Prader-Willi syndrome (PWS) is a complex genetic disorder with implications on the endocrine and neurologic systems, metabolism, and behavior. Early in life, PWS is characterized by hypotonia and failure to thrive, followed by obesity and hyperphagia. Patients with PWS develop hypothalamic dysfunction which may lead growth hormone deficiency (GHD), hypogonadism, hypothyroidism, adrenal insufficiency, and poor bone mineral density (BMD). In addition to hypothalamic dysfunction, individuals with PWS have increased risk for obesity which may be complicated by metabolic syndrome and type 2 diabetes mellitus (T2DM). In this paper, we will review the current literature pertaining to the endocrine concerns of PWS and current recommendations for screening and management of these conditions.

Context: Prader-Willi syndrome (PWS) is a rare genetic disorder characterized by endocrine and neuropsychiatric problems including hyperphagia, anxiousness, and distress. Intranasal carbetocin, an oxytocin analog, was investigated as a selective oxytocin replacement therapy. Objective: To evaluate safety and efficacy of intranasal carbetocin in PWS. Design: Randomized, double-blind, placebo-controlled phase 3 trial with long-term follow-up. Setting: Twenty-four ambulatory clinics at academic medical centers. Participants: A total of 130 participants with PWS aged 7 to 18 years. Interventions: Participants were randomized to 9.6 mg/dose carbetocin, 3.2 mg/dose carbetocin, or placebo 3 times daily during an 8-week placebo-controlled period (PCP). During a subsequent 56-week long-term follow-up period, placebo participants were randomly assigned to 9.6 mg or 3.2 mg carbetocin, with carbetocin participants continuing at their previous dose. Main outcome measures: Primary endpoints assessed change in hyperphagia (Hyperphagia Questionnaire for Clinical Trials [HQ-CT]) and obsessive-compulsive symptoms (Children's Yale-Brown Obsessive-Compulsive Scale [CY-BOCS]) during the PCP for 9.6 mg vs placebo, and the first secondary endpoints assessed these same outcomes for 3.2 mg vs placebo. Additional secondary endpoints included assessments of anxiousness and distress behaviors (PWS Anxiousness and Distress Behaviors Questionnaire [PADQ]) and clinical global impression of change (CGI-C). Results: Because of onset of the COVID-19 pandemic, enrollment was stopped prematurely. The primary endpoints showed numeric improvements in both HQ-CT and CY-BOCS which were not statistically significant; however, the 3.2-mg arm showed nominally significant improvements in HQ-CT, PADQ, and CGI-C scores vs placebo. Improvements were sustained in the long-term follow-up period. The most common adverse event during the PCP was mild to moderate flushing. Conclusions: Carbetocin was well tolerated, and the 3.2-mg dose was associated with clinically meaningful improvements in hyperphagia and anxiousness and distress behaviors in participants with PWS. Clinical Trials Registration Number: NCT03649477

Background: Individuals with Prader-Willi syndrome (PWS) have hypothalamic dysfunction and may have central adrenal insufficiency (CAI). The prevalence of CAI in PWS remains unknown. Methods: Twenty-one subjects with PWS aged 4-53 years underwent a low dose adrenocorticotropic hormone (ACTH) stimulation test (LDAST) (1 mu g/m(2), maximum 1 mu g) followed by an overnight metyrapone test (OMT). Metyrapone (30 mg/kg, maximum 3 g) was administered at 2400 h. Cortisol, 11-deoxycortisol (11-DOC) and ACTH levels were collected the following morning at 0800 h. OMT was the standard test for comparison. Peak cortisol = 15.5 mu g/dL (427.6 nmol/L) on LDAST and 0800 h 11-DOC = 7 mu g/dL (200 nmol/L) on OMT were classified as adrenal sufficiency. Results: Twenty subjects had 0800 h 11-DOC values = 7 mu g/dL on OMT indicating adrenal sufficiency. One subject had an inconclusive OMT result. Six of the 21 (29%) subjects had peak cortisol < 15.5 mu g/dL on LDAST. Conclusions: We found no evidence of CAI based on OMT, yet 29% of our PWS population failed the LDAST. This suggests that the LDAST may have a high false positive rate in diagnosing CAI in individuals with PWS. OMT may be the preferred method of assessment for CAI in patients with PWS.

Introduction/Objectives The American Diabetes Association (ADA) and International Society for Pediatric and Adolescent Diabetes (ISPAD) have outlined standards for best practices in providing optimal diabetes care to children with type 1 diabetes (T1D). Our objectives were to design a metric that evaluated delivery of optimal diabetes care and to use this metric to drive improvement within our diabetes program. Methods Using published guidelines, we identified 11 elements of optimal diabetes care that should be reliably delivered at our institution as standard‐of‐care. We utilized our electronic medical record to aid in data collection and to notify staff when to deliver specific care elements (eg, lipid collection, depression screening, etc.). We designed the T1D Care Index (T1DCI), a metric which aggregates missed opportunities to deliver elements of optimal diabetes care over a given period into a cumulative score, with a lower T1DCI reflecting better care delivery and improved program performance. Results Tracking the T1DCI permitted recognition of areas to focus quality improvement efforts, guided interventions to improve processes for care delivery, and helped determine allocation of time and resources. Interventions resulted in improvement of care delivery across some elements of care. Overall, we observed a 26% reduction in the T1DCI after 12 months of utilization. Conclusions The T1DCI is a powerful metric to evaluate the ability of our diabetes program to standardize, quantify, and monitor delivery of optimal diabetes care to children with T1D, and to drive our program towards zero missed opportunities for quality care delivery.

Prader–Willi syndrome (PWS) is a complex neurodevelopmental genetic disorder characterized by hypotonia and hyperphagia. Consequently, individuals with PWS are at high risk of choking, and choking is a leading cause of morbidity and mortality. The aim of this quality improvement (QI) project is to provide choking prevention and first aid education from 0% to 80% of PWS caregivers seen in a multidisciplinary PWS clinic, and to assess the effectiveness of this education program. A QI initiative was developed to standardize and implement choking prevention and first aid education for PWS caregivers. Using a Likert scale, pre- and post-education assessments were conducted to measure caregiver (1) awareness of the PWS choking risk, (2) self-reported knowledge of choking prevention strategies, and (3) comfort in providing choking first aid. The American Heart Association Family and Friends^® CPR (Dallas, TX, USA) curriculum was utilized. Education was provided during a regularly scheduled PWS clinic appointment. At project conclusion, 45/52 (87%) of PWS caregivers received education. A post-education assessment revealed an improvement in PWS caregivers’ awareness of choking risk, self-reported knowledge of choking prevention strategies, and comfort in providing choking first aid. This QI project supports a practice change to implement choking prevention and first aid education as standard process within our PWS clinic.