bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT-056 Autosomal Dominant Hypophosphatemic Rickets in Premature Twins Resolved with Iron Supplementation
Authors: Alarcon Guido , Tarkoff Joshua , Diaz Alejandro 
Published: May 2020

Abstract
Introduction
Autosomal dominant hypophosphatemic rickets (ADHR) is a condition with variable phenotype in terms of age of presentation, severity, and possible resolution. ADHR is caused by mutations of FGF23, preventing its cleavage, producing high levels of FGF23, which leads to renal phosphate wasting. Studies in mice and adult humans, have shown a correlation between low iron levels and increased FGF23 levels. To our knowledge, three pediatric patients with ADHR resolved with iron supplementation have been reported in the literature.
Clinical case
We report on identical twins born at 28 weeks and 5 days by cesarean section due to premature rupture of membranes with complicated pregnancy due to twin-to-twin transfusion syndrome. Birth weights were 780 grams (2nd percentile) for twin A, 1,200 grams (50th percentile) for twin B. Hypophosphatemia was documented starting at 2 weeks of life and during the first 6 of months of life, with phosphorus levels between 2.9-3.9 mg/dL for twin A and between 2.4-5.1 mg/dL for twin B.
During their NICU admission phosphorus had a positive relationship with the hemoglobin level, which was more severe on twin A. Both were treated with calcitriol and a low dose of phosphorus starting on their 2nd month of life.
At 6 months of age, both had persistent hypophosphatemia, more prominently in twin A (2.7mg/dL) with high alkaline phosphatase (1,209 IU/L) and high FGF23 (343 RU/dL). At that time his hemoglobin was 9.8 g/dL and his hematocrit was 29.5%. Both were started on Polyvisol with iron.
At 14 months of life phosphorus and calcium were within normal limits, therefore calcitriol and phosphate were discontinued. At 15 months of age their hemoglobin, hematocrit, iron level, and TIBC levels were normal for both twins. Phosphorus was 4.6 and 4.3 mg/dL, alkaline phosphatase reduced significantly to 819 and 413IU/L, and FGF23 normalized to 100 RU/dL and 32 RU/dL on twin A and B respectively.
Upon physical examination at 15 months of age, twin A was at the 0.02% for length and weight/length at the 31%; twin B was at the 5% for length and weight/length at the 50%. Both twins had high arched palates. Twin A had craniosynostosis, left renal agenesis, bilateral epicanthal folds, overlapping 2nd toes, and clinodactyly of the fifth digits. Note the donor kid (twin A) had a more severe presentation.
Genetic testing showed heterozygous mutation c536G&gt;a (p.Arg179GLN) in the FGF23 gene. This is the same mutation previously reported to be related with ADHR resolved with iron supplementation
Conclusion
The study of patients with hypophosphatemia and hypophosphaturia should include evaluation of iron status (ferritin, TIBC). Treating iron deficiency on these patients might normalize phosphate levels. This would avoid cumbersome treatment with phosphate and calcitriol.
Laboratory values
Phosphorus:4-8 mg/dL
Alkaline Phosphatase: 130-317 IU/L
FGF23: 44-215 RU/dL
SUN-139 Luminescence-Based Drug Screen for Novel Androgen Receptor Antagonists for Prostate Cancer Therapy
Authors: Azur Romie Angelo G , Padolina Isagani D , Bagamasbad Pia D 
Published: May 2020

Abstract
The development and maintenance of the adult prostate is dependent on the action of androgens, which mediate its effect by binding to the androgen receptor (AR). Dysregulation in the AR signaling axis disrupts transcriptional homeostasis, shifting the balance towards uncontrolled proliferation and driving the progression towards prostate cancer (PCa). The prominent role of AR signaling in prostate carcinogenesis led to the development of androgen deprivation therapy (ADT) as the primary treatment strategy for managing PCa. Despite the success of ADT in early PCa cases, most patients develop resistance to ADT and the cancer ultimately recurs towards a lethal state termed castration-resistant prostate cancer (CRPC). Remarkably, AR signaling is still active in CRPC, suggesting that the progression towards CRPC is still reliant on AR activity. Current treatments are ineffective against CRPC, highlighting the need for alternative therapeutics that can combat the resistant nature of CRPC. To address the need for innovative approaches against CRPC, we used a robust luminescence-based bioassay that can identify novel AR antagonists. We screened plant extracts derived from local fauna by measuring their effect on AR-driven activity using a luciferase-based reporter assay in HeLa cells stably overexpressing hAR (HeLa-hAR). To identify candidate hits, HeLa-hAR cells were treated with DHT to induce AR-dependent luciferase activity, DHT with the AR antagonist bicalutamide as a positive control, and DHT plus the plant extracts. We identified one extract, A32, which showed significant inhibition of AR-dependent luciferase activity without having deleterious effects on cell viability. Secondary validation tests also showed that A32 exhibits a dose-dependent inhibition of AR-driven reporter activity. When testing the effect of A32 on gene expression in LNCaP cells, we observed a down-regulation in the expression of canonical AR target genes such as PSA to degrees similar to bicalutamide. These results suggest that A32 may be an AR antagonist or may target the AR signaling axis. Collectively, this study establishes the use of a luminescence-based reporter assay for the identification of novel AR antagonists from a plant extract library.
MON-077 A Case of Growth Hormone Deficiency in Sturge-Weber Syndrome
Authors: Hwang Jeongju , Yu Jeesuk 
Published: May 2020

Abstract
Introduction: Sturge-Weber syndrome (SWS) is a congenital neurocutaneous disorder characterized by a port wine stain on the skin in the distribution of the ophthalmic branch of the trigeminal nerve (vascular malformation of skin), glaucoma, and leptomeningeal angiomas. Central nervous system abnormalities may increase the risk of hypothalamic-pituitary dysfunction. One previous study showed that SWS patients had higher prevalence of growth hormone deficiency than the general population although the etiology is unclear. This case report describes a patient who was initially diagnosed with SWS and later confirmed with complete growth hormone deficiency.
Case: A 7-year-and-11-month-old boy who had been diagnosed with SWS visited a tertiary center for the evaluation of short stature [111.1cm (&lt;3 percentile)]. He was born at 37 weeks of gestational age with birth weight of 3230g by cesarean section and had a port wine nevus on the right side of the face since birth. He had a history of epilepsy first occurring at 6 months of age when he was diagnosed with SWS. There were two more attacks of seizure till 32 months of age. Brain magnetic resonance imaging revealed leptomeningeal angioma, choroidal hemangioma, and diffuse brain atrophy. He was diagnosed with glaucoma and had been managed with surgery and medication. There was no family history of SWS or any other brain anomaly. His mid-parental height was 167.7cm. All blood tests were normal including complete blood count, chemistry, and thyroid function test. Hand x-ray showed delayed bone age. Cocktail test was performed for the evaluation of short stature. As a result, he was diagnosed with complete growth hormone deficiency (peak GH on L-dopa test: 2.46 ng/mL, peak GH on glucagon test: 3.71 ng/mL). The recombinant growth hormone therapy was started at the age of 8 years and 1 month. He showed good response to GH treatment. His height became 125.8cm at the age of 9 years and 5 months (height velocity 9.2 cm/year), and 134.3cm at the age of 10 years and 6 months.
Conclusion: We experienced a case with Sturge-Weber syndrome and complete growth hormone deficiency which was successfully managed by recombinant growth hormone therapy. It may be better to consider the possibility of GH deficiency even if there are certain conditions that affect the growth itself.
SUN-272 Significant Response to Temozolomide in Two Aggressively Growing Pituitary Adenomas
Authors: Kreitschmann-Andermahr Ilonka , Grzywotz Agnieszka , Möller-Hartmann Claudia , Junker Andreas , Führer-Sakel Dagmer , Unger Nicole 
Published: May 2020

Abstract
Introduction: Aggressive atypical pituitary tumors are characterized by invasive growth, recurrence and resistance to standard therapies. We present two female patients with pituitary adenomas in whom multiple other therapies had failed, who presented with significant response to temozolomide. Case presentations: In patient #1 (w, 78y), the diagnosis of macroprolactinoma had been made in a community hospital and dopaminagonistic treatment with bromocriptin had been initiated. After failure to achieve significant tumor reduction under this treatment and persisting visual field disturbances, first transnasal-transphenoidal surgery (TSS) was performed in 07/2011, followed by cabergoline exposure in increasing dose due to failure to control prolactin levels. Repeat TSS and stereotactic radiosurgery were performed in both 2014 and 2018 because of invasive tumor growth and double vision. She was then put on temozolomide. Patient #2 (w, 58y) presented with apoplectic gonadotropinoma in 2013. She also underwent 3 courses of TSS as well as stereotactic radiosurgery because of repeated tumor growth leading to visual field disturbances and double vision. Despite these measures, the tumor could not be controlled and she, as well, was put on temozolomide in 2018. In both cases costs were reimbursed by the patient’s health care insurance and in both the first cycle was conducted with 150 mg/ body surface area (BSA) with escalation to 200 mg/BSA in the second. After only 2 cycles, double vision resolved in both patients and the tumor had shrunk by approximately 20% on MRI in patient #1 and even more in patient #2. In both patients, temozolomide dose was reduced again to 150 mg/BSA due to side effects. Nevertheless, in both patients tumor volume further continued to decrease under therapy. Conclusion: This promising clinical course after exposure to temozolomide with early, significant tumor shrinkage in two heavily pretreated patients with aggressive pituitary adenomas indicates that this therapy can be considered also in older patients and may yield astonishing results. Although temozolomide is increasingly becoming a therapeutic option for those patients whose pituitary tumors are refractory to standard therapies, further research and observance over time of temozolomide therapy in aggressive pituitary adenomas and carcinomas is indicated.
MON-062 46 XX DSD Due to POR Deficiency
Authors: Reddy Nithin Modhugu , Sethi Bipin Kumar , Kandula Srinivas G N S V , Chethan Dev 
Published: May 2020

Abstract
Background
PORD (P450 oxidoreductase deficiency) is a rare form of CAH with marked phenotypic variations due to differences in the degree of steroid hormone excess/deficiency. PORD results in17αhydroxylase/17,20lyase- CYP17, 21αhydroxylase- CYP21, and aromatase- CYP19A1 inhibition. In the absence of characteristic skeletal features of Antley Bixler phenotype, differentiating PORD from other types of CAH is challenging.
Case details
04 day child, second of the non-identical twins, product of 2nd degree consanguinity, third in birth order was brought with abnormal genitalia. The other male twin had no genital ambiguity but had pigmented scrotum. There was no adrenal crisis in index case or maternal virilization. First child is normal female. Child was hemodynamically stable weighed 02 kgs and measured 51 cms, had no hyperpigmentation, skeletal deformities or dysmorphic features. Phallus was 10mm, clitoral index 40mm2 with single urogenital opening and posteriorly fused labia (anogenital ratio 0.6).Gonads were not palpable. Karyotype was 46XX with normal Mullerian structures and non-visualized gonads on ultrasonography. Biochemical workup showed random plasma glucose level of 99mg/dl and normal electrolytes. Baseline serum 8am Cortisol was 1.15 mcg/dl (normal 5-18 mcg/dl) and 17OHP was 20 ng/ml (normal &lt; 02 ng/ml). Serum Androstenedione level was 0.39 nmol/L (normal 0.5-3.4 nmol/L).
In view of clinical, laboratory and imaging findings, presumptive diagnosis of 46 XX DSD due to 21 alpha hydroxylase deficiency CAH was made. Oral Hydrocortisone 15mg/m2 and Fludrocortisone 0.05 mg were initiated. Therapy was monitored with serum 17(OH)P levels and Androstenedione. Genetic testing for 21 alpha hydroxylase gene however came negative.
This led to further genetic mutational analysis, and there was a homozygous R457H POR gene mutation at exon 12 leading to protein change p.Arg457His (nucleotide change c.1370G&gt;A), confirming PORD. Retrospectively, maternal triple test done during the candidate pregnancy showed low serum estriol, suggestive of placental aromatase deficiency. Mineralocorticoid supplements were stopped thereafter.
Conclusions PORD needs to be considered and differentiated from garden variety of CAH in 46 XX DSD when elevation of 17(OH)P is modest with isolated cortisol deficiency and aromatase deficiency (evidenced by low maternal estriol levels and/or virilization), as its course and follow up are different.
MON-329 Diagnostic Utility of Overnight High Dose Dexamethasone Suppression Test for Differentiating the Etiology of ACTH Dependent Cushing’s Syndrome
Authors: Yadav Subhash B , Kumar Anand , Kanwar Jayabhanu 
Published: May 2020

Abstract
Background:
Bilateral inferior petrosal sinus sampling (BIPSS) has been the gold standard in differentiating a pituitary vs. an ectopic source of ACTH in Cushing’s syndrome however, it has many limitations. The ON-HDDST being simple to perform and the tests of choice in resource poor setting. The primary aim of our study was to consolidate the present knowledge regarding the diagnostic utility of ON-HDDST in localizing the source of ACTH.
Method:
We retrospectively studied 88 patients with ACTH dependent Cushing syndrome who underwent ONHDDST. Patient were considered as Cushing disease (CD) if either of the 3 criteria were met a) histopathological confirmed b) a central to peripheral gradient &gt;2 was seen in BIPSS or c) pituitary adenoma ≥ 6mm seen in MRI of pituitary. Patient were considered as ectopic ACTH syndrome if the tumor was localized at any peripheral location by imaging or histopathological confirmed after surgery or if BIPSS shown a central to peripheral gradient of &lt;2.
Result: Out of total 88 ACTH dependent Cushing syndrome patients, 68 (77.3%) were proven CD and 20 (22.7%) were ectopic. There was no difference in basal serum cortisol however, S. Cortisol after ONHDDST was significantly different between the two with a median of 547.7 nmol/l (341-770) in ectopic vs 273.5 nmol/l (142-689) in CD (p=0.02). A positive response to ONHDDST (≥50% suppression) was seen in about 44 (65%) patients with CD and 5 (25%) patients with ectopic disease (p = 0.002). Among CD patient, 35 (76.1%) of those with microadenoma, 7 (43.8%) amongst macroadenoma and 2 (33%) patient with no visible tumor on MRI shown positive response to ONHDDST. In ectopic group, cortisol suppressibility was seen in 3 (50%) patient with occult tumor but only in 2(14.3%) patient with. ROC curve plotted for percentage suppression of cortisol after ONHDDST shown as AUC equal to 0.68 (p = 0.01). The best test parameters with sensitivity (65%), specificity (85%) and Accuracy (69%) were seen at 50% cutoff level as were the likelihood ratio for positive test (4.3), AUC (0.75), PPV (93.6%), NPV (41.4%).
Conclusion: Our study has shown that ONHDDST has poor diagnostic value in differentiating between CD and ectopic ACTH syndrome whatever be the cutoff level of the cortisol suppression. However, this can still be utilized in setups where no alternative is available. For etiologic confirmation, another test with better sensitivity and specificity is preferable.
SUN-690 HNF4A Mutation in Siblings with Diazoxide Responsive Congenital Hyperinsulinism
Authors: Erkin-Cakmak Ayca , Chesser Hannah , Shieh Joseph , Ferrara Christine , Gitelman Stephen Eric , Capodanno Gina 
Published: May 2020

Abstract
Background: Congenital hyperinsulinism (HI) is the leading cause of severe, persistent hypoglycemia in infants. Transient HI seen at risk neonates due to prenatal stress and some of the congenital HI cases due to mutations in K-ATPase channel are responsive to diazoxide. It is not a common practice to obtain genetic evaluation for diazoxide responsive HI. However, children with dominant inactivating variants in HNF4A gene may present with diazoxide-responsive HI and mimic transient HI in infancy.
Objective: To describe two siblings with diazoxide responsive HI with HNF4A mutation associated with maturity onset diabetes of youth type 1 (MODY1).
Clinical Case: Case 1, term female with macrosomia and Case 2, preterm male appropriate for gestational age were born to same mother without gestational diabetes and with no perinatal stress. Siblings were non-dysmorphic and both presented with hypoglycemia during first week of life. Diagnosis of HI is confirmed based on inappropriately suppressed β-hydroxybutyrate at the time of hypoglycemia and inappropriate glycemic response to glucagon consistent with increased insulin action. Both siblings responded to diazoxide therapy. Family history was significant for late-onset diabetes in paternal extended family. Case 1 required very low dose diazoxide (2 mg/kg/day) during first year of life to sustain normoglycemia. She came off of diazoxide at 19 months of age. Case 2 is normoglycemic on 5mg/kg/day diazoxide at 4 months of age. Genetic evaluation through whole exome sequencing pursued upon diagnosis of Case 2 revealed paternally inherited heterozygous pathogenic start loss variant in HNF4A gene (c.3G&gt;T) in both siblings. Father was completely asymptomatic without any history of hypo- or hyperglycemia.
Conclusion: HNF4A gene encodes hepatocyte nuclear factor-4-alpha that regulates hepatic gluconeogenesis and lipid metabolism. Dominant inactivating variants in HNF4A gene associated with familial HI, are typically associated with increased size for gestational age, mild diazoxide-responsive hypoglycemia (which may be transient) and monogenic diabetes during adolescence. HNF4A mutations were described as one of the most common genetic cause of diazoxide-responsive congenital hyperinsulinism and are associated with MODY1. It is important to consider genetic evaluation in diazoxide responsive HI cases. Identifying children with HNF4A variant early on will impact their long-term follow-up leading to earlier diagnosis and treatment of MODY-1 and potentially improve long-term outcomes.
SAT-157 Diagnostic Performance of 18F-fluorodeoxyglucose Positron Emission Tomography in Indeterminate Adrenal Tumors
Authors: Ladygina Daria , Beltsevich Dmitry , Dolgushin Michael , Odzharova Akgul , Martinovich Alexander , Tekeev Boris , Kruchkova Oksana , Roslyakova Anna , Zheleznyakova Anna 
Published: May 2020

Abstract
Evidence on the diagnostic performance of 18F-fluorodeoxyglucose(18FDG) positron emission tomography(PET)/CT imaging of adrenal lesions is limited. We aimed to assess the diagnostic performance of this diagnostic modality in a high risk population for adrenal malignancy using an optimal reference standard. We included 21 patients operated in our clinic during 2019 for whom 8FDG PET was performed before adrenalectomy. 3 patients with pheochromocytoma were later excluded from statistical analysis, they were sent to PET before increased urine metanephrines were received. Unenhanced abdominal CT was performed in all the patients; median size was 4,5 (2.3-10) cm and median radiodensity was 32 (-7 to 43) Hounsfield units (HU). All patients with adrenocortical carcinoma and metastasis to adrenals from other organs had radiodensity of &gt;10 HU. Maximum standardized uptake (SUV max) was higher in malignant lesions when compared to benign lesions (median = 10,9 [5.4-29.6] vs 4.1 [2.6-7.22], respectively, P=.003). Similarly, median SUV max lesion to SUV max liver ratio (ALR) in malignant lesions was higher than in benign lesions (median = 2,18 [1.41-5.53] vs. 1.29 [0.67-2.13], respectively, P=.017).18FDG- PET/CT SUV max lesion &gt; 6.7 diagnosed malignancy with a sensitivity of 83,3%, specificity of 91,7%.
Conclusion: Noncontract CT radiodensity of ≤10 HU excludes malignancy even in a high risk population. For indeterminate adrenal lesions, given a superior specificity, 18FDG PET/CT could be considered as a second stage imaging.
SAT-393 Cognitive Function Evaluation in an Italian Cohort of Patients with Post-Operative Hypoparathyroidism
Authors: Saponaro Federica , Alfi Gaspare , Cetani Filomena , Matrone Antonio , Mazoni Laura , Apicella Matteo , Lai Elisa , Laurino Marco , Brancatella Alessandro , Zucchi Riccardo , Marcocci Claudio , Gemignani Angelo 
Published: May 2020

Abstract
Post-operative hypoparathyroidism (PoHypo) is the most common cause of hypoparathyroidism and it is the result of accidental parathyroid removal/injury during neck surgery. The lack of PTH alters calcium homeostasis and patients are at risk of renal complications, bone involvement, infections and psychiatric syndromes. Conventional therapy, that includes calcium supplements and activated vitamin D, does not restore the complete calcium homeostasis. From a neuropsychological point of view, patients complain with neurocognitive symptoms such as “brain fog”, impaired ability to focus, memory loss, depression. Poor quality of life (QoL), evaluated by non-specific questionnaires, has been demonstrated in these patients. The aim of this study is to evaluate the cognitive function by neuropsychological specific tests in patients with PoHypo and matched controls and their relationship with biochemical parameters. This is a prospective monocentric study; we enrolled outpatients who underwent total thyroidectomy for malignant cured disease, 34 with chronic (&gt;6 months) PoHypo (mean age 50.7 ys) and 31 without PoHypo (mean age 49.9 ys). The two groups did not differ significantly in TSH; PoHypo group had a relatively controlled serum calcium adjusted for albumin (SAlbCa) levels in therapy (mean 8.8±0.1mg/dl, 4 patients with &lt;8.2 mg/dl) and control group had normal SAlbCa levels (9.4 ±0.2mg/dl). In PoHypo patients a significant correlation was found between serum calcium, SAlbCa levels and the scores at the Trail-Making Test_A (a specific test evaluating attention capacity; r= -0.36; p&lt;.05, r= -0.37; p&lt;.05) and at the Semantic Fluency Test (validated for cognitive function; r= 0.32; p&lt;.05, r= 0.34; p&lt;.05). No significant correlations were found in the control group. A median split based on serum calcium levels (&gt; or &lt; than 9 mg/dl) was performed in both patients groups. PoHypo patients with serum calcium levels &lt;9 mg/dl performed worse than PoHypo patients with calcium&gt;9mg/dl, either at the Trail-Making Test_A (scores:34.00 vs 21.05, p&lt;.05) and Semantic Fluency Test (39.62 vs 47.4, p&lt;.05). Moreover, PoHypo patients with serum calcium &lt;9 mg/dl performed worse than matched control patients, either at the Trail-Making Test_A (scores:34.00 vs 27.61, p&lt;.05) and Semantic Fluency Test (39.62 vs 46.16, p&lt;.05). These findings suggest that PoHypo patient’s performance in cognitive tests is worse than matched controls and that this is correlated with serum calcium levels.