Sleep-related Disturbances in Prader-Willi Patients on Growth Hormone

There has recently been considerable alarm in the pediatric community related to reports of sudden death from apparent respiratory failure in childhood patients with Prader-Willi syndrome (PWS). Such reports have coincided with growth hormone (GH) therapy in some patients. A possible causative association between sudden death and GH therapy has been suggested, but not proven. This excellent study from the Netherlands explores the possible link between GH therapy and respiratory dysfunction in PWS patients.

Under the auspices of the Dutch Growth Foundation, led by Hokken-Koelega, a study was performed on a large number of PWS patients. Fifty-three prepubertal, mainly non-obese, patients aged from 2 to 7 years were enrolled into detailed studies of functional respiratory dynamics in a single sleep center. Thirty-five subjects underwent repeat assessment after the first 6 months of GH therapy. Baseline respiratory dynamics were quantified according to determination of airflow during sleep. The so-called apnea-hypopnea index (AHI) refers to significant reduction in airflow and was demonstrated to be highly abnormal with a high frequency, even in these relatively young patients and was unrelated to age, BMI, or incidence of tonsillar hypertrophy. A mainly central or ‘hypothalamic’ mechanism was hypothesized, although obstructive apnea was seen in 50% of the overweight subjects.

After 6 months of GH therapy the AHI improved slightly but not significantly. Obstructive apnea did not change. No increases in variables of respiratory risk were demonstrated related to GH therapy.

Festen DA, de Weerd AW, van den Bossche RA, Joosten K, Hoeve H, Hokken-Koelega AC. Sleep-related breathing disorders in prepubertal children with Prader-Willi syndrome and effects of growth hormone treatment. J Clin Endocrinol Metab. 2006;91:4911-5.

Editor’s Comment

The conclusions of this impressive study are reassuring concerning a hypothetical role of GH therapy contributing to increased mortality in PWS. These patients however are inherently vulnerable to episodes of reduced respiratory function, particularly in upper respiratory infections leading to tonsillar or adenoidal hypertrophy. The treatment of PWS with GH remains a controversial area.¹ The present study however provides data which is reassuring, suggesting that blame cannot be attributed to GH therapy, but that respiratory dysfunction is a common feature of the primary condition.

Martin O. Savage, MD

Reference - (linked to )

Lee PD. Growth hormone and mortality in Prader-Willi syndrome. Growth Genet Horm. 2006;22:17-23.

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Last Updated: 04/30/2008