Short-term effects of growth hormone on sleep abnormalities in Prader-Willi syndrome

Context: 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 whether GH affects sleep apnea in individuals with PWS. Design: Twenty-five patients with PWS had overnight polysomnography (PSA) at baseline and 6 wk 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. Results: As a group, GH improved apnea/hypopnea index by a mean of 1.2 events per 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 at the time of the second PSA and had tonsil/adenoid hypertrophy on otorhinolaryngological evaluation. Two patients with high serum IGF-I 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. Because 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 upper respiratory tract infections. Otorhinolaryngological evaluation is warranted if sleep apnea worsens on GH. IGF-I levels should be monitored, with the goal being physiological levels.