Growth hormone therapy for Prader-Willi syndrome can worsen sleep problems

Patients taking growth hormone should have sleep studies done before and after treatment initiation.

Issue: January 2006

While growth hormone improves sleep-obstructed breathing in most people with Prader-Willi syndrome, it can also worsen it, according to a new study. Because of this, all patients starting treatment should undergo sleep studies and be carefully monitored for problems.

Since 2000, children with Prader-Willi syndrome (PWS) have been offered growth hormone (GH) treatment because of evidence indicating the dysregulation of the GH/IGF axis associated with the syndrome. The results of this treatment have been mostly positive, but there have been previous reports of sleep-disordered breathing (including obstructive sleep apnea and other problems) worsening after initiation of GH treatment.

Janet Silverstein, MD, of the University of Florida College of Medicine in Gainesville, and colleagues conducted a study of sleep problems among PWS patients taking GH. Their results were published in the Journal of Clinical Endocrinology and Metabolism.

Study design

A total of 25 patients with PWS who had either never taken GH or who stopped taking it for at least three months were enrolled in the study. All patients underwent a baseline sleep study and another after six weeks of GH therapy. Two patients also agreed to a repeat polysomnography test after six months of treatment.

All 25 patients had some sleep-disordered breathing at the baseline sleep study. After six weeks of GH therapy, 19 patients showed improvement in the apnea/hypopnea index used to measure sleep-disordered breathing. The median improvement was a -1.2 events/hour overall (P=.02), and -2.9 events during REM sleep (P=.08). Both patients who had a follow-up study after six months showed improvement in apnea/hypopnea index.

The other six patients showed worsening of obstructive sleep apnea/hypopnea after GH therapy. Notably, four of these patients had concurrent upper respiratory infection; all four were in school or daycare and all showed improvements of obstructive sleep apnea after tonsillectomy and adenoidectomy.

Two patients had high serum IGF-I levels for bone age (patients were aged 22 and 24); the GH dose was lowered to normalize circulating IGF-I concentrations. One of the two then showed improvement in the apnea/hypopnea index, but the other had an increased apnea/hypopnea index; this patient was found to have tonsillar hypertrophy and underwent an adenotonsillectomy.

Results by age

Of the six patients who showed worsening apnea/hypopnea index at the second sleep study, all but one were under 18 years of age, and the “one adult who had an increase in apnea/hypopnea index on GH had underlying respiratory problems,” the investigators wrote.

Overall, GH tended to improve apnea/hypopnea index (mean -6.8; P=.08), obstructive events (obstructive index mean -6.1; P=.05) and central events (central index mean -8.7; P=.07) in patients either under age 2 or over age 18 vs. those between ages 2 and 18 (apnea/hypopnea index mean 4.2; obstructive index mean mean; central index mean -2.8).

“Children with PWS who are about to embark on GH treatment should have a sleep study done before initiation of treatment and following GH treatment to make certain there is no worsening of sleep apnea,” Silverstein told Endocrine Today. She is a member of the Endocrine Today Editorial Advisory Board.

Silverstein said that GH treatment could result in hypertrophy of lymphoid tissue in some PWS patients, resulting in enlargement of the adenoids and tonsils. These problems can also worsen during times of upper respiratory infection.

“There should be consideration of discontinuation of GH during times of severe upper respiratory infection symptoms,” she said. – by Dave Levitan

For more information:

Miller J, Silverstein J, Shuster J, et al. Short-term effects of growth hormone on sleep abnormalities in Prader-Willi syndrome. J Clin Endocrinol Metab. 2006;91:413-417.