Lteif, Aida

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 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 Melanocortin‐4 receptor (MC4R) deficiency is the most common cause of monogenic obesity; yet treatment options for children with MC4R mutations are limited. We describe significant improvement in weight in three patients with pathogenic or likely pathogenic MC4R mutations; two adolescents treated with semaglutide, and a younger child treated with metformin and topiramate. These findings indicate GLP‐1 receptor agonists, topiramate and metformin can be helpful in managing obesity associated with MC4R deficiency.

Abstract Context Pharmacological options for the treatment of early severe childhood obesity are limited. Objective This retrospective case series evaluates the effect of topiramate on weight and cardiometabolic parameters in young children with severe obesity, including those with hypothalamic etiologies. Methods This is a retrospective case series including 14 children with severe obesity, who were treated with topiramate prior to age 12 years. Anthropometric and metabolic data were analyzed. Results The median age at initiation of topiramate treatment was 10.1 years (range, 7.9-11.2 years) and 64% were boys. At baseline, the median body mass index (BMI) was 149% of the 95th percentile (range, 136%-200%). The median treatment duration was 14 months (interquartile range, 9.5-24 months), with a maximum tolerated dose of 75 mg (range, 50-150 mg). There was a median decrease in BMI% of the 95th percentile of 8% (95% CI, −15 to −1.02; P = .042), and a reduction in BMI z score by 0.37 (95% CI, −0.66 to −0.05; P = .028). The most notable response was in a child with hypothalamic obesity who experienced a 35-point reduction in BMI% of the 95th percentile over 24 months. While 11 of 14 children showed reduction in BMI, 3 had no change or increase in their BMI. No significant changes were observed in cardiometabolic markers or linear growth. Conclusion Topiramate monotherapy resulted in significant BMI reductions in young children with severe obesity, including those with hypothalamic obesity. Further prospective randomized controlled trials are warranted to assess its long-term efficacy for obesity management in young children.

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: R. El Mouallem: None. T. McKenzie: None. A.N. Lteif: None. Background- Pancreatic neuroendocrine tumors (PNETs) are rare, but their incidence is rising. Ethanol ablation is increasingly used in adult patients with insulinomas or small nonfunctional PNETs, particularly in patients who are ineligible for surgical resection. Ethanol ablation of a PNET has not been previously reported in the pediatric population. Clinical Case- A 12-year-old female with known multiple endocrine neoplasia type 1 (MEN1) and multifocal PNETs presented for evaluation of a 1.3 cm nonfunctional, Dotatate avid pancreatic uncinate lesion. A CT angiogram of the pancreas revealed an arterially enhancing 1.3 cm nodule, which measured 8 mm one year prior. There was no evidence of metastatic disease. Given the increasing size of the lesion and young age of the patient, operative intervention was pursued. Due to the depth of the lesion and its proximity to the pancreatic duct during operative pancreas ultrasonography, surgical enucleation was deemed non-feasible. During the procedure, 7 additional subcentimeter pancreatic lesions concerning for PNETs were identified in the pancreatic body, tail, head and neck-body junction. Ultrasound guided ethanol ablation of the primary lesion was performed. Follow-up imaging demonstrated a promising response. 7 months post ablation, a Dotatate PET CT scan showed persistent focal uptake in the region of the ablated nodule. However, by 9 months, MRI abdomen revealed a decrease in the size of the lesion, now measuring 6 mm, with stable Dotatate uptake. By 19 months post ethanol ablation, the previously hyper-enhancing lesion was no longer visible on MRI, demonstrating complete structural resolution. Conclusion- This case demonstrates that ethanol ablation is a promising treatment option for PNETs in the pediatric population. Given the complexities of surgical resection in children, particularly for deep or anatomically challenging lesions, ethanol ablation offers a potentially less morbid alternative with encouraging outcomes. Further research may establish this approach as a viable option for select pediatric patients. 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 Background Children with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency typically have height, weight, and body mass index (BMI) growth patterns that differ from the general population due to increased androgen and/or glucocorticoid exposures. With the recent surge in the development of new therapies, CAH-specific growth charts are needed to evaluate the effectiveness of these new treatments. Methods Retrospective data from patients aged 0 to 20 years with classic CAH, confirmed by hormonal testing and/or CYP21A2 genotyping, from 2 large clinical databases were analyzed. Specialized charts were developed using the lamda-mu-sigma semiparametric modeling method to generate CAH-specific percentile curves from 0 to 20 years. Nodal-point analyses were conducted to assess differences in incremental growth at 4, 8, 12, 16, and 20 years of age relative to Centers for Disease Control and Prevention (CDC) 2000 normative charts using 1-sided quantile tests and age of adiposity rebound estimated with curve derivative solutions. Results A total sample of 8692 visits from 515 patients was used. Growth (height-, weight-, BMI-for-age) channels of CAH patients were significantly different over the entire growing period and characterized by diminished pubertal spurt relative to the CDC reference. Onset of adiposity rebound based on BMI-for-age occurred earlier for CAH patients (females 3.3 years, males 3.9 years) compared to their normative counterparts (5-8 years). Conclusion Our study showed that at incremental time points throughout childhood, children with CAH collectively follow specific differences in growth trajectories as compared to unaffected children. These variations highlight the need for CAH-specific charts to assist in clinical management, appraisal of growth trajectories, and assessment of the impact of new therapies.

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.

This cohort study conducted among Minnesota children diagnosed with adrenoleukodystrophy through newborn screening examines correlation of C26:0 lysophosphatidylcholine (C26LPC) with clinical phenotype over 5 years and recommends adjusting early childhood surveillance regimens in children with lower C26LPC levels.