bluuebunny/crossref_metadata_2025_split huggingface dataset:
SUN-243 Deletion of KNDy Neuron-Specific KISS1 Disrupts Estrous Cyclicity and LH Pulsatility in Female Mice
Authors: Nandankar Nimisha , Negron Ariel L , Levine Jon E , Radovick Sally 
Published: May 2020

Abstract
Kisspeptin (encoded by Kiss1), a neuropeptide critically involved in neuroendocrine regulation of reproduction, is primarily synthesized in two discrete hypothalamic nuclei: the anteroventral periventricular area (AVPV) and arcuate nucleus (ARC). AVPV Kiss1 is important for the pre-ovulatory luteinizing hormone (LH) surge unique to females as well as estrogen-induced positive feedback control of GnRH and LH. In contrast, ARC Kiss1 neurons, which largely co-express the neuropeptides NKB and dynorphin (collectively known as KNDy neurons), are major regulators of pulsatile release of GnRH and LH, and mediate estrogen-induced negative feedback control of both GnRH and LH. Previous studies have not fully separated the specific roles for Kiss1 in the AVPV versus KNDy-ARC neurons in the downstream control of GnRH and LH release. Therefore, we generated a Pdyn-Cre/Kiss1fl/fl (KO) mouse model to target Kiss1 in the KNDy neurons to differentiate KNDy neuron-specific function from AVPV Kiss1 function in the maturation and maintenance of the reproductive axis. qRT-PCR data documented a significant reduction of Kiss1 expression in the mediobasal hypothalamus (containing ARC) compared to controls, whereas Kiss1 in the preoptic area (containing AVPV) was similar in both KO and controls. Immunofluorescent IHC confirmed a loss of kisspeptin immunoreactivity in the ARC of KO animals while expression in the AVPV remained intact. Markers of pubertal onset (day of vaginal opening and first estrus in females; day of preputial separation in males) were normal in KO mice, suggesting that AVPV Kiss1 and/or other neural signals may be sufficient for pubertal onset. In addition, body weight throughout pubertal growth was comparable between KO and control animals of both sexes. Interestingly, KO female mice had disrupted estrous cycles presenting with persistent diestrus and a small vaginal opening. In order to test our hypothesis that conditional deletion of Kiss1 in KNDy neurons disrupts or ablates episodic GnRH/LH pulsatile release, we collected serial tail blood samples from mice at diestrus and measured LH. KO female mice exhibited significantly fewer LH pulses in a 3-hour timespan compared to controls, suggesting that KNDy neurons were functionally compromised. These observations indicate the central role of KNDy neurons in the regulation of GnRH/LH pulsatility and estrous cyclicity. The functional effects of disrupted estrous cyclicity and slower LH pulses observed in KO females are currently under study to assess potential abnormalities in ovarian folliculogenesis and fertility. Future experiments will determine whether ARC Kiss1 deletion disrupts the KNDy-driven negative feedback response of LH to gonadectomy, as well as address potential sex differences in ARC Kiss1-mediated negative feedback control of LH release.
MON-385 Insulin Resistance and Osteoporosis in People Living with HIV
Authors: Premaor Melissa Orlandin , Caeran Gabriela , Almeida Luciana , Carvalho Jose , Stein Carolina , Moresco Rafael , Haygert Carlos , Comim Fabio Vasconcellos 
Published: May 2020

Abstract
The life expectancy of people living with HIV (PLHIV) increased considerably after the advent of antiretroviral therapy (ARV). Nowadays, it is almost the same as the general population. However, this increase in survival exposes PLVH to age-related morbidities, including chronic metabolic and bone diseases. PLHIV has a low bone mineral density (BMD) and a high prevalence of osteoporosis. Moreover, the frequency of diabetes mellitus (DM) seems to be twice the frequency of the general population. Insulin resistance and DM might be associated with bone diseases in PLHIV. Our study aim was to evaluate the association between insulin resistance and osteoporosis in PLHIV. We carried out a cross-sectional study at the municipality of Santa Maria, South Brazil. PLHIV age 50 yrs or over on treatment with ARV were included. All subjects registered to receive ARV in the university hospital during the period 2016 to 2018 were invited to participate. Those who accepted responded to a standardized questionnaire, performed a bone density scan and a lateral spinal X-ray, underwent peripheral blood collection, and had their weight and height measured. Insulin resistance was considered present when HOMA-IR&gt; 2.7 (Gelonese, 2009). The TyG index was also calculated (VASQUES, 2011). Of the 101 PLHIV who agreed to participate, 84 underwent both insulin and BMD measurements. The prevalence of osteoporosis was 19%. Vertebral fractures were twice as frequent in individuals with osteoporosis (73.3% vs. 36.5%, p = 0.018). Participants with osteoporosis had lower BMI and triglyceride values than those without it. The frequency of insulin resistance calculated by HOMA-IR was 68.2%, and it was associated with glucocorticoid use, smoking, and BMI. HOMA-IR [4.8(6.6) vs. 8.68(9.6), p =0.013], and TyG [5.0(0.3) vs. 5.2 (0.4), p=0.029] mean values were lower in the group with osteoporosis; however, this association disappeared after correction for BMI in the logistic regression model. In conclusion, in our study, PLHIV with osteoporosis have lower insulin resistance than PLHIV without it. Nevertheless, this finding appears to be relating to a lower BMI. Further studies are needed to assess the effect of insulin resistance on fracture risk in PLVH.
GELONEZE, B. et al. HOMA1-IR and HOMA2-IR indexes in identifying insulin resistance and metabolic syndrome: Brazilian Metabolic Syndrome Study (BRAMS). Arq Bras Endocrinol Metabol. 2009 Mar;53(2):281-7
VASQUES, A. C. et al. Análise Crítica do Uso dos Índices do Homeostasis Model Assessment (HOMA) na Avaliação da Resistência à Insulina e Capacidade Funcional das Células-C Pancreáticas. Arq. Bras. Endocrinol. Metab., 2008;52/1:32-39.
SAT-170 Clinical Course of Adrenal Myelolipoma: A Long-Term Longitudinal Follow-Up Study
Authors: Hamidi Oksana , Raman Ram Narayan , Lazik Natalia , Ariza-Iniguez Nicole , McKenzie Travis J , Bancos Irina 
Published: May 2020

Abstract
Myelolipoma is the second most common adrenal tumor. Yet, systematic approach to these tumors remains poorly defined. Thus, we aimed to describe natural history of myelolipoma and to identify predictors of tumor growth and need for surgery. We conducted a retrospective longitudinal follow-up study of consecutive patients with myelolipoma. A total of 321 myelolipomas (median size, 2.3 cm [range, 0.5-18.0]) were diagnosed in 305 patients at median age of 63 years (25-87). Most myelolipomas were discovered incidentally (86.6%), whereas others were discovered on imaging done for cancer staging (8.8%) or during workup of mass effect symptoms (4.6%). Median duration of follow-up was 54 months (range, 0.03-267). Compared with myelolipomas &lt;6 cm, tumors ≥6 cm were more likely to be right-sided (59% vs 41%, P=0.02), bilateral (21% vs 3%, P &lt;.0001), cause mass effects symptoms (32% vs 0%, P&lt;.0001), have radiographic hemorrhagic changes (14% vs 1%, P&lt;.0001), and undergo adrenalectomy (52% vs 5%, P&lt;.0001). There was no difference in sex or age at diagnosis between the groups. Hemorrhagic changes were noted in 9 (3.0%) patients with median tumor size of 7.0 cm (range, 1.8-18.0). Concomitant adrenal hormone excess was diagnosed in 12/126 (9.5%) patients. Primary aldosteronism was noted in 9 patients: due to concomitant ipsilateral (n=3) or contralateral adrenocortical adenoma (n=3), or bilateral idiopathic adrenal hyperplasia (n=3). Autonomous cortisol excess was noted in 3 patients: due to concomitant contralateral (n=2) or ipsilateral adrenocortical adenoma (n=1). Of 162 patients with ≥6 months of imaging follow-up, tumor size change ranged from -10 to 115 mm (median, 0 mm) and tumor growth rate ranged from -5.6 to 140 mm/year (median, 0 mm/year). Tumor growth ≥1.0 cm (n=26, 16.0%) was associated with larger initial tumor size (3.6 vs 2.3 cm, P=0.02) and hemorrhagic changes on imaging (12% vs 2%, P=0.007), compared with &lt;1 cm size change. Myelolipomas with ≥1.0 cm growth were more likely to undergo adrenalectomy (35% vs 8%, P&lt;.0001). Among 37 (12%) patients that underwent adrenalectomy for myelolipoma, surgical indications included: large tumor size/tumor growth (32%), diagnostic surgery (27%), mass effect symptoms (14%), concomitant ipsilateral tumor leading to hormonal excess (11%), acute hemorrhage (8%), and concomitant resection during non-adrenal surgery (8%). In conclusion, most myelolipomas are discovered incidentally, whereas myelolipomas ≥6 are more likely to cause mass effect symptoms, have radiographic hemorrhagic changes, and more commonly undergo resection. Hormonal excess is rare and is usually attributed to concomitant adrenocortical adenoma or hyperplasia. Tumor growth ≥1.0 cm is associated with larger myelolipoma and presence of hemorrhagic changes. Surgical resection should be considered in symptomatic patients with large tumors, evidence of hemorrhage, or tumor growth.
SUN-616 Poor Diagnostic Concordance Between Fasting Plasma Glucose and Glycosylated Hemoglobin in a Black South African Population
Authors: Wade Alisha N , Crowther Nigel , Gomez-Olive F Xavier , Wagner Ryan G , Manne-Goehler Jennifer , Berkman Lisa , Salomon Joshua A , George Jaya , Gaziano Thomas , Cappola Anne Rentoumis , Tollman Stephen 
Published: May 2020

Abstract
Background: While elevations in fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) are both recognized by the American Diabetes Association (ADA) as diagnostic of hyperglycemia, previous comparisons of these tests have demonstrated discordant individual classifications and population estimates. This may be due to additional postprandial glycemia reflected by HbA1c and, in African-descent populations, to non-glycemic factors that contribute to higher HbA1c at any given level of glycemia. We hypothesized that glycemic classifications based on FPG or HbA1c would differ in a Black South African population and investigated factors associated with discordance.
Methods: 889 Black adults with previously undiagnosed diabetes, aged 40-79 years, from the population-based Health and Ageing in Africa: a Longitudinal Study of an INDEPTH Community in South Africa (HAALSI) cohort were included. Concordance between ADA FPG (normoglycemia [NG] &lt;100 mg/dl, prediabetes [pre-DM] 100-125 mg/dl, diabetes [DM] ≥ 126 mg/dl) and HbA1c (NG &lt;5.7%, pre-DM 5.7-6.4%, DM ≥ 6.5%) classifications was assessed using Cohen’s kappa statistic and logistic regression models were used to identify predictors of discordance.
Results: Median age was 55 years (IQR 49-62) and 49.3% of the sample was male. Median glucose was 86.4 mg/dl and median HbA1c was 5.4%. Pre-DM, as defined by HbA1c, was present in 204 participants (22.9%), while FPG-defined pre-DM was present in 122 (13.7%). DM defined by HbA1c was present in 146 (16.4%), while FPG-defined DM was present in 36 (4.0%). Concordance between the two tests was poor (kappa statistic 0.18; 95%CI 0.13-0.24). Self-reported history of tuberculosis (OR 1.90, p=0.026) and higher HbA1c (OR 4.70, p&lt;0.001) were associated with increased likelihood of discordance, whereas higher fasting glucose was associated with decreased likelihood of discordance (OR 0.58, p&lt;0.001). There was no association between discordance and hemoglobin, HIV status, BMI, waist circumference or hip circumference.
Conclusion: FPG and HbA1c exhibit poor concordance in classifying hyperglycemia in this Black South African population, with HbA1c-based definitions identifying higher prevalences of pre-DM and DM. Further work is needed to confirm whether these discrepancies are due solely to elevations in postprandial glucose. In the interim, clinicians should consider confirming elevated HbA1c concentrations with oral glucose tolerance testing, particularly in those with a history of tuberculosis, prior to making a diagnosis of DM in this population.
SUN-384 A Dedicated Primary Fracture Prevention Program Decreased Low Trauma Hip Fracture Rates over Six Years
Authors: Grotzke Marissa Paige , Rosenblum Yanina 
Published: May 2020

Abstract
BACKGROUND: Improvements in secondary prevention of osteoporotic fractures are widely reported following the dissemination of Fracture Liaison Services, however, few models for the primary prevention of such fractures have been described. Available published data indicates osteoporosis screening rates in the United States, most significantly in men, remain consistently less than 20% (Cheng N, Green ME). We have previously published how an interdisciplinary Bone Health Team (BHT) improves screening and treatment initiation rates in the outpatient setting. Here we describe the changes in low trauma hip fracture hospitalizations in the six years since initiation of BHT screenings.
METHODS: The BHT began osteoporosis screening in February 2013. Hip fracture admission rates at our facility for each year starting in 2007 were assessed utilizing codes ICD 9 820*/ICD 10 S72.*; our facility is not a trauma center and receives no trauma injuries. Data was divided into a period from October 2007 to September 2013 and October 2013 to September 2019, the latter period based upon the average timeline from identification to treatment initiation and expected efficacy for the first screening group.
RESULTS: From October 2007 to September 2013 there were 216 individuals admitted with a new hip fracture diagnosis, representing 0.54% of the averaged 40,362 individuals served by our facility during that time. Ages ranged from 48 to 94 years, with 156 (72.2% of fractures; 0.39% of all individuals) of individuals meeting age-based screening criteria (aged ≥65 for women and ≥70 for men) at time of fracture. Nine individuals with hip fractures had greater than one discrete hip fracture, confirmed as separate by chart review.
From October 2013 to September 2019 there were 156 individuals admitted with a new hip fracture diagnosis, representing 0.37% of the averaged 46,327 individuals during that time. Ages ranged from 26 to 99 years. Of the hip fractures, 110 (70.5% of fractures) were in individuals meeting age-based screening criteria representing 0.24% of the averaged total individuals served and a 38.5% decrease (p&lt;0.0001) in hip fracture admissions when compared to the prior six years. One individual had greater than one discrete hip fracture, representing an 88.9% lower rate (p&lt;0.0001) of repeated fractures compared to the prior timeframe.
Men represented 355 (95.4%) of the 372 fractures seen from 2007 to 2019. CONCLUSION: A statistically significant decrease in hip fracture admission rates in women aged ≥65 and men ≥70 and in repeat hip fractures was observed in the 6 years since BHT inception compared to the 6 years prior.
MON-452 Poorly Differentiated Thyroid Carcinoma Metastatic to the Adrenal Gland
Authors: Mathias Priyanka , Manavalan Anjali , Aleksic Sandra , Bloomgarden Noah , Schubart Ulrich 
Published: May 2020

Abstract
Background: Poorly differentiated thyroid carcinoma (PDTC) constitutes 1-15% of all thyroid cancers.1 Invasive adrenal metastases secondary to PTDC are exceedingly rare.
Clinical Case: A 64-year-old woman with a non-toxic multinodular goiter presented with right upper quadrant abdominal pain and distension for three months. CT imaging revealed a 13.5 cm right suprarenal retroperitoneal mass invading the liver and inferior vena cava (IVC), concerning for adrenocortical carcinoma. She underwent resection of the mass with en block right adrenalectomy, partial hepatectomy, and IVC resection. Pathology demonstrated metastatic thyroid cancer with necrosis of the adrenal gland and IVC. Immunohistochemical staining was positive for PAX8, TTF1, and thyroglobulin (Tg). Completion thyroidectomy revealed an encapsulated 2 cm focus of PDTC with Hurthle cell phenotype in the right thyroid lobe. The mitotic activity was 5/10 per HPF. There were focal areas of tumor necrosis, 3 foci of capsular invasion, and extensive angioinvasion. Surgical margins were free of tumor invasion. Eight resected lymph nodes were negative for malignancy (Stage T1bN0M1; AJCC 8, Stage IVb). Genetic testing was positive for somatic mutations of NRAS, TERT, PTEN, and GNAS with broad copy number loss on chromosome 22q conferring aggressive tumor behavior.3
MRI of the brain and spine ruled out additional metastases. A radioactive iodine (RAI) whole-body scan (WBS) showed residual uptake of 7.6% in the right thyroid bed and a focus of increased uptake at the right sternoclavicular joint. A therapeutic dose of 206 mCi of I-131 was administered. A post-therapy WBS demonstrated focal activity in the right thyroid bed, distal right clavicle, and lower lung lobes. Chest CT and MRI of the right shoulder revealed no structural evidence of metastases corresponding to radiotracer uptake. The stimulated Tg level prior to RAI was 323 ng/mL with a TSH of 66 uU/mL (0.4-4.6 uU/mL). Tg antibodies were undetectable. She was maintained on 150 mcg of levothyroxine with the goal of TSH suppression. Tg levels declined to 4.8 ng/mL at three months, and to 0.3 ng/mL eight months post-RAI.
Discussion: PDTC is an aggressive thyroid cancer subtype with distant metastasis reported in 36-85% of cases.2 Distant metastasis is predictive of poorer outcomes, with patients three times more likely to die from the disease than those without metastatic disease.1 Adrenal metastasis of thyroid cancer is rare, and unlike in our patient, usually asymptomatic and frequently detected on a post-therapy scan. Despite a dramatic response to therapy, given the poorly differentiated features of the primary tumor, a whole-body PET-CT is warranted to evaluate for RAI refractory disease.
References:
1. Ibrahimpasic T et al. J Clin Endocrinol Metab. 2014;99(4):1245-52.
2. Sanders EM Jr et al. World J Surg. 2007;31(5):934-45.
3. Cheng DT et al. J Mol Diagn. 2015;17(3):251-64.
MON-260 Sinonasal Papilloma Masquerading as a Pituitary Macroadenoma
Authors: Cohen Melissa , Wilson John , Toft Daniel Joseph 
Published: May 2020

Abstract
Background: Sinonasal tumors are rare, with annual worldwide incidence of approximately 1 in 100,000, and are not commonly considered in the differential diagnosis of pituitary tumors (1). Sinonasal tumors are well known for their invasiveness, tendency to recur and association with malignancy. We present a case of sinonasal papilloma presenting as a large suprasellar mass.
Clinical Case: A 61 year-old male with a past medical history including type 2 diabetes mellitus presented with chief complaints of headaches and visual disturbances over the past 6 months. Prior to admission he experienced episodes of left eye midline deviation associated with diplopia. New onset dysphagia associated with leftward tongue deviation prompted him to seek medical attention. The social history was notable for chemical exposures in his work at a hair salon; he is sexually active with his husband. He has had no sexually transmitted infections and has been vaccinated against human papilloma virus (HPV). CT of the brain showed a large sellar mass.
A subsequent MRI of the pituitary demonstrated a large destructive mass centered on the clivus elevating the pituitary gland into the suprasellar cistern. The mass measured 6 cm x 4.5 cm in the axial plane with displacement without invasion of the cavernous sinuses. The mass extended anteriorly into the ethmoid sinuses and extended posteriorly into the prepontine cistern displacing the basilar artery.
Pituitary hormonal analysis included a 250 mcg Cosyntropin stimulation test resulting with a random cortisol of &lt;1.0 ug/dl rising to 17.7 ug/dl following Cosyntropin administration. Additional anterior pituitary results included FSH of 3.8 mIU/ml (1.5-14 mIU/ml), LH of 1.3 mIU/ml (1.4-7.7 mIU/ml), total testosterone of 230 ng/dl (300-700 ng/dl), and prolactin 11.1 ng/ml (2.6-13 ng/ml).
Ophthalmology was consulted for visual field testing which proved normal, however a partial left cranial nerve VI palsy was noted likely secondary to cavernous sinus involvement. A biopsy of the sellar mass was obtained by bedside nasal endoscopy. The initial biopsy was consistent with a non-dysplastic, inverted sinonasal papilloma with negative HPV and P16 serologies. The patient underwent resection of the pituitary mass, with surgical pathology showing superficially invasive squamous cell carcinoma arising from sinonasal papilloma.
Conclusion: This is one of the very few cases reported in the literature of a sinonasal papilloma masquerading as a pituitary mass. Sinonasal papilloma should be considered when evaluating large destructive suprasellar tumors. Although a benign tumor, the local aggressiveness of sinonasal papilloma and the potential to give rise to squamous cell carcinoma highlights the significance of identifying this lesion.
SUN-391 Denosumab Treatment of Patients with Osteoporosis and Idiopathic Hypercalciuria
Authors: Chu Winston S , Chu James W 
Published: May 2020

Abstract
Background: Idiopathic hypercalciuria (IHC) is associated with reduced bone mineral density (BMD) and higher risk of osteoporotic fractures. Denosumab is a RANK-ligand inhibitor that prevents osteoporosis-related fractures. No previous published studies have specifically evaluated denosumab treatment of osteoporosis patients with IHC.
Methods: Retrospective chart review from a private endocrinology clinic identified 31 consecutive patients with osteoporosis (prior fragility fracture and/or t-score ≤-2.5 on bone density scan) with concomitant diagnosis of IHC (defined as urine calcium &gt; 4.0 mg/kg weight/d when intaking low-moderate calcium amounts), who had received at least 3 denosumab injections. Comparisons were made for BMD measurements determined by dual-energy x-ray absorptiometry done before denosumab initiation, and after the latest dose.
Results: There were 28 women and 3 men, with average age of 71.9 ± 8.9 years. 20 subjects had prior total of 31 fragility fractures. Baseline 24-hr urine calcium was 331 ±65 mg/day. Average exposure to denosumab therapy was 9.0 ± 4.8 doses. 27 of these patients received concomitant thiazide diuretics during the course of their denosumab therapy. Baseline t-scores were -2.4 ± 0.8 at lumbar spine, -1.5 ± 0.7 at total hip and -1.8 ± 0.5 at femoral neck. After denosumab therapy, the t-scores were respectively -1.9 ± 0.9, -1.3 ± 0.8 and -1.6 ± 0.7. Mean increases in BMD were seen at the lumbar spine of 6.2 ± 8.4%, at the total hip of 3.2 ± 6.0%, and at the femoral neck of 2.5 ± 8.0%
19 patients were considered to have (+) BMD responses, based on consistent increases in BMD and/or t-scores across all spine and hip sites. 4 patients had (-) BMD responses, based on decreased BMD and/or t-scores across all sites. 6 patients had mixed responses and 2 did not have comparative BMD data. Baseline urine calcium did not seem to correlate with clinical responses. Those patients with longer duration of thiazide and/or denosumab use had higher likelihood of (+) BMD responses. However, during the course of follow-up, 4 subjects suffered 7 fragility fractures while treated with denosumab: 3 with (+) and 1 with (-) BMD responses.
Conclusion: Denosumab can effectively increase BMD in a cohort of osteoporosis patients with IHC, the majority of whom also received thiazide. However, increased BMD response did not necessarily predict lower risks of fragility fractures. Further research needs to evaluate the role of denosumab therapy in such high-risk patients.