Context Prader-Willi syndrome (PWS) is a complex hypothalamic disorder, combining hyperphagia, hypotonia, intellectual disability and pituitary hormone deficiencies. Annual mortality of patients with PWS is high (3%). In half of the patients, the cause of death is obesity related and / or of cardiopulmonary origin. Health problems leading to this increased mortality often remain undetected due to the complexity and rareness of the syndrome Objective To assess the prevalence of health problems in adults with PWS retrospectively Patients, Design and Setting We systematically screened 115 PWS adults for undiagnosed health problems. All patients visited the multidisciplinary outpatient clinic for rare endocrine syndromes at the Erasmus University Medical Center, Rotterdam, the Netherlands. We collected results of medical questionnaires, interviews, physical examinations, biochemical measurements, poly(somno-)graphy and radiology Main outcome measures Presence or absence of endocrine and non-endocrine comorbidities in relation to living situation, body mass index, genotype and demographic factors Results Seventy patients (61%) had undiagnosed health problems, while one in every four patients had multiple undiagnosed health problems simultaneously. All males and 93% of females had hypogonadism, 74% scoliosis, 18% hypertension, 19% hypercholesterolemia, 17% type 2 diabetes mellitus and 17% hypothyroidism. Unfavourable lifestyle was common: 22% exercised too little (according to PWS criteria) and 37% did not see a dietitian Conclusions Systematic screening revealed many undiagnosed health problems in PWS-adults. Based on patient characteristics, we provide an algorithm for diagnostics and treatment, with the aim to prevent early complications and reduce mortality in this vulnerable patient group

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Context Prader–Willi syndrome (PWS) is associated with several hypothalamic-pituitary hormone deficiencies. There is no agreement on the prevalence of central adrenal insufficiency (CAI) in adults with PWS. In some countries, it is general practice to prescribe stress-dose hydrocortisone during physical or psychological stress in patients with PWS. Side effects of frequent hydrocortisone use are weight gain, osteoporosis, diabetes mellitus, and hypertension—already major problems in adults with PWS. However, undertreatment of CAI can cause significant morbidity—or even mortality. Objective To prevent both over- and undertreatment with hydrocortisone, we assessed the prevalence of CAI in a large international cohort of adults with PWS. As the synacthen test shows variable results in PWS, we only use the metyrapone test (MTP) and insulin tolerance test (ITT). Design Metyrapone test or ITT in adults with PWS (N = 82) and review of medical files for symptoms of hypocortisolism related to surgery (N = 645). Setting Outpatient clinic. Patients or Other Participants Eighty-two adults with genetically confirmed PWS. Main Outcome Measure For MTP, 11-deoxycortisol > 230 nmol/L was considered sufficient. For ITT, cortisol > 500 nmol/L (Dutch, French, and Swedish patients) or > 450 nmol/L (British patients) was considered sufficient. Results Central adrenal insufficiency was excluded in 81 of 82 patients. Among the 645 patients whose medical files were reviewed, 200 had undergone surgery without perioperative hydrocortisone treatment. None of them had displayed any features of hypocortisolism. Conclusions Central adrenal insufficiency is rare (1.2%) in adults with PWS. Based on these results, we recommend against routinely prescribing hydrocortisone stress-doses in adults with PWS.

Context Features of Prader-Willi syndrome (PWS) overlap with features of growth hormone (GH) deficiency, like small hands and feet, short stature, increased body fat and low muscle mass and strength. In children with PWS, GH treatment (GHt) improves physical health and cognition. GHt has become standard of care in PWS children, but in adults this is not yet the case. Objective To provide an overview of the current knowledge on GHt in PWS adults. Data source Medline, Embase and Cochrane Central Register of Controlled Trials databases. Study selection Randomized controlled trials (RCTs) and non-randomized (un)controlled trials (NRCTs) that reported data for adults with PWS, who received GHt for at least six months. Data extraction Data on body composition, body mass index (BMI), cardiovascular endpoints, bone, cognitive function, quality of life and safety were extracted. Data synthesis Nine RCTs and 20 NRCTs were included. Body composition improved during 12 months of GHt with an increase in mean (95% CI) lean body mass of 1.95 kg (0.04 – 3.87 kg), and a reduction of mean (95% CI) fat mass of -2.23% (-4.10% to -0.36%). BMI, low-density lipoprotein cholesterol levels, fasting glucose levels and bone mineral density did not change during GHt. There were no major safety issues. Conclusion GHt appears to be safe and improves body composition in adults with PWS. As poor body composition is closely linked to the observed high incidence of cardiovascular morbidity in adults with PWS, improving body composition might reduce cardiovascular complications in this vulnerable patient group.