Leopold, Kaitlin

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 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: 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

SummaryObjectiveTo examine change in weight status following initiation of lisdexamfetamine in children with attention deficit hyperactivity disorder (ADHD) and overweight or obesity.Study DesignA retrospective chart review included children aged 2 to <18 years treated with lisdexamfetamine for ADHD. Body mass index (BMI) data for up to 2 years after initiation of lisdexamfetamine were analysed using linear mixed effects models with autoregressive‐1 correlation structure on time of follow‐up per patient.ResultsThe analysis included 330 children ≤18 years, median age 10 years (interquartile range 8.1–13) comprising 55 children with severe obesity, 88 with mild‐moderate obesity, 131 with overweight and 56 with healthy weight, 68% male and 32% female. At 2 years after initiation of lisdexamfetamine in the severe obesity group, the BMI Z‐score decreased by −0.41 (95% confidence intervals [CI] [−0.57, −0.25], p < 0.001) and BMI percent of the 95th percentile decreased by −11.2% (95% CI [−15.8 to −6.7], p < 0.001). In the mild–moderate obesity group, BMI Z‐score decreased by −0.44 (95% CI [−0.56, −0.31], p < 0.001) and BMI% of the 95th percentile decreased by −11.1% at 24 months (95% CI [−13.9 to −8.4], p < 0.001). In the mild–moderate obesity and overweight groups, younger children (ages 4–10) showed greater reduction in their BMI (p < 0.001 and p = 0.029, respectively).ConclusionReduction in BMI for age was noted for up to 2 years following initiation of lisdexamfetamine in children with ADHD and overweight and obesity. Further studies are warranted to study the weight loss effect of lisdexamfetamine in children with obesity.

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 Disclosure: K. Leopold: None. S. Polites: None. L. Binkovitz: None. L. Casas: None. A.N. Lteif: None. Title: An Unexpected Cause of Ga-68 Dotatate PET/CT Somatostatin Receptor Avidity in a Pediatric Patient with Hereditary Paraganglioma-Pheochromocytoma Syndrome due to an SDHA Mutation. Introduction: Individuals with Succinate Dehydrogenase (SDHx) gene mutations have an increased risk of paragangliomas and pheochromocytomas beginning in childhood.Clinical Case: A 9 year old male with Cornelia de Lange syndrome and a paternally inherited SDHA pathogenic gene variant (c1534C&gt;T) presented with worsening migraine headaches and skin pallor with activity. 24 hour urine fractionated metanephrines were mildly elevated, with metanephrine 122 mcg/24h (29-92 mcg/24 h), normetanephrine 187 mcg/24 h (34-169 mcg/24 h), and total metanephrine 309 mcg/24 h (47-223 mcg/24 h). Ga-68 DOTATATE PET/CT showed a focus of moderately increased radiotracer activity in the anterior aspect of the distal gastric antrum with a max SUV 8.2 corresponding to a 9x7 mm nodule on CT in the same area, suggestive of underlying somatostatin receptor positive lesion such as a paraganglioma. MRI with contrast completed to further characterize the lesion showed no visible mass corresponding to the focal area of radiotracer uptake on DOTATATE PET/CT. Repeat 24 h urine metanephrines continued to show mild elevation of metanephrine (138 mcg/24h), normetanephrine (200 mcg/24h), and total metanephrines (338 mcg/24h). 24 hour urine catecholamines, 5-Hydroxyindoleacetic acid, and homovanillic acid were normal. An upper endoscopic ultrasound was completed which confirmed the presence of a lesion near the stomach but not arising from the stomach wall and not consistent with a gastrointestinal stromal tumor. CT enterography with IV contrast showed a 6x6 mm enhancing mass within the distal right lateral gastric wall. Due to ongoing symptoms, mild elevations in urine fractionated metanephrines, and a clear mass on US and CT, the patient underwent laparoscopic abdominal exploration where a 14x14x13 mm mass with surrounding gastric and duodenal serosa was excised with primary closure of the bowel. Pathology showed ectopic pancreatic tissue in the wall of the small bowel and stomach. Repeat Ga-68 DOTATATE PET/CT 5 months following surgery showed resolution of the distal gastric somatostatin receptor avidity. Clinical Lesson: This is the first case of ectopic pancreatic tissue mimicking a paraganglioma in a pediatric patient with hereditary paraganglioma-pheochromocytoma syndrome. False positive imaging should be considered in patients with SDHx mutations when the uptake is atypical in location and when the elevation in urine metanephrines is mild. Presentation: 6/3/2024

AbstractBackgroundWe sought to evaluate the association between vitamin D deficiency and the severity of coronavirus disease 2019 (COVID‐19) infection.MethodsMultiple databases from 1 January 2019 to 3 December 2020 were searched for observational studies evaluating the association between vitamin D deficiency and severity of COVID‐19 infection. Independent reviewers selected studies and extracted data for the review. The main outcomes of interest were mortality, hospital admission, length of hospital stay and intensive care unit admission.ResultsSeventeen observational studies with 2756 patients were included in the analyses. Vitamin D deficiency was associated with significantly higher mortality (odds ratio [OR]: 2.47, 95% confidence interval [CI]: 1.50–4.05; 12 studies; hazard ratio [HR]: 4.11, 95% CI: 2.40–7.04; 3 studies), higher rates of hospital admissions (OR: 2.18, 95% CI: 1.48–3.21; 3 studies) and longer hospital stays (0.52 days; 95% CI: 0.25–0.80; 2 studies) as compared to nonvitamin D deficient status. Subgroup analyses based on different cut‐offs for defining vitamin D deficiency, study geographic locations and latitude also showed similar trends.ConclusionsVitamin D deficiency is associated with greater severity of COVID‐19 infection. Further studies are warranted to determine if vitamin D supplementation can decrease the severity of COVID‐19.