Is There Growth Hormone Deficiency in Prader-Willi Syndrome?

Background: In Prader-Willi syndrome (PWS) a reduced growth hormone (GH) response to several stimulators has been documented in many studies, but none have focused on very young children. We evaluated the pattern of GH secretion in very young PWS patients. Patients and Methods: Twenty-seven genetically confirmed PWS children (10 females, aged 0.4-5 years, mean: 2.2 ± 1.4 years) were included. All subjects underwent standard provocative tests (clonidine, CLO; and arginine, ARG) and one combined test [growth hormone-releasing hormone (GHRH) plus pyridostigmine (13 patients) or GHRH plus arginine (14 patients)]. Insulin-like growth factor-1 (IGF-1) levels were also measured. Results: While standard tests (CLO and ARG) showed low GH peak in 85.2 and 70.4% of the patients, respectively, the combined test was found to be normal in 85.2%. IGF-1 was low in 66.7% of patients. Out of 27 patients, 3 (11%) showed a normal GH peak with both standard tests (group A), 6 (22%) to one of the standard tests (group B) and 18 (67%) presented a low response to both standard tests (group C). Four subjects showed low response to both the combined and standard tests and reduced IGF-1. Conclusion: Our data suggest that very young PWS children seem to have impaired hypothalamic GHRH secretion with a normal GH pituitary reserve.

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“…This finding supports the assumption that GH secretion in PWS may be insufficient to promote normal levels of circulating IGF-1 [34]. …”

Section: Discussionsupporting

confidence: 88%

“…Furthermore, a negative correlation was found between GH peak response to the combined test and BMI and BMI SDS, suggesting that BMI influences GH response to provocative tests, as reported in non-PWS subjects [34,35,36,37]. In our PWS cohort only 2 patients were obese.…”

Section: Discussionsupporting

confidence: 62%

Growth Hormone Response to Standard Provocative Stimuli and Combined Tests in Very Young Children with Prader-Willi Syndrome

et al. 2014

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“…In simple obesity, GH secretion after provocative stimuli is indeed decreased, but IGF-I levels are normal or even elevated. In PWS individuals on the other hand, IGF-I levels are lower in both obese and non-obese PWS individuals when compared to normal weight and obese controls [2,9,10,11,12,13,15,16,17,18,19]. …”

Section: Introductionmentioning

confidence: 99%

The GH/IGF-I Axis and Pituitary Function and Size in Adults with Prader-Willi Syndrome

et al. 2011

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Background: In adults with Prader-Willi syndrome (PWS), limited information is available about pituitary function, more specifically the prevalence of growth hormone deficiency (GHD). The aim of this study was to gain more insight into endocrine function in PWS adults, with emphasis on GH secretion. Methods: 15 randomly selected adult PWS individuals were included and 14 healthy brothers and sisters served as a control group. Main outcome measures were IGF-I, IGFBP-3 and peak GH level after a combined GHRH-arginine test. Other pituitary hormone deficits are diagnosed based on serum levels of the concerning hormones. The size of the pituitary gland was measured on MRI images. Results: In PWS adults, IGF-I levels were low and IGFBP-3 levels normal when compared to healthy controls. GHD was diagnosed in 8–38% of the PWS patients, depending on the criteria used. Hypogonadism was present in 87% of the patients. Hypothyroidism and adrenal insufficiency could also be demonstrated. Anterior pituitary size was lower in PWS individuals when compared to healthy controls. Conclusion: In this study, pituitary hormone deficiencies are demonstrated in a considerable number of adults with PWS, hypogonadism and GHD being most prominent. Furthermore, the anterior pituitary is smaller in comparison with healthy controls.

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“…The hypothalamic dysfunction causes growth hormone (GH) deficiency [3], hypogonadism [4,5,6] and a dysregulation of energy balance with hypoactivity [7, 8] and insatiable hunger [9,10,11], resulting in an increased fat and decreased lean body mass [12, 13]. In addition to control of nutrient intake and enhancement of activity, beneficial effects of early therapy of GH deficiency in PWS have been demonstrated [14,15,16]: short stature is normalized and muscle mass enhanced [8, 12,17,18,19,20].…”

Section: Introductionmentioning

confidence: 99%

Clinical Effects of Treatment for Hypogonadism in Male Adolescents with Prader-Labhart-Willi Syndrome

Eiholzer¹,

Grieser²,

Schlumpf³

et al. 2007

Horm Res Paediatr

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Background: In boys with Prader-Labhart-Willi syndrome (PWS), hypogonadism causes pubertal arrest and reduces pubertal muscle growth. Formerly, it was assumed that therapy with gonadal hormones accentuates behaviour abnormalities in PWS. Our aim was to assess the clinical effects of human chorionic gonadotropin (hCG) therapy on pubertal development, muscle mass and behaviour in adolescents with PWS. Methods: 6 peripubertal boys with PWS undergoing long-term treatment with growth hormone were examined 6-monthly for at least 2 years before and after pubertal arrest (13.5 ± 0.3 years, mean ± SEM) and the beginning of hCG therapy (500–1,500 IU twice weekly, intramuscularly). Height, weight, pubertal stage, bone age, body composition (by dual-energy X-ray absorptiometry), testosterone levels and behaviour abnormalities (obtained from parents) were assessed. Results: Testicular volume and lean mass were reduced in pubertal boys with PWS. During hCG therapy, testosterone levels and lean mass significantly increased (at the beginning and after 2 years of hCG therapy: 2.3 ± 0.9 and 10.7 ± 1.3 nmol/l, –3.1 ± 0.3 and –1.4 ± 0.6 SD, respectively), and fat mass stabilized at 38%. The characteristically observed PWS-associated problems, mood instability, aggressiveness and difficulties in social interaction, did not deteriorate during therapy. Conclusion: In the present study, timely application of hCG to treat hypogonadism in boys with PWS promoted virilization and normalized muscle mass without detrimental effects on behaviour. Larger studies comparing hCG therapy with testosterone replacement would be useful.

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Is There Growth Hormone Deficiency in Prader-Willi Syndrome?

Cited by 44 publications

References 53 publications

Growth Hormone Response to Standard Provocative Stimuli and Combined Tests in Very Young Children with Prader-Willi Syndrome

Growth Hormone Response to Standard Provocative Stimuli and Combined Tests in Very Young Children with Prader-Willi Syndrome

The GH/IGF-I Axis and Pituitary Function and Size in Adults with Prader-Willi Syndrome

Clinical Effects of Treatment for Hypogonadism in Male Adolescents with Prader-Labhart-Willi Syndrome

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