bluuebunny/crossref_metadata_2025 huggingface dataset:
12615 Extremely High-dose Insulin Requirement In A Child With Covid-19 Infection
Authors: Pratibha R , Langner T R
Published: October 2024

Disclosure: R. Pratibha: None. T.R. Langner: None.

Background: COVID-19 infection has been associated with new diagnosis of diabetes, worsening of hyperglycemia, and increased frequency and severity of diabetic ketoacidosis (DKA) in type 1 diabetes (DM) patients. Stress- related and steroid induced hyperglycemia are also well described during COVID infection with poor glycemic control being linked to more severe SARS-CoV-2 infection outcomes. While insulin needs increase during infection, extremely high insulin requirement is uncommon and not described in the pediatric population. We present here a case of mild COVID infection with transient markedly high insulin requirements. Clinical Case A 16-year-old-African-American- female with history of fairly well controlled type 2 diabetes mellitus on closed loop system insulin pump (Omnipod) with continuous glucose monitor (CGM), was admitted with COVID-19, aspiration pneumonia and hyperglycemia. She had been diagnosed 10 months prior with Hemoglobin A1c (HbA1c) of 11.4% and mild diabetic ketoacidosis (DKA). Diabetes antibodies were negative. Four months prior to admission her HbA1c was 7.8%. Upon this hospitalization she had no hypoxemia or respiratory failure and did not need steroids. Procalcitonin level 0.09 ng/mL was normal. Developmental delay, non-ambulatory and non-verbal status, an underlying mitochondrial neurological disease with G tube and ventilator dependence added to the medical complexity. HbA1c (8.1%) and Fructosamine 316 (n 200-285 mcmol/L) were not indicative of poor control. While her pneumonia resolved promptly, blood sugar (BG) elevation prolonged her hospitalization. She was not in DKA. Despite increasing her basal rate by 50% and an additional 20% higher temporary basal rate via her insulin pump there was little response. She was switched to Insulin drip by the 7th day. Her Insulin rate had increased to 26 units per hour (at 0.64 Units/Kg/hour) by day 8. This high insulin-dose need lasted for around 36 hours, before gradually reducing over a week. She has a history of recurrent pancreatitis. Lipase 335 U/L was elevated initially but started reducing within 2 days and had normalized by day 13. She was transitioned back to her pump although at higher basal rate than the previous home regimen, by 14th day. Conclusion While a constellation of factors such as stress, steroids, underlying poor glycemic control may cause hyperglycemia in COVID-19, these do not explain the high insulin demand in our patient. COVID infection with impaired insulin secretion, mild pancreatitis may have contributed to the brief remarkably high-dose insulin requirement, but it appears to be increased insulin resistance which could possibly explain the transient derangement. To our knowledge this has previously not been described in a pediatric diabetic patient.

Presentation: 6/3/2024
12606 Gamification In The Management Of Children And Adolescents With Diabetes: A Systematic Review
Authors: Hespanhol Larissa C , Lins de Menezes Vanessa , Souto Maia Paula Christianne G G , Balieiro Caroline Cristine Almeida , Oliveira Amador Wellgner Fernandes , Lira Rafaelle C
Published: October 2024

Disclosure: L.C. Hespanhol: None. V. Lins de Menezes: None. P. Souto Maia: None. C.A. Balieiro: None. W. Oliveira Amador: None. R. Lira: None.

Background: Educating children and adolescents with diabetes about their own condition presents a significant challenge. Gamification has been proposed as an innovative approach to ease the transition to self-care by engaging and empowering children and adolescents in their diabetes management. Purpose: The purpose of this systematic review is to examine published research on using gamification and technology within diabetes care for young patients. Methods: PubMed, Lilacs and EMBASE were systematically searched in January 2024 to include articles focusing on the use of new virtual technologies to improve the clinical and laboratory conditions of children and adolescents with diabetes. The protocol was registered in PROSPERO (ID: CRD42024499381) adhering to PRISMA recommendations. We assessed the risk of bias using RoB-2 and ROBINS-I. Results: A total of 24 studies were included, of which 7 were randomized trials. Age of participants ranged from 5 to 19 years. We identified five gamification strategies (i.e., applications, video games, minigame, robot, or web game) within seven clinical domains (i.e., psychosocial impairment, glycemic control, autonomy, reduced frequency of error, health lifestyle, nutrition, or knowledge about disease). 246 (27%) patients demonstrated reduced emotional distress and increased enjoyment. Reduction of errors such as hypoglycemia and emergency preparedness was identified in 354 (39%) of patients and improvement in glycemic control measured by HbA1c was described in 277 (30%) of patients. Conclusion: Our systematic review gamification has shown promise in fostering autonomy by providing tools that educate young individuals regarding glycemic control, lifestyle choices, injection practices, carbohydrate counting, and other pertinent aspects of diabetes management.

Presentation: 6/1/2024
7795 Gender based differences in peripubertal growth patterns may offer insight into the twofold representation of boys compared to girls among children referred for growth hormone stimulation tests
Authors: Dekel Yuval , Horowitz Lee , Gendelman Raya , Cohen Michal
Published: October 2024

Disclosure: Y. Dekel: None. L. Horowitz : None. R. Gendelman: None. M. Cohen: None.

Background: Growth hormone (GH) stimulation tests are essential in the diagnostic assessment of pediatric GH deficiency (GHD). However, the tests bare multiple limitations, resulting from both intrinsic and child-related factors. Thus, referral decisions are key in making a correct diagnosis. Several studies demonstrated a gender bias in referral for short stature evaluation with a higher proportion of boys referred and diagnosed with GHD. Moreover, the boys had higher height z-scores upon referral. About 100 GH stimulation-tests are conducted annually at our pediatric endocrinology unit. We aimed to characterize the children that underwent GH stimulation-testing between 2017-2021, specifically focusing on differences based on: 1) gender 2) GH secretion status (deficient vs. sufficient). Methods: A retrospective review of charts of children aged 0-18 years that performed GH stimulation-tests at the Rambam pediatric endocrinology unit between the years 2017-2021 was conducted. Children followed at an outside clinic that had a first GH stimulation-test elsewhere, were excluded. Data was collected through the electronic database and by manually screening medical charts. The IBM SPSS statistics package 21 version was used for analysis. Results: Four-hundred children were included in the study, 266 boys (66.5%) and 134 girls (33.5%). Mean age 8.8±4.2 years, mean height z-score -2.3±0.7 and mean mid-parental height standard-deviation-scores (MPH-SDS) -0.6±0.7. The mean difference between MPH-SDS and child height-z-score was 1.7±0.8 SDS. Mean age was younger in girls compared with boys, 7.3±3.3 and 9.6±4.4 years respectively (p<0.001). Age distribution differed between genders, while refferals peaked between 3-4 years of age in both girls and boys, a second peak at 13-14 years of age was evident only in boys. Interestingly, there was no significant difference between boys and girls in height z-score, difference from MPH-SDS or rates of GHD. Overall, 93 (23.3%) children were diagnosed with GHD, 32 girls (24%) and 61 boys (23%). Children with GHD were younger and had higher BMI-SDSs compared to GH sufficient children, age 7.8±3.8, 9.2±4.3 years respectively (p=0.003), BMI z-score 0.17±1.38, -0.47±1.15 respectively (p<0.001). Conclusion: Twice as many boys than girls were referred for GH stimulation tests in our cohort. Based on differences in age distribution, the peripubertal physiologic growth deceleration that occurs later in boys, likely contributes to this finding. This male-to-female ratio is similar to ratios reported in the literature regarding short stature referrals; however, in contrast to the literature, in our cohort it could not be explained by an anthropometric bias in referral criteria.

Presentation: 6/3/2024
7003 Comparative Study Of The Properties And Differences Of Steroidogenesis Inhibitors In Vitro
Authors: Taki Yuki , Kono Takashi , Kono Satomi , Hashimoto Naoko , Nagano Hidekazu , Tanaka Tomoaki
Published: October 2024

Disclosure: Y. Taki: None. T. Kono: None. S. Kono: None. N. Hashimoto: None. H. Nagano: None. T. Tanaka: None.

Objective: Osilodrostat (Osi) is utilized as an inhibitor of cortisol (F) synthesis and is a potent inhibitor of CYP11B2, in addition to CYP11B1. Therefore, we investigated the aldosterone (Ald) and cortisol concentration-dependent inhibitory effects of Osi in vitro, using tissues from 9 cases [5 Aldosterone-producing adenoma (APA) and 4 Cortisol-producing adenoma (CPA)] operated at our institution. Methods: Adrenal tumor surgery specimens were treated with collagenase and cultured on plates. After 3 days, the medium was changed and incubated with osilodrostat or metyrapone (0.0001 to 10 µM). After another 3 days, the medium was collected, and Ald/F concentrations were measured. The IC50 of both drugs for Ald/F were then compared. Results: In APA cases, Osi inhibited at significantly lower concentrations (IC50: 0.003 µM) than Met (0.782 µM; p=0.0159) for Ald; in CPA cases, Osi inhibited with similar potency to Met (IC50: 0.061 µM vs 0.466 µM, p=0.2286) for F. In all cases, Osi inhibited at significantly lower concentrations for Ald than F (IC50: 0.003 µM vs 0.028 µM, p=0.0008). Discussion: Osi is a potent inhibitor of Ald and F production, and its use for PA alone is challenging because clinical trials of Osi for PA were terminated due to concerns about adrenal insufficiency. Therefore, we suggest that Osi may be useful in PA-associated CPA patients for whom surgery is not indicated or as a preoperative drug therapy.

Presentation: 6/1/2024
8304 Growth trajectories of children born preterm and full-term with low birth weight to preschool ages; a nationwide study
Authors: Kang E , Cha J , Na J , Ryu S , Choi Y J , Kim J
Published: October 2024

Disclosure: E. Kang: None. J. Cha: None. J. Na: None. S. Ryu: None. Y. Choi: None. J. Kim: None.

Context: Children born preterm (PT) and full-term with low birth weight (FT-LBW) are known to be at considerable risk of poor growth outcomes. Objective: To investigate the growth trajectories of children born PT and FT-LBW from birth to preschool ages. Methods: A total of 1,150,508 newborns were included in the study, comprising 41,454 children born PT and 38,250 children born FT-LBW, who participated in the first three rounds (4-6, 9-12, 18-24 months) of the National Health Screening Program for Infants and Children (NHSPIC). Growth measurements were obtained from the NHSPIC database and converted into the Z-scores. Growth data at two, four, and six years of age were measured as outcome variables. The impact of being born small on poor growth outcomes was investigated using a generalized estimating equation and Cox proportional hazards regression analysis. Results: The median birth weight of three groups was 2.3kg for PT, 2.4kg for FT-LBW, and 3.2kg for FT control group, respectively. The incidence of short stature defined as height Z-score < -2 standard deviation score (SDS) and failure to thrive (BMI Z-score < -2 SDS) was highest in FT-LBW group, followed by the PT group, and control group. At four years of age, the incidence rates were 6.0% vs. 5.2% vs. 1.9% for short stature and 4.6% vs. 3.9% vs. 1.7% in FTT. The β estimate of height outcome was lower in both the PT and FT-LBW groups with -0.326 SDS in PT and -0.456 SDS in FT-LBW group. Conclusion: The FT-LBW group was consistently shorter and lighter throughout the preschool period than the PT group. This highlights the significance of growth monitoring in high-risk populations.

Presentation: 6/3/2024
6441 Hyperthyroidism in a patient with Lyme disease
Authors: Epstein Jessy , Berman Casey
Published: October 2024

Disclosure: J. Epstein: None. C. Berman: None.

Background: Lyme disease is known to cause inflammation in many organs. There are few case reports in the literature that discuss the association between Lyme disease and thyroiditis. This case underscores the need to further research the association between Lyme disease and thyroid physiology. Clinical Case: A 15-year-old female with a history of polycystic kidney disease is referred to a pediatric endocrinologist for primary amenorrhea and hyperthyroidism. Initial thyroid function tests demonstrated suppressed TSH of 0.03 mIU/L with an elevated free T4 level of 4.0 ng/dL and total T3 of 437 ng/dL. The patient was asymptomatic with normal vital signs, and physical exam was normal without goiter, tremor, tongue fasciculations, or exophthalmos. Thyroid ultrasound demonstrated a mildly heterogenous appearance without nodules. Incidentally, Lyme disease was concurrently diagnosed based on a positive screen confirmed with immunoblot. There was no known tick exposure or rash, but the patient had recently spent time outdoors in upstate New York. Doxycycline was started for the treatment of Lyme disease and repeat thyroid tests one week later showed a decrease in free T4 and total T3 levels, although still elevated. Thyroid antibodies including thyroid peroxidase (TPO), thyroglobulin and thyroid-stimulating immunoglobulin (TSI) were negative. After finishing doxycycline treatment, she developed a hypothyroid state with a TSH of 6.39 mIU/L, free T4 of 0.6 ng/dL, and a normal total T3 of 148 ng/dL. Free T4 has since normalized however TSH remains elevated. The patient continues to be monitored closely without pharmacologic treatment. The evolution of this patient’s thyroid function is consistent with thyroiditis and appears similar to the course of Hashitoxicosis, however antibodies remain negative. There is literature that suggests molecular mimicry between Borrelia proteins and thyroid autoantigens due to amino acid sequence homology. Some Borrelial proteins are found to share antigenic properties with multiple thyroid related proteins, specifically the TSH receptor, TPO, thyroglobulin and sodium iodine symporter, potentially leading to thyroiditis. Three case reports describe adults with hyperthyroidism in the setting of Lyme disease, however in these cases thyroid antibodies (TPO +/- thyroglobulin) were positive. Two of these patients were asymptomatic, similar to our patient. This phenomenon has never been described in a pediatric patient and illustrates the need to consider Lyme disease as a potential cause of destructive, transient, thyroiditis.

Presentation: 6/1/2024
7349 Identifying the Onset of Puberty in Boys Born Small for Gestational Age (SGA)
Authors: Suco Sofia M , Keselman Ana Claudia , Ballerini Maria Gabriela , Rodriguez Maria E , Ropelato Maria G , Rosenbrock Solange , Braslavsky Debora , Rey Rodolfo Alberto , Grinspon Romina P
Published: October 2024

Disclosure: S.M. Suco: None. A.C. Keselman: None. M.G. Ballerini: None. M.E. Rodriguez: None. M.G. Ropelato: None. S. Rosenbrock: None. D. Braslavsky: None. R.A. Rey: None. R.P. Grinspon: None.

Introduction: Some children born SGA have an earlier pubertal onset and more rapid progression. Therefore, it is essential to identify the onset of puberty to proceed in a timely and appropriate manner. As it has also been suggested that there may be some gonadal dysfunction, the classic markers of pubertal onset, for example, testicular volume ≥ 4ml, may not be appropriate in these cases. Objective: To describe the clinical and biochemical characteristics of pubertal maturation in boys born SGA and determine parameters that best identify pubertal onset. Methods: We perform a retrospective, descriptive study of a cohort of boys born SGA with longitudinal follow-up, at a tertiary pediatric public hospital in Buenos Aires, Argentina. The subjects were selected from 1997 to 2023. Main outcome measures were serum levels of LH and AMH and testicular volume (TV). Additionally, height velocity, bone age, IGF1 and HOMA-IR were also collected to analyze its association with puberty. Pubertal onset was defined as serum LH ≥ 0.3 U/L and/or a decrease in serum AMH ≥ 30%. Results: The cohort included 25 boys born SGA, 24% were born prematurely and 60% were referred for short stature. In 18 boys (72%) AMH decline occurred with testicular volume < 4ml, at a median age of 9.8 yr (IQR 8.3 – 11 yr), and with median TV of 2ml. In 5 boys, LH was ≥ 0.3 U/L when AMH decline >30%. In 14 boys (56%) TV was <4ml when serum LH was ≥ 0.3 U/L. The median age for LH ≥0.3 was 11.3yr (IQR 10.4 – 12.2 yr), with a median TV of 3ml. In 3 boys the decrease in AMH occurred concomitantly with the increase in LH, while in 6 it occurred before.Alongside with the AMH decline, acceleration of bone age was observed in 35%, increase in growth velocity in 29%, increase in IGF1 concentrations in 24% and an increase in HOMA-IR in 26% of the boys. Concomitantly with an LH ≥0.3 U/L, acceleration of bone age was observed in 19%, increase in growth velocity in 25%, increase in IGF1 concentrations in 30% and an increase in HOMA-IR in 50% of the boys. Conclusion: The increase in testicular volume to 4ml, a classic parameter used as a marker of pubertal onset, may not be appropriate in a subgroup of children born SGA. Probably other parameters such as the increase in serum LH or the decrease in AMH should be considered.

Presentation: 6/1/2024
6849 Insulin Edema in newly diagnosed T1DM Pediatric Patient
Authors: Ansar Aisha , McNerney Kyle
Published: October 2024

Disclosure: A. Ansar: None. K. McNerney: None.

Background: Insulin edema is a rare complication of insulin therapy, especially in the pediatric populations. The pathogenesis is not fully understood but has been linked to Insulin’s role in renal sodium handling and vascular permeability. It has been seen with the initiation of insulin in newly diagnosed patients or the intensification of insulin therapy in those with poor glycemic control.Clinical Case: A previously healthy 12 year old girl presented to the ED with polyuria, polydipsia and fatigue. She was alert and oriented but had kussmaul breathing. She was tachycardic but all other vitals were appropriate. Lab work up showed that she was in DKA with pH 7.07 and bicarbonate 7 mmol/L. Her corrected sodium and electrolytes were normal. Her HbA1C was elevated at 11.7% (4.0-5.6%). Initial fluid resuscitation was performed with 20 mL/kg NS fluids. She was transferred to our Pediatric ICU and was started on the DKA protocol consisting of intravenous insulin infusion at 0.1 unit/kg per hour and 2-bags of dextrose and non-dextrose containing intravenous fluids. She was given a new diagnosis of Type 1 Diabetes. She was transitioned to subcutaneous insulin 22 hours later with multiple daily injections with insulin lispro and glargine, with total dose of insulin at 0.7 unit/kg per day. She was transferred to the general care floor and received diabetes education while in the hospital. On the fifth day after discharge, patient started complaining of leg tightness, puffiness around her eyes and generalized swelling of both feet. She returned to the ED, where she was found to be hemodynamically stable and normotensive with a blood pressure of 113/54 mmHg. Her weight had increased 8.8 kg from the weight at discharge. Her physical exam was notable facial and bilateral periorbital edema, abdominal distension, and 2+ bilateral non-pitting non-tender edema of both legs extending to her medial malleolus. Neurologic exam was performed which was unremarkable. Work up was performed to rule out other causes of edema, including a complete blood count, electrolytes, kidney and liver function tests, all of which were normal. She received 20 mg of furosemide and was instructed to perform fluid restriction to 1 L/m2/day and sodium restriction to <2 grams per day at home. She followed up in clinic 3 days after her ED visit where her weight had decreased by 4.2 kg and her edema had mostly resolved with only 1+ bilateral non-pitting edema. Her total dose of insulin remained at 0.7 unit/kg per day, with acceptable blood glucose levels at home. Her fluid restriction was discontinued and patient was instructed to follow up as usual, and she had no further edema in follow-up. Conclusion: This was a rare case of a newly diagnosed pediatric patient presenting with Insulin edema, which is essential for clinicians to recognize, so they can identify patients presenting with this uncommon side effect to rule out conditions that may present in a similar manner.

Presentation: 6/2/2024
7563 Investigation of the safety of GH treatment for Noonan syndrome -single center experience
Authors: Ishimaru Masanori , Fukui Sadahiro , Tanimoto Eri , Nakamura Chizuko , Ujita Nagisa , Miyagi Hajime , Doi Hibiki , Igarashi Mizuho , Kashima Takemoto , Yoshii Keisuke , Naiki Yasuhiro , Horikawa Reiko
Published: October 2024

Disclosure: M. Ishimaru: None. S. Fukui: None. E. Tanimoto: None. C. Nakamura: None. N. Ujita: None. H. Miyagi: None. H. Doi: None. M. Igarashi: None. T. Kashima: None. K. Yoshii: None. Y. Naiki: None. R. Horikawa: None.

[Background] Growth hormone (GH) treatment for Noonan syndrome (NS) was approved in Japan in 2017. Although there have been no reports of serious adverse reactions associated with GH treatment for NS, there have been reports of myocardial thickening and warnings about malignant tumours which might be related to GH treatment. [Objective] To investigate the short- and long-term safety of GH treatment in patients with NS treated with GH at our hospital. [Methods and results] Medical records of 21 patients with NS (12 males and 9 females) treated with GH at our hospital from August 2006 to April 2023 were investigated retrospectively. Genetic diagnosis was performed in 13 patients, the others were clinically diagnosed. The patients ranged in age from 3 y 1 m to 11 y 6 m at the start of treatment, and the duration of treatment ranged from 11 m to 9 y 5 m. 2 patients had existing hypertrophic cardiomyopathy (HCM), and no patients experienced malignant neoplasmas or other hematologic abnormalities before treatment. The height was on average -3.60 SD at the start of treatment and had improved to an average of -2.10 SD at the most recent measurement. GH treatment was well-tolerated and no new severe adverse events were observed except for two who developed HCM after initiation of GH treatment. One patient developed HCM at the age of 17y and 0 m, 7 y 4 m after starting treatment. The treatment was continued in consultation with a cardiologist and completed at the age of 17 y and 4 m. Another patient was diagnosed as HCM 2 years and 3 months after the start of treatment. At the age of 7 y 2 m, 3 y 5 m after starting treatment, GH treatment was temporarily stopped by the cardiologist's decision. [Discussion] More than half of the children with Noonan syndrome have been reported to have short stature, indicating the effectiveness of GH treatment. Improvement of short stature has also been observed in our GH-treated cases. On the other hand, malignant tumours occur more frequently in NS and 50% of patients, with or without cardiomyopathy, are reported to have abnormal electrocardiograms. Long-term effect of GH and long-acting GH treatment on neoplasm formation and/or cardiac diseases should be carefully monitored. [Conclusion] The safety issues of GH treatment in Noonan syndrome should be monitored carefully.

Presentation: 6/3/2024
7966 Long-Term Safety and Efficacy of a Hydrocortisone Oral Granules in a Young Child with Congenital Adrenal Hypertrophy
Authors: Bertossi M , Lowe C , Van Meter Q L
Published: October 2024

Disclosure: M. Bertossi: None. C. Lowe: None. Q.L. Van Meter: Consulting Fee; Self; Eton Pharmaceuticals. Speaker; Self; Eton Pharmaceuticals.

Introduction: Congenital adrenal hyperplasia (CAH) is the most common cause of pediatric adrenal insufficiency. Children diagnosed with CAH need exogenous glucocorticoid therapy throughout their lifetime. Because low dose hydrocortisone (HC) tablets are not available, patients and their caregivers must either split/crush hydrocortisone tablets or rely on HC that has been compounded from adult medications. In late 2020, a pediatric specific HC formulation, an oral granule, became available with doses as low as 0.5 mg. There are minimal data concerning the long-term use of this novel HC formulation. Subject and Method: This case study is a girl (DOB 11/2016) with CAH who has been administered the HC oral granule formulation for over 3 years. Results: The subject is a 7-year-old female who was diagnosed at birth with CAH. At an outside institution, she administered 6.25 mg HC, divided into three doses of 2.5 mg in the morning, 1.25 mg in the afternoon, and 2.5 mg in the evening (2.5/1.25/2.5; 9 mg/m2). She was also administered 0.15 mg fludrocortisone qd. Her dose was increased to a total dose of 7.5 mg, administered 2.5 mg three times/day (10 mg/m2) because of a high 17-OHP concentration, 1048 mg/dL. Other hormone levels were unremarkable. Her 17-OHP levels increased to 2662 mg/dL after 3 months of the increased dose. Because of the development of Cushing’s symptoms, she was switched to the 7.0 mg HC granules (2.5/2.0/2.5; 9.5 mg/m2 total dose). After the switch to the HC granules, her 17-OHP levels was 293 ng/dL. Because of rising 17-OHP levels, her dose needed to be increased twice over the past 2 yrs. Her current dose is 12 mg HC granules (4/4/4; 11 mg/m2 total dose), and her three most recent 17-OHP levels were 73, 101, and 89 ng/dL, respectively. She is also taking 0.2 mg fludrocortisone po, q am. Throughout HC granule therapy, she had no incidence of adrenal crisis. Her most recent calculated bone age was 8 yr 10 mo, with her chronological age was 6 yr, 8 mo with no evidence of virilization. Growth curves suggest that she is neither under- nor over-dosed on her HC therapy. Conclusion: This case may be the longest, continuous administration of the novel HC granules in US for a child with CAH. The results show the potential to better titrate HC dosing, especially with the narrow therapeutic window of HC in children with CAH. Her daily dose was adjusted by titrating in small increments to result in good outcomes, such as better hormonal control, the lack of virilization and continuous growth. Further evaluations of the long-term use of HC granules are needed to occur to establish the long-term risks and benefits of this novel HC granule.

Presentation: 6/3/2024
8424 Complex Management Of Adrenal Insufficiency In Pregnancy: A Challenging Case
Authors: Avanessian T , Alsamarraie H
Published: October 2024

Disclosure: T. Avanessian: None. H. Alsamarraie: None.

Background: Physiologic changes, including changes in the HPA axis and RAAS, during pregnancy pose challenges in the management of adrenal insufficiency in pregnant women. This case report discusses the management of adrenal insufficiency in a young primigravida female with Addison’s disease. Clinical Case: At 19.5 weeks of gestation, a 26-year-old primigravida, previously diagnosed with Addison’s disease 5 years ago, presented to an acute care center for syncopal episodes. The pregnancy had been complicated by persistent nausea and vomiting, labeled as hyperemesis gravidarum, and recurrent syncopal episodes, resulting in 6 ED visits and 3 hospitalizations, with symptoms improving each time after IV hydration and then returning within a few days. At presentation, the patient reported lightheadedness, sweating, palpitations, dyspnea, fatigue, nausea, vomiting, and a 10 lb weight loss since the beginning of pregnancy. The pre-pregnancy regimen was hydrocortisone 10 mg in the morning and 5 mg in the afternoon, with fludrocortisone 0.1mg daily. At 8 weeks of gestation, due to increased fatigue and hypotension, the hydrocortisone dose was doubled, while fludrocortisone was continued the same. During admission, blood pressure ranged from 67/37 to 90/56 mmHg, and heart rate ranged between 93-103 bpm. On labs, electrolytes were normal, and the serum renin level was elevated at 5.803 ng/ml/hr (0.167-5.380). Treatment included IV hydration and hydrocortisone 40 mg in the morning and 20 mg in the afternoon. Despite symptom improvement, blood pressure remained low. Thus, fludrocortisone was increased to 0.1 mg twice daily. Within 3 days, all symptoms improved, allowing for the down-titration of the hydrocortisone dose. The patient was discharged with hydrocortisone 30 mg at 8 AM, 10 mg at 3 PM, 5 mg at 7 PM, and fludrocortisone at 0.1 mg twice daily. Conclusion: Managing symptoms of adrenal insufficiency during pregnancy is challenging due to the overlap of symptoms and signs with physiologic manifestations of pregnancy. The use of biochemical testing is limited, given the physiological activation of RAAS and progressive increases in renin, CRH, ACTH (from both pituitary and placental sources), and cortisol during pregnancy. Monitoring mineralocorticoid requirements is further complicated by physiological changes in blood pressure and interstitial fluid status. While some literature suggests that adjusting fludrocortisone may not be necessary, as an increase in glucocorticoid dose can compensate, determining the correct dose of glucocorticoid and mineralocorticoid replacement should be tailored to each patient and their specific symptoms. References:1. Lee, J. H., & Torpy, D. J. (2023). Adrenal insufficiency in pregnancy: Physiology, diagnosis, management and areas for future research. Reviews in endocrine & metabolic disorders, 24(1), 57-69.

Presentation: 6/1/2024
6544 M6A methylation of PLCβ in the hypothalamus regulates GnRH synthesis and secretion by interfering Ca2+ signaling pathway
Authors: Yin Xiaoqin , Zang Shaolian , Li Pin
Published: October 2024

Disclosure: X. Yin: None. S. Zang: None. P. Li: None.

Backgrounds: In recent years, the incidence of precocious puberty has increased rapidly, posing a serious threat to girls' physical and mental health. Epigenetic changes, especially m6A methylation modification, may be an important influencing factor. Researches had found that m6A modification plays an irreplaceable role in the development and functional homeostasis of the nervous system. A variety of factors could changed RNA m6A level in the hypothalamus and affect the process of adolescent sexual development. In the study,we aimed to explore the specific role of m6A methylation in precocious puberty, and to identify its downstream target genes by multi-omics approach and to verify its function. Hypothesis The demethylase FTO regulated the m6A modification of the target gene in the hypothalamus to affect the synthesis and secretion of GnRH and regulate the initiation of puberty. Methods: The modification abundance of m6A was investigated by the girls with central precious puberty (CPP). The changes of m6A modification in total RNA and the expression of important modulator genes were detected by colorimetry and qRT-PCR respectively in the hypothalamic ARC nucleus of female rats at three different developmental stages (juvenile, early puberty and puberty) and precocious rat model. MeRIP and mRNA sequencing was used to screen target genes which related to puberty development. Knockdown or overexpression of FTO were constructed using plasmid or lentivirus transfection. The target mRNA targeted regulated by FTO was verified with RNA-seq, qRT-PCR, WB and Flow cytometry. Results This study confirmed that the level of RNA m6A in the peripheral blood of the precocious group was significantly higher than that of the control group. The level of RNA m6A in the hypothalamus of female rats gradually increases with the development of puberty, and the expression of demethylase gradually decreases. MeRIP-seq combined with mrNA-seq screening analysis showed that the m6A modification of PLCβ in the ARC nucleus of the hypothalamus was reduced, and its mRNA expression was significantly increased in sexually precocious female rats. Combined with bioinformatics analysis, it was found that there were multiple m6A modified motif sites on the mRNA of PLCβ, and luciferase experiment confirmed that there was a regulatory relationship between them. After over-expressing FTO, the mRNA and protein expression of PLCβ were significantly increased, and the up-regulation of FTO expression induced a significant increase in intracellular Ca2+ concentration, the expression of CAM, and the activation of Ca2+ signaling pathway. Conclusions In the ARC nucleus of the hypothalamus, FTO affects the synthesis and secretion of GnRH by regulating the m6A modification level of PLCβ through the Ca2+ signaling pathway, and interferes with the initiation of female sexual development.

Presentation: 6/1/2024
7978 Metabolic Outcomes in Transgender Youth Receiving Affirming Hormonal Therapy
Authors: Salama Mostafa , Basmaci Rami , Rajjo Tamim , Chuzhyk Olena , Lteif Aida Nadim , Nofal Alaa Al
Published: October 2024

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 < 0.001), as did BMI Z scores (mean difference 0.257, p < 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 < 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
7335 Myxedema Coma in an Adolescent Patient: A rare, lethal manifestation of profound hypothyroidism
Authors: Rodriguez Christian , Mejias Exa M , Berrios Luis R , Currais Carolina
Published: October 2024

Disclosure: C. Rodriguez: None. E.M. Mejias: None. L.R. Berrios: None. C. Currais: None.

Myxedema coma is a rare, life-threatening condition that represents the most severe manifestation of profound hypothyroidism. It is characterized by extensive end-organ dysfunction. Therefore, it is crucial to have a high index of suspicion in order to identify it promptly and initiate treatment. We report a case of an adolescent patient with past medical history of Type 1 Diabetes Mellitus and hypothyroidism who was initially admitted to pediatric wards due to hypertension, constipation and acute kidney injury (AKI). The patient was transferred to the pediatric intensive care unit (PICU) after he developed multi-organ failure secondary to myxedema coma. His laboratory work up was remarkable for severe hypothyroidism with a thyroid-stimulating hormone (TSH) > 679, uncontrolled diabetes mellitus (Glycosylated Hemoglobin 13.1%) and chronic kidney disease (Creatinine 2.56). During his hospital course, he required long term hemodialysis, mechanical ventilation and underwent cardiorespiratory resuscitation multiple times. Since myxedema coma is an uncommon manifestation of pediatric hypothyroidism, pediatric guidelines are not available. We aim to reinforce the awareness of myxedema coma and encourage physicians to have a high index of suspicion as the widespread availability of TSH assays and its use can aid in the diagnosis and treatment of these patients. Furthermore, we emphasize an interdisciplinary approach to avoid mortality and long-term complications.

Presentation: 6/1/2024
7537 Composite Pheochromocytoma-Ganglioneuroma Secreting Vasoactive Intestinal Peptide: A Case Report
Authors: Brochu Benjamin , Collin Yves , Temmar Rabia , Bernier Frederic , Dandurand Karel , St-Jean Matthieu , Massicotte Marie-Hélène
Published: October 2024

Disclosure: B. Brochu: None. Y. Collin: None. R. Temmar: None. F. Bernier: None. K. Dandurand: None. M. St-Jean: None. M. Massicotte: None.

Background: Composite pheochromocytoma-ganglioneuroma is a rare tumor combining features of both pheochromocytoma/paraganglioma (PPGL) and neurogenic tumors. Cosecretion of vasoactive intestinal peptide (VIP) is even less common and highlights the diverse secretory potential of these tumors. Clinical Case: An 80-year-old woman presented with severe chronic diarrhea that had been progressively worsening over the past 10 years. The diarrhea was associated with chronic hyponatremia between 128 and 132 mmol/L. She also had mild hypertension, with a mean blood pressure of 145/90 mm Hg. An abdominal CT scan revealed a right adrenal mass of 68 mm x 44 mm x 50 mm with a density of 19 HU without contrast. A 24-hour urinary collection demonstrated normetanephrines (NM) levels at 3.5 times the upper limit of normal. A 68Ga-DOTATATE PET/CT demonstrated significant uptake only in the adrenal mass. Because of the ongoing severe diarrhea, that is unusual in the context of NM secreting PPGL, serum VIP level was measured and came back at nearly three times the upper limit of normal. A provisional diagnosis of pheochromocytoma with VIP and catecholamines cosecretion was made and surgical resection by laparotomy was performed without complication. Pathology demonstrated a composite tumor combining a pheochromocytoma and a ganglioneuroma, with a Pheochromocytoma of the Adrenal gland Scaled Score (PASS) score of 3. Tumor immunohistochemical staining was positive for VIP in both pheochromocytoma and ganglioneuroma cells. After surgery, diarrhea and hyponatremia resolved and blood pressure normalized. Conclusion: This is one of the very rare cases described in the current literature of a composite pheochromocytoma coproducing catecholamines and VIP. While the two tumors might have developed synchronously, the finding of VIP secretion in the pheochromocytoma and the ganglioneuroma suggest that both tumors might originate from the same cell.

Presentation: 6/1/2024
7644 Novel Candidate Genes for SRY-Negative 46,XX Differences of Sex Development with Testicular Differentiation
Authors: Ferrari Maria Tereza Martins , Nishi Mirian Yumie , Jorge Alexander Augusto Lima , Benedetti Anna Flavia Figueiredo , Batista Rafael Loch , Silva Elinaelma Suelane do Nascimento , Martinez Alejandro , Mericq Veronica , Carvalho Filomena Marino , Mendonca Berenice Bilharinho , Domenice Sorahia
Published: October 2024

Disclosure: M.M. Ferrari: None. M.Y. Nishi: None. A.A. Jorge: None. A.F. Benedetti,: None. R.L. Batista: None. E.S. Silva: None. A. Martinez: None. V. Mericq: None. F.M. Carvalho: None. B.B. Mendonca: None. S. Domenice: None.

Introduction: Gonadal development in mammals is a dynamic and complex process, which requires the interaction of multiple factors in a meticulous feedback control and self-regulation system. Defects in genes involved in this process may cause differences of sex development (DSD). In rare cases, the gonads of 46,XX individuals differentiate completely into testes (46,XX testicular DSD, 46,XX TDSD), or with the coexistence of testicular and ovarian tissues in the same individual (46,XX ovotesticular DSD, 46,XX OTDSD). Strategies of large-scale parallel sequencing have enabled the simultaneous analysis of known genes, as well as the identification of novel candidate genes contributing to molecular diagnosis of these conditions. Objective: To establish the molecular diagnosis of a cohort of SRY-negative 46,XX T/OTDSD patients using the whole exome sequencing (WES) technique. Patients and Methods: Twenty-three families (24 patients) were evaluated, 22 patients with sporadic disease, and one family with two affected siblings. Histological diagnosis of OTDSD was confirmed in all patients, except in two with the presumptive (non-histological) diagnosis of TDSD. WES was performed using the Illumina platform. The variants were classified according to ACMG criteria. Results: Six different candidate genes associated with the 46,XX DSD phenotype were identified in the 23 families (26%) studied; all in patients with OTDSD diagnosis. Two variants were classified as likely pathogenic in FLNB and SOX10 genes, and four as VUS in IMMP2L, SOX8, PRKACG, and CLASP1 genes. The unavailability of analysis of case-parent trio samples hampered the classification of some of the novel candidate allelic variants. All these candidate genes were selected as potential causes of OTDSD, based on evidence of direct or indirect interactions of these proteins with SOX9. In the two siblings with 46,XX OTDSD, the allelic variant c.397delT (p.Ser133Leufs*7) in IMMP2L was identified in a heterozygous state and was absent in the unaffected family members (mother and third XY sibling). A potential role of Immp2l had been previously associated with the etiology of XX female-to-male sex reversal in sheep lineage. Conclusion: Although establishing the genetic etiology of gonadal development abnormalities in individuals with 46,XX TDSD/OTDSD remains a challenge, the results of this study generated new information and perspectives on the mechanisms involved in gonadal development.

Presentation: 6/3/2024
9356 Occurrence Of Dyslipidemia During Modified Atkins Diet In Children With Intractable Epilepsy And Effect Of Lipid-Lowering Agents On Dyslipidemia
Authors: Yoo Ji Eun , Kim Seo Jung , Chae Hyun Wook
Published: October 2024

Disclosure: J. Yoo: None. S. Kim: None. H. Chae: None.

Introduction: The Modified Atkins Diet (MAD), as a type of Ketogenic diet (KD) therapy, is utilized as a treatment for intractable epilepsy. Compared to the classic KD, it has a lower ratio of fat to carbohydrate plus protein, resulting in higher compliance among patients. Dyslipidemia is known as a major complication of KD, but when it comes to MAD, there is a scarcity of long-term studies investigating lipid level alterations in children.In this study, our objective is to examine the impact of the MAD on serum lipid levels in children and adolescents with intractable epilepsy. Method: A total of 106 patients with intractable epilepsy aged under 19 who initiated MAD from January 2016 to December 2021 and maintained MAD for a minimum of 12 months were enrolled. Laboratory test for lipid level were conducted at baseline, 1 month, 3 months, 6 months, and subsequently at 6-month intervals after initiation of MAD. The prevalence rate of dyslipidemia and lipid levles by period after MAD was analyzed. Dyslipidemia is defined as having any one of the following criteria: total cholesterol ≥200 mg/dL, LDL (Low-density lipoprotein) ≥130 mg/dL, HDL (High-density lipoprotein) <40 mg/dL, and triglyceride ≥100 mg/dL for children aged 0-9 and ≥130 mg/dL for adolescents aged 10-18.3. Result: The prevalence rate of total dyslipidemia observed at baseline, 1 month, 3 months, 6 months, 12 months, 18 months, 24 months, 30 months, and 36 months, were 31.1%, 67.6%, 69.5%, 68.2%, 59.5%, 60.5%, 53.7%, 47.1%, and 31.3%, respectively. When the average value and prevalence rate for each type of dyslipidemia were analyzed, total cholesterol and LDL levels showed an increase from the 1-month period compared to the baseline, peaked at the 3-month period, and gradually decreased from the 6th month with statistical significance. In the case of triglycerides, the prevalence rate of hypertriglyceridemia was highest at 3 months, but the average value was highest at 1 month with statistical significance. However, in HDL, both the average value and the prevalence rate of hypo-HDL cholesterolemia did not exhibit a significant difference over the entire period. Conclusion: MAD increases the incidence of dyslipidemia until three months after initiation, but in most cases, it tends to decrease even without treatment after six months.

Presentation: 6/1/2024