bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUN-100 Mice Lacking Paternally Expressed DLK1 Reach Puberty at a Lower Body Weight Than Littermate Controls
Authors: Macedo Delanie B , Abreu Ana Paula , Tellez Silvia L , Naule Lydie , Kim Han Kyeol , Capo-Battaglia Athena , Song Yong Bhum , Roberts Stephanie , Latronico Ana Claudia , Carroll Rona Stephanie , Kaiser Ursula B 
Published: May 2020

Abstract
Body fat content along with a variety of genetic, environmental and psychosocial factors are responsible for the development and maintenance of reproductive function, especially in females. Epidemiologic studies indicate a relationship between increased body mass index and earlier puberty in girls. In contrast, a significant delay in puberty and menarche is seen in girls who are very physically active and have markedly diminished body fat. This link between reproduction and metabolism was reinforced with the recent report of loss-of-function mutations in the Delta-like homolog 1 (DLK1) gene in girls with central precocious puberty (CPP) and increased body fat. DLK1 is a paternally expressed gene located on chromosome 14q32.2 in a locus associated with Temple syndrome (TS), an imprinting disorder caused mainly by maternal parental disomy (mUPD). Dlk1 knockout mice display pre- and postnatal growth retardation, a phenotype that overlaps with human mUPD14. However, precocious puberty, a common finding associated with TS, was not carefully characterized in these mice. We used a Dlk1 deficient mouse model to determine the effects of Dlk1 on pubertal maturation. We confirmed by RT-qPCR that Dlk1 mRNA was undetectable in the mediobasal hypothalamus, where kisspeptin and other regulators of puberty are expressed, of Dlk+/p- mice (which inherited the mutant allele from their father) whereas it was present in Dlk+/+ mice. As reported previously, body weight was significantly lower in juvenile male and female Dlk+/p- mice, compared to wild-type littermate controls. Interestingly, mutant and control female mice achieved vaginal opening, a marker of puberty onset, at a similar age (Dlk+/p-: 29.8 ± 1.5 days, n=11 vs. Dlk+/+: 29.1 ± 0.7 days, n=15, p=0.6) despite a considerably lower body weight in the Dlk1 deficient mice at the time of vaginal opening (Dlk+/p-: 10.1 ± 0.8 g vs. Dlk+/+: 14.3 ± 0.3 g, p&lt;0.0001). Similarly, in the Dlk+/p- males, preputial separation occurred at a lower body weight than in controls (Dlk+/p-: 12.4 ± 0.3 g, n=9 vs. Dlk+/+: 14.1 ± 0.2 g, n=19, p&lt;0.0001). We hypothesize that the lack of Dlk1 at the hypothalamic level may be attenuating the effect of the low body weight on determining pubertal onset. These findings suggest that DLK1 is an important link between body weight and pubertal development in mice, as has been shown in humans.
SAT-543 Human Hair Aldosterone Measurements for Evaluation of Primary Aldosteronism
Authors: Demidowich Andrew Paul , Camacho Jancarlos , Sierra Maria de la Luz , Belyavskaya Elena , Lysikatos Charalampos , Kamilaris Crystal , Suzuki Mari , Zilbermint Mihail , Hannah-Shmouni Fady , Stratakis Constantine A 
Published: May 2020

Abstract
Background: Primary Aldosteronism (PA) is the most common cause of endocrine hypertension in US. Diagnostic techniques such as a 24 hour urine collection or saline suppression test (SST) can be laborious for both patients and staff. Our group previously showed that human hair cortisol measurements correlated with urine and serum cortisol levels in patients with endogenous cortisol excess. In this study, we explored whether human hair aldosterone correlated with other measures of aldosterone production. Methods: 41 adult subjects were evaluated at the NIH Clinical Center for adrenal disorders. A pencil-width of hair near the occiput was removed, and the 1cm segment closest to the scalp was analyzed by enzyme immunoassay for aldosterone, reported as pg aldosterone/mg dry hair. Not all subjects underwent complete workup for PA. Data were transformed as necessary to maintain assumptions of normality. Student’s t-test and Pearson correlations were used for statistical analysis.
Results: Of the evaluated subjects, 18 were diagnosed with PA, 22 subjects did not have PA, and 1 subject was indeterminate. The mean hair weight was 33.0±13.7mg. For hair samples weighing greater than 10mg, hair weight was not correlated with hair aldosterone concentration (p=0.40). There was no difference in measured hair aldosterone between the subjects with and without PA (2.01±1.09 vs. 2.52±2.45 pg/mg; p=0.82). Among all subjects, hair aldosterone did not correlate with serum aldosterone (p=0.92), aldosterone-to-renin ratio (ARR; p=0.94), 24 hour urine aldosterone (Ualdo; p=0.85), or the serum aldosterone at the 4 hour time point of a SST (4hrAldo; p=0.98). Serum aldosterone, ARR, Ualdo, and 4hrAldo all correlated highly amongst each other (all p’s&lt;0.001).
Conclusions: Hair aldosterone levels do not correlate with other markers of PA. Further work is needed to understand whether optimization of study conditions could improve the usefulness of hair aldosterone measurements in the evaluation of PA.
MON-907 Silent Presentation of Urinary Bladder Paraganglioma: A Case Report
Authors: Kirupakaran Johnathan , Rodriguez Giovanna , Bahtiyar Gul 
Published: May 2020

Abstract
Background: Paraganglioma is a rare extraadrenal, neuroendocrine tumor of the sympathetic or parasympathetic ganglia (1). Bladder paraganglioma accounts for 1% of all paragangliomas and 0.05% of all bladder tumors (1,2). Characteristic presentation of this tumor includes hypertensive crisis and postmicturition syncope (3).
Clinical Case: 35 year old Middle Eastern man with no pertinent past medical history presented with gross hematuria associated with dysuria, purulent penile discharge, urinary frequency, suprapubic pain, and bilateral flank pain for eight months for which he was given a course of an unknown antibiotic in his home country. Social history revealed smoking half a pack of cigarettes/day for 7 years. Has no family history of cancer. On physical exam he had normal blood pressure with mild tenderness to palpation in suprapubic region. U/A was remarkable for hematuria. Patient was treated for UTI with a course ciprofloxacin without resolution of symptoms. Culture returned negative.
CT abdomen/pelvis yielded an approximately 1.9 cm enhancing mural nodule involving the anterior aspect of the bladder. Free metanephrine, nor-metanephrine, plasma catecholamine, and urine vanillylmandelic acid were within normal limits. Cystoscopy and transurethral resection of the tumor (TURBT) was completed; a 5-6mm tumor was visualized and resected. Surgical pathology demonstrated tumor growth into the lamina propria and muscularis propria. Neoplastic cells in the sample were diffusely positive for synaptophysin and chromogranin. S100 protein immunostain highlighted sustentacular cells. The diagnosis of paraganglioma was made based on surgical pathology. Post TURP MRI yielded an approximately 1.7 x 0.9 cm transmural hypervascular enhancing mass lesion involving the anterior aspect of the bladder. Given transmural extension of the tumor, an open partial cystectomy was performed. The tumor was resected successfully with resolution of symptoms.
Conclusion: This is an exceedingly rare example of a hormonally silent paraganglioma, mimicking the presentation of a UTI. This case may present the unique consideration of tobacco specific carcinogens as a potential risk factor for the development of bladder paraganglioma.
References
1. Benn, DE, Robinson, BG, & Clifton-Bligh, RJ. (2015). “Clinical Manifestations of Paraganglioma Syndromes Types 1-5”. Endocrine-Related Cancer, vol. 22, T91-T103.
2. Loveys, FW, Pushpanathan, C, & Jackman, S. Urinary Bladder Paraganglioma: AIRP Best Cases in Radiologic-Pathologic Correlation”. RadioGraphics, vol 35, no. 5, 1433-1438.
3. Priyadarshi, V, & Pal DK (2015). “Paraganglioma of Urinary Bladder”. Urology Annals, vol 7, no. 3, 402-404.
OR13-03 Understanding Why Older People with Low Trauma Fractures Die Prematurely
Authors: Tran Thach , Bliuc Dana , O’Donoghue Sean , Hansen Louise , Abrahamsen Bo , Bergh Joop van den , Geel Tineke van , Geusens Piet , Vestergaard Peter , Nguyen Tuan V , Eisman John A , Center Jacqueline 
Published: May 2020

Abstract
There is increasing evidence that all proximal and not just hip fractures are associated with increased mortality risk. However, the cause of this increased mortality is unknown. We sought to determine the post-fracture trajectories of subsequent hospital admissions and mortality to develop an understanding of why patients with non-hip fractures die prematurely.
This nationwide Danish population-based study included all individuals aged 50+ years who sustained an incident fragility fracture between 2001 and 2014. High-trauma fractures or individuals with fracture prior to 2001 were excluded. Fracture patients were matched 1:4 by sex, age and comorbidity status with non-fracture subjects alive at the time of fracture. Comorbidities included 33 unique medical conditions of the Charlson or Elixhauser comorbidity index. We modelled the contribution of specific fractures on the risk of subsequent admissions or death within the following 2 years.
There were 212,498 women and 95,372 men with fracture followed by 30,677 and 19,519 deaths, respectively over 163,482 and 384,995 person-years of follow up. Mean age at fracture was 72± 11 for women and 75± 11 for men. Proximal fractures including hip, femur, pelvis, rib, clavicle and humerus had increased mortality compared with their matched non-fracture counterparts with HRs ranging from 1.5-4.0, while distal fractures such as ankle, forearm, hand or foot fractures had similar or lower mortality risk.
Almost 75% of men and 60% of women had ≥1 comorbidity. For every additional comorbidity, risk of mortality increased for all fracture types. However, only for proximal fractures did the fracture itself independently increase mortality risk over and above co-morbidity status.
The 2-yr post fracture admission and mortality patterns differed between proximal and distal fractures. Proximal, but not distal fracture subjects had greater risk of any major hospital admission (including cardiovascular disease, cancer, stroke, diabetes, pneumonia and pulmonary disease) within 2 years compared with their non-fracture counterparts. Distal fractures in general had similar admission patterns as their non-fractured matched counterparts.
Furthermore, 2 year mortality risk was increased for proximal fractures whether or not they were admitted to hospital post fracture. By contrast, mortality risk was similar or reduced for distal fractures compared with non-fracture controls.
This study has not only confirmed the increased mortality following proximal fractures but has demonstrated differing clinical trajectories between proximal and distal fractures that contribute to this increased mortality. These findings provide important insights as to why proximal fracture subjects die prematurely that may lead to specific avenues for intervention.
MON-436 Cribriform-morular Variant of Papillary Thyroid Carcinoma: A Case Report
Authors: Shaheen Zainab , BenHamed Nesreen Aburrahman , Elhamdani Rawan Mehiar 
Published: May 2020

Abstract
Background:
Cribriform - morular variant is a rare variant of papillary cancer with 1–2 % prevalence. There are no established guidelines to screen for thyroid cancer in patients with APC gene mutations and FAP. We present a case of a young female with APC gene mutation and thyroid cancer.
Case:
Female, 25 years-old, without anemia, underwent colonoscopy at age 22 and multiple polyps were seen. One polyp showed intramucosal carcinoma with high-grade dysplasia. She was diagnosed with FAP. She was found to have APC gene mutation on genetic analysis. No family history of FAP was reported.
Chest and abdominal CT showed multiple thyroid nodules.
Thyroid ultrasound showed 3 nodules. The largest is in the mid R lobe, measuring 1 cm, and is isoechoic to hypoechoic, containing some small central cystic areas. The nodules in the left lobe measure 0.6 and 0.7 cm.
FNA of the right thyroid nodule showed follicular neoplasm. Afirma was suspicious.
She underwent total thyroidectomy.
Pathology report showed multifocal tumor in both right (0.8 cm) and left lobe (0.5 cm). Histologic type was Papillary carcinoma, cribriform - morular variant. All surgical margins were negative. No angio-lymphatic invasion or extra thyroidal extension was identified.
Pathologic stage classification was m pT1a pN0 pM0.
Patient did not receive RAI ablation.
Patient doing well and no further recurrence of thyroid cancer is noted.
Discussion:
Patients with FAP have a greatly increased risk for colorectal cancer and also have an elevated risk for other cancers including thyroid cancer (1%-2% compared to 1% in general population). According to ACG guidelines of 2015, annual thyroid screening by ultrasound should be recommended to individuals affected with FAP. Additionally, thyroid cancer found in unscreened patients with FAP was more advanced as compared to patients screened for cancer requiring less aggressive approaches. On ultrasonography, most nodules had benign-looking features (well-defined, hypoechoic, oval to round shapes without calcification), but some nodules had capsular invasion and larger height: width shape. In preoperative FNA, they were diagnosed as CMV-PTC/PTC but could also present as follicular neoplasm or PTC-follicular variant. Compared to conventional PTC, CMV-PTC had a lower frequency of lymph node metastases at presentation (12%) and distant metastases (3%) as well as lower recurrence rates (8.5%) and patient mortality rates (2%). Physical exam and clinical history is not sufficient to screen for cancer.
In patients with APC gene mutations and FAP, there should be high suspicion for diagnosing thyroid cancer as the nodules are usually benign looking and small in size. As noted in the case, nodules were found incidentally, and tumor size was small with benign looking nodules. Additionally, screening should be focused more on young females below the age of 35 because of the high prevalence of cancer.
SAT-748 Advantages and Limitations of an Integrative Measurement for All Serum Androgens and Anti-Androgens
Authors: Schaufele Fred J , Mody Armaiti , Huddleston Heather Gibson 
Published: May 2020

Abstract
Background: Analytic measurements of a hormone in bodily fluids are a cornerstone of clinical evaluation. However, clinical presentation may be affected also by currently unmeasured modulators of hormonal function. An alternative could be to measure the cumulative effect of all factors present in a bodily fluid on the function of a hormone receptor. Prior studies showed an androgen receptor (AR) BioAssay to accurately measure urine androgens in males undergoing testosterone (T) supplementation (1). The factors integrated by the AR BioAssay include androgens, anti-androgens and, in serum, androgen binding proteins affecting ligand availability.
Methods: The AR BioAssay was exposed to male and female serum samples obtained from the CDC’s Hormone Standardization (HoSt) Program, and to female serum samples from the UCSF PCOS Tissue Bank registry. AR activity was quantified against a testosterone standard curve and recorded as ‘T-equivalent’ (‘T-eq’) androgen activity units.
Results: In 40 CDC HoSt sera added directly (no extraction) to AR BioAssay cells, androgen activities ranged from 2.57 to 298 ng ‘T-eq’/dl. In the 20 ‘male’ CDC HoSt sera (T&gt;150 ng/dl), the androgen activity measurements were uniformly less (0.35 ± 0.10) that of the T-measurement. By contrast, in the 20 ‘female’ CDC HoSt sera, in which T concentrations are typically lower than the affinity of T for sex hormone binding globulins such that more of the T is available to the AR BioAssay, the measured androgen levels were on average 1.45-fold higher than the T concentration. This androgen to T comparison showed high variability in females with 5 of 20 CDC HoSt samples having androgen concentrations more than double that of T (maximum, 6.1-fold). In female serum samples from the PCOS registry, androgens were higher in patients with a PCOS diagnosis (57.7 +/-17.6 ng ‘T-eq’/dl; n = 23) compared to women not meeting formal PCOS criteria (38.1 +/-10.8 ng ‘T-eq’/dl; n = 4); androgen values again averaged 1.40-fold (maximum, 4.9-fold) that of the T measurements, regardless of PCOS diagnosis.
Conclusions: Androgen-binding globulins appear to most influence androgen activity levels in male serum. In females, the lower T concentrations may minimize the impact of androgen-binding proteins and permit the impact of non-T androgens to be more pronounced with possible clinical consequence. Further investigations are needed to determine whether functional androgen measurements may improve clinical diagnosis of certain conditions.
Reference: (1) Bailey et al (2016) PLoS One11(3):e0151860
MON-157 The Effect of Exogenous Cushing’s Syndrome on All-Cause and Cause-Specific Mortality: A Systematic Review
Authors: Limumpornpetch Padiporn , Morgan Ann W , Tiganescu Ana , Stewart Paul Michael , Pujades-Rodriguez Mar D M 
Published: May 2020

Abstract
Chronic oral glucocorticoid (GC) exposure from therapeutic anti-inflammatory or immunosuppressive use is the most common cause of Cushing’s syndrome (CS). Previous studies of glucocorticoid therapy and mortality have produced inconsistent results and systematic reviews have only focused on endogenous CS. This is the first study that aimed to investigate all-cause and cause-specific mortality in association with exogenous CS from chronic oral GC therapy. The protocol was designed according to the principles of the PRISMA statement and registered in PROSPERO reference CRD42017067530. A literature review was performed in PubMed/MEDLINE (1966 to 31 Mar 2019), EMBASE (1974 to 31 Mar 2019), web of science (1900 to 31 Mar 2019), CINAHL (1981 to 31 Mar 2019) and reference lists within selected articles. Of 104,064 studies, 127 met the inclusion criteria, encompassing 51,380 patients. The Risk Of Bias In Non-randomized Studies of Interventions (ROBIN-I) tool was chosen and modified for evaluation of quality. The weighted percentage mortality by 5 groups of diseases including vasculitis, connective tissue diseases, inflammatory diseases, haematologic diseases and respiratory tract diseases, was 18.1, 12.7, 16.1, 28.2 and 5.7, respectively. The leading causes of death were cardiovascular disease (25.6%), malignancy (15.6 %), infection (13.4) and respiratory failure (10.8%). Although these studies showed high mortality in patients exposed to GC, estimates were not adjusted for known confounders and available data do not allow disentangling the relative contribution of CS vs. the underlying disease or non-GC immunosuppressive therapies. More extensive, high quality, prospective studies are needed to evaluate these associations and to identify modifiable risk factors.
MON-509 RET Mutations in the MEN1 Syndrome: Is It an Innocent Bystander?
Authors: Rais Nadeem M , Kumar Anshul , Jain Swetha , Mathur Sandeep Kumar , Scaria Vinod , Prakash Savinitha , Joshi Apoorva 
Published: May 2020

Abstract
Introduction
MENIN and RET mutations in MEN1 families, are rare, and, when they co-exist either mutation may predominate the clinical picture.
We report a family, with both mutations, and, suspect that the RET mutation may not be an innocent bystander.
Clinical Cases
GM (36M): 2009: Presented with skin lesions and a lactotroph adenoma causing chiasmal compression. Treatment: Hypophysectomy and Cabergoline. This resulted in restoration of sexual function and fertility.
2013: Developed hyperparathyroidism [Calcium 10.6mg% (8.5-10.5); PTH 610pg/ml (10-65); MIBG Scan: parathyroid adenomas]. Treatment: Subtotal parathyroidectomy with allotransplant.
2015: Developed Zollinger-Ellison Syndrome [multiple gastric ulcers; S Gastrin: 516pg/ml; (0-180)]. Treatment: Pantoprazole.
MRI Abdomen: Calcific atrophic pancreas and bilateral non-functioning adrenal adenomas.
HM (32M): 2008: Skin lesions and Lactotroph adenoma. Treatment with Cabergoline resulted in restoration of sexual function and a reduction in breast and tumour size.
2013: Hyperparathyroidism [Calcium 10.9mg%; PTH: 166pg/ml; Calcium excretion: 1160mg/24hrs (100-250); BMD: Osteopenia. MIBG 123 Scan: Avid uptake in Right Inferior parathyroid gland]. He underwent a subtotal parathyroidectomy with allotransplant.
2015: Recurrent Hyperparathyroidism (Calcium 10.7mg%; PTH: 116pg/ml; MIBG 123 scan: Hyperfunction of the transplanted gland). Stable on treatment with Cinacalcet.
Their mother, AM (42F): 1980: Detected to have a lactotroph adenoma when investigated for primary infertility and galactorrhoea. She was treated with Bromocriptine and delivered the boys in 1980 and 1984 respectively. She had recurrent renal calculi and hydronephrosis (? hyperparathyroidism). She succumbed to renal failure following surgery for a benign pancreatic cystadenoma in 1990.
Discussion
Whole exome sequencing of GM and HM showed pathogenic mutations of both, MENIN and RET gene. The precise mutation was a stop gain mutation at exon 3 MENIN.C511T:p.Q171X . They (GM/HM) also harboured a mutation in the RET gene at exon 14 c. G2492T: p.G831V; g. chr10. This may be the first family in which the rare combination of these two mutations has been reported.
The genomics and the clinical presentation suggest that the MENIN mutation predominates in the family, but the presence of bilateral adrenal adenomas in GM are significant on account of RET mutation. The latter may be a harbinger of serious disease in the future. The situation is further compounded by the recurrence of hyperparathyroidism in the allograft of HM. This may be caused due to chance or an unknown genetic/ epigenetic phenomenon in the two MEN mutated genes and RNA sequencing of the tumour tissue may explain the genetic phenomenon. The latter two events suggest that the RET mutations in MEN1 may not be an innocent bystander.