bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT-373 A Case of X Linked Hypophosphatemic Rickets Due to DE Novo Phex Gene Mutation
Authors: Badran Ahmed , Bargman Renee 
Published: May 2020

Abstract
Introduction
Rickets is a condition that can affect bones of infants and children. It is characterized by growth plate demineralization and can occur secondary to, most commonly, vitamin D deficiency or various problems with vitamin D, Calcium or Phosphate metabolism.
Hypophosphatemic rickets (HR) is a type of rickets that is inherited by X linked dominant pattern mainly however it can be also inherited by autosomal dominant and recessive patterns in rare cases. X linked dominant type (XLH) affects about 1 in 20,000 newborns. Each of the other hereditary forms of HR has been identified in only a few families.
Clinical features of XLH is similar to other types of rickets including metaphyseal widening, palpable rachitic rosaries, frontal prominence, malformation of the horizontal depression along the lower border of the chest, insufficient weight gain and leg bowing.
Case presentation:
A 10-month-old infant presented to endocrinology with vitamin D deficiency, low serum phosphorus and hyperparathyroidism. Physical examination showed macrocephaly with frontal bossing, widening of the wrists and rachitic rosaries. His lab results showed low 25 OH vitamin D (11 ng/ml) (N:20-50 ng/ml), low phosphorus (PO4) (3.3 mg/dl) (N:4-6.5 mg/dl), high PTH (113 pg/ml) (N: 20-65pg/ml), high alkaline phosphatase (ALP) (836 IU/L) (N: 135-518 IU/L) and normal calcium (Ca2+) (9.6 mg/dl) (N:9-11 mg/dl). Vitamin D treatment was started however his follow up lab results showed persistent hypophosphatemia for age (2.8mg/dl) and elevated ALP (600IU/l) despite normalization of vitamin D (38 ng/ml). Additional lab tests were done showing high PO4 excretion (19.5 mg/dl)(N:1:3.5 mg/dl), Ca/Cr ratio 0.005 (N &lt;0.14), inappropriately normal FGF23 level (129 RU/ml) (N: &gt;124 RU/mL). Genetic testing showed de novo mutation in PHEX gene (871C&gt;T) which is consistent with XLH.
PHEX gene mutation is the most common mutation associated with XLH. Normally this gene can directly or indirectly regulate a protein called fibroblast growth factor 23 (produced from FGF23 gene). This protein normally inhibits renal reabsorption of phosphate into the bloodstream. Gene mutations increase the production or reduce the breakdown of fibroblast growth factor 23 leading to an overactivation of this protein and reduction of phosphate reabsorption by the kidneys, resulting in hypophosphatemia.
The patient was maintained on Burosomab (0.4 mg/kg biweekly); a recombinant human monoclonal antibody (IgG1) that binds to and inhibits the activity of fibroblast growth factor 23 (FGF23) and increases the phosphate reabsorption in the renal tubules.
Conclusion:
XLH due to PHEX gene mutation should be considered in rachitic children who have persistently low phosphate levels despite treating vitamin D deficiency.
SUN-665 Peripheral CB1R Blocker Improves Metabolism in Diet Induced Obese Mice Independent of Hepatic FGF21
Authors: Liu Jie , Godlewski Grzegorz , Liu Ziyi , Cinar Resat , Xiong Keming , Kunos George 
Published: May 2020

Abstract
Obesity is associated with an overactive endocannabinoid system, and selective blockade of CB1R in peripheral tissues, including the liver, reverses HFD-induced metabolic abnormalities by restoring normal lipid and glucose homeostasis. Fibroblast growth factor-21 (FGF21) has emerged as a major endocrine regulator derived from the liver that reduces adiposity and hepatic steatosis and improves glucose tolerance and insulin sensitivity, with changes similar to those induced by CB1R blockade. Here we investigated whether FGF21 mediate the metabolic effects of CB1R blockade in DIO mice.
In C57BL/6J wild-type mice, HFD caused a robust increase in hepatic Fgf21 mRNA and serum FGF21 levels, which were reversed by chronic CB1R blockade to levels observed in STD or vehicle-treated hepatocyte-specific CB1R-/- (LCB1-/-) mice, indicating activation of CB1R in the liver is largely involved in HFD-induced “FGF21-resistant” state. In contrast, the expression of the FGF21 receptor Fgfr1 and co-receptor β-klotho (Klb) were dramatically reduced by HFD in both epididymal fat and brain tissue in wild-type mice, and these effects were reversed by peripheral CB1R antagonist JD5037 treatment.
To address whether FGF21 mediated the metabolic effects of CB1R blockade, we repeated JD5037 treatment in liver-specific FGF21-/- (FGF21-LKO) mice. Surprisingly, JD5037 treatment was almost equally effective in both HFD-fed wild-type and in FGF21-LKO mice in reducing body weight and hepatic steatosis, attenuating hyperinsulinemia and hyperleptinemia. The current data suggest that peripheral CB1R blockade in obese mice improves insulin sensitivity and energy expenditure independently of hepatic FGF21.
SUN-514 Thyrotoxic Periodic Paralysis in Adolescence Patient a Case Report and Literature Review
Authors: He Luke , Lawrence Veronica , Moore Wayne V , Yan Yun 
Published: May 2020

Abstract
BACKGROUND: Thyrotoxic periodic paralysis (TPP) is an uncommon disorder characterized by acute flaccid paralysis due to hypokalemia. It is diagnosed primarily in Asian adult males and is rare in children and adolescents. Here we report an adolescent male patient of Vietnamese descent who presented to the emergency department with an episode of syncope, muscle weakness, and shortness of breath one day after the initiation of methimazole treatment for Graves’ disease. The laboratory revealed significant hypokalemia. In this report we also included and summarized the reported cases of TPP in adolescent patients since 1997.
Clinical Case: A 17-year-old Vietnamese American male who was recently diagnosed with Graves’ disease presented to the emergency department after an episode of syncope, muscle weakness, and difficulty breathing. Two months previously, he began having episodes of tachycardia. He was diagnosed with hyperthyroidism with a TSH of 0.007 mIU/mL and free T 4 &gt; 7 ng/dL (0.8-1.9). He was subsequently evaluated by Cardiology and started on atenolol. He was then seen by Endocrinology 5 days after and started on methimazole 15 mg twice daily. On the next morning after starting methimazole, he reported feeling weak and passed out. His father had found him on the floor, weak and unable to move, approximately 30 minutes after his father “heard a thud upstairs”. The patient recalled that his legs gave out and he “hitting his face on a table”. In the emergency department, he was tachycardic at 116 bpm, widened pulse blood pressure of 131/50 mmHg with normal respiratory rate 24 BR/min. He had diffused and significant muscle weakness on his all extremities including grip strength.
His potassium was 1.6 mmol/L (3.5 - 5.2) and magnesium 1.6 mmol/L (1.6-2.3). The rest of his chemistry panel was unremarkable. He had EKG changes consistent with hypokalemia with U waves, also revealing atrial rhythm with first degree AV block, intraventricular conduction delay, and QTc prolongation at 588 (&lt;450). His chest x-ray was normal. Normal saline was administered, and potassium replacement was given with 40 mEq of KCl followed by D5 NS with 40 meq/L KCl at maintenance. He continued taking atenolol and methimazole. He was also given an IV dose of magnesium. His muscle strength returned completely and potassium level returned to normal range at 4.6 mmol/L after 24 hours of treatment.
Conclusion: TPP is a rare cause of acute paralysis and can lead to cardiac arrhythmia and death without accurate diagnosis and prompt treatment. Our case should raise awareness of this disorder among pediatricians, emergency department physicians and endocrinologists. Acute paralysis with hypokalemia should also prompt the physician to consider evaluating thyroid function as a differential diagnosis in young Asian men.
OR16-05 Single-Cell Sequencing Identifies Novel Regulators of Thyrotrope Populations and POU1F1-Independent Thyroid-Stimulating Hormone Expression
Authors: Cheung Leonard , Daly Alexandre , Brinkmeier Michelle , Camper Sally Ann 
Published: May 2020

Abstract
We implemented single-cell RNA sequencing (scRNAseq) technology as a discovery tool to identify factors enriched in differentiated thyrotropes. Thyroid-stimulating hormone (TSH) is produced in the pars distalis of the anterior pituitary (AP) and primarily acts on the thyroid gland to regulate metabolism through T3/T4. However, TSH is also produced by cells in the pars tuberalis (PT), which is comprised of a thin layer of cells that extends rostrally from the pars distalis along the pituitary stalk to the median eminence in the hypothalamus. TSH produced by PT thyrotropes acts on hypothalamic tanycytes to regulate seasonal reproduction. PT thyrotropes likely descend from rostral tip thyrotropes that arise at e12.5 of mouse development, which transcribe the TSH beta subunit (Tshb) without detectable expression of the transcription factor POU1F1. POU1F1 is required for Tshb transcription in thyrotropes of the adenohypophysis, and it acts synergistically with GATA2 to drive cell fate. The molecular mechanisms driving Tshb expression independently of Pou1f1 in PT thyrotropes are unclear.
Thyrotropes are the least abundant endocrine cell-type in the pituitary gland. We used genetic labeling and fluorescence-activated cell sorting (FACS) to enrich for thyrotropes for single-cell sequencing. We performed scRNAseq on 7-day-old GFP-positive pituitary cells from Tshb-Cre; R26-LSL-eYFP and intact whole pituitaries, recovering more than 15,000 cells altogether. We observe two distinct populations of cells expressing Tshb. The larger thyrotrope population has approximately twenty fold higher levels of Tshb and five fold higher Cga transcripts than the smaller population, and they are also distinguished by expression of Pou1f1, TSH-releasing hormone receptor (Trhr), and deiodinase 2 (Dio2), consistent with expectations for AP thyrotropes. The smaller thyrotrope population does not express Pou1f1, but those cells are characterized by expression of TSH receptor (Tshr) and melatonin receptor 1A (Mtnr1a), consistent with expectations for PT thyrotropes. They express mildly increased levels of Eya3 and Six1, although these genes are expressed in other cell-types including AP thyrotropes, stem cells, and gonadotropes. They have two-fold higher levels of Gata2 transcripts and uniquely express the transcription factor Sox14. SOX14 is a SoxB2 family transcription factor that counteracts the transcriptional activity of SoxB1 family members, such as Sox2. In conclusion, our scRNAseq has identified novel markers of PT thyrotropes and unveils novel insights into the similarities and differences in the development and function of pituitary thyrotrope subpopulations.
SUN-712 Familial 46, XY Complete Female External Sex Development with a Non-Mosaic Inherited SRY Gene Variation
Authors: Vaiani Elisa , Chen Yen-Shan , Ramirez Pablo , Baquedano Maria Sonia , Malosetti Maria del carmen , Racca Joseph , Touzon Maria Sol , Marino Roxana , Costanzo Mariana , Bailez Marcela , Berensztein Esperanza , Galuzzo Laura , Weiss Michael Aaron , Belgorosky Alicia 
Published: May 2020

Abstract
Context: SRY, an architectural transcription factor containing a SOX-related high-mobility group (HMG) box, initiates testis formation in the mammalian bipotential gonadal ridge. Inherited human SRY mutations can be associated with differences in sexual differentiation (DSD) with variable phenotypes in a family.
Objective: To describe the clinical, histopathological and molecular features of a novel inherited SRY allele (pMet64Val; consensus box position 9) observed within an extensive pedigree: two 46, XY sisters with primary amenorrhea (16 and 14 years of age; probands P1 and P2), their normal father and brother, and an affected paternal XY grandaunt.
Design, Setting, Participants and Outcome Measurements: Following DNA sequencing to identify the SRY mutation, hormonal studies of the probands and histopathological examination of their gonads were performed. Functional consequences of p.Met64Val (and other mutations at this site) were also investigated.
Results: Breast development in P1 and P2was Tanner II and IV, respectively. Müllerian structures and gonads resembling ovaries were found in each sister. Histopathology revealed gonadal dysgenesis, gonadoblastoma and dysgerminoma. AMH/MIS, P450 SCC, and P450 aromatase were expressed in gonadoblastoma tissues. Variant p.Met64Val impaired Sox9 transcriptional activation associated with attenuated occupancy of the testis-specific enhancersEnh13 and TESCO.
Conclusion: The partial biological activity of p.Met64Val SRY, maintained at the threshold of SRY function, rationalizes opposing paternal and proband phenotypes (the “the father-daughter paradox”).Sex steroids biosynthesis by gonadoblastoma may delay genetic diagnosis and recognition of gonadal tumors. Quantitative assessment of inherited SRY alleles highlights the tenuous transcriptional threshold of developmental decision-making in the bipotential gonadal ridge.
SAT-003 Prolactin Is Expressed in Uterine Leiomyomas and May Promote Their Growth
Authors: DiMauro Alessandra R , Dahal Ankit , Okeke Ifunanya , Lerman Irina , Amitrano Andrea , Seger Christina , Kumar Divya , Bhagavath Bala , Taya Manisha , Hammes Stephen R 
Published: May 2020

Abstract
Uterine leiomyomas, commonly referred to as fibroids, are benign, estrogen sensitive smooth muscle tumors that occur in the myometrium of the uterine wall. Leiomyomas are common, as it is estimated that 60% of reproductive-aged women are affected, and 80% of women develop leiomyomas during their lifetime. In fact, uterine leiomyomas are the leading cause of abnormal menstrual bleeding or menstrual pain, as well as the number one reason for hysterectomy. Novel treatment options are necessary as current treatments are limited to anti-estrogen therapy or hysterectomy. Estrogen is known to have an effect on the etiology of leiomyomas, but little is known about the proliferative roles of other hormones in leiomyomas. One hormone of interest is prolactin (PRL) which is primarily secreted from the pituitary to regulate lactation, but has been linked to proliferation in breast cancer, perhaps via local prolactin production in breast tissue. With this background, we examined local PRL production and its effects on leiomyomas. RNA isolation and quantitative PCR of human leiomyoma samples (n=20) relative to adjacent myometrium in the same patients confirmed significant expression of both PRL (p= 0.0028) and dopamine receptor D2, a known regulator of PRL production in the pituitary (p&lt;0.0001), with no difference in prolactin receptor expression. Using both immunohistochemistry and immunofluorescence of human leiomyomas samples, we find increased prolactin expression in leiomyomas when compared to adjacent myometrium or control uteri. These results suggest that leiomyomas contain cells producing PRL, which in turn may promote signaling in smooth muscle leiomyoma cells to regulate proliferation. Accordingly, we find that PRL robustly activates STAT5 and MAPK signaling in the rat leiomyoma cell line ELT3. Functional assays were also conducted to evaluate the ability of PRL to induce migration, invasion and proliferation of ELT3 cells. Together, our findings suggest that local prolactin production in leiomyomas may promote their growth, migration, invasion and proliferation. It is possible that this local production is mediated by the dopamine receptor D2. Thus, anti-PRL therapy or dopamine receptor D2 modulation may prove useful in treating this prevalent and often debilitating disease.
SAT-043 Utility of Ultrasensitive Inhibin B Measurement for the Management of Men with Non-Obstructive Azoospermia
Authors: Barbotin Anne-Laure , Kumar Ajay , Kalra Bhanu , Savjani Gopal , Mitchell Valarie , Pigny Pascal 
Published: May 2020

Abstract
Inhibin B measurement by conventional assay(s) may be useful in the assessment of spermatogenesis in infertile male patients, especially in cases of azoospermia. Indeed, numerous previous studies have shown that Inhibin B could be helpful to predict a positive testicular sperm extraction (TESE). However, an undetectable Inhibin B concentration (&lt;10pg/mL) does not predict a TESE failure in all cases. These findings explained that most medical centers have precluded the use of Inhibin B assay in the pre-operative hormonal assessment of azoospermic men. Recently, an ultrasensitive Inhibin B assay has been developed allowing the measurement of concentrations below 10pg/mL. The current study aims to assess the clinical relevance of this new assay in men with azoospermia with undetectable Inhibin B levels by conventional assay(s).
Methods: This retrospective study included 71 non-obstructive azoospermic men who had undetectable Inhibin B levels (i.e. &lt;10pg/mL by Gen II ELISA from Beckman Coulter, USA) and who underwent a TESE procedure between 2013 and 2019 in the Lille University Hospital. Serum LH, FSH and testosterone levels were systematically measured by routine immunoassays. Cryopreserved serum samples were used to perform ultrasensitive Inhibin B assay (Ultrasensitive Inhibin B, AL-195, Ansh Labs, USA). Additional hormonal assays including Inhibin A, Activin B and Activin A were performed on available subset of samples.
Results: The TESE was successful, allowing sperm cryopreservation in 32.5 % (25/71) of the cases. No significant statistical difference was found in FSH, LH, or testosterone levels between patients with positive or negative TESE. By contrast, men with positive TESE had more than twice higher serum ultrasensitive Inhibin B levels (median 5.03pg/mL [1.93-8.5] vs. 2.19pg/mL [0.2-4.72], p=0.006). An ultrasensitive Inhibin B serum level &gt;3.67 pg/mL (determined by ROC analysis) was associated with increased odds ratio (OR= 4.82; 95% CI: 1.647-12.93) for positive TESE. Inhibin A, Activin B and Activin A serum concentrations did not differ significantly between the two groups.
Conclusion: FSH measurement which is routinely performed in men with azoospermia was not predictive of successful TESE whereas, Inhibin B was found to be a valuable marker in predicting TESE success in this population using ultrasensitive Inhibin B assay.
MON-454 Lower Extremity Leiomyosarcoma Metastatic to a Benign Thyroid Nodule
Authors: Gupta Suruchi K , Gavrila-Filip Alina 
Published: May 2020

Abstract
Background: Metastases to the thyroid gland from non-thyroidal malignancies have been reported in 1.4-3% of patients undergoing thyroid surgery for malignant thyroid tumors, but only 4% of these are due to sarcomas1. Metastases in a pre-existing thyroid nodule are even more rare. We present a patient with a lower extremity leiomyosarcoma that metastasized to a pre-existing benign thyroid nodule.
Clinical Case: A 70-year-old woman was referred to the Thyroid Nodule Clinic for a 5 cm thyroid nodule replacing most of the right thyroid lobe. Twenty years earlier the patient had a left thyroid lobectomy for a benign nodule. One year before presentation, she was diagnosed with a high grade lower extremity leiomyosarcoma with lung metastases and started on treatment. A large right thyroid nodule pressing on the trachea was incidentally found on an initial chest CT performed for sarcoma staging. On PET-CT, the nodule was not FDG-avid. On ultrasound, the thyroid nodule was solid and heterogeneous, iso- to hyperechoic with smooth margins, inspissated colloid and grade 3 vascularity. Fine needle aspiration (FNA) of the nodule showed benign cytology (Bethesda II). The patient did not have local compressive symptoms and decided not to undergo surgical removal of the nodule.
The thyroid nodule was initially stable on periodic follow-up CT scans and thyroid ultrasounds. However, a thyroid ultrasound performed 2.5 years later showed a change in the nodule echogenicity without change in size. The nodule had become hypoechoic, heterogeneous and well-defined with grade 2 vascularity. FNA revealed a poorly differentiated malignant spindle cell neoplasm, similar to biopsies of other metastatic sites, supporting a diagnosis of metastatic high grade sarcoma. The patient underwent a right thyroidectomy; pathology revealed a 4.1 cm metastatic sarcoma with multifocal angioinvasion with tumor present at the surgical margin. Follow-up neck ultrasounds showed no evidence of local recurrence, while the patient was receiving chemotherapy for pulmonary metastases. The patient died 3 years later due to a massive pulmonary embolism.
Conclusion: To our knowledge, this is the first report of a lower extremity leiomyosarcoma metastatic to a benign thyroid nodule. Although metastasis of an extra-thyroidal malignancy to a pre-existing benign thyroid nodule is very rare, patients with thyroid nodules and a history of malignancy should have regular surveillance of the nodule by ultrasound, and any changes in the nodule features concerning for malignancy should be evaluated with FNA of the nodule.
1. Chung, A. Y., Tran, T. B., Brumund, K. T., Weisman, R. A., & Bouvet, M. (2012). Metastases to the thyroid: a review of the literature from the last decade. Thyroid, 22(3), 258-268.
OR20-04 Modeling Uterine Disorders Utilizing Adult Uterine Stem Cells
Authors: Chowdhury Indrajit , Banerjee Saswati , Xu Wei , Driss Adel , Amin Radhika , Delsarte L Rachel , Keck Katherine , Sidell Neil , Taylor Robert N , Nezhat Ceana , Ali Mohamed , Yang Qiwei , Al-Hendy Ayman , Thompson Winston E 
Published: May 2020

Abstract
Endometriosis and uterine fibroids (leiomyomas) are benign gynecological disorders affecting 5-15% of women of reproductive age. They cause a wide range of symptoms including mild to severe pelvic pain and infertility. Due to a paucity of proper study models, hormonal and cellular mechanisms driving the pathology of endometriosis and fibroid development and growth remain unclear. Therefore, in the current study, we established 3D spheroid/organoid cultures from human uterine epithelial and Stro-1+/CD44+ myometrial stem cells and also from cells isolated from normal proliferative phase endometrium. Uterine organoid cultures were derived from endometrial epithelial and myometrial cells isolated from women who were not receiving exogenous hormones at the time of laparoscopy or hysterectomy. They were embedded in Matrigel, and grown in culture media. To determine whether spheroids/organoids were responsive to steroid hormones, the cultures were treated in presence or absence of estradiol (E2), progesterone (P4) or the combination (E2+P4) in serum free culture media. Time-dependent spheroid/organoid-growth curves and morphological analyses were used to define growth characteristics of endometrial and myometrial organoids. Subsequently, immunohistochemical colocalization of steroid hormone receptors (estrogen receptor alpha (ER-α) and progesterone receptor (PR-A\B), alpha smooth muscle actin (α-SMA; myometrial cell marker), vimentin (stromal cell marker) and E-cadherin (endometrial epithelial cell marker) was assessed. Epithelial organoids expressed only E-cadherin in the absence of hormonal treatment. Myometrial organoids expressed α-SMA and vimentin. No expression of E-cadherin was observed in myometrial organoids. However, we observed the expression of ER-α and PR-A\B when organoids were treated with E2+P4 in a time-dependent manner. Stro-1+/CD44+ myometrial stem cells differentiated into α-SMA and fibroblast/stromal cells and response to sex hormones. These findings suggest human uterine organoid cultures retained their characteristic cellular responses to E2+P4 and could be maintained long-term in ex vivo culture. Thus, the current 3D uterine organoid systems show high expansion capacity with retention of phenotypical and functional properties, which can be used for uterine pathophysiological studies, drug discoveries and drug repositioning.