurodevelopmental disease due to lack of the expression of the paternal genes in the q11 to q13 region of chromosome 15. The main characteristics of PWS are muscular hypotonia, hyperphagia, obesity, behavioral problems, cognitive disabilities, and endocrine deficiencies, including growth hormone (GH) deficiency. Sleep apnea and abnormal sleep patterns are common in PWS. GH treatment might theoretically have a negative impact on respiration. Objective Here we present the effect of GH treatment on polysomnographic measurements. Methods Thirty-seven adults, 15 men and 22 women, with confirmed PWS were randomly assigned to 1 year of GH treatment (n = 19) or placebo (n = 18) followed by 2 years of GH treatment to all. Polysomnographic measurements were performed every 6 months. A mixed-effect regression model was used for comparison over time in the subgroup that received GH for 3 years. Results At baseline median age was 29.5 years, body mass index 27.1, insulin-like growth factor 115 µg/L, apnea-hypopnea index (AHI) 1.4 (range, 0.0-13.9), and sleep efficiency (SE) 89.0% (range, 41.0%-99.0%). No differences in sleep or respiratory parameters were seen between GH- and placebo-treated patients. SE continuously improved throughout the study, also after adjustment for BMI, and the length of the longest apnea increased. AHI inconsistently increased within normal range. Conclusion SE improved during GH treatment and no clinical, significantly negative impact on respiration was seen. The etiology of breathing disorders is multifactorial and awareness of them should always be present in adults with PWS with or without GH treatment.

Funder

Novo Nordisk Scandinavia AB

Publisher

The Endocrine Society

Subject

Biochemistry, medical,Clinical Biochemistry,Endocrinology,Biochemistry,Endocrinology, Diabetes and Metabolism

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