Citations

Background: Pharmacological options for severe obesity in early childhood are limited. While lisdexamfetamine is approved for attention-deficit/hyperactivity disorder (ADHD) and binge eating disorder, its role in managing obesity in children without these conditions has not been well studied. This case series assessed the effect of lisdexamfetamine on weight in young children with severe obesity but without ADHD or binge eating disorder. Methods: We conducted a retrospective chart review of six children with severe obesity treated with lisdexamfetamine for weight management. Demographic, anthropometric, and metabolic data were collected. One patient had Prader–Willi syndrome (PWS); the others had no known syndromic obesity. Results: Median age at treatment initiation was 6.5 years (range: 4.5–14), with equal male and female distribution. Median treatment duration was 12 months (range: 12–24), and mean maximum tolerated lisdexamfetamine dose was 35 mg (range: 10–60). In patients without syndromic obesity (n = 5) including one child with hypothalamic obesity, lisdexamfetamine significantly reduced body mass index (BMI) percent of the 95th percentile at 12 months (median change –24%, range: −18 to −28, p = 0.031), equating to a 13.8% reduction in BMI. Height percentile remained unchanged ( p = 0.59). The patient with PWS did not achieve lasting weight loss. Three children reported decreased appetite. Conclusions: Lisdexamfetamine was associated with weight loss in young children with severe obesity without genetic syndromes. Further studies are warranted to assess the long-term efficacy and safety of lisdexamfetamine in the management of pediatric obesity.

Abstract There is limited data on the effect of antiobesity medications in individuals with Bardet-Biedl syndrome (BBS). Here, we present a case of an adult with BBS who experienced significant weight loss following treatment with a combination of topiramate and phentermine. A 31-year-old female with BBS, with homozygous pathogenic variant in the BBS2 gene, presented with obesity, dyslipidemia, and obstructive sleep apnea. At 29 years of age, her body mass index (BMI) was 43.3 kg/m2 (reference range 18.5-24.9 kg/m2), and she was initiated on 50 mg topiramate daily for migraine prophylaxis. With lifestyle modifications, BMI dropped to 40.5 kg/m2. Subsequently, phentermine 30 mg daily was added. Eight months after adding phentermine, BMI significantly decreased to 31.5 kg/m² (27% decrease in BMI), with improvement in glycemic and lipid parameters. She developed paranoia due to a social stressor prompting a brief hold of phentermine and resumption at a lower dose. This case highlights the weight loss response with phentermine and topiramate combination therapy in a patient with BBS. Further research is needed to explore the efficacy and safety of conventional antiobesity medications in isolation, as sequential or combination therapy to setmelanotide, to most effectively impact weight and metabolic burden in patients with BBS.

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 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.

Abstract Disclosure: M. Salama: None. R. Basmaci: None. T. Rajjo: None. O. Chuzhyk: None. A.N. Lteif: None. A. Al Nofal: None. Objective: Heightened societal acceptance of transgender youth and increased awareness of their unmet medical needs have led to a rise in referrals for hormonal therapy. There is limited literature available on the metabolic outcomes of hormone therapy on transgender youth. We investigated how the different metabolic markers of cardiovascular disease change after the initiation of gender-affirming hormonal therapy in transgender adolescents. Methods: A Retrospective, observational cohort study based on chart review of all children with gender dysphoria (under 18 years of age) who were evaluated in the Pediatric Endocrinology Clinic in a tertiary care center between January 2015 and December 2022. Children's demographic information, baseline weight, height, BMI, hematocrit, lipid profile, ALT, prolactin, and HbA1C levels were obtained before and after the initiation of gender-affirming hormonal therapy. The Wilcoxon signed-rank test was employed for paired analysis, while the chi-square test was used as appropriate. Results: We identified 106 transgender youth who were included in the analysis, with a median age at the start of hormonal therapy of 16 years (IQR: 15-17); comprising 68 trans-males (64%) and 38 trans-females (36%). The median treatment duration was 34 months (IQR: 18-54). Among trans-males, ALT levels increased post-treatment (mean difference 6.851 U/L, p &lt; 0.001), as did BMI Z scores (mean difference 0.257, p &lt; 0.001) and LDL-C (mean difference 12.734 mg/dl, p = 0.002), triglycerides (mean difference 10.18 mg/dl, p = 0.009), non-HDL-C (mean difference 12.8 mg/dl, p = 0.002), and total cholesterol (mean difference 10.18 mg/dl, p = 0.02). No significant differences were observed in HbA1C and HDL-C post-treatment. Among transfemales, BMI Z-scores were higher post-treatment (mean difference 0.27, p = 0.007), with increased total cholesterol (mean difference 19.88 mg/dl, p = 0.008), LDL-C (mean difference 12.6 mg/dl, p = 0.02), and HDL-C (mean difference 11.38 mg/dl, p &lt; 0.001). Other variables did not significantly differ pre-and post-treatment. Ten transfemales with measured prolactin levels pre- and post-treatment showed no statistically significant differences. Conclusion: This pilot study revealed increased BMI Z scores following the commencement of hormone therapy in both trans-male and trans-female youths. Moreover, masculinizing treatment led to increased ALT levels. Furthermore, the cardiometabolic profile exhibited diverse alterations, particularly higher LDL-C levels in both cohorts. These findings underscore the necessity for close monitoring of these parameters during the treatment of transgender youth. Larger prospective randomized controlled trials are essential to comprehensively assess the impact of gender-affirming therapy on transgender youth. Presentation: 6/2/2024

Abstract Disclosure: M. Salama: None. A.N. Lteif: None. Introduction: Intravenous propofol is widely employed for procedural sedation, monitored anesthesia care, and induction of general anesthesia. It can be administered as a bolus or an infusion. While extensively used, reports in adults and animal studies suggest potential implications of propofol on adrenal steroidogenesis. In this study, we present findings detailing transient adrenal suppression in two pediatric patients following propofol infusion. Case: The first case involves a 5-year-old boy diagnosed with left cerebellar high-grade glioma, having undergone tumor resection and proton beam irradiation. Morning cortisol levels measured twice post-propofol sedation (20 mg bolus followed by infusion at a rate of 275 mcg/kg/min prior to radiation therapy were 3.1 and 1.2 mcg/dl (ref range: 2.4-15 mcg/dl), accompanied by an undetectable ACTH level. Subsequent non sedated cortisol testing done four days later revealed a robust reading of 24 mcg/dl, with an ACTH level of 46 pg/ml.The second case is a 4-year-old boy diagnosed with right cerebellar high-grade astrocytoma glioma, who underwent total resection two months before his initial cortisol assessment. Following proton beam irradiation and propofol sedation (20 mg bolus followed by propofol infusion at a rate of 300 mcg/kg/min) for therapy, his morning cortisol obtained 45 minutes after starting propofol infusion was low at 2 mcg/dL (ref range: 2.4-15 mcg/dl). A repeat cortisol test eight days later showed an increase to 5.6 mcg/dL. Notably, neither patient was on exogenous steroids or medications impacting the adrenal axis. Discussion: The transient decline in cortisol and ACTH observed in these cases gains significance as the patients were not on any medication known to potentially induce adrenal suppression. Additionally, the gliomas were not parasellar in location and radiation had just begun. These findings align with prior reports linking propofol administration with the suppression of the hypothalamic-pituitary-adrenal axis. The impact of propofol on adrenal function needs to be considered especially in pediatric patients undergoing procedures or treatments. Conclusion: Our cases shed light on the potential transient influence of propofol on adrenal function in pediatric patients. Further studies are warranted to comprehensively evaluate the effects of propofol injections and infusions on adrenal function in pediatric cohorts. Presentation: 6/3/2024

Abstract Context Variants in melanocortin 4 receptor (MC4R) pathway-related genes have been associated with obesity. The association of these variants with cardiometabolic parameters are not fully known. Objective We compared the severity of obesity and cardiometabolic risk markers in children with MC4R pathway-related clinically reported genetic variants relative to children without these variants. Methods A retrospective chart review was performed in children with obesity who underwent multigene panel testing for monogenic obesity. Results Data on a total of 104 children were examined, with 93 (89%) identified as White. Thirty-nine (37.5%) patients had clinically reported variants in the MC4R pathway, and the remaining 65 patients did not have reported MC4R pathway-related variants. Among the MC4R-related variants, PCSK1 risk alleles were most common, reported in 15 children (14%). The maximum body mass index percent of the 95th percentile was not different between groups (P = .116). Low-density lipoprotein cholesterol (LDL-C) was not different between groups (P = .132). However, subgroup analysis demonstrated higher LDL cholesterol in children with the PCSK1 c.661A&gt;G risk allele relative to those with MC4R-related variant of uncertain significance (P = .047), negative genetic testing (P = .012), and those with non-MC4R related variants (P = .048). The blood pressure, fasting glucose, hemoglobin A1C, total cholesterol, alanine transaminase, and high-density lipoprotein cholesterol were not different between groups. Conclusion Variants in the MC4R pathway-related genes were not associated with severity of obesity and cardiometabolic risk markers except for the c.661A&gt;G PCSK1 risk allele, which was associated with higher LDL-C levels.

Abstract Objectives Plant-based milk alternatives are increasingly utilized in children with cow milk allergy, lactose intolerance, and personal preference. However, notable differences exist in mineral content between cow milk and plant-based alternatives. Almond milk, in particular, varies in mineral and caloric content across different brands. This case report highlights a toddler who developed hypercalcemia and hypophosphatemia attributed to almond milk consumption. Case presentation A fourteen-month-old girl with a history of biliary atresia underwent liver transplant at seven months of age. She was exclusively consuming almond milk for two months prior to presentation. She was admitted to the hospital for severe hypercalcemia (14.6 mg/dL) and hypophosphatemia (1.6 mg/dL). She had elevated random urine calcium to creatinine ratio (2.56 mg/g) and low urine phosphorus to creatinine ratio (<0.44 mg/g) were noted. Parathyroid hormone (PTH) level was appropriately suppressed (<6 pg/mL), while 1,25 dihydroxyvitamin D level was slightly elevated at 88 pg/mL. Initial management included intravenous fluids, followed by a switch to a formula with higher phosphorus and lower calcium concentrations. The patient was discharged after six days with normalized calcium and phosphorus levels, which remained within the normal range. Conclusions Although plant-derived milk serves as a viable alternative to cow milk, careful consideration of mineral content, particularly in infants and toddlers, is imperative. Sole reliance on almond milk for nutritional needs in this population is not recommended. Caregivers should be informed about the potential risks associated with almond milk consumption in infants and toddlers.