Faculty Bibliography

INTRODUCTION/BACKGROUND:This survey investigates brain MRI practices for isolated GHD among Pediatric Endocrine Society (PES) members, focusing on gadolinium-based contrast agents (GBCAs) versus non-contrast MRI. METHODS:A 15-question survey was distributed to 1,553 PES members, capturing data on GBCA usage, non-contrast imaging access, and awareness of gadolinium retention. RESULTS:A total of 85% of respondents routinely order brain MRIs for isolated GHD, with 60% using GBCAs. Most respondents have access to high-resolution non-contrast imaging, though 54% are unaware of gadolinium retention risks. CONCLUSION/CONCLUSIONS:High-resolution non-contrast MRI demonstrates diagnostic efficacy, suggesting a shift away from GBCAs in clinic practice for isolated GHD. The survey forms the basis to update PES guidelines in the evaluation of isolated GHD.

Teplizumab (TzieldTM, Provention Bio), a monoclonal antibody directed at T-cell marker CD3, is the first medication approved by the FDA to delay progression from stage 2 to stage 3 type 1 diabetes. To date, the overwhelming majority of pediatric endocrinologists do not have experience using immunotherapeutics and seek guidance on the use of teplizumab in clinical practice. To address this need, the Pediatric Endocrine Society (PES) Diabetes Special Interest Group (Diabetes SIG) and Drug and Therapeutics Committee assembled a task force to review clinical trial data and solicit expert recommendations on the approach to teplizumab infusions. We present considerations on all aspects of teplizumab administration, utilizing evidence where possible and providing a spectrum of expert opinions on unknown aspects. We discuss patient selection and prescreening, highlighting the safety and considerations for monitoring and treatment of side effects. We propose a schedule of events, a protocol for administration, and discuss practice management aspects. We advocate for the need for further long-term systematic surveillance studies to continue evaluating the efficacy and safety of teplizumab.

The coronavirus disease 2019 (COVID-19) pandemic disrupted health care, creating challenges for people with diabetes and health care systems. Diabetes was recognized as a risk factor for severe disease early in the pandemic. Subsequently, risk factors specific for people with type 1 diabetes were identified, including age, hemoglobin A1c level, and lack of continuous glucose monitoring . Telemedicine, especially when accompanied by diabetes data, allowed effective remote care delivery. However, pre-existing racial disparities in access to diabetes technology persisted and were associated with worse outcomes. Events of the COVID-19 pandemic underscore the importance of continuing to develop flexible and more equitable health care delivery systems.

CONTEXT/BACKGROUND:Pediatric obesity is a serious health problem in the United States. While lifestyle modification therapy with dietary changes and increased physical activity are integral for the prevention and treatment of mild to moderate obesity in youth, only a modest effect on sustained weight reduction is observed in children and young adults with severe obesity. This underscores the need for additional evidence-based interventions for children and adolescents with severe obesity, including pharmacotherapy, before considering invasive procedures such as bariatric surgery. EVIDENCE ACQUISITION/METHODS:This publication focuses on recent advances in pharmacotherapy of obesity with an emphasis on medications approved for common and rarer monogenic forms of pediatric obesity. EVIDENCE SYNTHESIS/RESULTS:We review medications currently available in the United States, both those approved for weight reduction in children and "off-label" medications that have a broad safety margin. CONCLUSION/CONCLUSIONS:It is intended that this review will provide guidance for practicing clinicians and will encourage future exploration for successful pharmacotherapy and other interventions for obesity in youth.

BACKGROUND:An increase in newly diagnosed type 1 diabetes (T1D) has been posited during the COVID-19 pandemic, but data are conflicting. We aimed to determine trends in newly diagnosed T1D and severity of presentation at diagnosis for pediatric and adolescent patients during COVID-19 (2020) as compared to the previous year (2019) in a multi-center analysis across the United States. METHODS:This retrospective study from seven centers in the T1D Exchange Quality Improvement Collaborative (T1DX-QI) included data on new onset T1D diagnosis and proportion in DKA at diagnosis from January 1 to December 31, 2020, compared to the prior year. Chi-square tests were used to compare differences in patient characteristics during the pandemic period compared to the prior year. RESULTS:Across seven sites, there were 1399 newly diagnosed T1D patients in 2020, compared to 1277 in 2019 (p=0.007). A greater proportion of newly diagnosed patients presented in DKA in 2020 compared to 2019 (599/1399(42.8%) v. 493/1277(38.6%), p=0.02), with a higher proportion presenting with severe DKA (p=0.01) as characterized by a pH<7.1 and/or bicarbonate of <5mmol/L. Monthly data trends demonstrated a higher number of new T1D diagnoses over the spring and summer months (March to September) of 2020 compared to 2019 (p<0.001). CONCLUSIONS:We found an increase in newly diagnosed T1D and a greater proportion presenting in DKA at diagnosis during the COVID-19 pandemic compared to the prior year. Future longitudinal studies are needed to confirm these findings with population level data and determine the long-term impact of COVID-19 on diabetes trends. This article is protected by copyright. All rights reserved.

CONTEXT:Identification of modifiable risk factors, including genetic and acquired disorders of lipid and lipoprotein metabolism, is increasingly recognized as an opportunity to prevent premature cardiovascular disease (CVD) in at-risk youth. Pediatric endocrinologists are at the forefront of this emerging public health concern and can be instrumental in beginning early interventions to prevent premature CVD-related events during adulthood. AIM:In this article, we use informative case presentations to provide practical approaches to the management of pediatric dyslipidemia. CASES:We present 3 scenarios that are commonly encountered in clinical practice: isolated elevation of low-density lipoprotein cholesterol (LDL-C), combined dyslipidemia, and severe hypertriglyceridemia. Treatment with statin is indicated when the LDL-C is ≥190 mg/dL (4.9 mmol/L) in children ≥10 years of age. For LDL-C levels between 130 and 189 mg/dL (3.4-4.89 mmol/L) despite dietary and lifestyle changes, the presence of additional risk factors and comorbid conditions would favor statin therapy. In the case of combined dyslipidemia, the primary treatment target is LDL-C ≤130 mg/dL (3.4 mmol/L) and the secondary target non-high-density lipoprotein cholesterol <145 mg/dL (3.7 mmol/L). If the triglyceride is ≥400 mg/dL (4.5 mmol/L), prescription omega-3 fatty acids and fibrates are considered. In the case of triglyceride >1000 mg/dL (11.3 mmol/L), dietary fat restriction remains the cornerstone of therapy, even though the landscape of medications is changing. CONCLUSION:Gene variants, acquired conditions, or both are responsible for dyslipidemia during childhood. Extreme elevations of triglycerides can lead to pancreatitis. Early identification and management of dyslipidemia and cardiovascular risk factors is extremely important.

Introduction: An increase in newly diagnosed type 1 diabetes (T1D) has been posited during the COVID-19 pandemic, but data have been conflicting.
Objective(s): We aimed to determine trends in newly diagnosed T1D and severity of presentation at diagnosis for pediatric and adolescent patients during COVID-19 year (2020) as compared to the previous year (2019) in a multi-center data analysis across the United States.
Method(s): This retrospective multi-center study included data from seven large U.S. clinical centers recruited from the T1D Exchange Quality Improvement Collaborative (T1DX-QI). Data on diagnosis, diabetic ketoacidosis (DKA), and clinical characteristics were collected from January 1 to December 31, 2020, compared to the prior year. Chi-square tests were used to compare differences in patient characteristics during the pandemic compared to the pre-pandemic comparison group.
Result(s): Across seven member sites, there were 1399 newly diagnosed patients with T1D in 2020, compared to 1277 in 2019 (p=0.007). Of the newly diagnosed patients, a greater number, presented in DKA in 2020 compared to 2019 (599/1399 (42.8%) v. 493/1277 (38.6%), p<0.001), and a higher proportion of these patients presented with severe DKA (p=0.01) as characterized by a pH<7.1 or bicarbonate of <5mmol/L. The mean age at diagnosis was not different, but there were fewer females (p=0.004), and fewer NH White youth diagnosed in 2020 (p<0.001). Newly diagnosed T1D patients in 2020 were less likely to have private insurance (p=0.001). Monthly data trends demonstrated a higher number of new diagnoses of T1D over the spring and summer months (April to September) of 2020 compared to 2019 (p=0.007).
Conclusion(s): We found an increase in newly diagnosed T1D and a greater proportion of newly diagnosed T1D patients presenting in DKA at diagnosis during the COVID-19 pandemic compared to the prior year. Future longitudinal studies are needed to confirm these findings with population level data and determine the long-term impact of COVID-19 on diabetes trends

OBJECTIVES/OBJECTIVE:There have been few large-scale studies utilizing exome sequencing for genetically undiagnosed maturity onset diabetes of the young (MODY), a monogenic form of diabetes that is under-recognized. We describe a cohort of 160 individuals with suspected monogenic diabetes who were genetically assessed for mutations in genes known to cause MODY. METHODS:. The average age of onset of hyperglycemia or diabetes diagnosis was 19 years (median 14 years) with an average HbA1C of 7.1%. RESULTS:. For those probands with available family members, 100% of the variants segregated with diabetes in the family. Cascade genetic testing in families identified 75 additional family members with a familial MODY mutation. CONCLUSIONS:Our study is one of the largest and most ethnically diverse studies using exome sequencing to assess MODY genes. Tiered testing is an effective strategy to genetically diagnose atypical diabetes, and familial cascade genetic testing identified on average one additional family member with monogenic diabetes for each mutation identified in a proband.

Congenital diaphragmatic hernia (CDH) in neonates may occur as an isolated finding, in association with other anomalies, or as part of a genetic syndrome. We report the first case of an infant with CDH who presented with hyponatremic seizures due to adrenal hypoplasia congenita (AHC). The patient underwent repair of CDH defect. After an uncomplicated postoperative course while on discharge planning, he developed a seizure episode associated with severe hyponatremia and hyperkalemia. Extensive diagnostic workup revealed an NR0B1 gene variant confirming the diagnosis of X-linked AHC. The patient was eventually discharged home on hydrocortisone, fludrocortisone, and salt supplements. There are a few case reports of adrenal insufficiency in neonates with CDH, manifesting with symptoms before and immediately after reparative surgery. Clinical presentation of our patient was unique in manifesting as neonatal seizure secondary to severe hyponatremia after a stable postoperative phase. The patient's electrolytes and hemodynamic status remained stable before, during, and after surgery for CDH. This case underlines the importance of taking detailed family history and continued vigilance for signs and symptoms of adrenal insufficiency in infants with repaired CDH by pediatricians and intensivists.