Diagnosis and treatment of GH deficiency in Prader–Willi syndrome

Grugni, Graziano; Marzullo, Paolo

doi:10.1016/j.beem.2016.11.003

Cited by 48 publications

(42 citation statements)

References 91 publications

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“…Other www.nature.com/scientificreports www.nature.com/scientificreports/ studies prompted similar evidence of a positive correlation between irisin and fat-free mass 15,18,40,41 . Hence, the positive correlation observed between irisin and muscle mass agrees with the divergent obese phenotypes of the populations studied 42 . It should be noted that the correlation analysis was only conducted in the obese populations as a whole after excluding lean controls, so as to determine the specific effect of PWS and excluding the potential statistical interference relating to the lean group.…”

Section: Discussionsupporting

confidence: 80%

“…Previous work showed that obese PWS subjects harbor lower muscle mass and FFM than BMI-matched obese individuals without PWS, while being similar to FFM values observed in lean controls 5,43 . Moreover, individuals with common obesity are tipically engaged in stronger spontaneous workout than PWS, who exhibit muscle hypotonia and poor attitude to exercise 42 . Hence, the loss of significance in the correlation observed in our study between irisin and muscle mass when corrected for PWS status likely reflects the divergent phenotype of our obese populations.…”

Section: Discussionmentioning

confidence: 99%

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Irisin levels in genetic and essential obesity: clues for a potential dual role

Mai

Grugni

Mele

et al. 2020

Sci Rep

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irisin is conventionally regarded as a myokine involved in the browning of white adipose tissue, energy expenditure and glucose tolerance. its potential link to fat accumulation and metabolic dysfunction is debated. We sought to explore the relationship between circulating irisin and components of body composition in two different phenotypes of severe obesity. For this purpose, 30 obese adults with Prader-Will syndrome (PWS) (age 35.7 ± 1.5 y, BMI 45.5 ± 1.5 kg/m 2) and 30 adult controls with common obesity (age 34.9 ± 1.7 y, BMI 46.8 ± 1.4 kg/m 2) underwent analysis of irisin levels, metabolic profile, body composition and resting energy expenditure (REE). Normal irisin levels were obtained from a group of 20 lean donors (age 32.4 ± 1.5 y, BMI 23.8 ± 0.8 kg/m 2). Expected differences in body composition and metabolic profile existed between study groups. PWS exhibited lower muscle mass (p < 0.001), FFM (p < 0.001), REE (p < 0.001), as well as insulin (p < 0.05), HOMA-IR (p < 0.05) and triglycerides levels (p < 0.05) than controls with common obesity. In PWS, irisin levels were significantly lower and overall less dispersed than in controls with common obesity (p < 0.05), while being similar to values recorded in lean subjects. to explore the relation between irisin and body composition in obesity, univariate correlation analysis in the obese populations as a whole showed positive associations between irisin and muscle mass (p = 0.03) as well as REE (p = 0.01), which disappeared when controlled for the pWS status. noticeably, a positive association became evident between irisin and %fM after controlling for the pWS status (p = 0.02). Also positive were associations between irisin and insulin (p = 0.02), HOMA-IR (p = 0.02) and triglycerides (p = 0.04). In stepwise multivariable regression analysis, irisin levels were independently predicted by the pWS status (p = 0.001), %FM (p = 0.004) and triglycerides (p = 0.008). Current results suggest that obese adults with PWS harbor lower irisin levels than individuals with common obesity. the divergent models of obesity herein studied suggest a potential link between circulating irisin and muscle mass and metabolic dysfunction relating to adiposity. Prader-Willi syndrome (PWS) is a rare genetic disorder characterized by neonatal hypotonia associated with poor suck, followed by the lack of a sense of satiety with obsessive craving for food in childhood and gradual development of morbid obesity in adulthood unless eating is externally controlled 1-4. Further clinical features include body dysmorphisms, developmental disability, cognitive and behavioral disorders, endocrine dysfunctions leading to short stature, hypogonadism and hypothyroidism 1. PWS occurs because of the lack of expression of genes located on the paternal chromosome 15q11.2-q13. Three main genetic mechanisms have been recognized in determining PWS: deletion of the paternal chromosome 15 (del15q11-q13), maternal uniparental disomy of chromosome 15 (UPD15), and imprinting defects 2 .

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Section: Discussionsupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Irisin levels in genetic and essential obesity: clues for a potential dual role

Mai

Grugni

Mele

et al. 2020

Sci Rep

Self Cite

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“…The metabolic phenotype of PWS is different as compared to common obesity and some metabolic complications typically related to obesity, such as insulin resistance and reduced hepatic insulin extraction, are less severe than expected for the degree of fat accumulation 28 . In addition, PWS is associated with peripheral rather than central distribution of body fat 4 , less severe metabolic signatures in adipocytes 16 , and abnormalities in growth hormone secretion, ghrelin levels and adipokine patterns, when compared to common obesity 12, 14–16 .…”

Section: Discussionmentioning

confidence: 95%

Circulating angiopoietin-like 8 (ANGPTL8) is a marker of liver steatosis and is negatively regulated by Prader-Willi Syndrome

Mele

Grugni

Mai

et al. 2017

Sci Rep

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ANGPTL8 is a liver-derived protein related to insulin-sensitivity. Its relationship with obesity and liver function in Prader-Willi syndrome (PWS) is unknown. The present study investigated circulating ANGPTL8 in PWS and controls with common obesity, assessing its association to liver steatosis. For this purpose, 20 obese PWS and 20 controls matched for body mass index (BMI), sex and age underwent analysis of ANGPTL8 levels, glucose and lipid metabolism. Liver function tests and degree of liver steatosis by ultrasonography (US), fat-free mass (FFM) and fat mass (FM) by dual-energy x-ray absorptiometry (DEXA) were also assessed. In comparison to controls, obese PWS showed lower values of FFM (p < 0.0001) and higher FM (p = 0.01), while harbouring higher HDL cholesterol, lower triglycerides and OGTT-derived insulin levels, as well as a lower prevalence and severity of liver steatosis. With respect to obese controls, ANGPTL8 levels were significantly lower in PWS (p = 0.007) and overall correlated with transaminase levels and the severity of liver steatosis, as well as FFM (p < 0.05 for all). By a stepwise multivariable regression analysis, ANGPTL8 levels were independently predicted by PWS status (p = 0.01) and liver steatosis (p < 0.05). In conclusion, ANGPTL8 levels are lower in PWS than obese controls and are inversely associated with the severity of liver steatosis. Further studies should investigate the potential genetic basis for this observation.

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“…We analyzed patients case by case to understand why most patients did not have a GH stimulation test after completion of growth ( n = 79, 83.2%), although it is recommended by current guidelines ( 19 , 20 ). The main reason ( n = 35, 44.3%) was the presence of marked behavioral disorders.…”

Section: Resultsmentioning

confidence: 99%

Impact of transitional care on endocrine and anthropometric parameters in Prader–Willi syndrome

Paepegaey

Coupaye

Jaziri

et al. 2018

Endocrine Connections

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ContextThe transition of patients with Prader–Willi syndrome (PWS) to adult life for medical care is challenging because of multiple comorbidities, including hormone deficiencies, obesity and cognitive and behavioral disabilities.ObjectiveTo assess endocrine management, and metabolic and anthropometric parameters of PWS adults who received (n = 31) or not (n = 64) transitional care, defined as specialized pediatric care followed by a structured care pathway to a multidisciplinary adult team.Patients and study designHormonal and metabolic parameters were retrospectively recorded in 95 adults with PWS (mean ± s.d. age 24.7 ± 8.2 years, BMI: 39.8 ± 12.1 kg/m²) referred to our Reference Center and compared according to transition.ResultsAmong the entire cohort, 35.8% received growth hormone (GH) during childhood and 16.8% had a GH stimulation test after completion of growth. In adulthood, 14.7% were treated with GH, 56.8% received sex-hormone therapy, whereas 91.1% were hypogonadic and 37.9% had undergone valid screening of the corticotropic axis. The main reason for suboptimal endocrine management was marked behavioral disorders. Patients receiving transitional care were more likely to have had a GH stimulation test and hormonal substitutions in childhood. They also had a lower BMI, percentage of fat mass, improved metabolic parameters and fewer antidepressant treatments. Transitional care remained significantly associated with these parameters in multivariate analysis when adjusted on GH treatment.ConclusionA coordinated care pathway with specialized pediatric care and transition to a multidisciplinary adult team accustomed to managing complex disability including psychiatric troubles are associated with a better health status in adults with PWS.

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Diagnosis and treatment of GH deficiency in Prader–Willi syndrome

Cited by 48 publications

References 91 publications

Irisin levels in genetic and essential obesity: clues for a potential dual role

Irisin levels in genetic and essential obesity: clues for a potential dual role

Circulating angiopoietin-like 8 (ANGPTL8) is a marker of liver steatosis and is negatively regulated by Prader-Willi Syndrome

Impact of transitional care on endocrine and anthropometric parameters in Prader–Willi syndrome

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