J Clin Endocrinol Metab. 2006 Feb.
Short-term effects of growth hormone on sleep abnormalities in Prader-Willi syndrome.
Miller J, Silverstein J, Shuster J, Driscoll DJ, Wagner M.
Division of Pediatric Endocrinology, University of Florida, Box 100296, J. Hillis Miller Medical Center, Gainesville, FL, USA.
[ PubMed ]

Abstract
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.

Excerpts from (02/24/06) Science Daily: Growth Hormone, Obesity Can Trigger Sleep Apnea In Some Kids:

Growth hormone helps hundreds of children with a rare disorder that causes them to gorge on food, but for some, starting treatment can worsen a dangerous nighttime breathing problem, University of Florida researchers have found.

Sleep apnea disrupts breathing during sleep and is common among morbidly obese children, including those with Prader-Willi syndrome, a disease that compels them to eat nonstop. Researchers say that uncovering how to treat obesity and related problems in children genetically wired to be overweight could help them better battle childhood obesity in general.

Growth hormone has shown to be one of the most effective ways to treat children and adults with Prader-Willi. But University of Florida researchers found that starting treatments can worsen or trigger sleep apnea in obese children exposed to colds, potentially leading to death, according to findings published online recently in The Journal of Clinical Endocrinology and Metabolism.

"Every kid we studied had abnormal sleep at the beginning, before growth hormone," said Jennifer Miller, M.D., a UF assistant professor of pediatrics and the study's lead author. "On growth hormone, most of them got better but not all of them. The ones that got worse tended to be school age. Some of them were just entering school and then they were coming home with upper-respiratory infections.

"The combination of starting growth hormone, still having weak muscle tone, having an illness and/or being obese tends to put you at risk for having really bad obstructive sleep apnea."

The researchers urge doctors to monitor patients' sleep before and during treatment for signs of obstructive sleep apnea, such as loud snoring or abnormal daytime sleepiness. Sleep studies are recommended for all obese children, not just those with Prader-Willi, Miller added.

[...]

Obesity also can lead to severe respiratory problems as fat accumulates in the upper body and throat, and these effects cause the most problems for obese patients, including those with Prader-Willi, said [Bryan E. Hainline, M.D., Ph.D., an Indiana University associate professor of pediatrics who specializes in pediatric metabolism and genetics]. The UF study highlights this, he added.

Growth hormone was approved in the United States to treat Prader-Willi in 2000, but several children with the disease died after beginning the treatments. All died in their sleep and had been battling infections. To understand the problem, UF researchers decided to study how growth hormone affected sleep, monitoring patients on the therapy closely and performing sleep studies before and during treatment, Miller said.

The researchers studied 25 children and adults with Prader-Willi syndrome, a large sample for such a rare disorder. Four school-age children had increased difficulty breathing at night shortly after the treatment began. All began having problems after they were exposed to upper respiratory infections in school, the findings show.

The children's muscles were so weak at the beginning of the treatment they couldn't breathe with a stuffed-up nose, Miller said. Growth hormone worsened the problem, causing the tonsils to swell and exacerbating their sleep apnea.

"We realized it was an infection issue," Miller said. "They didn't have the strength to overcome any resistance."

To keep patients safe, the researchers suggest doctors perform sleep studies on children before and during treatment. Some children may also need to have their tonsils removed if necessary. This helps, but because of their poor muscle tone and obesity, Prader-Willi patients have more risks to anesthesia, Miller said.

"The important part is for parents to realize that being on growth hormone, while it's good for most people, there is a subset that's vulnerable to having problems during sleep," she said. "That's why the sleep study should be done, because we don't know who it's going to be."