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

Hasanain Hamid Shukur, Laith Hussain-Alkhateeb, Stense Farholt, Ole Nørregaard, Anders Palmstrøm Jørgensen, Charlotte Hoybye, Hasanain Hamid Shukur, Laith Hussain-Alkhateeb, Stense Farholt, Ole Nørregaard, Anders Palmstrøm Jørgensen, Charlotte Hoybye

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.

Trial registration: ClinicalTrials.gov NCT00372125.

Keywords: GH treatment; Prader-Willi syndrome; polysomnography; sleep-related breathing disorders.

© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.

Figures

Figure 1.
Figure 1.
Flowchart of a 12-month, double-blind, randomization, growth hormone (GH) and placebo-controlled trial followed by a 24-month, open-phase extension with GH treatment. PWS, Prader-Willi syndrome.

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