Citations

Abstract Purpose Sellar and parasellar lesions in children have heterogeneous clinical presentations and variable endocrine morbidity. Population-based data describing endocrine outcomes across lesion types and management strategies remain limited. Methods We conducted a retrospective, population-based cohort study of patients aged 18 years or younger who were diagnosed with sellar or parasellar lesions between 1976 and 2021 in a multicounty region. Clinical presentation, lesion characteristics, management, and endocrine outcomes were abstracted from medical records. Associations were evaluated by lesion type, lesion size (< 10 mm vs. ≥10 mm), and management approach. Results Among 104 patients, endocrine abnormalities at diagnosis differed by lesion type (p = 0.0004) and were most frequent among patients with pituitary adenomas. Endocrine dysfunction at presentation was more common with lesions ≥ 10 mm than with lesions < 10 mm (74.2% vs. 49.2%; p = 0.0217). Post-treatment endocrine abnormalities were also more common with lesions ≥ 10 mm (64.5% vs. 13.1%; p < 0.0001). Surgical treatment was associated with a higher prevalence of post-treatment endocrinopathy, although this association may reflect lesion size, diagnosis, and treatment selection. Conclusions Endocrine morbidity was common in this population-based pediatric cohort and was associated with lesion type and size. Clinically relevant endocrine abnormalities also occurred in smaller lesions, supporting endocrine evaluation regardless of lesion size and the need for longitudinal surveillance in patients with sellar and parasellar disease.

Abstract Context Central precocious puberty (CPP). Objective To summarize the available supporting evidence for the Endocrine Society guidelines about the management of CPP. Methods Multiple databases (MEDLINE, EMBASE, Scopus) were searched to identify studies that addressed the Endocrine Society Guideline Development Panel's 10 clinical questions. Identified studies were selected and appraised, and data were extracted by pairs of independent trained reviewers. Results The systematic review yielded 3796 citations, of which 32 citations were included. The systematic review and meta-analysis demonstrate that in children with CPP, with no central nervous system symptoms, the rate of magnetic resonance imaging identification of pathogenic lesions (ie, hamartomas and brain tumors) was 6% (35 noncomparative studies with 5541 children with CPP). For girls with idiopathic CPP, gonadotropin-releasing hormone agonist (GnRHa) treatment was associated with +2.7 cm adult height gain compared to those who did not receive treatment (21 comparative observational studies with 1835 girls [mean age 8.20 ± 1.08 years]). The review did not identify any studies that assessed the clinical questions on: benefits of additional evaluation in cases of early thelarche, differentiation of slowly vs rapidly progressing CPP, order of biochemical testing to establish and monitor the diagnosis of CPP, genetic testing for individuals diagnosed with CPP, and chronological age and/or bone age for discontinuation of GnRHa treatment. Conclusion This systematic review addresses various aspects of CPP evaluation and treatment of CPP and will support the development of the Endocrine Society guidelines.

ABSTRACT Objectives To evaluate the impact of semaglutide on body mass index (BMI) and cardiometabolic markers in adolescents with obesity and genetic variants associated with monogenic or syndromic obesity. Methods A retrospective chart review was conducted in adolescents with severe obesity who underwent multigene panel testing and were treated with semaglutide. Results Twenty‐seven adolescents (mean age 15 ± 1.9 years); BMI % of the 95th percentile 158 ± 29; (70% White) were treated with semaglutide for a mean of 10 ± 4.7 months. Participants were classified into three groups: (1) Dominant or Known Risk Variants ( n = 7); (2) Carriers of Rare Variants in Recessive Genes ( n = 10); and (3) Negative or Unmatched Genetic Findings ( n = 10). All groups showed reductions in BMI, which was not different between the groups. Adolescents with dominant or known risk variants experienced a significant decrease in BMI % of the 95th percentile (−17, (IQR −26 to −10) p = 0.022) and in BMI by −9.4% ± 7% ( p = 0.035). Significant improvements in median non‐HDL cholesterol (−16 mg/dL), total cholesterol (−15 mg/dL), and HbA1c (−0.3%) were noted in children with dominant or known risk variants ( p = 0.036). Conclusions Semaglutide was associated with significant reductions in BMI and cardiometabolic markers in adolescents (majority White) with dominant or known risk variants for monogenic obesity.

Abstract Disclosure: L. Saba: None. K. Leopold: None. A.N. Lteif: None. A. Al Nofal: None. Objectives: Glucagon-like peptide-1 receptor (GLP-1R) agonists are currently approved for the treatment of type 2 diabetes and obesity in patients aged ≥10 and ≥12 years, respectively. While studies in adults with type 1 diabetes mellitus (T1DM) suggest potential glycemic benefits of GLP-1R agonists, data on their role in pediatric patients with T1DM and concomitant obesity remains limited. This case series evaluates the safety and efficacy of GLP-1R agonists as an adjunct to insulin therapy in pediatric patients with T1DM and obesity. Methods: A single-center retrospective review examined pediatric patients with T1DM and obesity who initiated GLP-1R agonists at &lt;18 years of age. Data were collected from chart review and analyzed from 120 days prior to GLP-1R agonist initiation until medication discontinuation, transfer of care, or January 1, 2025. Results: 5 patients (aged 12-17 years, 4 female) with T1DM and obesity all received the GLP-1R agonist semaglutide at a mean of 5.2 years post-T1DM diagnosis. 3 patients had ≥2 positive T1DM autoantibodies, 1 had positive ZnT8 antibodies only, and 1 lacked autoantibody testing. All patients were receiving insulin therapy; 4 were utilizing insulin pumps. The overall treatment duration ranged from 194-437 days (mean: 9 months), with 3 patients experiencing interruptions (42-187 days) due to insurance or supply issues. Pre- and during-treatment data were compared with a mean interval of 140 days between GLP-1R agonist start date and comparison time point (range: 69-226 days). All patients showed reductions in glucose management indicator or hemoglobin A1c by an average of 1.2%. 3 of 4 patients with available data had decreased weight-adjusted total daily insulin requirements by 30-33% (absolute dose reduction of 0.1-0.3 units/kg/day), while 1 patient had no change. Time in range increased in all 5 patients by an average of 14.2%. The average BMI change was -9%. Adverse effects included nausea, vomiting, and abdominal pain in patient 1 leading to GLP-1R agonist discontinuation; this patient also experienced 4 episodes of diabetic ketoacidosis during treatment. Increased hypoglycemia frequency was observed in patients 2, 3, and 4, however, none required glucagon administration. To mitigate hypoglycemia risk, pump settings were proactively adjusted in patients 1 and 4. Conclusions: Beyond promoting weight loss, GLP-1R agonists show promise as an adjunctive therapy in pediatric patients with T1DM and obesity by improving glycemic control and reducing insulin requirements. The observed reduction in insulin requirements per body weight suggests an underlying degree of insulin resistance in these patients. Preemptive decrease in insulin doses with each increase in GLP-1R agonist dose should be considered to mitigate hypoglycemia risk. Larger studies are needed to assess long-term safety and efficacy in the pediatric population with T1DM and obesity. Presentation: Saturday, July 12, 2025

Abstract Disclosure: A. Al Nofal: None. K. Benkhadra: None. M. Nduwimana: None. A. Mohammad: None. A. Abbas: None. Z. Wang: None. M. Murad: None. Background: Hybrid closed-loop (HCL) systems for automated insulin delivery are increasingly used in diabetes management. However, their safety and efficacy in pregnant women with pre-existing type 1 diabetes remain uncertain. Aim: To assess the safety and effectiveness of HCL systems in pregnant women with pre-existing type 1 diabetes compared to current standard of care. Methods: A comprehensive search of several databases was conducted from inception to January 3rd, 2024. Pairs of independent reviewers screened abstracts. Abstracts included by at least one reviewer were reviewed in full text by a pair of independent reviewers. The DerSimonian and Laird random effects model with the Hartung-Knapp-Sidik-Jonkman method was used to pool effect sizes across the included studies. Results: Five randomized controlled trials (RCTs) with 274 pregnant women with type I diabetes met the inclusion criteria. Our meta-analysis showed no significant difference between HCL and standard of care regarding overall time in range (TIR), time above range (TAR), and time below range (TBR). However, overnight, women using HCL showed significantly higher TIR (mean difference: 10.18%, CI 7.42-12.94%) and lower TBR (mean difference: -0.67%, CI -0.91 to -0.43%) compared to those using standard care. Additionally, there were no significant differences between HCL and standard of care in term of LGA, SGA, neonatal hypoglycemia, and maternal severe hypoglycemia or hyperglycemia. Conclusion: HCL systems for management of pre-existing type I diabetes during pregnancy are associated with similar outcomes without increased risk of complications when compared to standard of care. This is derived from limited number of RCTs with low risk of bias but significant imprecision, which warrant low confidence. Presentation: Sunday, July 13, 2025

Abstract Disclosure: M. Salama: None. F. Pinto e Vairo: None. D. Hassan: None. S. Pittock: None. A. Lteif: None. O. Olson: None. A. Al Nofal: None. K. Leopold: None. S. Kumar: None. Objective: This study aimed to evaluate the effects of semaglutide on body mass index (BMI) and cardiometabolic profiles in adolescents with genetic variants associated with a likely high risk of monogenic obesity. Methods: A retrospective chart review was conducted for adolescents with severe obesity who underwent multigene panel testing for monogenic obesity and were treated with semaglutide. Results: Data from 27 adolescents were analyzed. At baseline, the median BMI percent of the 95th percentile (IQR) was 148 (135-189), with a mean age (SD) of 15.5 years (1.93) at treatment initiation and a median (IQR) treatment duration of 8 months (6-12). The median semaglutide dose (IQR) was 1.7 mg weekly (1.0- 2.4). Seven participants comprised the ‘’likely monogenic risk’’ group, characterized by predicted deleterious variants in dominant genes and/or carrying known dominant risk alleles. Twenty patients formed the “indetermined/negative “group, defined as harboring single rare variants in recessive genes or negative panel testing. In the likely monogenic risk group, weight loss was 8.5% with a median decrease in BMI % of the 95th %ile of 17 (95% CI 1.5- 22, p = 0.02). In the indetermined/negative group, weight loss was 7.6% with a median decrease in BMI % of the 95th %ile of 14 (95% CI 11.5- 27.5, p = &lt;0.001). There was no statistically significant difference in median BMI % of the 95th % ile reduction between the two groups (p = 0.8) or BMI percent change (p = 0.89). Cardiometabolic changes in the likely monogenic risk group included reductions in HbA1c by 0.3% (95% CI: 0.15- 0.4, p = 0.03), total cholesterol by 15 mg/dL (95% CI: 7- 48, p = 0.03), and non-HDL cholesterol by 16.5 mg/dL (95% CI: 12- 40, p = 0.03). No significant changes were observed in fasting blood glucose, triglycerides, LDL cholesterol, HDL cholesterol, or ALT levels. The indetermined/negative group exhibited a significant reduction in HbA1c by 0.25% (95% CI 0.1 - 0.7| p = 0.009). Conclusion: Semaglutide treatment was associated with significant reductions in BMI and improvements in several cardiometabolic parameters in adolescents with likely high-risk monogenic obesity variants. These findings suggest semaglutide as a potentially effective therapeutic option for managing severe obesity in this population. Larger prospective studies are warranted to confirm and further assess these outcomes. Presentation: Monday, July 14, 2025

Abstract Context Women with preexisting diabetes mellitus (PDM) are at increased risk of pregnancy-related complications. Objective To summarize the available supporting evidence for the Endocrine Society guidelines about management of PDM in pregnancy. Data Sources MEDLINE, EMBASE, Scopus, and other sources through February 2025. Study Selection Studies were selected by pairs of independent reviewers. Data Extraction Data were extracted by pairs of independent reviewers. Data Synthesis We included 17 studies. Meta-analysis showed no significant difference between hybrid closed-loop insulin pump (HCL) and standard of care regarding time in range (TIR), time above range (TAR), and time below range (TBR). HCL had better overnight TIR and TBR. For women with type 2 diabetes mellitus (T2DM), intermittent use of continuous glucose monitoring (CGM) was not associated with a significant change in the risk of large for gestational age (LGA) neonates (2 randomized controlled trials [RCTs], 102 patients). Adding metformin to insulin was associated with a lower risk of LGA (2 RCTs, 1126 patients). Three retrospective studies (1724 patients) suggested increased neonatal complications when delivery was induced before 39 weeks of gestation (particularly before 38 weeks) in women with preexisting type 1 (T1DM) and T2DM, although this evidence was subject to likely confounding. One retrospective study showed no increase in neonatal complications with periconceptional exposure to glucagon-like peptide-1 receptor agonists. We could not identify comparative studies assessing a screening question about the possibility of pregnancy or a carbohydrate restrictive diet. Conclusion This systematic review addresses various aspects of managing PDM in pregnancy and will support the development of the Endocrine Society guidelines.

Background Previous studies have demonstrated disparities in the utilization of diabetes technology among youth with type 1 diabetes (T1D) based on race and socioeconomic status (SES). Few studies have examined these differences on a national scale or among youth with commercial health insurance. Aim To investigate differences in the fill rates of insulin pumps and continuous glucose monitors (CGMs) among commercially insured children with T1D across diverse racial and SES groups. Methods Using medical and pharmacy claims included in the OptumLabs Data Warehouse, we calculated the proportion of youth <18 years with T1D who had a fill for an insulin pump or a CGM, overall and stratified by race/ethnicity and annual household income, between 2011 and 2021. Results Among 13,246 youth with T1D, 36.1% had CGM and 30.9% had pump fills. White youth had higher CGM and pump fills than black (CGMs: 35.8% vs 22.5%; pumps: 31.9% vs 21.2%, p<0.001) and Hispanic (CGMs: 35.8% vs 32.6%, p=0.047; pumps: 31.9% vs 25.0%, p<0.001). Youth from households with income <US$40,000 had lower CGM and pump fills than those with income ≥US$200,000 (CGM 25.4% vs 43.8%; pumps: 22.4% vs 38.8%, p<0.001). Within similar incomes <US$40,000, black youth had fewer CGM and pump fills than white youth (CGM: 15.2% vs 27.9%, p=0.006; pumps: 12.9% vs 25.5%, p=0.004). This racial difference disappeared with income ≥US$200,000 (CGMs: 47.5% for black vs 43.1% for white; pumps: 45.9% for black vs 38.3% for white, p=0.45 and p=0.57, respectively). Conclusions In a cohort of commercially insured youth with T1D, both race and income are important factors that can independently influence the use of diabetes technology. Racial disparities decrease with higher income and disappear at incomes ≥US$200,000. Black youth with income <US$40,000 are at the highest exclusion risk from essential technologies. Greater effort is needed at both the system and individual levels to mitigate these disparities.

Abstract Context Pituitary adenomas and cysts are rare in pediatric patients and improved understanding can guide management recommendations. Objective To report incidence, presentation, management, and outcomes in a pediatric population-based cohort with pituitary adenomas and cysts, and to explore the relationship between these lesions and brain magnetic resonance imaging (MRI) rates, as well as lesion size and headaches with disease progression. Methods In this retrospective cohort study of pediatric patients (≤18 years) with incident pituitary adenomas and cysts in Olmsted County, MN, from 1976 to 2021, 234 unique patients were identified using diagnostic codes through the Rochester Epidemiology Project, with 37 confirmed cases of pituitary adenoma or cyst included. Incidence rates were calculated using census data. Descriptive statistics were used for extracted clinical data. Results Incidence of pediatric adenomas and cysts was 2.29 cases per 100 000 person-years. Of the 37 cases, 68% were nonfunctioning adenomas or cysts, 27% were prolactinomas, and there was 1 each of growth hormone (GH)– and thyrotropin (TSH)-secreting adenomas. Median lesion diameter was 5.5 mm (IQR, 4.0-8.0). Median follow-up was 7.4 years (IQR, 4.5-15.4). Four patients had disease progression which stabilized with second-line therapy. Brain MRI rates did not correlate with lesion incidence. No clinically meaningful relationship was found between lesion size or headache and disease progression. Conclusion Pituitary adenomas and cysts are rare in pediatric patients. Most are small, nonfunctioning, and stable on long-term follow-up. Larger studies on small nonfunctioning pituitary lesions are needed to enhance understanding of their natural history and develop long-term management recommendations.

Abstract Hypophosphatasia (HPP) is characterized by defective bone mineralization due to reduced function of tissue-nonspecific alkaline phosphatase (TNSALP) caused by pathogenic ALPL gene variants. Hypercalcemia is more common in the perinatal and infantile forms and may be mitigated or prevented with enzyme replacement therapy asfotase alfa (AA). Here, we report a patient who developed severe hypercalcemia while receiving AA. Hypercalcemia was initially managed with intravenous fluids, dietary calcium restriction, and maximizing AA dose. Despite these measures, she required an additional hospital admission, at which time calcitonin 4 IU/kg every 12 hours was initiated. On this regimen, her calcium normalized without recurrence of severe hypercalcemia. Over the subsequent 8 months, restrictions of calcium intake were slowly lifted, and calcitonin was tapered and discontinued with maintenance of calcium within the normal range. This case underscores the significance of vigilant monitoring of calcium levels and dietary intake in infants diagnosed with HPP. While calcitonin is typically not considered as a sustained treatment for hypercalcemia, the present case illustrates the efficacy of adjunct calcitonin therapy, in conjunction with restricted calcium intake and maximum AA dosing, in managing severe hypercalcemia in an infant with perinatal HPP.