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This version published online on November 29, 2005
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2005-1279
A more recent version of this article appeared on February 1, 2006
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*Prader-Willi Syndrome

Submitted on June 8, 2005
Accepted on November 17, 2005

Short-Term Effects of Growth Hormone on Sleep Abnormalities in Prader-Willi Syndrome

Jennifer Miller MD*, Janet Silverstein MD, Jonathan Shuster PhD, Daniel J Driscoll PhD, MD, and Mary Wagner MD

Division of Endocrinology, Department of Pediatrics, University of Florida College of Medicine; Department of Statistics, University of Florida College of Medicine; Division of Genetics, Department of Pediatrics, University of Florida College of Medicine; Division of Pulmonology, Department of Pediatrics, University of Florida College of Medicine

* To whom correspondence should be addressed. E-mail: millejl{at}peds.ufl.edu.

Context. Growth hormone treatment (GH) was approved for Prader-Willi Syndrome (PWS) in 2000. Fatalities in individuals with PWS soon after beginning GH treatment prompted concern about GH worsening sleep apnea.

Objective. We sought to determine if GH affects sleep apnea in individuals with PWS.

Design. 25 patients with PWS had overnight polysomnography (PSA) at baseline and six weeks after starting GH.

Setting. The study was conducted in a sleep lab using a standardized procedure.

Patients. The patients studied had genetically confirmed PWS.

Main Outcome Measures. PSA results were analyzed for frequency and severity of central and obstructive apnea/hypopnea events and total apnea/hypopnea index (AHI).

Results. As a group, GH improved AHI by a mean of 1.2 events/hour (P = 0.02) and central events by a median of 1.7 events per hour (P < 0.001). Fourteen patients had improvement in obstructive events by a mean of 1.7 events per hour. Six patients had worsening of obstructive events on GH. Four of these patients had upper respiratory tract infections (URI) at the time of the 2nd PSA, and had tonsil/adenoid hypertrophy on otorhinolaryngologic (ENT) evaluation. Two patients with high serum IGF-1 levels had increased obstructive events.

Conclusions. Most of our PWS patients had improvement after short-term GH treatment, but 32% had worsening of sleep disturbance. A subset of PWS patients are at risk during this window of vulnerability shortly after initiation of GH. Since it is difficult to predict who will worsen with GH, patients with PWS should have PSA before and after starting GH and should be monitored for sleep apnea with URI. ENT evaluation is warranted if sleep apnea worsens on GH. IGF-1 levels should be monitored, with the goal being physiologic levels.


Key words: GH • PWS • sleep apnea




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