bluuebunny/crossref_metadata_2025 huggingface dataset:
SUN-350 Bone Marrow Adipose Tissue Is Associated with Fracture Prevalence in Anorexia Nervosa
Authors: Dang Tran , Faje Alexander T , Meenaghan Erinne , Bredella Miriam , Klibanski Anne , Fazeli Pouneh K
Published: May 2020

Anorexia nervosa, a psychiatric disorder predominantly affecting women, is characterized by self-induced starvation, low body weight, low subcutaneous and visceral fat depots, and low bone mass. More than 85% of women with anorexia nervosa have bone mineral density (BMD) values more than one standard deviation below the mean of women of comparable age. Although there is a significantly increased risk of fracture in women with anorexia nervosa, low BMD has not been shown to consistently predict the increased fracture rate in this population. Despite low subcutaneous and visceral adipose tissue stores, women with anorexia nervosa have increased bone marrow adiposity, which is inversely associated with BMD. We hypothesized that increased bone marrow adipose tissue would be associated with the increased fracture rate in women with anorexia nervosa. We studied sixty-two women: 34 with anorexia nervosa (mean age + SEM: 28.3 + 0.9 years) and 28 normal-weight controls of similar age (28.3 + 1.1 years; p=0.72). We examined associations between lifetime self-reported fracture history and 1) BMD of the lumbar spine (L1-L4), lateral spine (L2-L4), total hip, and femoral neck measured by dual energy X-ray absorptiometry and 2) bone marrow adipose tissue at the spine (L4 vertebra) and hip (femoral metaphysis, diaphysis and epiphysis) measured by 1H-magnetic resonance spectroscopy. Women with anorexia nervosa had significantly lower BMD at the spine and hip (p<0.0001 at all sites) and significantly higher bone marrow adipose tissue at the L4 vertebra (p<0.0001) and femoral metaphysis (p=0.001) as compared to normal-weight controls. Forty-seven percent (n=16) of women with anorexia nervosa versus 39% (n=11) of normal-weight controls reported a lifetime history of fracture (p=0.54). In women with anorexia nervosa, there was no significant association between fracture history and BMD at the spine or hip (p=0.27-0.98). In the group as a whole, bone marrow adipose tissue was greater in the L4 vertebra in individuals with a history of fracture compared to those without a fracture history (p=0.02). In subjects with anorexia nervosa, those with a history of fracture had greater bone marrow adipose tissue at the L4 vertebra (p=0.01) and femoral diaphysis (p=0.01) compared to those without a history of fracture; these differences in bone marrow adipose tissue remained significant after controlling for BMI (p=0.01-0.03) and also after controlling for BMD (p<0.01 for both). Higher bone marrow adipose tissue is associated with increased fracture prevalence and may be a better predictor of fracture risk than BMD in women with anorexia nervosa. Future prospective studies will be necessary to better understand the association between bone marrow adiposity and fracture risk in this population.
MON-615 Retrospective Analysis of the Contribution of Cannabis Usage to Diabetic Ketoacidosis at an Urban Teaching Hospital
Authors: Kha Christine K , Phan Ellyn , Simon Nicole
Published: May 2020

Diabetic ketoacidosis (DKA) is an acute life-threatening complication of diabetes mellitus. It is responsible for greater than 100,000 hospital admissions per year in the US (1). There are few studies regarding the relationship between drug usage and acute diabetic complications (2). Since 2001, cannabis usage among US adults have more than doubled, as state legal restrictions have eased and attitudes towards cannabis have become more permissive. Cannabis is the most commonly used illicit drug in the US (3). Some studies suggested cannabis usage was associated with improvement in insulin sensitivity and pancreatic beta cell function. Other research demonstrated cannabis usage may contribute to diabetes-related hospitalizations.

A retrospective analysis was performed at an urban teaching hospital to examine the relationship between cannabis usage and risk for DKA upon presentation. From March 2017 to February 2019, all non-pregnant patients aged 18 years and older, and who met criteria for DKA admission upon medical records review, were included in the study. Demographics, vitals, biochemistry, and toxicology were evaluated. Overall, 188 admissions for DKA were identified in a total of 130 patients, and 43% (81/188) were readmissions by 23 patients.

Illicit substance usage was addressed by history in 72% (135/188) of all admissions, among which 24% (33/135) reported cannabis usage. 36% (67/188) of all admissions, 73% (24/33) of the self-reported cannabis usage group, and 46% (37/81) of the readmissions, underwent general toxicology screening that did not include detection for cannabis. 11% (20/188) of all admissions, 24% (8/33) of the self-reported cannabis usage group, and 16% (13/81) of the readmissions, completed toxicology screening specifically for cannabis.

All of the self-reported cannabis usage admissions (33/33) and readmissions (81/81) presented with additional aggravating factors for DKA such as medication noncompliance, polysubstance abuse, and infection. Finally, 20 of the overall 130 patients admitted during this timeframe presented with new onset DKA, where none reported cannabis usage, 20% (4/20) completed general toxicology screening, and none underwent cannabis specific toxicology screening.

From the observational retrospective analysis at this hospital, there is a need for awareness about substance abuse screening, especially in adults with a history of recurrent hospital admissions for DKA. Knowledge among health care providers and patient education regarding the effect of cannabis usage on metabolic factors and its diabetes complications, including diabetes self-management at time of drug usage, can be further explored in prospective studies.

References: (1) Umpierrez (2006) Diabetes Care, 29(12), 2755-2757. (2) Brown et al., (2017) JAMA, 317(2), 207. (3) Haffajee et al., (2018) NEJM, 379(6), 501-504.
SUN-257 Evidence that Urocortin 2 Contributes to the Suppressive Effect of Metabolic Stress on LH Secretion in Female Mice
Authors: McCosh Richard B , Kreisman Michael J , Tian Katherine , Breen Kellie M
Published: May 2020

Pulsatile luteinizing hormone (LH) secretion is disrupted by numerous stimuli including metabolic stress. Insulin-induced hypoglycemia is a model of metabolic stress that suppresses LH secretion in numerous species including mice. Our recent work provides evidence that this inhibition of LH secretion occurs via suppression of neurons that contain kisspeptin (Kiss1), neurokinin B (NKB) and dynorphin (Dyn) in the arcuate (ARC) nucleus (KNDy cells). Thus, our current objective is to identify the neural components responsible for the suppression of KNDy cells during metabolic stress. Several lines of evidence support the hypothesis that the neuropeptide urocortin 2 (UCN2) has a key role in the inhibition of LH during stress in rats. First, ICV injection of UCN2 suppresses LH secretion. Second, an antagonist to the receptor for UCN2 reverses the suppression of LH during metabolic stress. Finally, restraint and osmotic stress increase UCN2 mRNA abundance in the paraventricular nucleus (PVN). To determine if UCN2 neurons in the PVN are activated during metabolic stress we performed immunohistochemistry for UCN2 and c-Fos in tissue collected 120 min after saline or insulin (0.75mU/kg) injection (n = 2/group, ovariectomized, adult, C57/BL6). Insulin significantly increased both the number of UCN2 cells (saline: 109.0 ± 8.5, insulin: 156.3 ± 10.8 cells) and the percentage of UCN2 cells that expressed c-Fos (saline: 13.1 ± 2.5%, insulin: 31.2 ± 0.8%). Next, we administered UCN2 (7.23nmol) via ICV injection to determine if this molecule suppresses LH secretion and/or mRNA abundance of KNDy genes. LH was measured in serial blood samples collected from 60 min prior to and 30-90 min following injection. Tissue was collected 3 h after ICV injection to confirm injection site and quantify mRNA abundance in ARC micropunches. In saline-treated mice (n = 5 successful injections), mean LH concentration and the number of LH pulses did not differ across sampling periods (mean: 6.4 ± 0.4 ng/mL vs. 6.0 ± 0.4 ng/mL; pulses: 2.6 ± 0.2 vs. 3.0 ± 0.3, pre vs. post). In contrast, in mice with successful UCN2 injections (n = 4) there was a significant reduction in both mean LH and the number of LH pulses following UCN2 (mean: 5.0 ± 0.3 ng/mL vs. 1.4 ± 0.2 ng/mL; pulses: 3.0 ± 0.0 vs. 0.25 ± 0.25, pre vs post). UCN2-treated animals had a significant reduction in the abundance of mRNAs encoding Kiss1 (~35%) and NKB (~40%) compared to saline-treated animals; the abundance of Dyn mRNA did not differ between treatments. These data demonstrate that PVN UCN2 cells are activated during metabolic stress and that UCN2 is sufficient to suppress LH secretion and the expression of genes involved in stimulating LH pulses. These data support the hypothesis that UCN2 released from neurons in the PVN impairs KNDy cell function and LH secretion during acute stress.
SAT-211 Is Doxazosin the Right Choice for Preoperative Management of Pheochromocytoma in Pregnancy?
Authors: Bustos Mario , DiCenso Daniela Maria , Ayala Alejandro
Published: May 2020

Pheochromocytoma (PCC) in pregnancy is a very rare condition, with a reported incidence of less than 0.2 per 10.000 pregnancies (1), having fetal and maternal mortality of 50% if untreated (2). Choosing between selective vs. nonselective alpha blockers as preoperative management in pregnancy is controversial.

We report a case of a 39-year-old female having episodes of nervousness, hand tremors, palpitations, diaphoresis, and headaches since 2012; she also had a history of multiple miscarriages and uncontrolled hypertension(HTN) since 2018. In 2019, she was found to have plasma metanephrines 690pg/mL (0-62) and plasma normetanephrine of 3803pg/mL(0-145). Repeat labs showed: plasma metanephrines 2.071pg/mL(0-62), normetanephrine 6.289pg/mL(0-145), norepinephrine 4.268pg/mL(0-874), epinephrine 555pg/mL(0-62). CT abdomen showed a 6.2x5.1x6.4cm left adrenal mass, with 44 Hounsfield units and less than 50% of washout. She was started on Doxazosin 2mg/d, which eventually was increased to 6mg/d with optimal blood pressure (BP) control. After her preoperative workup, she was found to be 7 weeks pregnant. OB-GYN recommended left adrenalectomy before 14 weeks gestation. She had left open adrenalectomy, with normal range postoperative BP, off of antihypertensive medications.

The diagnosis of PCC in pregnancy should be considered in the setting of paroxysmal HTN, with no proteinuria, episodic palpitations, diaphoresis, facial flushing, and orthostatic hypotension. Anterior adrenalectomy early in pregnancy is recommended. The increased intraabdominal pressure, fetal movements, uterine contractions, delivery process, and abdominal surgical intervention can trigger the catecholamine release by the PCC, which could lead to placental abruption and miscarriage; and the rebound hypotension may lead to severe hypoxia, causing fetal demise (2). Definitive preoperative treatment between selective vs non-selective alpha-blockers remains controversial. Phenoxybenzamine, appeared to produce better attenuation of intraoperative HTN, however, it is associated with more maternal intraoperative/postoperative hypotension, and reflexive tachycardia. It crosses the placenta and accumulates in the fetus, increasing the risk of neonatal hypotension and respiratory depression (3,4,5). On the other hand, Doxazosin, can be displaced by high levels of catecholamines, but it is less associated with intraoperative/postoperative hypotension (6,7), with no reports of neonatal hypotension, and respiratory depression. Due to the lack of presynaptic a2-adrenoceptor blockade there is less reflex tachycardia, reducing the use of Beta-blockers (8). Doxazosin seems to be a safe, affordable alternative for preoperative management of PCC in pregnant patients.
MON-303 Giant Growth Hormone Secreting Pituitary Adenomas: A Single Institution Case Series
Authors: Koylu Bahadir , Sendur Suleyman Nahit , Oguz Seda Hanife , Dagdelen Selcuk , Erbas Tomris A
Published: May 2020

The prevalence of growth hormone (GH)-secreting pituitary adenoma is around 11-13% of all pituitary adenomas. Giant GH-secreting pituitary adenomas (≥ 4 cm) are rare tumors, and its prevalence of among acromegalic patients is <5%.

This is a retrospective cohort study including patients with giant GH-secreting pituitary adenomas. The study population consisted of 10 patients (5 M/5 F). The mean age at diagnosis was 33.0±12.9 yrs (11-55 yrs). The mean delay between first symptom onset and diagnosis was 2.9 years. The most frequent symptoms were acral enlargement and facial changes (80%), followed by headache (70%) and visual deterioration (50%). One patient had epilepsy. Amenorrhea was presented in three females but obvious galactorrhea in two. The mean adenoma diameter was 42.6±4.7 mm (40-51 mm) at diagnosis. The vast majority of adenomas presented suprasellar extension (100%) or cavernous sinus invasion (80%). Cystic adenomas accounted for 50%. At presentation, mean GH and IGF-1 levels were 40.0±21.4 ng/mL (14.8-51.0) and 2.62±1.09 x ULN (1.08-3.96), respectively. Six patients presented with PRL cosecretion. At diagnosis maximal tumor diameter was not correlated with GH or IGF-1 levels.

All patients underwent pituitary surgery as first-line treatment. Three cases were treated with an endoscopic approach and four cases with a microscopic approach. Transcranial approach was also employed in three cases. Postoperative mean GH and IGF-1 levels were 14.9±16.1 ng/mL (0.6-51.0) and 2.25.±0.82 x ULN (1.48-3.74), respectively. After first surgery, only one patient had more than 50% reduction in IGF-1 levels. Five patients (50%) underwent repeat surgery on two to three procedures because remission was not achieved. Postoperative somatostatin receptor ligands (SRLs) were used by all patients. Six patients were treated with dopamine agonist in combination with SRL. Six patients (60%) received postoperative radiotherapy.

The mean follow-up period was 12.6±5.3 yrs (4-21 yrs). The mean GH and IGF-1 levels were 1.47±1.54 ng/mL (0.08-5.25) and 0.73±0.44 x ULN (0.08-1.56), respectively at the last visit. Residual adenoma was present at the last MRI in eight patients (mean diameter 9.0±3.6 mm). Panhypopituitarism rose from 10% at baseline to 30% at the last visit. During follow-up, one patient diagnosed breast cancer, while another diagnosed thyroid papillary cancer.

Giant GH-secreting pituitary adenomas can have a clinically aggressive behavior with mass effect. Moreover, treatment in patients with giant GH-secreting pituitary adenoma is complex and multimodal therapy is necessary.
SUN-743 Understanding the Role of Pancreas and Testis Specific lncRNA86 in Estrogen-Dependent Signaling in Breast Cancer
Authors: Ramos Enrique Ivan , Yang Barbara , Choudhari Ramesh , Sanchez-Michael Laura , Sedano Melina , Gadad Shrikanth
Published: May 2020

Long noncoding RNAs (lncRNAs) are emerging as key regulators of diverse cellular processes, but their roles in breast cancer biology are just beginning to be elucidated. In this study, integration of powerful techniques, RNA-seq data from subcellular fractionated RNA with GRO-seq data has yielded a comprehensive catalog of estrogen-regulated lncRNAs in MCF-7 cells. Analysis of RNA-seq data from samples representing molecular subtypes of breast cancer and normal tissue types, revealed that many lncRNAs (such as lincRNA86) show distinct expression patterns. LincRNA86 shows highest normal expression in pancreas followed by testis in normal human tissues. The hypothesis is lincRNA86 regulate estrogen-dependent signaling in breast cancer. In functional assays, knockdown of lncRNA86 inhibits the growth of ER-positive breast cancer cells. Amplified expression of lncRNA86 in breast cancer correlates with clinical outcome. LncRNA86 have now been fully annotated (transcription start and stop site, 5’ cap, polyA tail, and exon/intron structure), and cloned. We are now performing detailed molecular analyses to better understand the underlying mechanisms of action of the lncRNA. We are also currently have experiments underway to view cancer phenotypes: estrogen-dependent tumor growth. Collectively, our preliminary results suggest that lincRNA86 plays a critical role in ERα-dependent pathways.
MON-202 Germline SDHB Exon 1 Deletion Is Associated with Absence of 131I-metaiodobenzylguanidine (MIBG) Uptake in Malignant Paragangliomas
Authors: Petenuci Janaina , Fagundes Gustavo Freitas Cardoso , Motta Flavia Tedesco , Magalhães Aurea Luiza F , Guimaraes Augusto G , Benedetti Anna Flavia Figueredo , Afonso Ana Caroline F , Pereira Maria Adelaide A , Coura-Filho George B , Zerbini Maria Claudia N , Siqueira Sheila , Srougi Victor , Tanno Fabio Y , Chambo Jose Luis , Ferrari Marcela S S , Neto Joao Evangelista Bezerra , Latronico Ana Claudia , Hoff Ana O , Mendonca Berenice Bilharinho , Fragoso Maria Candida B V , Almeida Madson Q
Published: May 2020

Introduction: Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors arising from chromaffin cells. More than 30% of patients with PPGLs have a hereditary predisposition. Malignancy in PPGLs is defined by the presence of local invasion or metastasis in nonchromaffin tissues. Germline SDHB mutations are found in approximately 40% of malignant PPGLs, mainly paragangliomas (PGLs). However, SDHB mutations are not a prognostic factor in malignant PPGLs. To date, no genotype-phenotype correlation has been reported in malignant PPGLs associated with SDHB mutations. Aim: To investigate clinical and imaging features of patients with malignant PGLs harboring germline SDHB exon 1 deletion or splicing site mutation. Methods: We retrospectively evaluated 22 unrelated individuals with malignant PPGLs. Six out of 22 (27%) malignant PPGLs harbored germline SDHB mutations. Three patients had SDHB exon 1 deletion and 3 splicing site mutation (2 with c.201-2A>G and one with c.423 + 1G>A). All SDHB defects were classified as likely pathogenic. Results: In the exon 1 deletion group, 2 patients had abdominal PGLs (one also had a neck PGL) and one had only head and neck PGLs. In the splicing site mutation group, all 3 patients had abdominal PGLs (one also had a neck PGL). Median age at diagnosis was 26 yrs (16 to 45) and 33 yrs (26 to 53) in the exon 1 deletion and splicing mutation groups, respectively. Two patients (one in each group) had metastasis at diagnosis. All 6 patients had bone metastasis, but liver and/or lung metastasis were more frequent in patients with SDHB exon 1 deletion (66 vs. 33%). Interestingly, metastasis from malignant PGLs harboring SDHB splicing site mutations were 131I-metaiodobenzylguanidine (MIBG) avid in all cases, whereas metastatic lesions from malignant PGLs harboring SDHB exon 1 deletion did not present any MIBG uptake on diagnostic imaging studies. Therefore, all 3 patients with SDHB exon 1 deletion were treated with chemotherapy (cyclophosphamide, vincristine and dacarbazine). In contrast, all 3 patients with splicing site mutations have been treated with MIBG therapy. Median follow-up was 87 months (8 to 360 months). Only one patient (exon 1deletion group) died because of disease progression. Conclusion: We first demonstrated here that germline SDHB exon 1 deletion is associated with absence of MIBG uptake in malignant PGLs. This finding needs to be confirmed in an expanded cohort of malignant PPGLs.
MON-373 Low Bone Mineral Density Does Not Equal Osteoporosis: The Finding of XLHR with a Novel Phex Mutation
Authors: Tran Kelvin , Mortensen Michael , Elshimy Ghada , Vinales Karyne Lima , Correa Ricardo Rafael
Published: May 2020

Introduction: X-linked Hypophosphatemic rickets (XLHR) is a rare form of rickets that mainly affects children but, in some cases, it can be missed and not diagnosed until later in life. We present a post-menopausal female that was misdiagnosed with osteoporosis for many years until complete work up was done, and she was found to have osteomalacia due to hypophosphatemia. Clinical case: A 59-year-old female was evaluated following admission to the hospital for a worsening femur fracture on imaging and had received ORIF. She was diagnosed with osteoporosis at the age of 45 and endorses a history of multiple femur fractures from low impact trauma. Despite previous bisphosphonate therapy, she continued to have recurrent fractures.[RC1] She reported no family history of early osteoporosis, but her mother was diagnosed with rickets as a child. Secondary workup for osteoporosis revealed normal 25OH vitamin D, SPEP, TSH, PTH and serum calcium, endomysial antibodies, and 24-hour urine calcium levels. However, the patient had persistently elevated alkaline phosphatase levels (150-200) and low phosphate levels (1.8-2.4). This raised the possibility of Paget’s disease, so a bone scan and lumbar X-ray were obtained which were normal. Given low phosphate levels, fibroblast growth factor (FGF)-23 was obtained and was elevated. This left the differential between tumor-induced osteomalacia (TIO) vs hypophosphatemic rickets. Ga-DOTATE scan and PET scan were negative, so the patient subsequently underwent genetic testing. She was found to have a phosphate regulating endopeptidase homologue (PHEX) gene mutation and was finally diagnosed with XLHR Her PHEX mutation was caused by a novel variant, c.1366 T>C or W456R, which has only been documented once in the literature. The patient was treated with 2 gm per day of phosphate supplementation in divided doses and calcitriol 0.25 mcg once daily which normalized her phosphate and 1,25 vitamin D levels. 1 month later after treatment, she reported significant improvements in bone pain, and her DEXA scans were stable for the following 4 years. Discussion: XLHR is a heterogeneous group of inherited disorders characterized by hypophosphatemia and impaired bone mineralization leading to rickets. It results from mutations affecting the PHEX gene of which more than 300 pathogenic variants have been described. The mutation causes excess FGF-23 which leads to osteomalacia and chronic hypophosphatemia. This condition can be difficult to distinguish from TIO as both present with low phosphate and elevated FGF-23 but can be differentiated with genetic testing. Recognition of the correct diagnosis is prudent to providing correct treatment. The current treatment for XLH is calcitriol and phosphorus replacement. Recently, burosumab was FDA approved in 2018 for treatment in adults.
MON-288 TSH Deficiency in Patients on Somatostatin Analog for TSH-PitNET
Authors: Illouz Frederic , Chanson Philippe , Sonnet Emmanuel D , Brue Thierry Christian , Ferriere Amandine , Raffin-Sanson Marie-Laure , Vantyghem Marie-Christine , Raverot Gerald , Munier Mathilde , Rodien Patrice , Briet Claire
Published: May 2020

Background: Somatostatin analogs (SSA) are efficiently used to control central hyperthyroidism in patients with thyrotropin-secreting pituitary neuroendocrine tumor (TSH-PitNET). The aim of this study was to describe the frequency of thyrotropin (TSH) deficiency under SSA in patients with TSH-PitNET. Methods: We retrospectively recruited patients presenting a central hyperthyroidism due to TSH-PitNET. Inclusion criteria were patients treated in first, second or third line by short or long-acting SSA, with central hyperthyroidism before SSA. Patients treated by radiotherapy or dopamine agonist were excluded. TSH deficiency was defined by either a low FT4 or low FT4 and FT3, associated with non-elevated TSH concentrations during SSA therapy. We analyzed the frequency of TSH deficiency and the characteristics of patients with or without TSH deficiency. Results: 46 patients were included in the study. SSA were used as the first-line therapy in 21 of 46 patients (46%). Central hyperthyroidism was controlled in 36 of 46 patients (78%). TSH deficiency appeared in 7 of 46 patients (15%), after a median time of 4 weeks (4–7) after the starting of SSA, and for a median duration of 3 months (2.5–3). The TSH deficiency occurred after 1 to 3 injections of long-acting SSA. There were no differences in terms of clinical and hormonal features and size of adenomas between patients with or without TSH deficiency. Conclusions: In patients with central hyperthyroidism due to TSH-PitNET, SSA can induce TSH deficiency. Thyrotropic function should be assessed before each injection of SSA in order to adapt the frequency of injection when control of thyrotoxicosis rather than tumor reduction is purpose of the treatment.
SAT-275 Bitemporal Hemianopia as a Result of Cabergoline Therapy for Macroprolactinoma
Authors: Díaz-Balzac Carlos A , Williams Zoe R , Vates G Edward , Shafiq Ismat
Published: May 2020

Background: Cabergoline is first-line treatment for prolactin-secreting pituitary macroadenoma (prolactinoma). Side effects such as nausea, valvulopathy and neuropsychiatric symptoms are well recognized complications of its use. A rare complication is vision loss secondary to empty-sella syndrome. Clinical case: A 27-years old women was diagnosed in 2009 with macroprolactinoma with a prolactin level of 2,523.91ng/mL (normal 3.3-26.7ng/mL), during work up of frontal headaches, amenorrhea and infertility. The rest of her pituitary work up was normal. She was started on dopamine receptor agonist therapy with Cabergoline 0.25mg two times a week. Her headaches improved within a few month. The prolactin level normalized and MRI at 1 year after starting Cabergoline therapy showed significant decrease in pituitary adenoma to 3mm. She continued Cabergoline therapy for 3 years, after which time it was discontinued. For the next 6-8 years she was on and off Cabergoline therapy for mild elevation of prolactin and galactorrhea/headache symptoms, with improvement of symptoms on Cabergoline. However, nine years after diagnosis and Cabergoline treatment, she developed vision loss, characterized by bitemporal hemianopia. MRI showed partial empty sella with downward displacement of the optic chiasm. Cabergoline therapy was stopped with some improvement of visual symptoms on exam. Here latest prolactin level is at 134ng/ml. Surgical management with chiasmapexy is being explored. Conclusion: Vision loss secondary to optic nerve traction from chiasmal herniation in the setting of an empty sella can be a consequence of Cabergoline therapy. No predictors or risk factors are known for the development of this complication. Furthermore, no clear evidence is available of benefit from discontinuation/continuation of therapy. Novel surgical management with chiasmapexy is being explored as a solution to stabilize the optic chiasm and resolve visual symptoms without further complications.
MON-283 IGF-1 Levels During Normal Pregnancy
Authors: Thomas Guillermo Javier , Peverini Agustina , Smithuis Fernando , Fabbro Dolores , Tkatch Julieta , Rosmino Josefina , Aranda Claudio , Guitelman Mirtha , Oneto Adriana
Published: May 2020

Pregnancy is associated with a physiological GH excess, where maternal pituitary GH is suppressed by effect of placental GH on the hepatic receptor, increasing IGF-1 serum levels1. However, it is also described that estrogens and progesterone are responsible for reduction in IGF-1 by direct hepatic action through the inhibition of the JAK-STAT pathway that results in GH resistance, being more clear at the beginning of pregnancy.2 Acromegaly is a rare disorder in which GH axis is deregulated and IGF-1 is the most reliable biochemical marker for diagnosis and monitoring. It is know that secondary hypogonadism associated with these pathology decreases fertility rates. Nonetheless, improvement of acromegaly treatment and greater access to assisted reproductive technology increase pregnancy rates in this population. The follow-up of pregnant acromegalic women acquires relevance for the comorbidities of this association and depends on the adequate interpretation of the IGF-1 values. Then, due to changes in concentration and action of IGF-1 during pregnancy3, it is important that each laboratory establish their specific reference values. For that reason we analyzed serum samples from 80 healthy pregnant women living in the Metropolitan Area of Buenos Aires (AMBA): 22 were in the 1st trimester (1T), 29 in the 2nd (2T) and 29 in the 3rd (3T). All women were between 30 and 40 years old, had no endocrinopathies or metabolic diseases. Serum IGF-1 was measured by Immulite 2000 Siemens, and Prism8 GraphPad was used for statistical analysis, calculating ranges for each trimester defined as 2,5 and 97,5 percentiles. Ranges obtained were: 64,5-165,0 ng/ml, 78,9-201,0 ng/ml and 96,1-344,0 ng/ml for 1T, 2T and 3T, respectively. Significant differences were observed between 3T and the other trimesters (1T and 2T). We also compared these ranges with our reference values from healthy non-pregnant women in the same age, and found that 3T has significantly higher values ​​of IGF-1 (55,8-188,4 ng/ml vs. 96,1-344,0 ng/ml respectively). In conclusion, IGF-1 levels during the first two trimesters of pregnancy remain within the normal range, and there is a significant increase during the third trimester. Given that IGF-1 plays an essential role during pregnancy, it is important to report ranges in healthy pregnant women to contribute in the follow-up of patients with acromegaly who get pregnant. Although our results are in agree with the available literature, it is necessary to increase the number of healthy pregnant women to establish reference values of IGF-1.

1Frankenne et al (1988). The physiology of growth hormones in pregnant women and partial characterization of the placental GH variant. Journal of Clinical Endocrinology and Metabolism 66:1171-1180

2Leung et al (2004). Estrogen regulation of growth hormone action. Endocrine Reviews 25:693-72

3Muhammad et al (2017). Pregnancy and acromegaly. Pituitary 20:179-184
MON-120 The Implementation of a Scholarly Activity Curriculum: Impact Assessment
Authors: Mosaferi Tina , De Silva Jayamalee , Leung Angela M , Praw Stephanie Smooke
Published: May 2020

Introduction:

As detailed in the 2018 ACGME Common Program Requirements statement for fellowship institutions, “The physician is a humanistic scientist who cares for patients. This requires the ability to think critically, evaluate the literature, appropriately assimilate new knowledge, and practice lifelong learning.” Endocrinology fellowship programs are tasked with the expectation of creating an environment that fosters scholarly pursuit. It is under the discretion of each program to consider its institutional resources and community needs in order to meet this ACGME requirement.1

With the goal of enhancing trainee scholarly activity, our fellowship program created a Scholarly Activity Curriculum in 2017. The core curriculum pillars include delineating a yearly timeline of objectives and expectations, facilitating regular individual mentoring, permitting allotment of protected time, and advocating involvement in faculty scholarship and national conferences.

Objective:

To assess the impact of the 2017 Endocrinology Fellowship Scholarly Activity Curriculum with respect to its ability to increase trainee scholarship.

Methods:

The scholarly activities of the fellowship classes of 2017-2020 were extracted from archived Fellow Scholarly Activity Update presentations and exit-interview curricula vitae. The activities were categorized as conference presentations (oral/poster), basic scientific research, clinical scientific research, quality improvement, book chapters, review articles, case reports, and teaching activities. With the 2017 and 2018 classes representing the pre-curriculum study group and the 2019 and 2020 classes representing the post-curriculum study group, the number of activities per study group per scholarly category were tabulated and compared.

Results:

An increase in scholarly activity was noted in five of the delineated categories: conference presentations (80%), clinical scientific research (86%), review articles (100%), case reports (100%), and teaching activities (38%). The remaining three categories of basic scientific research, quality improvement, and book chapters showed no change.

Conclusions:

The implementation of the 2017 Endocrinology Fellowship Scholarly Activity Curriculum was associated with a rise in trainee scholarly activity. Four of eight categories showed an 80% or more increase. Interestingly, the fellows involved in basic scientific research both pre and post-curriculum implementation were limited to those in the Specialty Training and Advanced Research (STAR) Program. Finally, identifying the need to increase involvement in quality improvement research, our program has implemented a 2019 Quality Improvement Curriculum.

1Common Program Requirements (Fellowship). ACGME. https://www.acgme.org/What-We-Do/Accreditation/Common-Program-Requirements. 2018. Accessed Nov 2019.
MON-206 Diagnosis of Non-Functional Masses in Adrenal Gland Topography - Experience of a Tertiary Health Center
Authors: Brondani Vânia Balderrama , Charchar Helaine , Tanno Fabio Y , Srougi Victor , de Freitas Ricardo M C , Fenelon Sandro S , Pereira Maria A A , Chambo Jose L , Mendonca Berenice B , Almeida Madson Q , Villares Fragoso Maria Candida Barisson
Published: May 2020

Introduction: Masses in adrenal topography are diagnosed frequently due to the increase in radiological imaging in clinical practice. Adrenal incidentalomas occur between 4% and 10% of the patients above 50 years undergoing abdominal imaging, and the majority are benign pathologies. Objective: To analyze the characteristics of the masses located in adrenal gland topography not originating from the adrenal gland. Methods: We retrospectively assessed patients from our tertiary hospital who underwent surgical treatment for masses in adrenal gland topography between 2006 and 2018. All patients had hormonal evaluations, according to the European and American Societies of Endocrinology guidelines. Two expert radiologists reviewed all images. Forty-six patients were included in the study, and the surgical specimens were analyzed by the same experienced pathologist. Patients with confirmed adrenocortical carcinoma (ACC) were excluded from this cohort. Results: Thirty-two (69.6%) patients were female. The median age was 49.5 years old (range 18-82yo). Abdominal or lumbar pain was the most frequent reason for medical investigation (43.5%). Adrenal incidentalomas represented 38.4% of the cohort. None of these patients had any clinical signs of adrenal hyperfunction, nor hormonal alteration. Twenty-four patients (52.17%) presented a mass on the left side, and only two cases presented bilateral adrenal masses. The median size was 8.6cm (1.3-18cm). The mean of Hounsfield Units (HU) on a non-contrasted CT was 25HU (0-50HU). Several etiologies were found: 8 cases (18%) of ganglioneuroma; 6 cases (13,5%) of adrenal cysts; 4 cases (9%) of leiomyosarcoma and adrenal hemorrhage; 3 cases (6.5%) of infectious disease; 2 cases (4.5%) of lymphangioma, schwannoma, and sarcoma. We also found single cases of renal cell carcinoma, poorly differentiated small cell neuroendocrine carcinoma, hepatocellular carcinoma, high grade dedifferentiated liposarcoma, epithelioid neoplasia, epithelial neoplasia with neuroendocrine differentiation, malignant peripheral nerve sheath tumor of the adrenal gland, poorly differentiated neuroblastoma, high grade lymphoma, myelolipoma, acute splenitis, arteriovenous malformation, and prostate cancer metastasis. Discussion and Conclusion: Ganglioneuroma was the most frequent diagnosis in adrenal incidentalomas in our cohort. In general, these conventional radiological exams could not differentiate lesions originated in the adrenal glands from lesions of other origins. In this large cohort, we could identify non-adrenal origin in approximately 45% of the patients with masses in the adrenal topography.
SUN-605 Mediastino-Abdominal Lipomatosis: Deep Accumulation of Fat Mimicking a Respiratory Disease
Authors: Correa Ricardo Rafael , Elshimy Ghada , Alsayed Mahmoud
Published: May 2020

Introduction: Multiple systemic lipomatosis (MSL) is a rare disorder with unknown etiology. It is characterized by the massive development of non-encapsulated lipomas in subcutaneous tissues. Lipomatosis of the face, head, neck, extremities, abdomen, and pelvis have been reported in the literature. Case: We report a case of a 65 years old female (BMI: 34 kg/m2) with past medical history of hypertension, hyperlipidemia(DLD) diabetes mellitus type 2 and sleep apnea that was brought into emergency room (ER) for worsening shortness of breath. In the ER, she was having an oxygen saturation of 75% and required intubation. The patient was afebrile, with a BP of 120/75 mm Hg and a heart rate of 70/minute. Trans-thoracic echocardiogram revealed normal ejection fraction and normal pulmonary pressure with no wall motion abnormality. CXR showed no infiltration or consolidation. CT angiogram (CTA) ruled out pulmonary embolism but it was notable for large deposits of fat involving the abdomen and thorax, with invasion into the mediastinum and the space between the liver and diaphragm. Mesenteric fat was increased. Tissue was biopsied, which confirmed the diagnosis of fatty invasion. Discussion: Abdominal lipomatosis is characterized by massive enlargement of the abdomen due to intraperitoneal and retroperitoneal fatty deposits. Phenotypically patients can appear to be thin or obese, however, it is more common in the overweight population like our patient. Mediastinal lipomatosis is a benign cause of mediastinal widening, however patients can develop respiratory symptoms like exertional dyspnea due to compression of airways. MSL affects white caucasian between 25-60 years old and it is associated with DLD, impaired glucose tolerance, hyperuricemia, macrocytic anemia, and peripheral neuropathy. The pathophysiology is not fully understood, some theories stated that it is related to defective lipid mobilization in lipomatocytes, other suggested disorder in the mitochondria of brown fat. Conclusion: CT and MRI of the abdomen and chest are very helpful in the diagnosis of MSL but a tissue biopsy is what makes the final diagnosis. There is no definitive treatment; the recommendations are a healthy lifestyle including a low-fat diet, abstinence from alcohol and exercise. In severe cases, surgery is recommended.
SAT-469 Vitals for the Prompt Recognition of Myxedema Crisis in a Critically Ill Patient
Authors: Funke Katalina , Aljehani Faisal , Loftley Aundrea
Published: May 2020

Myxedema coma is a rare but life-threatening condition if not treated promptly. The time from initial presentation to diagnosis may be prolonged in patients with severe illness whose presenting features are common to myxedema crisis. A 94-year-old male admitted to the neuroscience intensive care unit for acute stroke monitoring after intra arterial thrombolysis was treated for myxedema three days after initial labs revealed severe hypothyroidism and a myxedema score greater than 60. A diagnostic scoring system for the diagnosis of myxedema coma gives points for the following to easily identify patients with high likelihood of decompensated state of extreme hypothyroidism. Given the potential for under recognition of myxedema crisis in severe illness the clinician must pay close attention to vital signs and have a high level of suspicion for myxedema crisis and low threshold for treatment if myxedema score indicates high likelihood despite concomitant critical illness
SUN-182 Rare Case of Adrenocortical Carcinoma with Tumor Extension into the Inferior Venacava, Right Atrium and Right Ventricle
Authors: Siddiqi Asmat Qayoom , Cryar Keith , Yang Jungyoon
Published: May 2020

Introduction: Adrenocortical carcinoma is a rare and highly aggressive malignancy with an incidence rate of 1-2 per million population per year. It is an aggressive tumor with early metastasis to lungs, liver, bone and lymph nodes. Venous tumor thrombosis to inferior venacava (IVC), atrium or ventricle is rare and is considered as a tumor extension instead of metastatic disease, but with a poor prognostic outcome.

Clinical Case: We present a rare case of adrenocortical carcinoma with tumor extension into the IVC, right atrium and right ventricle. A 62-year-old female with history of breast cancer on anastrozole presented to the clinic for a routine screening colonoscopy. Patient was noted to have uncontrolled hypertension before the procedure, so was sent to the ER. Upon further interviewing she complained of increasing abdominal distension, hirsutism, and bilateral lower extremity swelling over the past six months. CT abdomen revealed a large 10 x11 x13 cm heterogeneously enhancing mass arising above the right kidney, with extensive tumor extension into the IVC, right atrium and right ventricle. MRI too characterized a large mass in the right adrenal gland with tumor thrombus extension into the IVC, right atrium, and right ventricle. Hormonal studies demonstrated elevated cortisol, dehydroepiandrosterone-sulfate and testosterone levels. A 1 mg dexamethasone suppression test inadequately suppressed cortisol levels, consistent with Cushing’s syndrome due to endogenous over secretion of cortisol. Free plasma and urine metanephrine levels were normal. Plasma renin and aldosterone concentration were within normal limits. With the cooperation of a multidisciplinary team, patient underwent right adrenalectomy with removal of tumor thrombus from right atrium and right ventricle under cardiopulmonary bypass. Surgical pathology confirmed adrenocortical carcinoma. She was started on mitotane as adjuvant therapy. Patient was also noted to have a lung nodule with biopsy showing oncocytic neoplasm favoring metastasis from adrenal cortex. She did receive chemotherapy for the lung metastasis with decrease in the size of the nodule.

Conclusion: Adrenal cortical carcinoma is a rare disease and the venous tumor thrombus to IVC, atrium and ventricle is even rarer and has a poor prognostic outcome. Complete tumor resection is the only curative approach with adjuvant therapies aiming to decrease the risk of recurrence only. Due to the aggressive nature of the tumor and quick development of metastasis, early diagnosis gives the best chance of resection and hence the greatest chances of survival.
OR14-03 The Transcriptional Coactivation Function of EHMT2 Restricts Chronic Glucocorticoid Exposure Induced Insulin Resistance
Authors: Lee Rebecca Arwyn , Tsay Ariel , Chang Maggie , Li Danielle , Wang Jen-Chywan
Published: May 2020

Glucocorticoids are required for metabolic adaptations during times of stress. However, chronic glucocorticoid exposure is associated with metabolic disorders such as insulin resistance. Glucocorticoids mainly convey their signals through an intracellular glucocorticoid receptor (GR). GR is a transcription factor that requires interactions with transcriptional coregulators to modulate the transcription of GR primary target genes, which in turn regulate specific aspects of physiology. Euchromatic Histone Methyltransferase 2 (Ehmt2) is a transcriptional coregulator for GR that can act as a corepressor or a coactivator. We found that glucocorticoid-induced insulin resistance was exacerbated when Ehmt2 levels were reduced in the liver. Intriguingly, this phenotype resulted from the transactivation function of Ehmt2. This is because a mutation at the lysine 182 automethylation site, which is required for the coactivation but not the corepression function of Ehmt2, results in similar exacerbated GC-induced insulin resistance. These results suggest that Ehmt2 coactivation dependent GR primary target genes restrict the extent of glucocorticoid-induced insulin resistance. Gene expression analysis identified Dusp4 (a.k.a. Mkp-2) as an Ehmt2 coactivation dependent GR-activated gene, which when overexpressed in liver, attenuated glucocorticoid-induced insulin resistance. Thus, we have identified a novel GR-Ehmt2-Dusp4 axis that plays a key role in controlling the extent of the development of insulin resistance. Notably, the classical view of how GC induce hepatic insulin resistance is that GR activates genes that inhibit insulin signaling and enhance hepatic gluconeogenesis. Our study, however, provides a revolutionary concept in which the extent of GC-induced insulin resistance is controlled by the balance of GR-activated genes that promote insulin sensitivity or insulin resistance.
SAT-056 Autosomal Dominant Hypophosphatemic Rickets in Premature Twins Resolved with Iron Supplementation
Authors: Alarcon Guido , Tarkoff Joshua , Diaz Alejandro
Published: May 2020

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>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