bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUN-239 Effects of High-Fat Diet-Induced Obesity on Pulsatile LH Secretion and Hypothalamic KISS1 Expression in Female Rats
Authors: Minabe Shiori , Iwata Kinuyo , Watanabe Youki , Ozawa Hitoshi 
Published: May 2020

Abstract
Female obesity is associated with menstrual dysfunction leading to anovulation and infertility. It has recently been reported obesity-induced infertility is involved in the dysfunction of a kisspeptin neuron, a key player in reproduction via direct stimulation of gonadotropin releasing hormone (GnRH) and subsequent gonadotropin release in mammalian species. Previous studies reported that obesity due to high-fat diet (HFD) for 8 months induced a disruption in estrous cyclicity, caused by a decrease in Kiss1 (coding kisspeptin) expression in the hypothalamic arcuate nucleus (ARC) in female rodents. Here we showed the effects of shorter-term (4 months) HFD on pulsatile LH secretion and hypothalamic Kiss1 expression to show pathogenic mechanism underlying obesity-induced infertility. Female Wistar-Imamichi strain rats (7 weeks old) fed on either a standard diet (10% calories from fat) or a high-fat diet (45% calories from fat) for 4 months. Estrous cyclicity and body weight were monitored regularly. All animals were implanted with a jugular catheter and collected blood samples to analyze pulsatile LH secretion, after a week of the ovariectomy with low-dose replacement estradiol to negate influence of changes in ovarian steroid levels and mimic diestrous levels of plasma estrogen. On the next day of the blood sampling, rats were perfused with 0.05 M PBS followed by 4% paraformaldehyde and their brains were collected for in situ hybridization of Kiss1 and Gnrh1. The HFD-fed rats showed progressive increases in body weight, along with hyperphagia and adipose tissue accumulation, compared with control animals. Fifty-eight percent of the HFD-fed rats exhibited irregular estrous cycles, whereas remaining HFD-fed rats showed regular cycles. Two out of 7 rats showing HFD-induced irregular estrous cycles exhibited profound suppression of the LH pulse frequency and the number of Kiss1-expressing cells in the ARC, whereas remaining HFD-fed rats showed normal LH pulses and ARC Kiss1 expressions. The number of Kiss1-expressing cells in the ARC had close positive correlation with LH pulse frequency (R2=0.6872, P&lt;0.001) in both groups. Additionally, the number of Kiss1- or Gnrh1-expressing cells in the anteroventral periventricular nucleus or the preoptic area, were comparable between groups. Taken together, our finding reveals the possibility that irregular menstruation was also induced by changes in the kisspeptin-GnRH independent pathway during the incipient stage of obese infertility.
SAT-187 Altered Mental Status in a Patient with Bilateral Adrenal Masses
Authors: Mathews Sherin Elsa , Castellanos-Diaz Jessica , da Silva Alexis , Donahoo William Troy , Ghayee Hans Kumar , Barb Diana 
Published: May 2020

Abstract
Introduction
Primary adrenal lymphoma (PAL) is a very rare and aggressive form of Non-Hodgkin’s lymphoma originating from the adrenal glands and with no prior history of lymphoma. It can present with symptoms related to adrenal insufficiency due to tumoral destruction of normal adrenal tissue. Hypercalcemia has also been previously reported as a less common presentation of PAL. We describe here a case of PAL presenting with severe hypercalcemia and adrenal insufficiency.
Clinical Case
75 year male presented with 50 pound weight loss, fatigue and anorexia for several months. On admission, patient had altered mental status. Further investigation revealed severe hypercalcemia (corrected calcium for albumin =15mg/dl) and AKI (serum creatine=3.45mg/dl, blood urea nitrogen=89). He was started on IV fluids for the hypercalcemia and AKI. Additional work up revealed suppressed parathyroid hormone (PTH) levels of 9 (12 - 88 pg/mL), high normal PTH-related peptide 22 (14-27), low 25-OHD 7.34 (20-120 ng/ml), high normal 1,25-(OH)2-D 63.0 (19.9-79 pg/mL). His ACTH level was elevated ~159 (7.2-63.3 pg/ml) with low normal morning cortisol levels ~10 mcg/dl. Patient was started on IV stress dose steroids for concerns of adrenal insufficiency and calcitonin was also initiated for the treatment of hypercalcemia. CT of the abdomen showed bilateral adrenal masses, measuring 9.8 x 6.4 x 10.8 cm on the right and 9.3 x 5.2 x 9.6 cm on the left with marked retroperitoneal lymphadenopathy. After ruling out pheochromocytoma with negative plasma and urine metanephrines, biopsy of the adrenal mass revealed a highly aggressive diffuse B large cell lymphoma, with BCL2 and MYC overexpression. Concurrent flow cytometric analysis also identified an abnormal population of medium to large B cells expressing bright CD20, CD19, CD38, CD45 without CD10, CD5, CD23 or overt kappa or lambda expression. His calcium levels improved with hydration and steroids. Chemotherapy was later initiated.
Conclusion
Primary adrenal lymphoma is rare and aggressive type of NHL. While adrenal insufficiency is expected in this clinical scenario, hypercalcemia from 1,25-(OH)2-D excess is a relatively uncommon presentation. Adrenal insufficiency should be ruled out in bilateral infiltrative adrenal masses. Likely etiologies for hypercalcemia in our case appeared to be secondary to elevated 1,25-(OH)2-D production, humoral hypercalcemia of malignancy and worsened by untreated clinically evident adrenal insufficiency.
References
(1) Laurent C, Casasnovas O, Martin L, et al. Adrenal lymphoma: presentation, management and prognosis. QJM. 2017 Feb 1;110(2):103-109. doi: 10.1093/qjmed/hcw174
(2) Masood A, Tumyan A, Nussenzveig D R., Wakefield D N., Barb D, Ghayee H K., Maalouf N M. The Diverse Clinical Presentations of Adrenal Lymphoma. AACE Clinical Case Reports: Autumn 2017, Vol. 3, No. 4, pp. e307-e312. doi: 10.4158/EP161595.CR
MON-218 Clinical and Genetic Aspects of Pediatric Pheochromocytomas and Paragangliomas
Authors: Petenuci Janaina , Guimaraes Augusto , Benedetti Anna Flavia Figueredo , Fagundes Gustavo Freitas Cardoso , Pereira Maria Adelaide , D’Eur Joya Emilie Correa , Zerbini Maria Claudia , Siqueira Sheila , Yamauchi Fernando , Soares Silvia , Srougi Vitor , Tanno Fabio Y , Chambo Jose L , Denes Francisco T , Hoff Ana O , Latronico Ana Claudia , Mendonca Berenice Bilharinho , Fragoso Maria Candida B V , Almeida Madson Q 
Published: May 2020

Abstract
Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors derived from chromaffin cells. At least 30% of PPGL patients have hereditary predisposition. PPGLs in children are more often hereditary, multiple and extra-adrenal. To date, more than 14 tumor-susceptibility genes have been reported: Cluster 1 or hypoxic (VHL, SDHB, SDHD, SDHC, SDHA, SDHAF2, FH, ENGL1 and HIF2A) and cluster 2 (RET, NF1, TMEM127 and MAX). The aim of this study was to evaluate clinical and molecular aspects of a Brazilian cohort of pediatric patients with PPGLs. Out of 262 patients with PPGLs, 26 (9 %) were diagnosed before 19 yrs of age (16 males and 10 females), with a median age of 14.5 yrs (range, 4 to 18). Genetic investigation was performed in 19 patients: 14 by automated Sanger sequencing (VHL, SDHB, SDHD and RET genes) and 5 by a custom next-generation sequencing (NGS) panel including all genes previously associated with germline mutations in PPGLs. Median tumor size was 5.5 cm (1.7 to 16). Pheochromocytomas (PHEOs), paragangliomas (PGLs) or both were diagnosed in 46%, 31% and 23% of the patients, respectively. Bilateral PHEOs were diagnosed in 61% of the cases, most of them asynchronous (75%). Genetic diagnosis was confirmed in 14 out of 19 (74%) patients and all variants were found in heterozygous state: 8 VHL missense mutations from 6 kindreds (p.R167W in 2 kindreds, p.R167Q in one and p.G114S in 3); 3 SDHB mutations (p.C98Y, c.201-2A&gt;G and p.L180L); 2 SDHD mutations (p.Y144_H145del and p.Q121*); and one RET mutation (p.C634R). All 8 VHL patients had bilateral PHEOs and 3 of them had also abdominal PGLs. All patients with SDHB mutations had abdominal PGLs. Two patients with SDHD mutation had head and neck paraganglioma (one of them had unilateral PHEO). Genetic investigation by NGS Panel was negative in all 5 cases: 2 malignant PPGLs (one PHEO and one PGL) and 3 PHEOs. Four out of 26 (15%) pediatric PPGLs were malignant: 2 with SDHB mutation and 2 with negative screening (one PHEO and one PGL). In conclusion, the majority of pediatric PPGLs (74%) were hereditary and almost exclusively caused by mutations in hypoxic genes. VHL (PHEOs) and SDHB (only PGLs) were the most frequent affected genes in this cohort of pediatric PPGLs. Support: CAPES grant to Petenuci J.
SUN-668 Elevated Osmolal Gap in Long-Term Complication of Type 2 Diabetes
Authors: Klimek Monika , Wojtysiak-Duma Beata , Duma Dariusz , Solski Janusz 
Published: May 2020

Abstract
Osmolal gap (OG) is the difference between the measured osmolality and calculated osmolality estimated by using the mathematical equation. Elevated OG indicates the presence of osmotically active particles undetected in the plasma of healthy individuals. Elevated OG has been observed in multiorgan trauma as a useful prognostic factor of patient survival [1, 2]. We hypothesized that elevated OG may occur in patients with type 2 diabetes (T2D) and may become a useful indicator of unmeasured endotoxins. One of the major mechanisms of this phenomenon may be non-enzymatic glycation of proteins in hyperglycemia, in which the osmotic active carbonyl compounds such as glyoxal, methylglyoxal, and 3-deoxyglucosone, are formed. Testing was performed for participants with T2D, aged 18 to 85. The osmolality measurement was performed with venous blood using the osmometer. The concentration of individual osmols (sodium, potassium, glucose, urea) was determined and on this basis, osmolality was calculated using the Dorwart-Chalmers formula: osmolality (mOsm/kg H2O) = 1.86 x [Na+] + glucose + urea + 9 (Dorwart, 1975). The clinical profile of patients was established based on history and physical examination (age, sex, age, duration of T2D, complications of T2D, HbA1c, LDL-cholesterol, triglyceride, BMI, coexisting diseases, medication). Data were analyzed using descriptive statistics. This study is currently ongoing, but preliminary data from the pilot study suggest an increased mean measured osmolality as well as elevated OG in patients with T2D compared to the reference values for healthy adults. These values differed depending on the type of long-term complications and the duration of the disease. In the pilot study, the highest OG was reported in diabetic retinopathy. A follow-up study with a larger sample may have a better ability to detect the statistical significance of the association of OG and complications of T2D. The association of the osmolal gap and complication of type 2 diabetes is poorly understood, and further investigation is warranted.
References:
[1] Inaba, H., Hirasawa, H., Mizuguchi, T. (1987), Serum Osmolality Gap In Postoperative Patients In Intensive Care. Lancet, 329 (8546): 1331-1335.
[2] Hirasawa, H., Odaka, M., Sugai, T., Ohtake, Y., Inaba, H., Tabata, Y., Kobayashi, H. and Isono, K. (1988), Prognostic Value of Serum Osmolality Gap in Patients with Multiple Organ Failure Treated with Hemopurification. Artificial Organs, 12: 382-387.
MON-711 Induction of Apolipoprotein A1 Gene Expression by the Rare Sugar Allulose
Authors: Parekh Shrina 
Published: May 2020

Abstract
Apolipoprotein A-I (apo A-I) is the primary protein component of high-density lipoprotein (HDL) and has many well documented properties which promote cardiovascular health. However, clinical trials designed to increase HDL levels by preventing its catabolism have failed in their primary endpoints in decreasing the risk of cardiovascular disease. Alternative strategies to increase de-novo apo A-I production may be more attractive. We recently demonstrated that the rare sugar allulose decreases oxidative stress and endoplasmic reticulum stress in both endothelial cells and hepatocytes. During these studies we demonstrated that allulose also induces apo A-I secretion by HepG2 cells. Apo A-I, albumin, and SP1 levels were measured by Western blot. Apo A-I and glyceraldehyde-3-phosphate (GAPDH) mRNA levels were measured by quantitative real-time polymerase chain reaction. The effect of allulose on apo A-I promoter activity was measured using transient transfection assays with several plasmids containing various segments and mutations in the apo A-I gene promoter. Apo A-I protein and mRNA levels in cells treated with allulose increased more than two-fold in a dose-dependent manner. These changes were due to the ability of allulose to induce apo A-I gene promoter activity. Using a series of deletion constructs, an allulose-response element was identified in the apo A-I gene promoter which was previously shown to confer induction of apo A-I gene expression by insulin and epidermal growth factor (EGF), the insulin response core element (IRCE). Mutation of the IRCE decreased the ability of allulose and insulin to induce apo A-I promoter activity. Allulose treatment also increased expression of the transcription factor SP1, which had been shown previously be essential for the effects of insulin and EGF on apo A-I promoter activity. In conclusion, allulose increased apo A-I gene expression in HepG2 hepatocytes. This effect was mediated by the IRCE in the apo A-I gene promoter and the transcription factor SP1. The rare sugar allulose may have novel anti-atherogenic properties, in part, by increasing HDL levels.
SUN-902 Bradycardia as a Presentation of Malignant Pheochromocytoma
Authors: Saleem Marwa , Vargas-Jerez Julia , Zahra Tasneem 
Published: May 2020

Abstract
Introduction
Pheochromocytoma usually presents with tachycardia, hypertension and other symptoms related to catecholamine release. Bradycardia has been reported in up to 10% of patients and is due to an unusual reflex to cathecolamine surge.
Case Report:
57-year-old morbidly obese female with a history of COPD, hypertension, paroxysmal bradycardia, and urinary incontinence was referred to endocrinology clinic after an adrenal mass was found incidentally as part of a work-up for microscopic hematuria and urinary incontinence. CT abdomen showed unilateral 3.3 x 3.9 cm left lobular adrenal mass. Family history was negative for malignancies or pheochomocytoma. Patient denied substance abuse or ethanol use. Her medications include amlodipine, hydrochlorothiazide and albuterol. Physical exam was remarkable for a BMI of 51.6 and bradycardia of 50 bpm and well controlled blood pressure. On further review of her history, patient had prior visits to outpatient and emergency department for chronic headaches, insomnia, palpitations and sweating. Patient had a previous admission 13 years prior for chest pain and hypertensive urgency associated with headache and junctional bradycardia.
Laboratory workup was significant for serum metanephrine levels of 749 pg/ml (normal &lt;42), serum normetanephrine 185 pg/ml(normal &lt;145), serum chromogranin A 130 ng/L(normal &lt;39) and 24hr urine metanephrine of 1340 ug/24hr (normal &lt;96) and urine normetanephrine of 357 ug/24hr (normal &lt;80). Previous ECG showed sinus bradycardia. Echo-cardiogram revealed normal ejection fraction with left atrial enlargement.
MIBG showed large focal area of intense radio-tracer accumulation in left mid abdomen and small focal lesions in the liver. Diagnosis of malignant pheochromocytoma was made and patient was referred to another institution for further management.
Conclusion:
Malignant pheochromocytoma is a rare neuroendocrine tumor that usually presents with tachycardia and hypertension. 10% of patients with malignant pheochromocytoma can debut with bradycardia due to sinus arrest. Although malignant and benign pheochromocytoma share the same clinical and histological features, the presence of metastasis is the main clue to differentiate them. Surgery remains the main treatment option even if complete debulking cannot be achieved. Nuclear radiation therapy or chemotherapy are two other therapeutic options that can be considered alone or in combination with surgery depending on the patients’ comorbidities. Lifetime surveillance is recommended as recurrence can occur up to 40 years after original resection.
References -Chen H, Sippel RS, O’Dorisio MS, Vinik AI, Lloyd RV, Pacak K. The North American Neuroendocrine Tumor Society consensus guideline for the diagnosis and management of neuroendocrine tumors: pheochromocytoma, paraganglioma, and medullary thyroid cancer. Pancreas. 2010 Aug;39(6):775-83.
SAT-374 The Many Faces of Parathyroid Carcinoma in the Philippines: A Case Series
Authors: Encarnacion Margaret C , Ramos Celeste O , Aquino Eduardo Thomas M , Mirasol Roberto C , Villa Michael L 
Published: May 2020

Abstract
Introduction: Parathyroid carcinoma is rare, affecting less than 1% of patients with primary hyperparathyroidism (PHPT). 1 Parathyroid carcinoma with concomitant papillary thyroid carcinoma is also rare, and the etiology is not fully defined.
Clinical Case: We present 3 patients with parathyroid carcinoma and discuss their presenting symptoms, characteristics, and treatment. Two women and 1 man (2 Filipinos and 1 Marshallese) with age range 53-68 years old had parathyroid carcinoma. Two had primary hyperparathyroidism, one had non-functioning type of parathyroid carcinoma. Two had concomitant bone or renal disease. All three had concurrent thyroid disease- 2 had papillary thyroid microcarcinoma, one had colloid goiter. Because each one had different indications for neck surgery, different surgical techniques were done. Parathyroid cancer size ranged from 2.0-5.2 cm, with capsular and vascular invasion in all three. One case had double parathyroid carcinoma. No lymph node metastasis was identified. On follow up, the patient with the largest tumor size had tumor recurrence within 1 year from surgery.
Conclusion: To the best of our knowledge, this is the first case series on parathyroid carcinoma in the Philippines, and includes the 7th case of double parathyroid carcinoma worldwide. Parathyroid carcinoma is a rare condition, and coupled with its highly variable presentation, as seen in the 3 cases, presents clinicians with a difficulty in arriving at a diagnosis. Histopathology remains the gold standard in diagnosis and is a key in guiding management. Since coexisting thyroid and parathyroid disease may occur, thyroid pathology should be evaluated in the presence of PHPT.
References:
1. Elizabeth Shane; Parathyroid Carcinoma, The Journal of Clinical Endocrinology & Metabolism, Volume 86, Issue 2, 1 February 2001, Pages 485-493, https://doi.org/10.1210/jcem.86.2.7207.
OR01-04 Kruppel-Like Factors 9 and 13 Cooperate to Maintain Mammalian Neuronal Differentiation
Authors: Avila-Mendoza Jose , Subramani Arasakumar , Denver Robert J 
Published: May 2020

Abstract
During development of the central nervous system, neural cells respond to several external cues that influence cell proliferation, differentiation, axonal growth and synaptogenesis. Thyroid hormone plays a critical role in each of these processes. Previously, we showed that Krüppel-like factor 9 (KLF9), a zinc finger transcription factor, is strongly and directly induced by liganded thyroid hormone receptors, and it mediates the actions of thyroid hormone on neuronal differentiation during late fetal development. Here we analyzed the molecular mechanisms by which KLF9 maintains neuronal structure, and inhibits regeneration in juvenile and adult neuronal cells. We also investigated the actions of the closely related transcription factor KLF13, which is paralogous to KLF9. We engineered the adult mouse hippocampus-derived cell line HT22 to control Klf9 or Klf13 expression by addition of doxycycline. We also used CRISPR/Cas9 genome editing to generate Klf9 or Klf13 knock out (KO), and Klf9+Klf13 double KO HT22 cell lines. To induce neurite outgrowth, we treated cells with forskolin (FK)+IBMX, which increases intracellular cAMP; elevated cAMP is a hallmark of regenerative responses of neurons to injury. Our results show that FK+IBMX increased neurite length in the parent HT22 cell line, and this action was enhanced in Klf9 and Klf13 single KO cells, and was even greater in double KO cells. By contrast, the stimulatory effect of FK+IBMX on neurite outgrowth was blocked by simultaneous forced expression of Klf9 or Klf13 in parent HT22 cells. This effect on neurite outgrowth was confirmed in primary mouse hippocampal neurons, where electroporation of expression plasmids for Klf9 or Klf13 suppressed FK+IBMX-induced neurite extension compared with empty vector-transfected cells. Analysis of RNA-seq data obtained from HT22 cells following 8 hr of induced Klf9 or Klf13 expression showed that both proteins impact the cAMP signaling pathway. Using transfection-reporter assays and chromatin immunoprecipitation, we confirmed that several genes in this pathway are direct targets of both KLFs. Our findings suggest that KLF9 and KLF13 may cooperate to maintain the differentiated state of mammalian neurons and thereby block regeneration, in part, by repressing the cAMP signaling pathway.