Effects of GH on Sleep Patterns in Prader-Willi Syndrome

Jennifer Miller, Janet Silverstein, Abby Wagner, Daniel J. Driscoll, Divisions of Pediatric Endocrinology, Genetics & Pulmonary, Box 100296, Department of Pediatrics, College
of Medicine, University of Florida, Gainesville, FL 32610

INTRODUCTION: Children with Prader Willi Syndrome (PWS) have significant respiratory problems, including obstructive sleep apnea (OSA) due to increased neck tissue mass and airway compression, hypothalamic dysfunction with disordered central control of breathing, abnormal arousal, and abnormal cardiorespiratory response to hypercapnia. Polysomnographic studies (PSS) of PWS patients show multiple episodes of asymptomatic apnea during sleep that are unrelated to weight, tonsillar/adenoid size, or evidence of airway obstruction.

Growth hormone (GH) treatment has been documented to improve the respiratory quotient in PWS patients, having a stimulatory effect on central respiratory drive and increased respiratory response to hypercarbia. However, OSA has been seen in non-PWS GH-treated patients possibly due to hypertrophy of upper airway lymphoid tissue.  Five recent reports of GH-treated PWS children resulted in sudden death, yet there are no published studies of PSS evaluating obstructive sleep apnea in PWS patients before and during GH treatment. This study was undertaken to evaluate the effect of GH on OSA and ventilatory drive in patients with PWS.

METHODS:  PSS was performed in a standard sleep laboratory with 8 patients with PWS. PSS included the following parameters: central and occipital EEG, right and left EOG, submentalis EMG, snoring, airflow, nasal pressure, chest and abdomen movement, arterial oxygen saturation, end-tidal CO2, anterior tibialis EMG, and two lead ECG.  Sleep was staged in 30 second epochs.   Studies were evaluated for evidence of sleep-disordered breathing (SDB) including central apnea, central hypopnea, OSA, obstructive hypopnea, hypoxemia and hypercarbia. 

RESULTS:  8 patients with PWS had sleep studies performed; 6 had been off GH treatment for at least 6 weeks, 2 had sleep studies done while taking GH, and 1 had sleep studies both before and during GH treatment.  6 of the 8 had snoring during the study.  All PWS patients off growth hormone had episodes of obstruction, either causing apnea or hypopnea, as well as episodes of central apnea or hypopnea during the sleep study.  The two patients who had a sleep study done while on growth hormone had no episodes of obstructive apnea, and fewer episodes of central apnea/hypopnea than those patients that were not on growth hormone.

DISCUSSION: All patients with PWS studied had some degree of either OSA or central sleep apnea.  Further studies must be done to determine which sleep patterns are ameliorated with GH treatment and to determine which, if any, sleep abnormalities are worsened by GH treatment. The only normal studies in our cohort were 2 children on GH, one of whom had had a previously abnormal study.

July 2003