Graziano Grugni
@auxologico.it
Division of Auxology
Istituto Auxologico Italiano
RESEARCH INTERESTS
Prader-Willi syndrome, Genetic Obesity, Obesity, GH deficiency
Scopus Publications
Scopus Publications
Claudio Maffeis, Francesca Olivieri, Giuliana Valerio, Elvira Verduci, Maria Rosaria Licenziati, Valeria Calcaterra, Gloria Pelizzo, Mariacarolina Salerno, Annamaria Staiano, Sergio Bernasconi,et al.
Springer Science and Business Media LLC
AbstractThis Position Statement updates the different components of the therapy of obesity (lifestyle intervention, drugs, and surgery) in children and adolescents, previously reported in the consensus position statement on pediatric obesity of the Italian Society of Pediatric Endocrinology and Diabetology and the Italian Society of Pediatrics. Lifestyle intervention is the first step of treatment. In children older than 12 years, pharmacotherapy is the second step, and bariatric surgery is the third one, in selected cases. Novelties are available in the field of the medical treatment of obesity. In particular, new drugs demonstrated their efficacy and safety and have been approved in adolescents. Moreover, several randomized control trials with other drugs are in process and it is likely that some of them will become available in the future. The increase of the portfolio of treatment options for obesity in children and adolescents is promising for a more effective treatment of this disorder.
Alice Marra, Adele Bondesan, Diana Caroli, Graziano Grugni, and Alessandro Sartorio
Springer Science and Business Media LLC
AbstractMetabolic syndrome (MetS) associated with obesity is a pathological condition increasing worldwide. Recent studies have demonstrated that the neutrophil to lymphocyte ratio (NLR) can be successfully used to stage MetS in obese adults. The aim of the study was to evaluate NLR values in 552 children/adolescents (M 219, F 333; 14.8 [12.9–16.3] years) and 231 adults (M 88, F 143; 52.3 [36.4–63.3] years) with morbid obesity, subdivided into subgroups according with the presence or absence of MetS. Adult patients with obesity showed a higher prevalence of MetS compared to the pediatric population (71% vs 26%), associated with a greater number of subjects with 3 and 4–5 altered components for MetS. NLR was higher (P-value = 0.041) in adults with MetS compared with those without. NLR values also positively correlated with the severity grade of the syndrome (P-value = 0.032). By contrast, in pediatric subjects with obesity with MetS, NLR values were comparable with those recorded in subjects without MetS (P-value = 0.861), no correlation being found with MetS severity (P-value = 0.441). Our study confirms the importance of NLR as an inflammatory indicator associated with MetS in adult subjects with severe obesity, while it excludes a similar role in children/adolescents.
Marco Salvatore, Paola Torreri, Graziano Grugni, Adele Rocchetti, Mohamad Maghnie, Giuseppa Patti, Antonino Crinò, Maurizio Elia, Donatella Greco, Corrado Romano,et al.
Springer Science and Business Media LLC
Abstract Background Prader–Willi syndrome (PWS) is a rare and complex genetic disease, with numerous implications on metabolic, endocrine, neuropsychomotor systems, and with behavioural and intellectual disorders. Rare disease patient registries are important scientific tools (1) to collect clinical and epidemiologic data, (2) to assess the clinical management including the diagnostic delay, (3) to improve patients’ care and (4) to foster research to identify new therapeutic solutions. The European Union has recommended the implementation and use of registries and databases. The main aims of this paper are to describe the process of setting up the Italian PWS register, and to illustrate our preliminary results. Materials and methods The Italian PWS registry was established in 2019 with the aims (1) to describe the natural history of the disease, (2) to determine clinical effectiveness of health care services, (3) to measure and monitor quality of care of patients. Information from six different variables are included and collected into this registry: demographics, diagnosis and genetics, patient status, therapy, quality of life and mortality. Results A total of 165 patients (50.3% female vs 49.7% male) were included into Italian PWS registry in 2019–2020 period. Average age at genetic diagnosis was 4.6 years; 45.4% of patients was less than 17 years old aged, while the 54.6% was in adult age (> 18 years old). Sixty-one percent of subjects had interstitial deletion of the proximal long arm of paternal chromosome 15, while 36.4% had uniparental maternal disomy for chromosome 15. Three patients presented an imprinting centre defect and one had a de novo translocation involving chromosome 15. A positive methylation test was demonstrated in the remaining 11 individuals but the underlying genetic defect was not identified. Compulsive food-seeking and hyperphagia was present in 63.6% of patients (prevalently in adults); 54.5% of patients developed morbid obesity. Altered glucose metabolism was present in 33.3% of patients. Central hypothyroidism was reported in 20% of patients; 94.7% of children and adolescents and 13.3% of adult patients is undergoing GH treatment. Conclusions The analyses of these six variables allowed to highlight important clinical aspects and natural history of PWS useful to inform future actions to be taken by national health care services and health professionals.
Karlijn Pellikaan, Naomi Q C Nguyen, Anna G W Rosenberg, Muriel Coupaye, Anthony P Goldstone, Charlotte Høybye, Tania Markovic, Graziano Grugni, Antonino Crinò, Assumpta Caixàs,et al.
The Endocrine Society
Abstract Context Prader-Willi syndrome (PWS) is a complex disorder combining hypothalamic dysfunction, neurodevelopmental delay, hypotonia, and hyperphagia with risk of obesity and its complications. PWS is caused by the loss of expression of the PWS critical region, a cluster of paternally expressed genes on chromosome 15q11.2-q13. As life expectancy of patients with PWS increases, age-related diseases like malignancies might pose a new threat to health. Objective To investigate the prevalence and risk factors of malignancies in patients with PWS and to provide clinical recommendations for cancer screening. Methods We included 706 patients with PWS (160 children, 546 adults). We retrospectively collected data from medical records on past or current malignancies, the type of malignancy, and risk factors for malignancy. Additionally, we searched the literature for information about the relationship between genes on chromosome 15q11.2-q13 and malignancies. Results Seven adults (age range, 18-55 years) had been diagnosed with a malignancy (acute lymphoblastic leukemia, intracranial hemangiopericytoma, melanoma, stomach adenocarcinoma, biliary cancer, parotid adenocarcinoma, and colon cancer). All patients with a malignancy had a paternal 15q11-13 deletion. The literature review showed that several genes on chromosome 15q11.2-q13 are related to malignancies. Conclusion Malignancies are rare in patients with PWS. Therefore, screening for malignancies is only indicated when clinically relevant symptoms are present, such as unexplained weight loss, loss of appetite, symptoms suggestive of paraneoplastic syndrome, or localizing symptoms. Given the increased cancer risk associated with obesity, which is common in PWS, participation in national screening programs should be encouraged.
M. Faienza, G. Brunetti, D. Fintini, G. Grugni, M. Wasniewska, A. Crinò, G. D’amato, L. Piacente, A. Oranger, M. Dicarlo,et al.
F. M. Panfili, A. Convertino, G. Grugni, L. Mazzitelli, S. Bocchini, A. Crinò, G. Campana, M. Cappa, M. Delvecchio, M. F. Faienza,et al.
Springer Science and Business Media LLC
Maurizio Delvecchio, Graziano Grugni, and Jennifer Wootton Hill
Frontiers Media SA
Devis Pascut, Pablo J. Giraudi, Cristina Banfi, Stefania Ghilardi, Claudio Tiribelli, Adele Bondesan, Diana Caroli, Alessandro Minocci, Graziano Grugni, and Alessandro Sartorio
Frontiers Media SA
IntroductionPrader-Willi syndrome (PWS) is a rare genetic disorder characterized by loss of expression of paternal chromosome 15q11.2-q13 genes. Individuals with PWS exhibit unique physical, endocrine, and metabolic traits associated with severe obesity. Identifying liver steatosis in PWS is challenging, despite its lower prevalence compared to non-syndromic obesity. Reliable biomarkers are crucial for the early detection and management of this condition associated with the complex metabolic profile and cardiovascular risks in PWS.MethodsCirculating proteome profiling was conducted in 29 individuals with PWS (15 with steatosis, 14 without) using the Olink Target 96 metabolism and cardiometabolic panels. Correlation analysis was performed to identify the association between protein biomarkes and clinical variables, while the gene enrichment analysis was conducted to identify pathways linked to deregulated proteins. Receiver operating characteristic (ROC) curves assessed the discriminatory power of circulating protein while a logistic regression model evaluated the potential of a combination of protein biomarkers.ResultsCDH2, CTSO, QDPR, CANT1, ALDH1A1, TYMP, ADGRE, KYAT1, MCFD, SEMA3F, THOP1, TXND5, SSC4D, FBP1, and CES1 exhibited a significant differential expression in liver steatosis, with a progressive increase from grade 1 to grade 3. FBP1, CES1, and QDPR showed predominant liver expression. The logistic regression model, -34.19 + 0.85 * QDPR*QDPR + 0.75 * CANT1*TYMP - 0.46 * THOP1*ALDH1A, achieved an AUC of 0.93 (95% CI: 0.63-0.99), with a sensitivity of 93% and specificity of 80% for detecting steatosis in individuals with PWS. These biomarkers showed strong correlations among themselves and were involved in an interconnected network of 62 nodes, related to seven metabolic pathways. They were also significantly associated with cholesterol, LDL, triglycerides, transaminases, HbA1c, FLI, APRI, and HOMA, and showed a negative correlation with HDL levels.ConclusionThe biomarkers identified in this study offer the potential for improved patient stratification and personalized therapeutic protocols.
Denise H. van Abswoude, Karlijn Pellikaan, Naomi Nguyen, Anna G. W. Rosenberg, Kirsten Davidse, Franciska M. E. Hoekstra, Ilse M. Rood, Christine Poitou, Graziano Grugni, Charlotte Høybye,et al.
Frontiers Media SA
BackgroundPrader-Willi syndrome (PWS) is a rare, complex, genetic disorder characterized by hyperphagia, hypotonia, delayed psychomotor development, low muscle mass and hypothalamic dysfunction. Adults with PWS often have obesity, hypertension and type 2 diabetes mellitus (DM2), known risk factors for cardiovascular disease (CVD) and chronic kidney disease (CKD). Early symptoms of CVD and CKD may be masked by intellectual disability and inability to express physical complaints. Furthermore, kidney diseases are often asymptomatic. Therefore, renal and cardiovascular disease might be missed in patients with PWS. Microalbuminuria is an early sign of microvascular damage in the kidneys and other vascular beds. Therefore, we screened our adult PWS cohort for the presence of elevated urinary albumin and (micro)albuminuria.MethodsWe retrospectively collected anthropometric measurements, blood pressure, medical history, medication use, urine dipstick and biochemical measurements form electronic patient files. In addition, we performed a systematic literature review on kidney disease in PWS.ResultsWe included 162 adults with genetically confirmed PWS (56% male, median age 28 years), of whom 44 (27%) had DM2. None had known CVD. All subjects had normal estimated glomerular filtration rate (eGFR) according to non-PWS reference intervals. Elevated urinary albumin or (micro)albuminuria was present in 28 (18%); 19 out of 75 (25%) had an increased urinary albumin-to-creatinine ratio (UACR) and 10 out of 57 (18%) had an increased urinary protein-to-creatinine ratio. Elevated urinary albumin was present at a young age (median age 26 (IQR 24-32) years) and was associated with an significantly higher BMI and LDL-cholesterol levels and higher prevalence of DM2, hypertension and dyslipidemia than those with normal UACR (p=0.027, p=0.019, p<0.001, p<0.001, p=0.011 and respectively).ConclusionUpon screening, one in every five adults with PWS had increased urinary albumin or (micro)albuminuria, early signs of microvascular disease. All had normal eGFR, according to non-PWS reference intervals, and none had a formal diagnosis of CVD. As muscle mass is low in PWS, creatinine levels and eGFR may be spuriously normal. Urinalysis in this patient group can be used as a screening tool for microvascular (kidney) disease. We propose an algorithm for the detection and management of microvascular disease in adults with PWS.
Munkh-Erdene Bayartai, Hannu Luomajoki, Gabriella Tringali, Roberta De Micheli, Graziano Grugni, and Alessandro Sartorio
Frontiers Media SA
IntroductionSpinal kinematics/motion are reported to be altered in adolescents and adults with essential obesity, while no information is available in patients with Prader-Willi syndrome so far. The aim of this study was to examine cross-sectionally the characteristics of spinal postures and mobility in 34 patients with PWS, in 35 age- and sex-matched adults with essential obesity, and in 37 normal-weight individuals.MethodsSpinal posture and mobility were assessed using a radiation-free back scan, the Idiag M360 (Idiag, Fehraltorf, Switzerland). Differences in spinal posture and mobility between the three groups were determined using a two-way analysis of variance.ResultsAdults with Prader-Willi syndrome had greater thoracic kyphosis [difference between groups (Δ) = 9.60, 95% CI 3.30 to 15.60, p = 0.001], less lumbar lordosis (Δ = -6.50, 95% CI -12.70 to -0.30, p = 0.03) as well as smaller lumbar and hip mobility than those with normal weight.DiscussionAlthough the characteristics of the spine in patients with Prader-Will syndrome appear to be similar to that found in subjects with essential obesity, Prader-Willi syndrome was found to influence lumbar movements more than thoracic mobility. These results provide relevant information about the characteristics of the spine in adults with Prader-Willi syndrome to be taken into careful consideration in the management of spinal conditions. These findings also highlight the importance of considering the musculoskeletal assessment of spinal postures and approaches targeting spinal and hip flexibility in adults with Prader-Willi syndrome.
Graziano Grugni, Alessandro Sartorio, Davide Soranna, Antonella Zambon, Lucia Grugni, Giuseppe Zampino, and Antonino Crinò
Frontiers Media SA
IntroductionPrader-Willi syndrome (PWS) is a complex disorder resulting from the failure of expression of paternal alleles in the PWS region of chromosome 15. The PWS phenotype resembles that observed in the classic non-PWS GH deficiency (GHD), including short stature, excessive fat mass, and reduced muscle mass. To date, a small number of studies on the long-term effects of GH treatment are available in adult subjects with PWS.MethodsIn this longitudinal study, 12 obese subjects with PWS (GHD/non-GHD 6/6) were treated for a median of 17 years, with a median GH dose of 0.35 mg/day. The median age was 27.1 years. Anthropometric, body composition, hormonal, biochemical, and blood pressure variables were analyzed in all subjects.ResultsWaist circumference was significantly lower at the end of the treatment period (p-value=0.0449), while body mass index (BMI) did not differ significantly. Compared to the baseline, a highly significant reduction of Fat Mass % (FM%) was observed (p-value=0.0005). IGF-I SDS values significantly increased during GH therapy (p-value=0.0005). A slight impairment of glucose homeostasis was observed after GH therapy, with an increase in the median fasting glucose levels, while insulin, HOMA-IR, and HbA1c values remained unchanged. Considering GH secretory status, both subjects with and without GHD showed a significant increase in IGF-I SDS and a reduction of FM% after GH therapy (p-value= 0.0313 for all).DiscussionOur results indicate that long-term GH treatment has beneficial effects on body composition and body fat distribution in adults with PWS associated with obesity. However, the increase in glucose values during GH therapy should be considered, and continuous surveillance of glucose metabolism is mandatory during long-term GH therapy, especially in subjects with obesity.
Denise H van Abswoude, Karlijn Pellikaan, Anna G W Rosenberg, Kirsten Davidse, Muriel Coupaye, Charlotte Høybye, Tania P Markovic, Graziano Grugni, Antonino Crinò, Assumpta Caixàs,et al.
The Endocrine Society
Abstract Context Prader–Willi syndrome (PWS) is a rare complex genetic syndrome, characterized by delayed psychomotor development, hypotonia, and hyperphagia. Hormone deficiencies such as hypogonadism, hypothyroidism, and growth hormone deficiency are common. The combination of hypotonia, low physical activity, and hypogonadism might lead to a decrease in bone mass and increase in fracture risk. Moreover, one would expect an increased risk of scoliosis due to hypotonia and low physical activity. Objective To study the prevalence and risk factors for skeletal problems (reduced bone mineral density, fractures, and scoliosis) in adults with PWS. Methods We retrospectively collected patient characteristics, medical history, medication, biochemical measurements, dual-energy X-ray absorptiometry scans, and spinal X-rays and reviewed the current literature. Results We included 354 adults with PWS (median age 31 years; 43% males), of whom 51 (14%) had osteoporosis (T-score below −2.5) and 143 (54%) had osteopenia (T-score −1 to −2.5). The most prevalent modifiable risk factors for osteoporosis were hypogonadism, insufficient dairy intake, sedentary lifestyle, and corticosteroid use. Male sex was associated with osteoporosis (P = .005). Growth hormone treatment was not associated with osteoporosis. A history of vertebral fractures was present in 10 (3%) and nonvertebral fractures in 59 (17%). Scoliosis was present in 263 (80%), but no modifiable risk factors were identified. Conclusion Besides scoliosis, osteoporosis is common in adults with PWS. Based on the literature and the risk factors for osteoporosis found in our cohort, we provide practical clinical recommendations to avoid skeletal complications in these vulnerable patients.
Stefano Lazzer, Filippo Vaccari, Mattia D’Alleva, Giorgio Bedogni, Diana Caroli, Graziano Grugni, and Alessandro Sartorio
Springer Science and Business Media LLC
Stefano Lazzer, Filippo Vaccari, Mattia D’Alleva, Giorgio Bedogni, Diana Caroli, Graziano Grugni, and Alessandro Sartorio
Springer Science and Business Media LLC
AbstractPrader–Willi syndrome (PWS), a multisystemic disorder caused by lack of expression of genes on the paternally inherited chromosome 15q11.2-q13 region, is characterized by hyperphagia and childhood-onset morbid obesity, A retrospective cohort study of 60 PWS patients, 38 females and 22 males, undergoing a 6-year rehabilitation program was analysed. Mean age at the time of first admission was 27 ± 7 years, body weight (BW) was 97 kg ± 29 kg and height was 1.53 ± 0.09 m. Twenty-four patients (40%) showed BW loss after 6 years of follow-up, seventeen (28%) remained stable and nineteen (32%) gained BW. Responsiveness in term of BW reduction was less frequent in patients with the UPD karyotype, karyotype del15 being more frequent among responsive patients. Furthermore, responsive PWS subjects had a higher BMI (47 vs. 36 kg/m2), waist (123 vs. 106 cm) and hip (136 vs. 118 cm) circumferences than non-responsive at the time of first hospitalization. Baseline body composition and metabolic parameters did not differentiate between responsive and non-responsive patients. Given the rarity of PWS and relative lack of studies, these results can be considered relevant because based on a relatively large number of PWS patients followed up for a long term period.
Claudia Dolci, Antonello E. Rigamonti, Annalisa Cappella, Daniele M. Gibelli, Graziano Grugni, Diana Caroli, Chiarella Sforza, and Alessandro Sartorio
MDPI AG
Background: Prader-Willi syndrome (PWS) is a rare genomic imprinting disorder associated to a complex neurodevelopmental phenotype and a distinctive facial appearance. The study investigated the relationships between the quantitative facial dysmorphism in PWS and clinical and biochemical markers of the disease and its treatment. Methods: Facial images of 15 Caucasian adult individuals with PWS (8 males, 42 ± 5 years; 7 females, 37 ± 8 years; BMI 38.87 ± 8.92 kg/m2) were acquired through stereophotogrammetry. From the 3D coordinates of 38 landmarks, linear distances and angles were calculated; they were expressed as z-score values by referring to 403 healthy subjects matched for age and sex and compared by Student’s t-test with Bonferroni correction for multiple testing. Patients underwent auxological and biochemical assessment of endocrine/metabolic dysfunction and nocturnal respiratory function. An exploratory correlation analysis was performed to investigate their associations with the facial phenotype; uncorrected p-values were used. Results and Conclusions: Individuals with PWS showed decreased bifrontal diameter, facial depths, palpebral fissures, mandibular ramus length, lower vermillion height, and modified relative position of exocanthia and nasion. Since these characteristics did not show any associations with clinical and biochemical markers of PWS, they could constitute robust distinctive facial features and contribute to the diagnosis of the disorder. Individuals with PWS showed also a larger mandibular width with smaller gonial angles, thinner upper vermillion, greater inclination of the orbit relative to the Frankfurt plane, and a smaller angle of the auricles versus the facial midplane. Relationships between these facial anthropometric features and body composition, glucidic metabolism indexes, nocturnal hypoxemia episodes, or duration of GH treatment were found, suggesting their potentially useful role in the clinical monitoring and management of the disease. However, they need to be confirmed by subsequent dedicated studies.
G. Radetti, G. Grugni, F. Lupi, A. Fanolla, D. Caroli, Adele Bondesan and A. Sartorio
Few data are currently available on the reliability of the different anthropometric, instrumental and biochemical indexes in recognizing the presence of metabolic syndrome (MetS) in children and adolescents with severe obesity. Therefore, the objective of our study was to find out the simplest and most accurate predictive index of MetS in this population at-risk. In 1065 children and adolescents (563 f, 502 m), aged 14.6 ± 2.1 years (range 10–17), with severe obesity [BMI-SDS 3.50 ± 0.36 (range 3.00–5.17)], the following indexes were evaluated: BMI, BMI-SDS, Tri-Ponderal Mass Index, Waist-to-Height ratio, TG/HDL-Cholesterol ratio, Cardiometabolic Index (CMI), and Visceral Adiposity Index (VAI). For each subject, all the components of MetS, defined according to the IDF criteria, were determined. Overall, the presence of MetS was found in 324 patients (30.4%), 167 males (33.3%) and 157 females (27.9%). According to the ROC analysis, three indexes (VAI, CMI and TG/HDL-Cholesterol ratio), performed significantly better than the other ones in identifying MetS, with no difference among them. In conclusion, the TG/HDL ratio, which just needs the evaluation of two simple biochemical parameters, offers the same accuracy as other more sophisticated indexes in recognizing MetS in children and adolescents with severe obesity, thus making it the best predictor to be easily used.
Stefania Mai, Danilo Fintini, Chiara Mele, Alessio Convertino, Sarah Bocchini, Graziano Grugni, Gianluca Aimaretti, Roberta Vietti, Massimo Scacchi, Antonino Crinò,et al.
Frontiers Media SA
Irisin is a myokine involved in the browning of white adipose tissue and regulation of energy expenditure, glucose homeostasis and insulin sensitivity. Debated evidence exists on the metabolic role played by irisin in children with overweight or obesity, while few information exist in children with Prader Willi Syndrome (PWS), a condition genetically prone to obesity. Here we assessed serum irisin in relation to the metabolic profile and body composition in children and adolescents with and without PWS. In 25 PWS subjects [age 6.6-17.8y; body mass index standard deviation score (BMI SDS) 2.5 ± 0.3] and 25 age, and BMI-matched controls (age 6.8-18.0y; BMI SDS, 2.8 ± 0.1) we assessed irisin levels and metabolic profile inclusive of oral glucose tolerance test (OGTT), and body composition by dual-energy X-ray absorptiometry (DXA). In PWS, we recorded lower levels of fat-free mass (FFM) (p <0.05), fasting (p<0.0001) and 2h post-OGTT insulin (p<0.05) and lower insulin resistance as expressed by homeostatic model of insulin resistance (HOMA-IR) (p<0.0001). Irisin levels were significantly lower in PWS group than in controls with common obesity (p<0.05). In univariate correlation analysis, positive associations linked irisin to insulin OGTT0 (p<0.05), insulin OGTT120 (p<0.005), HOMA-IR (p<0.05) and fasting C-peptide (p<0.05). In stepwise multivariable regression analysis, irisin levels were independently predicted by insulin OGTT120. These results suggest a link between irisin levels and insulin sensitivity in two divergent models of obesity.
Antonino Crinò, Michela Armando, Marco Crostelli, Osvaldo Mazza, Dario Bruzzese, Alessio Convertino, Danilo Fintini, Sarah Bocchini, Sara Ciccone, Alessandro Sartorio,et al.
MDPI AG
The characteristics of scoliosis were investigated in a large cohort of children and adults with Prader–Willi syndrome (PWS), analysing the role of age, gender, puberty, body mass index (BMI), genotype and growth hormone therapy (GHT) on its onset and severity. A retrospective cross-sectional study was performed in 180 patients with genetically confirmed PWS (96 females), aged 17.6 ± 12 years. Eighty-five subjects (47%) were obese. One hundred and fifty subjects (83.3%) were on GHT, while 30 patients had never been treated. Overall, 150 subjects (83.3%) were affected by scoliosis, 80.2% of children and adolescents and 87.8% of adults. A mild degree of scoliosis was observed in 58 patients (38.7%), moderate in 43 (28.7%) and severe in 49 (32.6%). Median age at diagnosis of scoliosis was 6.3 years, while the severe forms were diagnosed earlier (median age: 3.8 years). The cumulative probability at 5 years of age was equal to 0.403 and almost doubled at 15 years. No significant associations were found between scoliosis and genotype, gender, pubertal stage, GHT and BMI. A corset was prescribed to 75 subjects (50%) at a median age of 7.5 years, while 26 subjects (17.3%) underwent surgery at a median age of 13.1 years. Our data indicate that scoliosis is one of the major concerns for PWS patients that increases with age, and therefore suggest the need for regular systematic monitoring of spinal deformity from paediatric age.
Maria Rosaria Licenziati, Dario Bacchini, Antonino Crinò, Graziano Grugni, Danilo Fintini, Sara Osimani, Letizia Ragusa, Michele Sacco, Lorenzo Iughetti, Luisa De Sanctis,et al.
Frontiers Media SA
Background/ObjectivesThe present study aimed to validate the Italian version of the Hyperphagia Questionnaire (HQ), a 11-items questionnaire developed to assess hyperphagia in individuals with Prader-Willi syndrome (PWS). This is a complex neurodevelopmental disorder characterized by endocrine dysfunction, hypotonia, intellectual disability, psychiatric disorders and obesity.MethodsParents of 219 individuals with PWS (age range 3–54 years; Mage = 17.90; 108 Males), recruited in 12 hospitals in Italy responded to HQ during routine visits. In function of the level of analyses the sample was divided into two subgroups (<18> years) or into four age-subgroups (2.5–4.5; 4.5–8; 8–18; >18 years) corresponding to different clinical stages.ResultsConfirmatory factor analysis (CFA) confirmed the three hyperphagic subdimensions of the original structure (behavior, drive, and severity), but one item was dropped out, reducing the final version to 10 items. Using multi-group CFA, HQ showed satisfactory indexes of measurement invariance by age. Good indexes of internal consistency (Cronbach's alpha and McDonald's Omega coefficients) were found for each subdimension. The three hyperphagia subdimensions positively converged with other food-related measures: emotional overeating, food enjoyment, food responsiveness, and satiety responsiveness. A significant increase of all hyperphagic subdimensions was found across age groups. Higher hyperphagic levels were found in participants with higher body mass index. Hyperphagic drive differently increased in function of the interaction between age and underlying genetic mechanisms.ConclusionThe Italian version of the HQ is a psychometrically valid and reliable instrument for assessing hyperphagia in individuals with PWS. This tool may prove useful to evaluate the efficacy of pharmacologic and rehabilitative treatments.
Karlijn Pellikaan, Yassine Ben Brahim, Anna G. W. Rosenberg, Kirsten Davidse, Christine Poitou, Muriel Coupaye, Anthony P. Goldstone, Charlotte Høybye, Tania P. Markovic, Graziano Grugni,et al.
MDPI AG
Prader-Willi syndrome (PWS) is a rare neuroendocrine genetic syndrome. Characteristics of PWS include hyperphagia, hypotonia, and intellectual disability. Pituitary hormone deficiencies, caused by hypothalamic dysfunction, are common and hypogonadism is the most prevalent. Untreated hypogonadism can cause osteoporosis, which is already an important issue in PWS. Therefore, timely detection and treatment of hypogonadism is crucial. To increase understanding and prevent undertreatment, we (1) performed a cohort study in the Dutch PWS population, (2) thoroughly reviewed the literature on female hypogonadism in PWS and (3) provide clinical recommendations on behalf of an international expert panel. For the cohort study, we retrospectively collected results of a systematic health screening in 64 female adults with PWS, which included a medical questionnaire, medical file search, medical interview, physical examination and biochemical measurements. Our data show that hypogonadism is frequent in females with PWS (94%), but is often undiagnosed and untreated. This could be related to unfamiliarity with the syndrome, fear of behavioral changes, hygienic concerns, or drug interactions. To prevent underdiagnosis and undertreatment, we provide practical recommendations for the screening and treatment of hypogonadism in females with PWS.
Graziano Grugni, Antonio Fanolla, Fiorenzo Lupi, Silvia Longhi, Antonella Saezza, Alessandro Sartorio, and Giorgio Radetti
MDPI AG
To verify the accuracy of different indices of glucose homeostasis in recognizing the metabolic syndrome in a group of adult patients with Prader–Willi syndrome (PWS), 102 PWS patients (53 females/49 males), age ±SD 26.9 ± 7.6 yrs, Body Mass Index (BMI) 35.7 ± 10.7, were studied. The following indices were assessed in each subject during an oral glucose tolerance test (OGTT): 1 h (>155 mg/dL) and 2 h (140–199 mg/dL) glucose levels, the oral disposition index (ODI), the insulinogenic index (IGI), the insulin resistance (HOMA-IR) were evaluated at baseline, 1 h and 2 h. Although minor differences among indices were found, according to the ROC analysis, no index performed better in recognizing MetS. Furthermore, the diagnostic threshold levels changed over the years and therefore the age-related thresholds were calculated. The easily calculated HOMA-IR at baseline may be used to accurately diagnose MetS, thus avoiding more complicated procedures.
Karlijn Pellikaan, Yassine Ben Brahim, Anna G. W. Rosenberg, Kirsten Davidse, Christine Poitou, Muriel Coupaye, Anthony P. Goldstone, Charlotte Høybye, Tania P. Markovic, Graziano Grugni,et al.
MDPI AG
Prader-Willi syndrome (PWS) is a complex genetic syndrome characterized by hyperphagia, intellectual disability, hypotonia and hypothalamic dysfunction. Adults with PWS often have hormone deficiencies, hypogonadism being the most common. Untreated male hypogonadism can aggravate PWS-related health issues including muscle weakness, obesity, osteoporosis, and fatigue. Therefore, timely diagnosis and treatment of male hypogonadism is important. In this article, we share our experience with hypogonadism and its treatment in adult males with PWS and present a review of the literature. In order to report the prevalence and type of hypogonadism, treatment regimen and behavioral issues, we retrospectively collected data on medical interviews, physical examinations, biochemical measurements and testosterone replacement therapy (TRT) in 57 Dutch men with PWS. Fifty-six (98%) of the patients had either primary, central or combined hypogonadism. Untreated hypogonadism was associated with higher body mass index and lower hemoglobin concentrations. TRT was complicated by behavioral challenges in one third of the patients. Undertreatment was common and normal serum testosterone levels were achieved in only 30% of the patients. Based on the Dutch cohort data, review of the literature and an international expert panel discussion, we provide a practical algorithm for TRT in adult males with PWS in order to prevent undertreatment and related adverse health outcomes.
Antonello E. Rigamonti, Diana Caroli, Graziano Grugni, Silvano G. Cella, and Alessandro Sartorio
MDPI AG
Regular medical supervision represents a fundamental component of the clinical management of obesity. In fact, when frequently supplied it reduces the risk of failure associated with any body weight reduction program (BWRP), resulting in body weight gain. The aim of the present study was to establish the potential beneficial effects of increasing medical supervision on weight loss and other auxometric and cardiometabolic parameters in a population of children and adolescents with obesity (n = 158; F/M = 94/64; age range 9.7–17.3 years; body mass index, BMI = 37.8 ± 6.9 kg/m2), followed up for one year in a real-world setting, after and before a 3-week in-hospital BWRP. Weight loss was significantly associated with medical supervision and changes in several auxometric and cardiometabolic parameters such as fat mass, fat-free mass, waist and hip circumferences, total and LDL cholesterols, triglycerides, glucose, insulin, HOMA-IR, systolic blood pressure and IDF criteria for the diagnosis of metabolic syndrome. As expected, weight loss and, congruently, medical supervision, were significantly higher in responsive and stable subjects than in those belonging to the non-responsive group and in responsive subjects than those belonging to the stable group. While weight loss was significantly higher in subjects having class 2 and 3 obesity than those belonging to class 1 obesity group, medical supervision was significantly higher in subjects having class 3 than those having class 1 obesity. Weight loss was significantly higher in subjects suffering from metabolic syndrome than those without; nevertheless, no significant difference was found in medical supervision between these groups. Finally, sex was associated with no differences in weight loss and medical supervision. In conclusion, based on the results of a real-world experience, frequent medical supervision increases the weight loss associated with a longitudinal multidisciplinary BWRP, with a parallel improvement of a set of auxometric and cardiometabolic parameters. Prospectively, incentivising regular medical supervision should reduce the risk of BWRP failure and body weight gain, thus contributing to counteract the detrimental transition from simple obesity to metabolic syndrome in pediatric patients.
M. F. Faienza, G. Brunetti, G. Grugni, D. Fintini, A. Convertino, P. Pignataro, A. Crinò, S. Colucci, and M. Grano
Springer Science and Business Media LLC
Abstract Background Prader–Willi syndrome (PWS) is associated to distinctive clinical symptoms, including obesity, cognitive and behavioral disorders, and bone impairment. Irisin is a myokine that acts on several target organs including brain adipose tissue and bone. The present study was finalized to explore circulating levels of irisin in children and adult PWS patients. Methods Seventy-eight subjects with PWS, 26 children (15 females, mean age 9.48 ± 3.6 years) and 52 adults (30 females, mean age 30.6 ± 10.7) were enrolled. Irisin serum levels were measured in patients and controls. Its levels were related with anthropometric and metabolic parameters, cognitive performance and bone mineral density either in pediatric or adult PWS. Multiple regression analysis was also performed. Results Irisin serum levels in PWS patients did not show different compared with controls. A more in-depth analysis showed that both pediatric and adult PWS with DEL15 displayed significantly reduced irisin levels compared to controls. Otherwise, no differences in irisin concentration were found in UPD15 patients with respect to controls. Our study revealed that in pediatric PWS the 25(OH) vitamin-D levels affected irisin serum concentration. Indeed, patients who were not supplemented with vitamin D showed lower irisin levels than controls and patients performing the supplementation. Multiple regression analysis showed that irisin levels in pediatric and adult PWS were predicted by the genetic background and 25(OH)-vitamin D levels, whereas in a group of 29 adult PWS also by intelligent quotient. Conclusion We demonstrated the possible role of genetic background and vitamin-D supplementation on irisin serum levels in PWS patients.