Abstract Introduction As we introduce novel therapeutic strategies to treat young patients with central nervous system (CNS) tumors, it is critical to understand longitudinal impacts on brain development and overall health. PNOC COMP is a prospective study to collect data on long-term health outcomes, cognition, and quality of life (QOL). Methods Patients diagnosed 39 years old with CNS tumors were enrolled onto PNOC COMP concurrently with, or independent to, a PNOC therapeutic study. Study procedures included prospective collection of social determinants of health, self/proxy-report of QOL (Peds-QL, PROMIS, EORTC QLQ), self/proxy-report of executive function (BRIEF), functional independence (ABAS-3, MoFI), computerized cognitive assessments (Cogstate), long-term health effects, imaging (MRIs), and biospecimen banking of whole blood. Assessments were collected prior to treatment (baseline), during treatment, at end-of-treatment (EOT), and will continue to be collected for 20 years after EOT. This interim analysis includes data from study year 1 (Jan 2025-Jan 2026). Results 77 patients enrolled across 13 sites. Pathologic diagnosis included diffuse midline glioma (42%), pilocytic astrocytoma (14%), ependymoma (8%), other glioma (8%), medulloblastoma (7%), and atypical teratoid rhabdoid tumor (8%). Participants had median age of 10 years; 26% of patients were >/=18 years. # of patients who completed study procedures at each timepoint were 77 (baseline), 24 (3 months), 15 (6 months), 5 (9 months), and 4 (end-of-treatment). Baseline QOL measures were completed in 60% of pediatric (<18yo) and 75% of adult patients (>/=18yo), and in 62.7% of high-grade tumor patients and 62.5% of low-grade tumor patients. Of 42 eligible patients, 32 completed >/=1 Cogstate assessment, and 7 completed repeated (>/=2) Cogstate assessments. Conclusions PNOC COMP provides a framework to collect critical longitudinal information to inform upfront treatment decisions, provide anticipatory guidance regarding late effects, and minimize long-term deficits in children and young adults diagnosed with CNS tumors.

Background: The incidence of pediatric thyroid cancer has been increasing, and care varies due to socioeconomic disparities or differing practice patterns. Clinical guidelines call for care in multidisciplinary teams to minimize variance and provide protocols. Based on expert opinion, we hope to describe the form and function of such multidisciplinary teams for pediatric thyroid programs. Methods: A modified Delphi method to reach consensus statements over two rounds. Twenty-one experts with varying backgrounds responded to each statement on a 9-point Likert scale. Upon completion of the survey, the panel reviewed and shared the results and comments from participants and modified the statements accordingly. This process was repeated such that statements reached consensus, were deemed no consensus, or had no change in the mean. Results: There was an 88% and 83% completion rate for Rounds 1 and 2, respectively. A consensus was observed that there is a distinct definable model of care for pediatric thyroid patients. No consensus was reached for the age range of patients, but programs should care for children with medullary thyroid cancer, differentiated thyroid cancer, and patients with genetic predisposition syndromes. A comprehensive team includes, but is not limited to, a thyroid surgeon, a pediatric endocrinologist, a high-volume fine-needle aspiration (FNA) proceduralist, an oncologist, a nuclear medicine physician, a pediatric pathologist, a pediatric radiologist, and a nurse coordinator. Necessary support services involve care coordination, access to a multidisciplinary tumor board, ability to perform ultrasound-guided FNA, and access to molecular testing. The panel emphasized cross-institutional collaborative research prioritizing guidelines development, disease-specific outcomes, treatment toxicity, and the molecular landscape of thyroid cancer. Conclusions: These consensus statements can be beneficial in improving multidisciplinary care, by describing which elements of pediatric thyroid programs should be consistent across institutions. Overall, the panel agreed that pediatric thyroid centers should provide integrated care with defined team members, services, resources, and research priorities. This model has the potential to standardize various aspects of clinical care and enhance our ability to study patient outcomes, improve health care delivery, and increase scholarly collaboration.

Objective: The primary objective of this study was to evaluate the first full-scale implementation of the behavioral health program Novel Interventions in Children's Healthcare (NICH) in racially and ethnically diverse youth with diabetes and high degrees of social risk. We hypothesized that youth would demonstrate improved health outcomes and psychosocial functioning following program involvement. Methods: Youth with diabetes who enrolled in NICH (n = 26) and their caregivers completed measures of diabetes distress, depression, and diabetes strengths prior to and following program enrollment. Electronic health records were reviewed to describe change in hemoglobin A1C, change in continuous glucose monitoring use, and change in the number of hospital admission days from baseline to the time following program participation. Parametric and nonparametric tests were used to compare data. Results: Youth (mean age, 13.7 +/- 3.5 years, 92% from historically marginalized racial or ethnic groups, 96% with public insurance) demonstrated a significant (P < .01) mean hemoglobin A1C reduction of -1.1% (-12 mmol/mol) and increase in continuous glucose monitoring use (27%-73%) 1 year following NICH enrollment, and they had significantly fewer hospital admission days over time. Youth reported significant reductions in depressive symptoms, and caregivers reported significant reductions in diabetes distress after participation in NICH (P < .05). Conclusion: This study is the first to show successful full-scale implementation of NICH in a new geographic location with unique racial and ethnic diversity and social challenges, demonstrating associations with improved health and well-being. (c) 2025 AACE. Published by Elsevier Inc. This is an open access article under the CC BY license (http://

Disclosure: M. Lodish: Consultant for Neurocrine Biosciences, Inc. P.Y. Fechner: Research supportfrom Neurocrine Bioscience, Spruce Bioscience, and Diurnal UK Ltd and have served on an advisory board as a consultant for Neurocrine Bioscience. L.N. Trinh: None. M.S. Kim: Receives research funding from Neurocrine Biosciences, Spruce Biosciences, Adrenas Therapeutics, Diurnal, Serves on advisory boards for Eton Pharmaceuticals, Neurocrine Biosciences, Serves on steering committee for Spruce Biosciences, Receives royalties from UpToDate. M. Bettendorf: None. M. Salerno: None. M.T. Dattani: Received lecturing fees from Meck Serono, Pfizer, Novo Nordisk, Sandoz; served on advisory Boards for Pfizer, Novo Nordisk; consulted for: Sandoz, Pfizer, Besins. G.B. Rosales: Full-time employee of Neurocrine Biosciences, Inc. E. Roberts: Full-time employee of Neurocrine Biosciences, Inc. G.S. Jeha: Full-time employee of Neurocrine Biosciences, Inc. R.H. Farber: Full-time employee of Neurocrine Biosciences, Inc. J.L. Chan: Full-time employee of Neurocrine Biosciences, Inc.. Background: Crinecerfont, a corticotropin releasing factor type 1 receptor (CRF1) antagonist, is a first-in-class medication that is FDA-approved as an adjunct to glucocorticoid (GC) replacement to control androgens in patients with classic congenital adrenal hyperplasia (CAH). In two phase 3 trials, crinecerfont significantly reduced androstenedione (A4), enabling subsequent GC dose reductions in pediatric and adult patients with CAH. Objective: To analyze changes in GC doses in conjunction with A4 levels in CAHtalystTM Pediatric (NCT04806451). Methods: Patients with CAH, ages 4-17 years, were randomized 2:1 to 28 weeks of double-blind treatment with crinecerfont (25, 50, or 100 mg BID based on weight) or placebo. GC doses were kept stable for the first 4 weeks to measure the impact on androgens and then reduced (if possible based on A4) to a target dose of 8-10 mg/m2/d in hydrocortisone equivalents (HCe) by Week 28 while maintaining or improving A4 relative to baseline (BL). Achievement of a daily GC dose ≤11 mg/m2/d (protocol-defined “physiologic” range) while A4 was maintained or improved was assessed at Week 28 (secondary endpoint, with nominal P-value). Since A4 could be higher than the upper limit of normal (>ULN) at BL (and thus possibly elevated at Week 28 despite being maintained), a post hoc quadrant analysis was conducted based on A4 normal range, with participants categorized at BL and Week 28 by GC dose (≤11 mg/m2/d or >11 mg/m2/d [“supraphysiologic” range]) and A4 (≤ULN or >ULN). Results: All participants were taking supraphysiologic GC doses at BL per study inclusion criteria (GC >12 mg/m2/d HCe). At Week 28, 30% (20/67) achieved GC ≤11 mg/m2/d with crinecerfont while maintaining or improving A4, compared to no participants (0/31) with placebo (P=0.0009). In the post hoc quadrant analysis, most participants had A4 >ULN at BL: crinecerfont 83% (55/66); placebo 81% (25/31). At Week 28, 36% (24/66) of crinecerfont-treated participants achieved GC ≤11 mg/m2/d; of these, 50% (12/24) also had A4 ≤ULN. In contrast, no participants in the placebo group were taking GC ≤11 mg/m2/d at Week 28, and 68% (21/31) had A4 >ULN despite supraphysiologic GC dosing. Conclusion: In the 28-week CAHtalyst Pediatric study, 30% of participants receiving crinecerfont achieved a physiologic GC dose (≤11 mg/m2/d HCe) while maintaining or improving A4. Post hoc analyses showed 36% achieved a physiologic GC dose with crinecerfont regardless of A4 level; of these, 50% had normal A4. In contrast, no participants achieved a physiologic GC dose with placebo, and 68% had elevated A4 despite supraphysiologic GC dosing. Given the known adverse effects of elevated androgens and chronic supraphysiologic GC treatment, crinecerfont represents a therapeutic approach in which the dual goals of reducing androgen excess and decreasing GC to a more physiologic range can be achieved. Presentation: Saturday, July 12, 2025

Background: Disparities in glycemic outcomes and technology use in children with type 1 diabetes (T1D) from under-resourced backgrounds are well-documented. The feasibility of initiating automated insulin delivery (AID) soon after diagnosis of T1D is unknown in this population. This pilot study assessed the feasibility and acceptability of providing access to the Tandem Control-IQ Hybrid Closed-Loop (HCL) system to children with public insurance soon after diagnosis of T1D. Methods: Publicly insured child ren aged 6-17 years within 3 months of T1D diagnosis were eligible for the study. Participants were randomized 2:1 to HCL or control for 6 months. Continuous glucose monitoring data for both groups were collected at baseline, 3 months, and 6 months after enrollment. Caregivers and adolescents completed a closing survey on safety and user experience. Results: Seventeen participants were enrolled, 12 in the intervention group and 5 in the control group. The mean age was 11.5 ±2.5 years, 47% were female, 88% were from underrepresented racial or ethnic groups, 94% of caregivers did not have a college level degree, and 41% of families reported some degree of food insecurity. All families had access to smartphones, but 42% did not have access to a home computer. Of those who completed the study, a larger proportion of the intervention group compared to the control group achieved ADA benchmark of greater than 70% time in range (62% vs 0%, respectively, at 3 months, p=0.038; 37% vs 0% at 6 months, p=0.16). All caregivers in the intervention group reported satisfaction with HCL system and wished to continue using HCL technology. Conclusion: Early initiation of AID is feasible and acceptable in youth with recently diagnosed T1D from historically marginalized racial and ethnic groups and with social risk factors associated with lower technology adoption and less optimal glycemic outcomes. Clinicians should provide education and support for AID to these families early in diagnosis to promote equity in diabetes care. Disclosure K.Yen: None. S.Belapurkar: Other Relationship; T1D Exchange, Research Support; Dexcom, Inc., Tandem Diabetes Care, Inc., Medtronic. J.G.Hickey: None. L.Yglecias: None. K.S.Bal: None. L.Carelli: None. C.M.Loucel: None. M.Lodish: None. J.C.Wong: Research Support; Dexcom, Inc., Tandem Diabetes Care, Inc.

BACKGROUND:In children and adolescents/young adults (CAYA) with neurofibromatosis type I (NF1), associations between anthropometric measurements, plexiform neurofibroma (pNF) tumor volume (TV), and treatment history are unknown. METHODS:We retrospectively investigated anthropometrics in CAYA on the National Cancer Institute (NCI) NF1 Natural History Study who had pNF TV assessed by imaging (n = 106). We determined CDC height/weight percentiles and estimated Preece-Baines (PB) height growth curve parameters. We evaluated variables that could impact height/weight including: (1) pNF volume, (2) pNF directed therapy, and (3) serum IGF-1. RESULTS:23% of males and 20% of females had height <5th percentile; 13% of males had weight <5th percentile. Estimated median final adult height for males was 171.6 cm (CDC 23rd percentile) and for females was 156.2 cm (CDC 14th percentile). Inverse associations between height and weight percentiles and pNF volume were observed (Spearman's r = -0.277, -0.216, respectively). Estimated median final height was not meaningfully affected by patients who received pNF-directed treatment with MEK inhibitor. 52% of low serum IGF-1 measurements were concurrent with a height percentile <5th. CONCLUSIONS:Greater than expected percentages of patients had height/weight <5th percentile, and median final adult heights were <CDC 25th percentile. pNF volume was inversely associated with height/weight percentiles. IMPACT STATEMENT:Children and adolescents/young adults with neurofibromatosis type I (NF1) seen at a research hospital have lower height and weight percentiles than normative populations. Growth percentiles are inversely associated with plexiform neurofibroma tumor volumes and impacted little by MEKi treatment history in this subset of patients. These findings align with prior investigations of growth in the NF1 population but are the first to examine the association with tumor burden.

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Abstract Objectives Polycystic ovary syndrome (PCOS) increases non-alcoholic fatty liver disease (NAFLD) risk and severity in adults, but data in adolescents with diverse backgrounds are limited. We evaluated NAFLD prevalence and characterized NAFLD risk factors in overweight/obese adolescents by PCOS status. Methods Retrospective study of overweight (n=52)/obese (n=271) female adolescents (12–18 years old), evaluated clinically 2012–2020, was conducted comparing PCOS patients to age-matched non-PCOS controls. NAFLD was defined as ALT≥44U/L x2 and/or ≥80U/L x1, hepatic steatosis on imaging, or NAFLD on biopsy, in absence of other liver disease. Metabolic comorbidities were captured. Log-binomial regression models estimated prevalence risk ratios (PR). Results NAFLD prevalence was 19.1 % in adolescents with PCOS (n=161), similar to those without (n=162) (16.8 %, p=0.6). Adolescents with PCOS were more likely to have insulin resistance, hypercholesterolemia, and higher triglycerides (p<0.05). Those with PCOS and concomitant type 2 diabetes (T2DM) did have increased NAFLD risk (PR 2.5, p=0.04), but those with PCOS without T2DM did not (PR 0.9, p=0.8). Adolescents with PCOS and NAFLD, compared to those with PCOS without NAFLD, had a higher prevalence of metabolic comorbidities including hypercholesterolemia (77 vs. 48 %), T2DM (29 vs. 8 %), and hypertriglyceridemia (65 vs. 37 %) (p<0.01). Conclusions Almost 1 in 5 overweight/obese female adolescents had NAFLD, but PCOS did not increase NAFLD risk in this diverse cohort. Among young women with PCOS, concomitant T2DM did increase the risk for NAFLD. Closer monitoring of obesity comorbidities in adolescents with PCOS is essential for optimizing health and merits updating current guidelines.

Patients #9, #12, #14, and #17 experienced progressive disease while on vandetanib therapy. Calcitonin and CEA are shown as percent change from baseline at the start of vandetanib therapy (left y-axis). Tumor size is the sum of longest diameter of lesions per RECISTv1.0 (right y-axis).

Background: Social determinants of health (SDOH) lead to health disparities. Novel Interventions in Children's Healthcare (NICH) is a community-based program for youth with chronic conditions such as diabetes, with a high degree of social risk. We describe changes in depressive symptoms, diabetes distress, and diabetes strengths in youth with diabetes and their caregivers who completed one year in NICH at UCSF. Methods: NICH participants in this analysis had diabetes and were ≥12 years old. All completed the Patient Health Questionnaire-8 (PHQ-8), Problem Area in Diabetes-Teen (PAID-T), and those ≥14 years completed the Diabetes Strength and Resilience measure for adolescents (DSTAR-Teen) at baseline and one year. Caregivers completed the parent PAID-T (P-PAID-T). Paired t-tests were used to compare scores at baseline and one year when scores for both time points were available. Results: Participants included 15 youth with type 1 and 1 with type 2 diabetes. Mean age was 15.4 ± 1.6 years, 88% were from historically marginalized racial or ethnic groups, and 94% had public insurance. Families had a mean of 8 ± 4.8 social risk factors at baseline, the most common being educational barriers, mental health needs, and trauma. Mean PHQ-8 scores decreased from 8.4 ± 6.4 at baseline to 4.3 ± 5.4 at one year (p=0.014, n=10). Mean PAID-T scores trended towards decreasing from baseline (70.7 ± 19.8) to one year (58.8 ± 22.9, p=0.24, n=10), and mean P-PAID-T scores significantly decreased from 57.3 ± 17.8 to 45.3 ± 16.8 (p=0.044, n=6). Mean DSTAR-Teen scores increased from 44.6 ± 6.3 to 48.9 ± 8.1 at one year (p=0.065, n=8). Conclusions: Participation in NICH is associated with fewer depressive symptoms, less caregiver diabetes distress, and a trend towards reduced distress in youth and improved diabetes-specific strengths. Further research on SDOH among underrepresented populations is needed, as interventions mitigating social risk have potential to improve psychosocial outcomes. Disclosure A.Reed: None. M.A.Harris: None. M.Lodish: None. J.C.Wong: Research Support; Dexcom, Inc., Tandem Diabetes Care, Inc. C.E.Noya: None. D.V.Wagner: None. J.H.Lim: None. V.Glocker: None. K.S.Bal: None. M.Gonzales granados: None. A.Stone: None. M.T.Mcgrath: None. Funding The Leona M. and Harry B. Helmsley Charitable Trust

Absolute numbers of CD3+ and CD4+ HLA-DR+ activated T cells increase at day 21 and day 42 following ipilimumab infusion.

PDF file - 118K, Supplemental Data Table 1: Additional Eligibility Criteria. Supplemental Table 2: Drugs that are generally accepted as having a risk of causing Torsades de Pointes and were restricted during enrollment on this clinical trial. Supplemental Table 3: Schedule of Required Evaluations.

Doubling time of calcitonin and CEA for patient #12 was suggestive of progressive disease. Patient #12 experienced best response 434 days after starting vandetanib, with stable lesions in the thyroid bed (showed on T2-weighted MRI of the neck, A) and the mediastinum (showed on CT of the chest, B). In August 2016, the sum of longest diameter (per RECIST) of target lesions was consistent with SD (C,D) (note that not all target lesions are shown). Biomarker response in the two years prior (E) showed CEA doubling time 1.2 years (F) and calcitonin doubling time 1.67 years (G). Patient #12 was confirmed to have PD via RECIST February 2017.

Objective Hypospadias is a common congenital abnormality that has been increasing in prevalence over the last decades. Historically, 46, XY patients with severe hypospadias and descended scrotal testes at birth have frequently lacked a genetic diagnosis. Plat-forms for molecular genetic testing have become more readily available and can offer an insight into underlying genetic causes of severe hypospadias. The goal of this study was to define the anatomical characteristics of severe hypospadias that can accurately define patients with 46, XY severe hypo-spadias and determine the practical utility of per-forming molecular genetic testing in this group of patients. Methods Patients who met the criteria for 46, XY severe hypospadias were offered a molecular genetic work-up in consultation with pediatric genetics. Patients were identified through chart review. Data extrac-ted included karyotype, hypospadias phenotype including stretched penile length at diagnosis, age at genetic diagnosis, molecular genetic testing, path-ogenic gene variant(s), gender identity, and clinical course. All patients underwent clinical genetic testing via 46, XY Disorders of Sexual Development (DSD) panels offered by Invitae & REG;, GeneDx & REG;, or Blueprint Genetics & REG;. Results Of the 14 patients that underwent genetic testing, there were 5 previously published and 3 novel pathogenic or likely pathogenic variants in genes associated with 46, XY severe hypospadias (Table). Pathogenic variants were identified in AR (3), SRD5A2 [1], NR5A1 [2], WT1 [1], and ARTX [1]. Two patients had a variant of unknown significance, one in FREM2 and another in CEP41. Four had negative gene panels. The patient with the WT1 pathogenic variant was subsequently found to have developed a Wilms tumor and the patients with NR5A1 patho-genic variants are now undergoing adrenal insuffi-ciency surveillance. Discussion/Conclusion Patients with 46,XY severe hypospadias and descended testes in the scrotum at birth can benefit from molecular genetic testing as their underlying disorders may reveal pathogenic variants that could have potentially life-altering consequences and change surveillance and monitoring.

Weight-for-age and height-for-age growth curves. Male patient weights (A), heights (B) and female patient weights (C), and heights (D) were monitored during the follow up period. Patient weight-for-age and height-for-age values were compared to U.S. Center for Disease Control reference growth curves.

Patients #2, #5, #10, #11, #13, #15, and #16 experienced durable SD or PR during the follow up period. Calcitonin and CEA are shown as percent change from baseline at the start of vandetanib therapy (left y-axis). Tumor size is the sum of longest diameter of lesions per RECISTv1.0 (right y-axis).

Legends for all included Supplementary Figures

Growth hormone (GH) has been used for over 35 years, and its safety and efficacy has been studied extensively. Experimental studies showing the permissive role of GH/insulin-like growth factor 1 (IGF-I) in carcinogenesis have raised concerns regarding the safety of GH replacement in children and adults who have received treatment for cancer and those with intracranial and pituitary tumours. A consensus statement was produced to guide decision-making on GH replacement in children and adult survivors of cancer, in those treated for intracranial and pituitary tumours and in patients with increased cancer risk. With the support of the European Society of Endocrinology, the Growth Hormone Research Society convened a Workshop, where 55 international key opinion leaders representing 10 professional societies were invited to participate. This consensus statement utilized: (1) a critical review paper produced before the Workshop, (2) five plenary talks, (3) evidence-based comments from four breakout groups, and (4) discussions during report-back sessions. Current evidence reviewed from the proceedings from the Workshop does not support an association between GH replacement and primary tumour or cancer recurrence. The effect of GH replacement on secondary neoplasia risk is minor compared to host- and tumour treatment-related factors. There is no evidence for an association between GH replacement and increased mortality from cancer amongst GH-deficient childhood cancer survivors. Patients with pituitary tumour or craniopharyngioma remnants receiving GH replacement do not need to be treated or monitored differently than those not receiving GH. GH replacement might be considered in GH-deficient adult cancer survivors in remission after careful individual risk/benefit analysis. In children with cancer predisposition syndromes, GH treatment is generally contraindicated but may be considered cautiously in select patients.