bluuebunny/crossref_metadata_2025_split huggingface dataset:
THU234 An Adolescent Patient With Asymptomatic Hypocalcemia And Extensive Cerebral Calcification Due To Pseudohypoparathyroidism Type 1B: A Care Report
Authors: Alemzadeh Ramin , Ross Jordan Douglas , Guillen-Mendoza Daniel 
Published: October 2023

Abstract
Disclosure: R. Alemzadeh: None. J.D. Ross: None. D. Guillen-Mendoza: None.
Background: Pseudohypoparathyroidism (PHP) is a heterogeneous group of disorders due to renal resistance to parathyroid hormone (PTH) resulting in biochemical hypoparathyroidism but with skeletal sensitivity to PTH. Case Presentation: A 15-year-old African American male was incidentally found to have biochemical evidence of severe hypocalcemia during routine evaluation of his bilateral slipped capital-femoral epiphyses. The patient was at age-appropriate stage of puberty with normal height and without any features of hereditary osteodystrophy. However, he had history of mild developmental delay requiring school accommodations. On physical exam, there was some mild dyscoordination with finger and toe-tapping and a Myerson’s sign, negative tetany signs. The biochemical screening revealed markedly low serum calcium (4.9 mg/dL) with elevated phosphorus (7.8 mg/dL) and PTH (1314 pg/mL) levels. His hypocalcemia was accentuated by the presence of severe 25 hydroxy-vitamin D deficiency (7.5 ng/mL) with mild hypomagnesemia (1.4 mg/dL). He had normal renal and thyroid function tests with normal growth factors. There were minimal plasma cyclic AMP responses to a single dose of intravenous teriparatide (Ellsworth-Howard test) consistent with diagnosis of pseudohypoparathyroidism. The skeletal survey showed bowing and under-tubulation of the radius, ulna, tibia, and fibula as well as slipped capital femoral epiphysis bilaterally. His brain CT scan showed symmetrical severe dense calcifications in the basal ganglia, bilateral frontal, parietal and temporal subcortical white matter, pons and right dentate nucleus. Genetic testing did not reveal any GNAS mutations. The patient was initially treated with parenteral calcium followed by high-dose oral calcium supplements and calcitriol. His coexisting hypovitaminosis D and hypomagnesemia were corrected with oral high-dose cholecalciferol and magnesium sulfate, respectively. Conclusions: An incidental finding of severe asymptomatic hypocalcemia and elevated PTH without hereditary osteodystrophy phenotype raised the clinical suspicion of pseudohypoparathyroidism type 1B. This was associated with cerebral calcifications with increasing risk of worsening learning disabilities and minimal neurological findings.
Presentation: Thursday, June 15, 2023
THU237 A Case Of Primary Hypothyroidism, Dysglycemia And Epilepsy With PAX8 And SETD1A Mutation
Authors: Singh Santosh Kumar 
Published: October 2023

Abstract
Disclosure: S.K. Singh: None.
KEYWORDS: PAX8, SETD1A, DYSGLYCEMIA
INTRODUCTION: Hypothyroidism is associated with dysglycemia linked with insulin resistance and shared common genetic determinants.PAX 8 gene regulates the development of thyroid gland as well as the expression of TG,TPO and NIS genes.It impacts glucose homeostasis by favoring beta-cell survival and through thyroid hormones.Epilepsy in hypothyroid patients can be idiopathic or due to Hashimoto’s Encephalopathy (HE). Thyroid hormones can impact epileptogenesis through mitochondrial dysfunction, oxidative-stress and GABAergic transmission. THE INDEX PATIENT: A 13 year old female(weight and height age 1.5 years below her chronological age by Indian growth chart and a further lag of 18 months and 6 months, respectively by CDC chart)was diagnosed as a case of thyroprivic hypothyroidism with TSH - 100 mIU/L and positive anti-TPO antibody. She was euthyroid on 112 ug/d L-T4.She is on anticonvulsant since 12 years of age for tonic-clonic epilepsy. The MRI of brain showed focal gliosis with few small encephalomalacic streaks in right occipital lobe. On evaluation at 12.5 years of age, her fasting plasma glucose was 80 mg/dl and her HbA1c was 4.8% but 2-h post glucose was 233 mg/dl with another value of 270 mg/dl. Her father has T2DM and Hypothyroidism. Her mother is Hypothyroid. Her genetic study showed SETDIA and PAX8(-) mutations. DISCUSSION: PAX8 regulates development of thyroid gland and biosynthesis of thyroid hormones. It can impact glucose homeostasis by enhancing beta-cell survival by inhibiting apoptosis, immunomodulation, maintaining local anti-inflammatory milieu in pancreas, ensuring systemic levels of thyroid hormone to stimulate insulin secretion and protect beta-cells from environmental stressors.PAX8 mutation in a family has been shown to be associated with a spectrum of disorders encompassing Gestational Thyroid Dysfunction(GTD),Gestational Diabetes Mellitus(GDM) and T2DM.[1] Although mutation analysis was done only in the index patient, Hypothyroidism and Dysglycemia (post- glucose&gt;200 mg/dl)in the patient and family history of Hypothyroidism and T2DM could be linked with PAX8 mutation.SETD1A mutation has been linked with early-onset epilepsy with or without developmental delay. The mutation study can aid in deciding appropriate therapy including steroids for HE. CONCLUSION: This case highlights the significance of evaluation for PAX8 mutation in hypothyroid patients, even if anti-TPO positive, particularly when there is family history of thyroid dysfunction, GDM, T2DM. It also underlies the importance of SETD1A mutation analysis in hypothyroid patients with epilepsy.
Presentation: Thursday, June 15, 2023
THU243 Fitting Together The Pieces Of The Puzzle Between Isolated ACTH Deficiency And Immunodeficiency: DAVID Syndrome
Authors: Buchanan Katherine Virginia , Hurst Anna C E , Ashraf Ambika P 
Published: October 2023

Abstract
Disclosure: K.V. Buchanan: None. A.C. Hurst: None. A.P. Ashraf: None.
Objectives: DAVID syndrome is a rare genetic disorder with common variable immunodeficiency (CVID) and anterior pituitary hormonal deficiencies due to a pathogenic variant in NFKB2. We aim to describe asymptomatic ACTH deficiency identified after the diagnosis of CVID in a patient with DAVID syndrome. Methods: A retrospective chart review of a patient with DAVID syndrome was performed. Results: The patient is a 15 year and 9-month-old female with weight in the 71st percentile and height in the 64th percentile, who was diagnosed with DAVID syndrome at 10 years through a Primary Immunodeficiency panel which identified a pathogenic variant in NFKB2 c.2557C&gt;T,p.Arg853* and a variant of unknown significance in STAT2 c.1301C&gt;T (p.Thr434Met). The panel was performed due to the patient’s history of recurrent sinus infections, hypogammaglobulinemia, and alopecia totalis. The patient did not have symptoms of ACTH deficiency including hypoglycemia and hypotension. After the genetic diagnosis was made, an anterior pituitary hormone evaluation was performed which showed an ACTH &lt;5 pg/ml, AM cortisol &lt;0.2 mcg/dL, TSH 3.48 uIU/ml, FT4 0.82 ng/dL, thyroid peroxidase antibody 29 IU/mL (normal &lt;9), somatomedin-c 44 ng/mL (reference range 152-593), LH 5.36 mIU/mL, and FSH 14.25 mIU/mL. Adrenal insufficiency was diagnosed since the patient did not show incremental cortisol response (serum cortisol &lt;0.2 mcg/dL at 30 and 60 minutes) post Cosyntropin stimulation test. The patient had normal electrolytes. Hydrocortisone replacement therapy was initiated. A growth hormone stimulation test was not performed since the patient had normal height and interval height velocity. The thyroid function remained stable, and the patient attained menarche at age 14. Conclusions: This patient is unique in having asymptomatic, acquired, isolated ACTH deficiency diagnosed in later childhood, despite having frequent sinopulmonary infections since infancy as part of DAVID syndrome. Further research needs to be done to elucidate how NFKB2 variants contribute to acquired, isolated, central ACTH deficiency or autoimmune pituitary disease.
Presentation: Thursday, June 15, 2023
FRI016 Utilizing Game-based Learning In Medical Education
Authors: Daniel Sneha , Bangalore-Krishna Kanthi 
Published: October 2023

Abstract
Disclosure: S. Daniel: None. K. Bangalore-Krishna: None.
In the era of advancing technologies, several apps and software are available for learners that are fun, interactive, innovative, and collaborative. Kahoot! is one such game-based learning platform that facilitates formative assessment and promotes student learning. Kahoot! has been used extensively in higher education and has been successful not only in keeping the learners attentive and engaged but also provided with positive feedback and motivation. The philosophy of learning and education has shifted from being teacher-centered or subject-centered to being learner-centered and current learners tend to lean towards an abstract-active style of learning. We completed a focused discussion with the endocrine fellows and identified topics which were deemed challenging/difficult. We then developed a Kahoot!- based curriculum to review these topics. Each session included 2-3 review questions and 8-10 topic-based questions that were meticulously designed to cover the breadth of the topic followed by a 15-minute didactic session to review core concepts, including multiple clinical correlates to ensure relevance and applicability. Participants used their cellphones to log in and points were awarded (by the app) based on the accuracy and timeliness of responses. After 8 sessions, we conducted a brief survey with qualitative and quantitative questions to assess the effectiveness of the curriculum and contrasted this with the traditional curriculum which involved either a didactic session or watching videos with minimal interaction with an educator. All 8 pediatric endocrine fellows participated in the in-person, weekly sessions (8 total) and the survey. Results showed that 8/8 participants found this platform to be more interesting, easy to use, were motivated to learn during these sessions, engaging and encouraged participation without fear of being incorrect. Participants stated that these sessions helped them ask thought-provoking questions, understand previously complex concepts better and highlighted areas of knowledge deficits. Participants had additional suggestions to enhance deeper learning which we plan to incorporate. Our next step is to assess content retention at 3 months and 6 months after the sessions. With evolving technology and change in learning styles of current learners, game-based learning should be further explored in medical education, to keep learners engaged and make learning more fun, diverse, interactive, and inclusive.
Presentation: Friday, June 16, 2023
FRI595 Two Cases Of Severe Symptomatic Hypocalcemia Secondary To Vitamin D Deficiency Diagnosed Within The Same Week
Authors: Cooper Felicia Ilyssa , Jonsdottir Urdur , Rios Gabriela Guadalupe , Vyas Neha , Gurnurkar Shilpa 
Published: October 2023

Abstract
Disclosure: F.I. Cooper: None. U. Jonsdottir: None. G. Guadalupe Rios: None. N. Vyas: None. S. Gurnurkar: None.
Background: Vitamin D is a fat-soluble vitamin that plays a significant role in intestinal calcium absorption. Humans acquire vitamin D through sun exposure and diet, though few foods naturally contain vitamin D in the amount needed to prevent deficiency. Vitamin D deficiency can result in nutritional rickets, which may present with impaired growth, weakened bones, dental abnormalities, and fractures secondary to decreased calcium absorption. Hypocalcemia can lead to a wide variety of clinical manifestations from mild symptoms such as irritability, tremors, and muscle cramps to life threatening seizures and arrhythmias. Case: This case series describes two children presenting to our pediatric emergency department within the same week with severe hypocalcemia secondary to profound vitamin D deficiency. The first was a 2-year-old female with prior medical history of 29-week prematurity who presented with a first time generalized tonic clonic seizure. She had a limited diet that consisted mostly of non-fortified almond milk. As an infant, she was on breast milk but did not receive vitamin D supplementation. On presentation, she was noted to have exam findings and radiographic evidence of rickets. The second was a 13-year-old male with history of non-verbal autism presenting with one month of diarrhea, agitation, and progressive leg pain. The patient was described as a picky eater and spent minimal time outdoors. Both children were found to have severe hypocalcemia (6.6 mg/dL and 4.8 mg/dL, respectively) in the setting of vitamin D deficiency (vitamin D-25 6.8 ng/dL and 4.9 ng/dL, respectively). They were successfully treated acutely with intravenous calcium gluconate bolus (one dose of 495 mg and three 2,000 mg) and oral calcium, with normalization of ionized calcium levels and improvement of symptoms. They were treated long-term with oral calcium, calcitriol, and vitamin D supplementation. Conclusion: Vitamin D deficiency should be considered in severe symptomatic hypocalcemia in children. Vitamin D supplementation is necessary in all breast-fed babies and a large proportion of other children not meeting vitamin D requirements through diet and sun exposure.
Presentation: Friday, June 16, 2023
OR15-02 Changes In Liver Fat Content By CT 1 Year After Sleeve Gastrectomy In Adolescents With Severe Obesity
Authors: López López Ana Paola , Tuli Shubhangi , Lauze Meghan , Becetti Imen , Pedreira Clarissa C , Huber Florian A , Omeroglu Emre , Misra Madhusmita , Singhal Vibha , Bredella Miriam A 
Published: October 2023

Abstract
Disclosure: A.P. López López: None. S. Tuli: None. M. Lauze: None. I. Becetti: None. C.C. Pedreira: None. F.A. Huber: None. E. Omeroglu: None. M. Misra: None. V. Singhal: None. M.A. Bredella: None.
Introduction: Obesity is associated with non-alcoholic fatty liver disease (NAFLD). Sleeve gastrectomy (SG), the most commonly used metabolic and bariatric surgery, is an effective means of weight loss and has been shown to improve NAFLD in adults but data regarding the efficacy of SG in early stages of NAFLD where steatosis is the only pathology is evolving. We aim to assess the impact of SG on hepatic fat content, one year after SG in youth with severe obesity. Objective: To (i) identify changes in liver fat content using attenuation measurements on non-contrast CT [liver/spleen (L:S) ratio] in youth with obesity before and 12 months after sleeve gastrectomy (SG) compared with non-surgical controls with obesity (NS) and (ii) associations of changes in L:S with changes in body composition. Methods: 52 participants 13-25 years old with obesity were followed for 12 months. 25 subjects had SG (84% female), and 27 were NS (70% female). Non-contrast CT of the abdomen was performed for attenuation measurements of liver and spleen in Hounsfield Units (HU), expressed as L:S ratio. A lower L:S ratio indicates higher liver fat. A single-slice MRI of the abdomen at the level of L4 was performed to assess subcutaneous and visceral adipose tissue (SAT and VAT) cross sectional areas (cm2). Results: Mean age did not differ across groups. Body mass index (BMI) at baseline trended higher in SG vs. NS [44.18 (41.33, 53.72) vs. 42.16 (38.65, 46.96) kg/m2, (p=0.073)], and the mean 1-year decrease in BMI was greater in SG vs. NS (-12.48±0.83 vs. -0.21±0.52 kg/m2, p&lt;0.0001). VAT decreased in SG but increased in NS [-50.77 cm2 (-61.26, -34.09) vs. 13.55 cm2 (-10.27, 34.78), p&lt;0.0001], over 1 year. There was a within group increase in the L:S ratio in SG (0.13± 0.05, p= 0.014) but not NS over 1 year, with a trend for a difference between groups (p=0.055). All SG participants with an L:S ratio &lt;0.9 (threshold for the diagnosis of NAFLD) before surgery had a ratio of &gt;1.0 a year after surgery, consistent with resolution of NAFLD. Within SG, the 1-year change in L:S ratio was negatively associated with 1-year change in visceral fat (ρ=-0.52 p=0.017). Conclusions: Hepatic fat content as assessed by non-contrast CT improved after SG over 1-year in youth with obesity with resolution of NAFLD in all subjects. This was associated with improvements in body composition, especially visceral adiposity.
Presentation: Friday, June 16, 2023
SAT352 Reliability Of Two- And Three-dimensional Ultrasonographic Assessments Of Ovarian Morphology In Adolescents
Authors: Rahman Effat , Smith Bailey , Brink Heidi Vanden , Zaman Nabiha , Malik Anushka , Burgert Tania , Barral Romina , Lujan Marla Elaine 
Published: October 2023

Abstract
Disclosure: E. Rahman: None. B. Smith: None. H. Vanden Brink: None. N. Zaman: None. A. Malik: None. T. Burgert: None. R. Barral: None. M.E. Lujan: None.
Background: Distinct features of ovarian morphology using transabdominal ultrasonography (TAUS) have been observed in adolescents with polycystic ovary syndrome (PCOS). Standardized approaches to assess ovarian morphology using transvaginal ultrasonography result in excellent reliability and close agreement among multiple raters, which can lead to more precise estimates of follicle counts and ovarian size. The degree to which these methods translate to TAUS is unknown. Establishing standardized methods to analyze ovarian features via TAUS are needed to clarify the utility of ovarian morphology in the clinical evaluation of PCOS in adolescence. Objectives: To determine the reliability of follicle counts and ovarian size assessments obtained using 2D and 3D TAUS in early adolescence. Methods: Three raters evaluated images of 30 ovaries garnered from adolescents via TAUS (n=19, 6 - 20 months post-menarche) for the following 2D parameters: follicle number per ovary (2D FNPO), follicle number per cross-section (FNPS), ovarian volume (2D OV), ovarian area (OA) and stromal area (SA). Three dimensional assessments of follicle counts (3D FNPO) and ovarian volume (3D OV) were also performed using SonoAVCantralTM and VOCALTM software (GE Healthcare), respectively. Intraclass correlation coefficients (ICCs) were used to determine interrater reliability for each variable. An ICC &lt;0.5 was defined as poor, 0.50-0.75 as moderate, 0.75-0.90 as good, and &gt;0.900 as excellent reliability. Results: Across 2D measures of ovarian morphology, interrater reliability was highest for 2D FNPO (ICC = 0.698), followed by OA (0.655), SA (0.619), and FNPS (0.516). Ovarian volume measurements by 2D methods demonstrated poor reliability (0.297). Three-dimensional assessments of follicle counts were not associated with improved interrater agreement (0.609). By contrast, better reliability was detected for 3D OV versus 2D OV - albeit 3D measures still met criteria for poor reliability (0.397 vs 0.297). Conclusions: Assessments of ovarian morphology using TAUS are associated with moderate-to-poor reliability using standardized approaches. Follicle counts per ovary were moderately reliable with 2D and 3D TAUS, in contrast to OV which demonstrated poor reliability across raters irrespectively of modality. Poor reliability for measures of OV is concerning given current practice guidelines for the ultrasonographic assessment of PCOS advocate for measures of OV over FNPO when using TAUS. Factors impacting reliability, such as gynecological age, body habitus, and image quality will be evaluated in subsequent investigations to refine training, image acquisition protocols, and method development.
Presentation: Saturday, June 17, 2023
THU625 Med12 Mutation Activates Tryptophan-Kynurenine-ahr Pathway To Promote Growth Of Uterine Leiomyoma
Authors: Zuberi Azna , Huang Yongchao , Dotts Ariel J , Wei Helen , Coon V John S , Lizuka Takashi , Wu Olivia , Sotos Olivia , Chakravarti Debabrata , Dai Yang , Bulun Serdar Ekrem , Yin Ping 
Published: October 2023

Abstract
Disclosure: A. Zuberi: None. Y. Huang: None. A. Dotts: None. H. Wei: None. J. Coon V: None. T. Lizuka: None. O. Wu: None. O. Sotos: None. D. Chakravarti: None. Y. Dai: None. S.E. Bulun: None. P. Yin: None.
A.Z. and Y.H. contributed equally to this work.† Y.D., S.E.B., and P.Y. are co-senior authors.
‡To whom correspondence should be addressed: Serdar E. Bulun, M.D.Division of Reproductive Science in MedicineDepartment of Obstetrics and Gynecology Feinberg School of Medicine at Northwestern University 250 E. Superior Street, Suite 03-2306 Chicago, Illinois 60611-2914 Tel: 312-472-3636 Fax: 312-472-3740 Email: s-bulun@northwestern.edu Ping Yin, M.D., Ph.D. Division of Reproductive Science in Medicine Department of Obstetrics and Gynecology Feinberg School of Medicine at Northwestern University 303 E. Superior Street, Suite 10-111 Chicago, Illinois 60611 Tel: 312-503-1831 Fax: 312-503-0095 Email: p-yin@northwestern.edu. Conflict of interest: The authors have declared that no conflict of interest exists. Uterine leiomyomas (LM) cause heavy menstrual bleeding, anemia and pregnancy loss in approximately 10 million US women. Driver mutations in the mediator complex subunit 12 (MED12) gene in uterine myometrial cells initiate 70% LM tumors that grow in a progesterone-dependent manner. We showed a distinct chromatin occupancy landscape of MED12 and a shift of binding sites from proximal promoters to intronic/intergenic regions in mutant (mut-MED12) vs wild-type LM tissues. Integration of cistrome and transcriptome data identified tryptophan 2,3-dioxygenase (TDO2) as the top mut-MED12 target gene, which was massively upregulated in mut-MED12 LM. TDO2 catalyzes the conversion of tryptophan to kynurenine, which is an aryl hydrocarbon receptor (AHR) ligand and significantly elevated in mut-MED12 LM. Incubation of primary mut-MED12 LM cells with tryptophan or kynurenine stimulated AHR nuclear translocation, increased proliferation, inhibited apoptosis and induced AHR-target gene expression, whereas blocking the TDO2-kynurenine-AHR pathway by siRNA or pharmacologically abolished these effects. Progesterone receptor regulated the expression of AHR and its target genes. In vivo, TDO2 expression positively correlated with the expression of genes crucial for LM growth. In summary, activation of the TDO2-kynurenine-AHR pathway selectively in mut-MED12 LM induces tumor growth and may inform the development of targeted treatments and precision medicine.
Presentation: Thursday, June 15, 2023