Pediatric Endocrine Society Research Articles

Neonatal hypoglycemia: a review of the current diagnostic and management guidelines

Neonatal hypoglycemia is the most common metabolic disorder during the neonatal period. Despite its frequency of occurrence, there is no specific glucose concentration that defines it. Various symptoms and clinical manifestations characterize it, and its complications are related to its severity and duration. This review aims at comparing the recommendations of the American Academy of Pediatrics, the Pediatric Endocrine Society, and the Academy of Breastfeeding Medicine regarding the risk factors, the diagnosis, and the management of hypoglycemia. The complexity of hypoglycemia management and the research questions that need to be answered are highlighted by comparing the three guidelines. Preventing neonatal hypoglycemia by monitoring the maternal glucose concentrations, exploring and defining the optimal glycemic targets, investigating the long-term benefits after following these guidelines, and searching for less invasive diagnostic and therapeutic tools may help healthcare professionals make informed decisions to achieve better outcomes for these neonates.

DSD-related attitudes and beliefs held by pediatric endocrinologists and urologists: Insights from the North American disorders/differences of sex development (DSD) clinician survey

Disorders/Differences of Sex Development (DSD) encompass congenital conditions with atypical development of chromosomal, gonadal, or anatomical sex. Due to the rarity and complexity of these conditions, strong evidence for clinical practices is scarce, leading to controversies in management. This study, part of a broader project, examines changes over time in the attitudes and beliefs of DSD healthcare providers, focusing on factors contributing to patients' life satisfaction and the influence of medical specialty, gender, and age. Participants included active members of the Pediatric Endocrine Society (PES) and the Societies for Pediatric Urology (SPU) at three time points: 2003-2004 (T1), 2010-2011 (T2), and 2020 (T3). A survey covering predictors of patient life satisfaction, attitudes and beliefs regarding DSD care and outcomes, and participant characteristics was administered. Data were analyzed using descriptive statistics and Generalized Estimating Equations (GEE). Demographics: Participation rates were 56% (PES) and 64.7% (SPU) at T1, 41.1% (PES) and 52.3% (SPU) at T2, and 25.6% (PES) and 51.2% (SPU) at T3. Most participants were male (T1: 70.6%, T2: 61.7%, T3: 70.6%). Factors Affecting Life Satisfaction: Both endocrinologists and urologists ranked "gender identity consistent with assigned sex" as most important. Over time, the endorsement of some factors, such as performing genital surgery at Centers of Excellence, increased, while others, like the influence of prenatal androgen exposure determining gender identity, varied by specialty and gender. Attitudes and Beliefs: Across 18 statements, responses indicated three clusters with strong agreement, moderate agreement, and strong disagreement. Statements on the importance of family background and avoiding gender discordance were consistently endorsed, while those on delaying hypospadias repair until consent were least endorsed. The study highlights variability in beliefs about DSD management over time, influenced by specialty, gender, and age. Despite consensus on some care principles, discrepancies remain, particularly regarding the impact of prenatal androgens and the timing of surgical interventions. These findings underscore the need for regular interdisciplinary communication to align clinical practices with evidence-based guidelines and address subjective beliefs. The survey illustrates evolving perspectives among DSD healthcare providers, emphasizing the need for continued dialogue and education to bridge gaps between clinical evidence and practice. Collaborative efforts, such as the international I-DSD and the U.S. DSD Translational Research Network, are crucial for advancing patient-centered care in this field.

Recommendations for 46,XY Disorders/Differences of Sex Development Across Two Decades: Insights from North American Pediatric Endocrinologists and Urologists

Clinical decision-making for individuals with 46,XY disorders/differences of sex development (DSD) remains unsettled and controversial. The North American DSD Clinician Survey examines the recommendations of a large group of clinical specialists over the last two decades. Active members of the (Lawson Wilkins) Pediatric Endocrine Society and the Societies for Pediatric Urology were invited to respond to a web-based survey at three different timepoints: 2003–2004 (T1), 2010–2011 (T2), and 2019–2020 (T3). Data from 429 participants in T1, 435 in T2, and 264 in T3 were included in this study. The participants were presented with three XY newborn clinical case scenarios—micropenis, partial androgen insensitivity syndrome, and iatrogenic penile ablation—and asked for clinical management recommendations. The main outcomes assessed included the recommended gender of rearing, surgical decision-maker (parent or patient), timing of genital surgery, and age at which to disclose medical details and surgical history to the patient. For all scenarios, the overwhelming majority recommended rearing as male, including a significant increase across timepoints in those recommending a male gender of rearing for the infant with penile ablation. The proportions recommending female gender of rearing declined significantly across timepoints. In general, most recommended parents (in consultation with the physician) serve as surgical decision-makers, but these proportions declined significantly across timepoints. Recommendations on the timing of surgery varied based on the patient’s gender and type of surgery. There has been a shift in recommendations away from the “optimal gender policy” regarding gender of rearing and surgical interventions for patients with XY DSD.

Clinical phenotypes of adults with monogenic and syndromic genetic obesity.

Considering limited evidence on diagnostics of genetic obesity in adults, we evaluated phenotypes of adults with genetic obesity. Additionally, we assessed the applicability of Endocrine Society (ES) recommendations for genetic testing in pediatric obesity. We compared clinical features, including age of onset of obesity and appetite, between adults with non-syndromic monogenic obesity (MO), adults with syndromic obesity (SO), and adults with common obesity (CO) as control patients. A total of 79 adults with genetic obesity (32 with MO, 47 with SO) were compared with 186 control patientswith CO. Median BMI was similar among the groups: 41.2, 39.5, and 38.7 kg/m2 for patients with MO, SO, and CO, respectively. Median age of onset of obesity was 3 (IQR: 1-6) years in patients with MO, 9 (IQR: 4-13) years in patients with SO, and 21 (IQR: 13-33) years in patients with CO (p < 0.001). Patients with genetic obesity more often reported increased appetite: 65.6%, 68.1%, and 33.9% in patients with MO, SO, and CO, respectively (p < 0.001). Intellectual deficit and autism spectrum disorder were more prevalent in patients with SO (53.2% and 21.3%) compared with those with MO (3.1% and 6.3%) and CO (both 0.0%). The ES recommendations were fulfilled in 56.3%, 29.8%, and 2.7% of patients with MO, SO, and CO, respectively (p < 0.001). We found distinct phenotypes in adult genetic obesity. Additionally, we demonstrated low sensitivity for detecting genetic obesity in adults using pediatric ES recommendations, necessitating specific genetic testing recommendations in adult obesity care.

Clinical practice guidelines for the care of girls and women with Turner syndrome.

Turner syndrome (TS) affects 50 per 100 000 females. TS affects multiple organs through all stages of life, necessitating multidisciplinary care. This guideline extends previous ones and includes important new advances, within diagnostics and genetics, estrogen treatment, fertility, co-morbidities, and neurocognition and neuropsychology. Exploratory meetings were held in 2021 in Europe and United States culminating with a consensus meeting in Aarhus, Denmark in June 2023. Prior to this, eight groups addressed important areas in TS care: (1) diagnosis and genetics, (2) growth, (3) puberty and estrogen treatment, (4) cardiovascular health, (5) transition, (6) fertility assessment, monitoring, and counselling, (7) health surveillance for comorbidities throughout the lifespan, and (8) neurocognition and its implications for mental health and well-being. Each group produced proposals for the present guidelines, which were meticulously discussed by the entire group. Four pertinent questions were submitted for formal GRADE (Grading of Recommendations, Assessment, Development and Evaluation) evaluation with systematic review of the literature. The guidelines project was initiated by the European Society for Endocrinology and the Pediatric Endocrine Society, in collaboration with members from the European Society for Pediatric Endocrinology, the European Society of Human Reproduction and Embryology, the European Reference Network on Rare Endocrine Conditions, the Society for Endocrinology, and the European Society of Cardiology, Japanese Society for Pediatric Endocrinology, Australia and New Zealand Society for Pediatric Endocrinology and Diabetes, Latin American Society for Pediatric Endocrinology, Arab Society for Pediatric Endocrinology and Diabetes, and the Asia Pacific Pediatric Endocrine Society. Advocacy groups appointed representatives for pre-meeting discussions and the consensus meeting.

Precocious Puberty and GnRH Analogs: Current Treatment Practices and Perspectives among US Pediatric Endocrinologists.

Gonadotropin releasing hormone analogs (GnRHas) are used for treatment of precocious puberty. Over the last decade, several new formulations have been approved. The Drugs and Therapeutics Subcommittee of the Pediatric Endocrine Society (PES) undertook a review to ascertain the current treatment options, prescribing behaviors, and practices of GnRHas among pediatric endocrinologists practicing within the USA. The survey consisted of four main subsections: (1) description of clinical practice; (2) self-assessment of knowledge base of pediatric and adult GnRHa formulations; (3) current practice for treating central precocious puberty (CPP); and (4) utilization of healthcare resources. There were 223 survey respondents. Pediatric endocrine practitioners were most familiar with the pediatric one-monthly preparation, the 3-month preparation, and the histrelin implant (Supprelin®) (88%, 96%, and 91%, respectively), with lower familiarity for 24-week triptorelin intramuscular (Triptodur®) (65%) and 6-month subcutaneous leuprolide (Fensolvi®) (45%). Only 23% of the respondents reported being extremely familiar with the availability of adult formulations, and 25% reported being completely unaware of cost differences between pediatric and adult GnRHa preparations. The implant was the most preferred therapy (44%), but in practice, respondents reported a higher percentage of patients treated with the 3-month preparation. While family preference/ease of treatment (87%) was the key determinant for using a particular GnRHa preparation, insurance coverage also played a significant role in the decision (64%). Responses regarding assessment for efficacy of treatment were inconsistent, as were practices and criteria for obtaining an MRI. The survey indicated there is more familiarity with older, shorter acting GnRHas, which are prescribed in greater numbers than newer, longer acting formulations. There is lack of consensus on the need for central nervous system (CNS) imaging in girls presenting with CPP between 6 and 8 years of age and use of laboratory testing to monitor response to treatment. Insurance requirements regarding CNS imaging and laboratory monitoring are highly variable. Despite having similar constituents and bioavailability, there are substantial cost differences between the pediatric and adult formulations and lack of evidence for safe use of these formulations in children. The survey-based analysis highlights the challenges faced by prescribers while reflecting on areas where further research is needed to provide evidence-based practice guidelines for pediatric endocrinologists.

Recommendations for 46,XX Congenital Adrenal Hyperplasia Across Two Decades: Insights from the North American Differences of Sex Development Clinician Survey

Several aspects of clinical management of 46,XX congenital adrenal hyperplasia (CAH) remain unsettled and controversial. The North American Disorders/Differences of Sex Development (DSD) Clinician Survey investigated changes, over the last two decades, in clinical recommendations by specialists involved in the management of newborns with DSD. Members of the (Lawson Wilkins) Pediatric Endocrine Society and the Societies for Pediatric Urology participated in a web-based survey at three timepoints: 2003–2004 (T1, n = 432), 2010–2011 (T2, n = 441), and 2020 (T3, n = 272). Participants were presented with two clinical case scenarios—newborns with 46,XX CAH and either mild-to-moderate or severe genital masculinization—and asked for clinical recommendations. Across timepoints, most participants recommended rearing the newborn as a girl, that parents (in consultation with physicians) should make surgical decisions, performing early genitoplasty, and disclosing surgical history at younger ages. Several trends were identified: a small, but significant shift toward recommending a gender other than girl; recommending that adolescent patients serve as the genital surgery decision maker; performing genital surgery at later ages; and disclosing surgical details at younger ages. This is the first study assessing physician recommendations across two decades. Despite variability in the recommendations, most experts followed CAH clinical practice guidelines. The observation that some of the emerging trends do not align with expert opinion or empirical evidence should serve as both a cautionary note and a call for prospective studies examining patient outcomes associated with these changes.

Klinefelter: Which Sexuality?

Klinefelter syndrome (KS) was described by Klinefelter, Reifenstein, and Albright in 1942, who described 9 adult males with gynecomastia, small and firm testes, azoospermia, and increased serum FSH with functional Leydig cells. In 1959, using cytogenetics, Jacobs and Strong described the existence of an extra X chromosome in a male with Klinefelter syndrome The International Consensus Conference organized by the Lawson Wilkins Pediatric Endocrine Society and the European Society for Pediatric Endocrinology in 2006 included KS in disorders of sexual development. Klinefelter syndrome is also characterized by a genetic dysfunction of the entire gonad that affects germ cells from early fetal life and Sertoli and Leydig cells from mid-puberty. Today we know much more. In this article, we have delved into the social, relational, and sexual quality of life of patients with KS, going beyond fertility studies.

Association Between Hypoglycemia and the Occurrence of Early Onset Sepsis in Premature Infants.

We examined the association between hypoglycemia and the occurrence of early onset sepsis (EOS) in premature infants admitted to the neonatal intensive care unit (NICU). We included infants discharged from 358 NICUs between 1997 and 2020 with gestational age <34 weeks, ≥1 culture collected in the first 3 days of life, and ≥1 serum glucose value recorded on the day of or day prior to culture collection. We used multivariable logistic regression and inverse probability weighting (IPW) and constructed models for three definitions of hypoglycemia: American Academy of Pediatrics (AAP), Pediatric Endocrine Society, and a definition based on neurodevelopmental studies. We performed subgroup analysis in EOS episodes caused by Gram-negative and Gram-positive organisms. Of the 62,178 infants and 64,559 cultures that met study inclusion criteria, 739 (1%) cultures were positive. The median (25th, 75th percentile) glucose value was 75 mg/dL (50, 106) on the day of or day prior to a positive culture versus 70 mg/dL (50, 95) on the day of or day prior to a negative culture. We found that hypoglycemia was not associated with the occurrence of EOS for all organisms and Gram-positive organisms, whereas there was a small but significant association between the lower AAP glucose cutoff value and EOS due to Gram-negative organisms (logistic regression: risk difference [RD] 0.24% [95% CI, 0.01-0.47]; IPW: RD 0.22% [95% CI, 0.00-0.43]). Hypoglycemia may be an early marker of EOS, particularly in episodes caused by Gram-negative organisms and when using a stricter definition of hypoglycemia.

Practice Variation among Pediatric Endocrinologists in the Dosing of Glucocorticoids in Young Children with Congenital Adrenal Hyperplasia.

A Pediatric Endocrine Society (PES) Drugs and Therapeutics Committee workgroup sought to determine the prescribing practices of pediatric endocrinologists when treating children <10 years of age with congenital adrenal hyperplasia (CAH). Our workgroup administered a 32-question online survey to PES members. There were 187 respondents (88.9% attending physicians), mostly from university-affiliated clinics (~80%). Ninety-eight percent of respondents prescribed the short-acting glucocorticoid hydrocortisone to treat young children, as per the Endocrine Society CAH Guidelines, although respondents also prescribed long-acting glucocorticoids such as prednisolone suspension (12%), prednisone tablets (9%), and prednisone suspension (6%). Ninety-seven percent of respondents indicated that they were likely/very likely to prescribe hydrocortisone in a thrice-daily regimen, as per CAH Guidelines, although 19% were also likely to follow a twice-daily regimen. To achieve smaller doses, using a pill-cutter was the most frequent method recommended by providers to manipulate tablets (87.2%), followed by dissolving tablets in water (25.7%) to create a daily batch (43.7%) and/or dissolving a tablet for each dose (64.6%). Thirty-one percent of providers use pharmacy-compounded hydrocortisone suspension to achieve doses of <2.5 mg. Our survey shows that practices among providers in the dosing of young children with CAH vary greatly and sometimes fall outside of the CAH Guidelines-specifically when attempting to deliver lower, age-appropriate hydrocortisone doses.

The Role of the AMH, SHBG and LH/FSH Ratio in the Diagnosis of Polycystic Ovary Syndrome in Adolescent

Objective: Polycystic ovary syndrome (PCOS) diagnosis is controversial in adolescents. Therefore, auxiliary markers are required for the diagnosis of PCOS. We aimed to evaluate whether luteinizing hormone (LH)/ follicle-stimulating hormone (FSH) ratio, free androgen index (FAI), anti-Mullerian hormone (AMH), and sex hormone-binding globulin (SHBG) levels are a useful test to screen adolescents with PCOS and to investigate which of them has more diagnostic value in the PCOS diagnosis. Material and Methods: A total of 56 girls with PCOS and 70 healthy girls consisted in this study. Pediatric Endocrine Society criteria were used to diagnose PCOS. Clinical examinations and hormonal assays were performed. Results: The LH/FSH ratio, and FAI levels were detected significantly higher, and SHBG levels were detected significantly lower in the PCOS group than in the control group (p&amp;lt;0.001). The best marker for PCOS diagnosis was found as AMH. In all adolescents with PCOS, irrespective of obesity/overweight, significantly higher AMH levels were observed compared to the control subjects (p&amp;lt;0.001). Also, we measured a LH/FSH ratio cut-off value of 1.48 ng/ml with 77% sensitivity and 77% specificity to differentiate cases with PCOS from healthy controls. Conclusion: AMH, FAI, and LH/FSH ratio could be usefull and valuable tests for the PCOS diagnosis in the presence of the PCOS criteria. AMH was found to be the strongest diagnostic marker in patients with PCOS.

Predicting Glycemic Control in a Small Cohort of Children with Type 1 Diabetes Using Machine Learning Algorithms

Type 1 diabetes, a chronic condition characterized by insulin deficiency, is associated with various complications and reduced life expectancy and is increasing in global prevalence. Maintaining glycaemic control in children with type 1 diabetes, as reflected by glycated hemoglobin levels (A1C), is a challenging task. The American Association of Diabetes (ADA), the Pediatric Endocrine Society, and the International Diabetes Federation (ISPAD) recommend the adoption of a harmonized A1C of &lt;7.5% across all pediatric groups. Our retrospective study included 79 children with type 1 diabetes and aimed to identify determinants pivotal to forecasting glycemic control, focusing on a single A1C cut-off value and exploring how machine learning algorithms can enhance clinical understanding, particularly with smaller sample sizes. Bivariate analysis identified correlations between glycemic control and disease duration, body mass index (BMI) Z-score at onset, A1C at onset above 7.5 g/dL, family income, living environment, maternal education level, episodes of ketoacidosis, and elevated cholesterol or triglyceride. Binary logistic regression stressed the association of ketoacidosis episodes (β = 21.1, p &lt; 0.01) and elevated A1C levels at onset (β = 3.12, p &lt; 0.01) and yielded an area under the receiver operating characteristic curve (AUROC) of 0.916. Two-step clustering emphasized socioeconomic factors, as well as disease complications and comorbidities, and delineated clusters based on these traits. The classification and regression tree (CART) yielded an AUROC of 0.954, slightly outperforming binary regression, providing a comprehensive view of interactions between disease characteristics, comorbidities, and socioeconomic status. Common to all methods were predictors regarding ketoacidosis episodes, the onset of A1C levels, and family income, signifying their overarching importance in glycaemic control. While logistic regression quantified risk, CART visually elucidated complex interactions and two-step clustering exposed patient subgroups that might require different intervention strategies, highlighting how the complementary nature of these analytical methods can enrich clinical interpretation.

FRI046 Clinical Phenotyping Of Adults With Genetic Obesity

Abstract Disclosure: M.S. Welling: None. M. Mohseni: None. R.E. Meeusen: None. M.R. Boon: None. C.J. de Groot: None. M.M. van Haelst: None. J.A. Visser: None. E.L. van den Akker: None. E.F. van Rossum: None. Introduction: In rare cases of obesity, genetic defects lead to hyperphagia and severe early-onset obesity. Genetic testing in patients with a suspected genetic obesity phenotype is important, as it can lead to patient-tailored treatment advice. For children, the Endocrine Society (ES) recommends genetic testing in children with early-onset of obesity (&amp;lt;5 years) and hyperphagia. It is unclear whether these recommendations can also be used in adult obesity care. Therefore, we aimed to phenotype adult patients with genetic obesity disorders. In addition, we assessed the suitability of the pediatric ES recommendations in these patients. Methods: We analyzed clinical data of patients with non-syndromic genetic obesity (NSO) and syndromic genetic obesity (SO), who visited our academic obesity center (Erasmus Medical Center, Rotterdam, the Netherlands). A standardized medical questionnaire, including topics concerning e.g. age of onset of obesity, hunger and satiation, was assessed. Anthropometrics, body composition (bio-impedance analysis), and resting energy expenditure (REE, indirect calorimetry) were measured. Differences between the NSO and SO groups were studied. Results: Sixty-six patients, of which n=26 with NSO and n=40 with SO, were included: median BMI and age at intake were 41.2 vs 39.2 kg/m2 and 25.7 vs 24.8 yrs, respectively (ns). The median age of onset of obesity was 2.5 [1-5] yrs in NSO and 9.5 [4-14] yrs in SO (p&amp;lt;0.001). Impaired appetite regulation was present in both groups: increased feelings of hunger in 64.0 vs 51.3% and impaired satiation in 47.1 vs 32.0% in NSO vs SO (ns). Binge eating was reported in 63.2% of SO, compared to 40.0% in NSO (p=0.071). The pediatric ES recommendations were fulfilled in 57.5% of NSO and 27.5% of SO (p=0.014). Compared to NSO, SO had a higher prevalence of intellectual deficit (3.8 vs 55.0%, p&amp;lt;0.001), autism (7.7 vs 26.3%, p=0.061) and retinal problems (0 vs 20.0%, p=0.015). There were no differences in body composition or REE. Conclusion: We report distinct phenotypic features concerning the age of onset of obesity, appetite regulation, and the presence of intellectual deficit, autism and retinal problems in adults with non-syndromic genetic obesity or syndromic genetic obesity. Additionally, this study demonstrates that the Endocrine Society’s recommendations for genetic testing in children with obesity, do not suit well for adults with obesity. Recommendations for genetic testing in adults with obesity are needed. Presentation: Friday, June 16, 2023

The Rising Incidence of Hyperinsulinemic Hypoglycemia: Connection With Maternal Health

ObjectiveDue to a perceived rise in hyperinsulinemic hypoglycemia (HH) cases over time, notably during the COVID-19 pandemic, institutional experiences between 2013 and 2021 were reviewed to evaluate trends, characteristics, and outcomes in children with HH. MethodsCharts of all children diagnosed with HH during the study period and evaluated by Pediatric Endocrinology were reviewed. HH was defined per Pediatric Endocrine Society guidelines. Regression analysis compared rates of change in HH cases and maternal risk factors over time. ResultsThe incidence of HH began to rise in April 2016 and became significant in March 2017 (P < .001), with a more rapid rate of rise during the first year of the COVID-19 pandemic (P < .001). Seventy-four children with HH were identified over 9 years; 43% (n = 32) were diagnosed in 2020-2021. Maternal hypertensive disorders demonstrated longitudinal association with hyperinsulinism cases (P < .001). ConclusionWhile HH diagnoses were on the rise for much of the 9-year study period, nearly half of all infants were diagnosed during the COVID-19 pandemic in 2020 to 21. The trends in HH diagnoses correlated with maternal hypertensive disorders. More studies exploring the roles of maternal health, hypertension, and stress and development of HH in offspring are needed.

Somatropin for Growth Hormone Deficiency

&#x0D; We identified 2 evidence-based guidelines that provide recommendations for the clinical management of children and adults with growth hormone deficiency.&#x0D; The American Association of Clinical Endocrinologists and American College of Endocrinology guideline provides recommendations on assessment, screening, diagnostic testing, treatment, and monitoring for a range of patients with different causes of adult growth hormone deficiency. The recommendations emphasize accurate diagnosis using appropriate growth hormone cut points for different growth hormone–stimulation tests and careful interpretation of serum growth hormone and insulin-like growth factor-1 levels. Treatment with recombinant human growth hormone should be carried out with consideration of the benefits and risks specific to each individual patient.&#x0D; The Pediatric Endocrine Society guideline provides recommendations for the clinical management of children and adolescents with growth failure due to growth hormone deficiency. The guideline lists various conditions for which growth hormone deficiency can be diagnosed by conventional approaches without growth hormone–stimulation testing. The treatment dose of growth hormone should be calculated based on weight and body surface area and not on insulin-like growth factor-1 levels. The guideline highlights that the initial growth hormone dose, subsequent dosing, and discontinuation of pediatric doses should be assessed based on each individual patient.&#x0D; Both guidelines recognize the uncertainty of long-term safety (i.e., posttreatment effects) of growth hormone treatment, which is a limitation of both guidelines.&#x0D;

Diagnosis and Management of Neonatal Hypoglycemia: A Comprehensive Review of Guidelines.

Hypoglycemia represents one of the most frequent metabolic disturbances of the neonate, associated with increased morbidity and mortality, especially if left untreated or diagnosed after the establishment of brain damage. The aim of this study was to review and compare the recommendations from the most recently published influential guidelines on the diagnosis, screening, prevention and management of this common neonatal complication. Therefore, a descriptive review of the guidelines from the American Academy of Pediatrics (AAP), the British Association of Perinatal Medicine (BAPM), the European Foundation for the Care of the Newborn Infants (EFCNI), the Queensland Clinical Guidelines-Australia (AUS), the Canadian Pediatric Society (CPS) and the Pediatric Endocrine Society (PES) on neonatal hypoglycemia was carried out. There is a consensus among the reviewed guidelines on the risk factors, the clinical signs and symptoms of NH, and the main preventive strategies. Additionally, the importance of early recognition of at-risk infants, timely identification of NH and prompt initiation of treatment in optimizing the outcomes of hypoglycemic neonates are universally highlighted. All medical societies, except PES, recommend screening for NH in asymptomatic high-risk and symptomatic newborn infants, but they do not provide consistent screening approaches. Moreover, the reviewed guidelines point out that the diagnosis of NH should be confirmed by laboratory methods of BGL measurement, although treatment should not be delayed until the results become available. The definition of NH lacks uniformity and it is generally agreed that a single BG value cannot accurately define this clinical entity. Therefore, all medical societies support the use of operational thresholds for the management of NH, although discrepancies exist regarding the recommended cut-off values, the optimal treatment and surveillance strategies of both symptomatic and asymptomatic hypoglycemic neonates as well as the treatment targets. Over the past several decades, ΝH has remained an issue of keen debate as it is a preventable cause of brain injury and neurodevelopmental impairment; however, there is no clear definition or consistent treatment policies. Thus, the establishment of specific diagnostic criteria and uniform protocols for the management of this common biochemical disorder is of paramount importance as it will hopefully allow for the early identification of infants at risk, the establishment of efficient preventive measures, the optimal treatment in the first hours of a neonate's life and, subsequently, the improvement of neonatal outcomes.

Written surgical informed consent elements in pediatric differences of sex development: pediatric urologist and endocrinologist perspectives

IntroductionElective aspects of surgical management of pediatric differences of sex development (DSD) are associated with controversy. We examined North American pediatric urologist and endocrinologist perspectives regarding recommended and existing informed consent elements for written consent documents prior to pediatric genital surgery.MethodsFocus groups with pediatric urologist and endocrinologist members of the Societies for Pediatric Urology (SPU, n=8) or Pediatric Endocrine Society (PES, n=8) were held to identify elements of informed consent for DSD-related urogenital surgery. Elements were subsequently included in web-based surveys in 2003 and 2020 (SPU: n=121 and 143; PES: n=287 and 111, respectively). Participants rated their level of agreement with including each element in informed consent documents. In 2020, participants reported whether documents they use in clinical practice incorporate these elements.ResultsFocus groups identified four elements of informed consent: on-going debate over pediatric genital surgery; potential needs for multiple procedures; possible gender change and surgical reversal; and non-surgical alternatives. Across both years and both specialties, a majority (79% to 98%) endorsed the four elements, with significant between-group differences. Significantly more PES than SPU participants reported not knowing whether specific elements were included in current written informed consent; of those who knew, the majority (66% to 91%) reported inclusion.DiscussionSpecialists agree with including these four elements in written informed consent documents. Endocrinologists are not always familiar with the exact elements included. The degree to which non-surgeon members of the care team should be involved in the written informed consent process is an open question.

1567-P: Hepatic ALKBH5 Regulation of Glucose and Lipid Metabolism

Obesity is a worsening global health crisis leading to increased risk of long-term complications such as type 2 diabetes (T2D), nonalcoholic steatohepatitis (NASH), dyslipidemia and cardiovascular disease. Identifying novel molecular mechanisms regulating the connection between obesity, hepatic insulin resistance and progression of NASH is critical to develop new therapeutic options for these patients. Previous work has shown that reversible N6-methyladenosine (m6A) RNA methylation patterns are altered in and regulate metabolic disease in the pancreatic beta cell and liver. However, these studies have primarily focused on the m6A writer proteins that direct placement of m6A methyl groups, while our study explores the role of m6A eraser protein AlkBH5 in regulating metabolic pathways in the liver. To test the hypothesis that hepatic ALKBH5 is required to maintain normal glucose homeostasis, insulin sensitivity and lipid metabolism under physiologic conditions and in response to metabolic stress we used liver-specific Alkbh5 knockout (A5KO) mice and evaluated changes in weight gain, body composition, glucose tolerance, insulin sensitivity, fasting insulin levels, and gluconeogenesis in response to a chow versus Western diet (WD). In physiologic conditions (chow), A5KO mice have decreased glucose tolerance with no other significant phenotypic changes compared to controls. Exposure to metabolic stress (WD) caused (1) greater weight gain with increased visceral fat in control compared to A5KO mice, (2) decreased glucose tolerance compared to chow in both genotypes, (3) decreased glucose mobilization in A5KO mice on WD compared to chow, with no significant differences in controls, and (4) no significant differences in global insulin sensitivity. These studies demonstrate that A5KO mice are protected against weight gain upon exposure to metabolic stress with decreased glucose tolerance and mobilization compared to controls, establishing a role for hepatic ALKBH5 in regulating glucose and lipid metabolism. Disclosure K.Aamodt: None. M.Polay: None. V.R.Salerno gonzales: None. R.Kulkarni: Advisory Panel; Novo Nordisk, Inversago, Biomea Fusion, Inc., REDD Pharma, Research Support; Inversago. Funding National Institute of Diabetes and Digestive and Kidney Diseases (5T32DK007699-39, 5T32DK007260-45); Pediatric Endocrine Society

223-OR: Identification of Novel Therapies for Monogenic Diabetes Using Connectivity Map (CMap)

Monogenic diabetes is an underdiagnosed form of diabetes that is caused by DNA variation of strong effect in a single gene. While it is an exciting area for targeted drug development, as some forms of monogenic diabetes can be treated with gene-specific therapies, there are currently few targeted therapies available. Additionally, existing treatments are not able to cure or modify the underlying disease. Therefore, to identify novel therapies, we leveraged CMap, a data resource developed at the Broad Institute that contains over one million gene expression signatures from treatment of cell types with perturbagens including drugs, bioactive small molecules, gene overexpression, and gene knockdown reagents. We analyzed connectivity, or the similarity between two gene expression signatures, to search for perturbagen gene expression signatures opposing gene expression changes associated with monogenic diabetes. We were able to identify 15 classes of medications with significantly enriched connectivity with HNF1A-knockdown by Mann-Whitney U-test (BH-adjusted P&amp;lt; 0.05). Included in these classes were sulfonylureas, which are known to have preferential therapeutic benefit for this specific condition, supporting this method for drug discovery. Other medications included HDAC inhibitors, tyrosine kinase inhibitors, and riboflavin. We also surveyed other genes causing monogenic syndromes that include diabetes, such as PPARG, where CMap indicated high connectivity with thiazolidinediones (BH-adjusted P=0.015), a type 2 diabetes drug class with known mechanism targeting PPARγ, opposing PPARγ-knockdown and beneficial for treating patients with PPARγ-driven familial partial lipodystrophy. Our findings support the use of expression signature mapping as a novel approach for identifying therapies for monogenic diabetes. Further exploration of databases like CMap and validation of identified medication classes could lead to new pharmacological treatments for diabetes. Disclosure R.J.Kreienkamp: None. C.Bryan: None. J.C.Florez: Consultant; AstraZeneca, Novo Nordisk, Other Relationship; AstraZeneca, Merck &amp; Co., Inc. M.Udler: None. Funding National Institutes of Health (T32GM774844, K24HL157960, K23DK114551); Pediatric Endocrine Society

Bringing the Pediatric Endocrine Spanish Speaking Community Together: First Virtual Pediatric Endocrine Meeting in Low- and Middle-Income Countries in Central and South America.

Pediatric endocrinology is a specialty that is struggling worldwide to maintain adequately trained professionals. Pediatric endocrine care in Central America and Caribbean countries is often performed by pediatricians or adult endocrinologists due to the limited number of pediatric endocrinologists. These health care providers are seldom members of endocrine societies and frequently lack formal training in the field. In this study, we describe the scope of a virtual conference in pediatric endocrinology and diabetes targeted to low- and middle-income countries to provide equal opportunities for access to medical education for health care professionals. The virtual conference was sponsored by the Pediatric Endocrine Society (North America), Asociación Costarricense de Endocrinología (previously, Asociación Nacional Pro Estudio de la Diabetes, Endocrinología y Metabolismo), and Asociacion Centroamericana y del Caribe de Endocrinologia Pediátrica. The conference was free to participants and comprised 23 sessions that were either synchronous with ability for real-time interactive sessions or asynchronous sessions, where content was available online to access at their convenience. Topics included idiopathic short stature, polycystic ovarian syndrome, diabetes mellitus, telemedicine, Turner syndrome, congenital adrenal hyperplasia, obesity, central precocious puberty, and subclinical hypothyroidism. The participants were asked to evaluate the conference after its completion with a questionnaire. A total of 8 speakers from Spain, Canada, Costa Rica, and the United States delivered the virtual event to 668 health care professionals from Guatemala, Venezuela, Dominican Republic, Costa Rica, Ecuador, Peru, Uruguay, Mexico, Honduras, Argentina, the United States, Bolivia, Chile, Panama, El Salvador, Nicaragua, Paraguay, Belize, Spain, and Colombia. Name, profession, and country were fully disclosed by 410 (61.4%) of the 668 health care professionals. The profession or level of training of participants were as follows: pediatric endocrinologists (n=129, 19.3%), pediatricians (n=116, 17.4%), general practitioners (n=77, 11.5%), adult endocrinologists (n=34, 5.1%), medical students (n=23, 3.4%), residents in various specialties (n=14, 2.1%), and others (n=17, 2.6%). A total of 23 sessions were offered, most of which were bilingual (Spanish and English). Feedback from the evaluation questionnaire indicated that the content of the conference was very relevant to the participants' professional practice. Additionally, the participants reported that they were very satisfied with the organization, the web-based platform, and the sessions of the conference. Lack of accessibility to the latest and cutting-edge medical education in pediatric endocrinology and diabetes for medical professionals from low- and middle-income countries can be overcome with a virtual conference. Online availability, low cost, and easy-to-use technology were well received from the participants, who were overall very satisfied by the quality and the relevance of the sessions to their professional practice.