Change in Body Mass Index in Youth in the First 5 Years after Type 1 Diabetes Mellitus Diagnosis.

OBJECTIVE: Examine body mass index (BMI) trajectories in American youth with type 1 diabetes over the first five years following diagnosis. RESEARCH DESIGN/METHODS: Retrospective record review of BMI trajectories in youth with type 1 diabetes diagnosed in 2015-2016. RESULTS: Near the time of diabetes diagnosis, 35.5% of youth had BMIs in the overweight/obesity range. These rates increased over time (p < 0.001), with 52.8% having overweight/obesity 5 years after diagnosis. Average age when BMI rose from healthy to overweight/obese or overweight to obese (rise group) was at 12.7 years, occurring 2.5 years after diagnosis. There were no differences between HbA1c, use of continuous glucose monitors (CGM), or use of insulin pumps between the rise group and those with healthy BMI throughout the study period. CONCLUSIONS: Alarmingly high rates of overweight/obesity in youth were observed within 5 years following type 1 diabetes diagnosis. Awareness and further research are necessary to address this independent risk factor for morbidities.

An update on clinical presentation and responses to therapy of patients with hereditary hypophosphatemic rickets with hypercalciuria (HHRH).

Pathogenic variants in solute carrier family 34, member 3 (SLC34A3), the gene encoding the sodium-dependent phosphate cotransporter 2c (NPT2c), cause hereditary hypophosphatemic rickets with hypercalciuria (HHRH). Here, we report a pooled analysis of clinical and laboratory records of 304 individuals from 145 kindreds, including 20 previously unreported HHRH kindreds, in which two novel SLC34A3 pathogenic variants were identified. Compound heterozygous/homozygous carriers show above 90% penetrance for kidney and bone phenotypes. The biochemical phenotype for heterozygous carriers is intermediate with decreased serum phosphate, tubular reabsorption of phosphate (TRP (%)), fibroblast growth factor 23, and intact parathyroid hormone, but increased serum 1,25-dihydroxy vitamin D, and urine calcium excretion causing idiopathic hypercalciuria in 38%, with bone phenotypes still observed in 23% of patients. Oral phosphate supplementation is the current standard of care, which typically normalizes serum phosphate. However, although in more than half of individuals this therapy achieves correction of hypophosphatemia it fails to resolve the other outcomes. The American College of Medical Genetics and Genomics score correlated with functional analysis of frequent SLC34A3 pathogenic variants in vitro and baseline disease severity. The number of mutant alleles and baseline TRP (%) were identified as predictors for kidney and bone phenotypes, baseline TRP (%) furthermore predicted response to therapy. Certain SLC34A3/NPT2c pathogenic variants can be identified with partial responses to therapy, whereas with some overlap, others present only with kidney phenotypes and a third group present only with bone phenotypes. Thus, our report highlights important novel clinical aspects of HHRH and heterozygous carriers, raises awareness to this rare group of disorders and can be a foundation for future studies urgently needed to guide therapy of HHRH.

Occult Metastatic Papillary Thyroid Cancer in an Adolescent.

Background/Objective: Occult papillary thyroid carcinoma (PTC) is PTC with metastasis but without identification of primary thyroid cancer on preoperative ultrasonography. Published reports on occult PTC in children are limited. Case Report: We describe a 16-year-old female with occult PTC who initially presented with a painless left sided cystic neck mass. Diffuse sclerosing variant papillary thyroid cancer was found in the resected neck mass and thyroid ultrasound did not show any nodules or features of carcinoma. After total thyroidectomy, pathological examination of the thyroid revealed papillary thyroid microcarcinoma. Discussion: We describe a rare case of occult diffuse sclerosing variant papillary thyroid cancer presenting as a cystic neck mass mimicking a second branchial cleft cyst in an adolescent patient. When metastatic PTC is found without evidence of nodule on thyroid imaging, occult PTC of the thyroid is the likely diagnosis. Conclusion: Total thyroidectomy ± neck dissection followed by TSH suppression and radioactive iodine therapy remains the appropriate diagnostic and therapeutic interventions.

Long-term Treatment of Pediatric Metastatic Papillary Thyroid Cancer With Lenvatinib.

Papillary thyroid carcinoma (PTC) is the most common pediatric thyroid malignancy and incidence is increasing. Standard treatment for PTC in pediatric patients includes surgical intervention, suppression of TSH with levothyroxine, and radioactive iodine therapy (RAI) in select patients. In the setting of metastatic PTC or PTC refractory to RAI therapy, tyrosine kinase inhibitors (TKIs), such as lenvatinib, may be used. Until recently, experience with these targeted agents were largely limited to adult patients with progressive or refractory PTC. More recently, increased experience with TKI therapy has been reported in the pediatric population, with case reports and small series describing short-term TKI use. We report the case of a 15-year-old girl with RAI-refractory metastatic PTC who achieved stable disease with long-term lenvatinib treatment for more than 5.5 years. Prospective, longitudinal studies of TKIs in RAI-refractory pediatric PTC are needed.

Leveraging seasonality and timing to optimize pediatric weight management interventions: Novel directions for future research.

National estimates suggest that more than 35% of American children, ages 2-19 years, are overweight or obese, which increases their risk for weight-related comorbidities including diabetes, cancer, cardiovascular disease risk factors, depression, and anxiety. While obesity prevention is most cost-effective, for youth with existing obesity, the United States Preventive Services Task Force recommends ≥26 h of comprehensive lifestyle intervention over 6-12 months. This include standard behavioral therapy, dietary counseling, and an emphasis on physical activity. Although such programs are effective in reducing weight status, there are many barriers to completing these programs. A novel consideration for both the prevention and treatment of childhood obesity is the recognition that the timing of intervention, both duration and time of the year, can impact family engagement and intervention effectiveness. This paper discusses the potential of targeting high-risk periods for weight gain and offering brief behavioral intervention, in hopes of inspiring research on novel approaches to the prevention and treatment of childhood obesity.

Symptomatic Hypocalcemia due to Nutritional Vitamin D Deficiency in Three Adolescents during the COVID-19 Pandemic.

Background: Symptomatic hypocalcemia secondary to vitamin D deficiency (VDD) is rare among adolescents without underlying medical disorders, but its prevalence is higher in known risk populations. We report on three adolescent males with low nutritional intake of vitamin D and calcium and limited sun exposure who presented with hypocalcemic tetany and muscle cramps due to VDD during the COVID-19 pandemic. Case Reports. Three adolescent males (age range 14 to 16 years) presented with symptomatic hypocalcemia: paresthesia, carpopedal spasms, and muscle cramps. All reported limited dairy intake and sun exposure. Laboratory studies showed mean ionized calcium (iCa) 2.73 mg/dl (range 2.69-2.8), mean phosphorus 4.17 mg/dl (range, 3-5.4), mean parathyroid hormone (PTH) 431.67 pg/mL (range, 320-527), and mean 25-hydroxyvitamin D (25(OH)D) 7.37 ng/mL (range 5.3-10.8). All the patients presented during the COVID-19 pandemic, and one had COVID-19 infection. All were treated with oral calcium and high dose ergocalciferol. Patients 2 and 3 were also treated with intravenous calcium gluconate infusion and oral calcitriol. Conclusion: Severe VDD with symptomatic hypocalcemia can occur among adolescents without underlying medical diagnoses due to dietary and behavioral habits that limit nutritional intake and sun exposure. Risk factors of the patients may have been potentiated by pandemic-related behaviors such as more time indoors at home related to social distancing, as well as diets with limited nutrient intake. Adolescents presenting with nonspecific musculoskeletal symptoms should be screened for VDD and hypocalcemia. Appropriate treatment and preventive measures can stop immediate and long-term complications.

The Rising Incidence of Hyperinsulinemic Hypoglycemia: Connection With Maternal Health.

OBJECTIVE: Due to a perceived rise in hyperinsulinemic hypoglycemia (HH) cases over time, notably during the COVID-19 pandemic, institutional experiences between 2013 and 2021 were reviewed to evaluate trends, characteristics, and outcomes in children with HH. METHODS: Charts of all children diagnosed with HH during the study period and evaluated by Pediatric Endocrinology were reviewed. HH was defined per Pediatric Endocrine Society guidelines. Regression analysis compared rates of change in HH cases and maternal risk factors over time. RESULTS: The incidence of HH began to rise in April 2016 and became significant in March 2017 (P < .001), with a more rapid rate of rise during the first year of the COVID-19 pandemic (P < .001). Seventy-four children with HH were identified over 9 years; 43% (n = 32) were diagnosed in 2020-2021. Maternal hypertensive disorders demonstrated longitudinal association with hyperinsulinism cases (P < .001). CONCLUSION: While HH diagnoses were on the rise for much of the 9-year study period, nearly half of all infants were diagnosed during the COVID-19 pandemic in 2020 to 21. The trends in HH diagnoses correlated with maternal hypertensive disorders. More studies exploring the roles of maternal health, hypertension, and stress and development of HH in offspring are needed.

Formative Development of a Weight Management Intervention for Adolescents with Type 1 Diabetes Mellitus and Obesity.

The prevalence of overweight and obesity in youth with type 1 diabetes mellitus (T1D) now exceeds that of youth without T1D. Comorbid T1D and excess adiposity are associated with multiple serious negative health outcomes. Unfortunately, youth with T1D are often excluded from and/or not referred to standard behavioral lifestyle interventions. This is often attributed to the complexities of managing T1D and an effort not to overburden persons who have T1D. Furthermore, standard behavioral weight management intervention recommendations can be perceived as contradicting T1D disease management (e.g., removing sugar-sweetened beverages from diet, energy balance with exercise, and caloric restriction). A weight management intervention specifically designed for youth with T1D is needed to provide treatment to youth with comorbid T1D and overweight/obesity. The current study interviewed adolescents with T1D and overweight/obesity (n = 12), their caregivers (n = 12), and pediatric endocrinologists (n = 9) to understand (a) whether they would be interested in a weight management intervention adapted for youth with T1D and (b) specific adaptations they would want and need. Five central themes emerged following applied thematic analysis: (1) program content, (2) programmatic messaging, (3) program structure, (4) social support, and (5) eating disorder risk. Results provide detailed recommendations for the adaptation of a behavioral weight management intervention for youth with T1D.

Increased Incidence and Severity of New Graves Disease Diagnoses in Youth During the COVID-19 Pandemic.

OBJECTIVE: Graves disease (GD), an autoimmune disease of the thyroid, is likely caused by a combination of genetic predisposition and environmental triggers. Recent data suggest that COVID-19 may be associated with the development of autoimmune disease. The aim of this study was to assess the incidence and characteristics of new GD diagnoses in youth prior to and during the COVID-19 pandemic. METHODS: We performed a retrospective chart review of all new GD diagnoses in patients aged 0 to 18 years diagnosed at a tertiary care pediatric hospital between January 1, 2018, and December 31, 2021. RESULTS: Over a 4-year period, 51 patients had been diagnosed with new-onset GD. We observed an increased incidence in new-onset GD during the pandemic compared with that in the 2 prior years (P = .01). During the pandemic period, heart rates (P = .03) as well as systolic (P = .005) and diastolic (P = .01) blood pressures were higher at initial evaluation, patients more frequently reported palpitations (P = .03) and tremors (P = .04), and an increased proportion of patients required beta-blockade treatment at diagnosis (P = .002). The percentage of patients requiring thionamide treatment and thionamide doses had been similar over time. CONCLUSION: We identified an increase in new-onset pediatric GD diagnoses during the COVID-19 pandemic. In addition, youths had increased severity of symptoms and more frequently required beta-blockade treatment at diagnosis. Further study of the relationship between COVID-19 and autoimmune thyroid disease is needed.

Incidence, Severity, and Presentation of Type 2 Diabetes in Youth During the First and Second Year of the COVID-19 Pandemic.

OBJECTIVE: To describe the evolving impact of the coronavirus disease 2019 pandemic on the incidence and presentation of new-onset pediatric type 2 diabetes. RESEARCH DESIGN AND METHODS: Retrospective medical record review of youth with new-onset type 2 diabetes comparing the prepandemic period (1 January 2017-29 February 2020) with the first (1 March 2020-31 December 2020) and second pandemic year (1 January 2021-31 December 2021). RESULTS: The annualized incidence of type 2 diabetes increased nearly threefold during the pandemic versus prior, with a 61% increase in the 2nd versus 1st year. BMI increased during the pandemic versus prior (129% of 95th percentile vs. 141%, P = 0.02). In the 1st year, patients were younger (12.9 years vs. 14.8, P < 0.001), with higher incidence of diabetic ketoacidosis and/or hyperglycemic hyperosmolar syndrome (20% vs. 3.5%, P = 0.02) versus prior. CONCLUSIONS: Providers should be aware of the escalating incidence of youth-onset type 2 diabetes to avoid delays in diagnosis and inform educational programs to combat the continued impact of the pandemic on health outcomes.

Severe Vitamin D Deficiency in Youth with Autism Spectrum Disorder During the COVID-19 Pandemic.

BACKGROUND: Decrease in sunlight exposure during periods of social distancing during the COVID-19 pandemic increased the risk of severe manifestations of vitamin D deficiency (VDD) in a particular "high-risk" population. Our objective was to highlight the importance of vitamin D screening in youth with autism spectrum disorder (ASD) and restrictive eating. CASE PRESENTATION: We describe 3 adolescent male patients with ASD who developed severe manifestations of VDD and hypocalcemia in late 2020 during the COVID-19 pandemic. All spent less time outdoors than in prior years because of isolation at home during the pandemic. Presenting symptoms included seizures and atraumatic fractures. All 3 were found to have hypocalcemia and severe VDD. Limited sun exposure because of isolation indoors during the COVID-19 pandemic was a likely contributing factor to the severity of VDD. All 3 were treated with intravenous calcium acutely, followed by oral calcium and vitamin D. Laboratory tests performed post-treatment showed biochemical resolution of hypocalcemia and VDD. CONCLUSION: These cases highlight the importance of screening "at-risk" youth for VDD. Clinicians should be cognizant that children and adolescents with ASD and restricted eating can have severe manifestations of hypocalcemia and VDD. Decreased sun exposure because of isolating indoors during the COVID-19 pandemic increased their risk for this.

Clinical Thyrotoxicosis Resulting from Liothyronine Augmentation of Antidepressant Therapy in an Adolescent.

Background/Objective. Thyrotoxicosis, a condition resulting from excessive peripheral thyroid hormone, is typically accompanied by thyroid function tests demonstrating a high free thyroxine (free T4) with appropriate suppression of thyroid-stimulating hormone (TSH). Case report. We describe a 17-year-old female presenting with symptoms of thyrotoxicosis along with suppressed TSH and low free T4, a laboratory pattern concerning for central hypothyroidism. Further history revealed that she was prescribed liothyronine as an adjunct therapy for depression. Discussion. Due to the short half-life of liothyronine, clinical signs and symptoms of thyrotoxicosis may develop before detection by interval lab monitoring. Conclusion. This case highlights the need for close monitoring and caution when treating adolescents with liothyronine and the importance of interpreting atypical laboratory findings within clinical context.

Delays in Presentation of New Onset Diabetes at the Start of the COVID-19 Pandemic.

OBJECTIVE: To compare the frequency, severity of presentation and initial presentations of new onset diabetes mellitus (DM) in youth in Rhode Island during the early phase of the COVID-19 pandemic compared to the same time frame in 2018 and 2019. METHODS: A retrospective cohort study of youth treated for new onset DM at Hasbro Children's Hospital between March 1 and May 15, 2020, compared to those diagnosed in the same period in 2018 and 2019. RESULTS: Fewer youth were diagnosed with new onset DM in Spring 2020 and the percentage of youth with DKA at time of DM diagnosis was higher in Spring 2020 compared to prior years (p=0.048). Age, gender, and DKA complications did not differ by year. CONCLUSION: Nearly 50% fewer youth were diagnosed with DM at the start of the COVID-19 pandemic compared to years prior, and those diagnosed with new onset DM in Spring 2020 were more likely to present with DKA. Delays in both initial health care evaluation and the recognition of DM symptoms may have contributed to the decline in overall DM diagnoses and the more severe presentations. Identification of DM symptoms is essential, especially during future surges of COVID-19 or other events that impact the healthcare system, to reduce the risk of DM complications including DKA.

Hypertensive Crisis in a Pediatric Patient Experiencing Clonidine Withdrawal.

Background: Clonidine, a central alpha-adrenoreceptor agonist, was initially developed as an antihypertensive. Though no longer commonly used for its original indication due to rebound hypertension after discontinuation, it is currently widely prescribed as a treatment for many pediatric indications including sleep disorders, behavioral concerns, and attention deficit hyperactivity disorder. Case Report. We describe a girl who developed prolonged symptoms of clonidine withdrawal, including hypertension and elevated serum metanephrines. Discussion. Clonidine withdrawal in pediatric patient can present with hypertensive urgency and other signs of sympathetic stimulation. Withdrawal can also lead to dramatic elevation in serum metanephrines. Treatment with a clonidine taper will reduce development of withdrawal symptoms. Conclusion: Given the rise in clonidine use in pediatric patients, clinicians should be aware of the risk of clonidine withdrawal and how to recognize and avoid its development.

Screening and counseling for nicotine use in youth with diabetes.

OBJECTIVE: To assess current practice patterns and identify knowledge gaps among pediatric endocrinologists in the United States regarding screening and counseling for combustible tobacco and e-cigarette use in youth with diabetes. INTRODUCTION: Electronic cigarettes (e-cigarettes) are the most used tobacco product among adolescents and may be associated with an increased risk of progression to combustible cigarette smoking, cardiovascular disease, and stroke. Diabetes mellitus is a known risk factor for cardiovascular disease, and nicotine products can increase this risk. We sought to assess current practice patterns and identify knowledge gaps among pediatric endocrinologists in the United States regarding screening and counseling for combustible tobacco and e-cigarette use in youth with diabetes. RESEARCH DESIGN AND METHODS: We conducted an anonymous, online-based survey of Pediatric Endocrine Society members who provide care to youth with Type 1 or Type 2 diabetes. The survey collected information about provider demographics and smoking habits, knowledge and attitudes regarding screening and counseling for combustible tobacco and e-cigarette use, and current practice patterns. RESULTS: The survey was completed by 106 individuals of whom 64 reported providing care to youth with diabetes mellitus and ever asking about combustible tobacco or e-cigarette use. The majority of respondents were female, attending providers, and working in academic medical centers. None reported a history of formal training in e-cigarette counseling but recognized the harms of e-cigarette use. Nearly all (98%) who ever screen for nicotine use reported routinely screening for combustible tobacco use, while 18% never screen for e-cigarette use (p < 0.01). Over 80% of respondents reported feeling confident or very confident about discussing the harms of combustible tobacco, compared to 58% reporting the same confidence in discussing harms of e-cigarette use (p < 0.0001). Over 90% of respondents agreed that pediatric endocrinology providers should ask about nicotine use with over half agreeing that counseling reduces the risk of initiating nicotine product use, and 30% reported lack of change with counseling as a barrier to discussing nicotine use. Lack of visit time was the most reported barrier to discussing nicotine use. More providers cited lack of knowledge regarding e-cigarettes compared to combustible tobacco as a barrier to discussing its use. CONCLUSIONS: Pediatric endocrinology providers recognize the harms of e-cigarette use, but more frequently ask about combustible tobacco use compared to e-cigarette use. This may be related to lower reported confidence and provider knowledge in counseling about e-cigarette use. Increased utilization of existing resources and expanding opportunities for providers to learn more about e-cigarettes may increase provider confidence and comfort in screening and counseling.

New-onset Adrenal Insufficiency Presenting with Adrenal Shock in a Pediatric Patient.

This case report describes new-onset adrenal insufficiency and adrenal shock in an 11-year-old male complaining of two weeks of malaise and weight loss. He was lethargic and pale in appearance. Work-up revealed hypoglycemia and hyponatremia without evidence for an infectious process. He was transported via a pediatric critical care transport team to a regional pediatric intensive care unit (PICU). He required intravenous fluids and vasopressors prior to arrival in the PICU. He had generalized weakness, and hyperpigmentation of his face and extremities. Adrenal insufficiency was suspected, and glucocorticoid administration led to improvement. Cortisol level was undetectable. At time of discharge, he was prescribed daily glucocorticoid and mineralocorticoid replacement, along with a stress dose glucocorticoid plan.