bluuebunny/crossref_metadata_2025_split huggingface dataset:
6441 Hyperthyroidism in a patient with Lyme disease
Authors: Epstein Jessy , Berman Casey 
Published: October 2024

Abstract
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

Abstract
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 &lt; 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 &gt;30%. In 14 boys (56%) TV was &lt;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

Abstract
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 &lt;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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

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