The Behavioral Impact of Growth Hormone Treatment for Children and Adolescents With Prader-Willi Syndrome: A 2-Year, Controlled Study

Abstract

ABSTRACT. Introduction. Prader-Willi syndrome (PWS) is characterized by obesity, hypotonia, hypogonadism, hyperphagia, short stature, and a neurobehavioral profile that includes cognitive deficits, learning problems, and behavioral difficulties that increase in both quantity and severity over time. PWS results from an alteration in the molecular composition of a critical region of C#15q. Morbid obesity resulting from hyperphagia is amplified by decreased energy expenditure and reduced physical activity. The hyperphagia has proven refractory to all psychopharmocologic intervention; the behavioral components are equally resistant to psychotropic intervention. PWS patients' body composition resembles that of individuals with growth hormone (GH) deficiency, including short stature and reduced lean body mass with concomitant increased fat mass. We hypothesized that GH administration to children with PWS, in addition to stimulating linear growth, would improve body composition, increase energy expenditure and fat utilization, and improve muscle strength, physical agility, and pulmonary function. Two recent reports from this study document significant positive effects of GH treatment on these children's physical parameters measured in a 2-year, controlled study. However, the behavioral impact of GH treatment in this population remains incompletely described.A psychosocial burden, including emotional, behavioral, and cognitive disturbances associated with short stature, has been previously described in a non-PWS population with GH deficiency and idiopathic short stature. An impaired quality of life and psychosocial status is also documented in otherwise normal adults with GH deficiency. In both populations, growth hormone replacement therapy (GHRT) is reported to improve alertness, activity level, endurance, irritability, tendency to worry, and extroversion resulting in better personal relationships with fewer conflicts. This report focuses on that portion of the study investigating the behavioral and psychosocial outcomes accompanying increased stature and improved physical status for persons with PWS treated with GHRT. We hypothesized that, as in other populations, GHRT for persons with PWS would have a significant positive effect on their psychosocial status as well as an improvement in their growth parameters. Methods.A 2-year, controlled study with control group crossover in the second year was used. Fifty-four consecutive children with genetically confirmed PWS were enrolled. Patients were 4 to 16 years of age at time of enrollment, had skeletal maturation <13 for girls and <15 for boys; all but 3 participants remained prepubertal (Tanner stage 1) throughout the study. Children who had previous therapy with GH were excluded, as were children with a scoliosis >20°. The SDI contains a second section measuring behavior functioning in the school environment, in the family, and in personal and social relationships. A wider scoring range is used and is question-specific. Parallel forms of this measure are available for ...

Effects of Growth Hormone Therapy on Glucose Metabolism and Insulin Sensitivity Indices in Prepubertal Children with Prader-Willi Syndrome

“…However, it has been demonstrated that in PWS patients GH treatment (GHT) reduces fat mass and increases body free fat mass percentage [4,12,13,14], improves respiratory muscle strength and endurance [15], and increases resting metabolic rate as well as physical strength and agility[14]. Changes in behaviour have also been observed [16] and beneficial effects on growth velocity have been demonstrated in many studies [6,12,13,14]. …”

Clinical management of behavioral characteristics of Prader&ndash;Willi syndrome

“…Eiholzer and colleagues 106 found, through parent reporting, that GH treatment increased alertness and enjoyment in physical activity in children with PWS. Similarly, Whitman and colleagues 122 found a significant reduction of depressive symptoms from baseline to time 1 (12 months) and retained at 24 months among those treated with GH. However, for children aged 11 years and younger, a significant increase in attention-deficit/hyperactivity symptoms was observed.…”

Health Supervision for Children With Prader-Willi Syndrome

“…In the first year of life, reduced growth velocity may not be readily identified, but both controlled clinical trials 22 There is mounting evidence from controlled clinical trials that GH therapy in children improves linear growth, lean mass and lean-to-fat ratio, 27 and respiratory drive, 26,28 and there has been suggestion of beneficial effects on bone density 27,29 and possible stabilization of behavior decline. 30 Studies are in progress to evaluate the use of GH in adults with PWS. 31 However, there is nothing to suggest that endogenous GH insufficiency improves in later life; therefore, it is reasonable to consider continuing therapy into adulthood.…”