bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT-365 Severe, Symptomatic Hypocalcemia Due to Denosumab and Vitamin D Deficiency in an Osteopenic Post-Menopausal Female
Authors: Berquist John , Kaplan Jason , Zazaian Andrew 
Published: May 2020

Abstract
BACKGROUND: Denosumab is a monoclonal antibody used in the treatment of osteoporosis to prevent bony injuries by increasing bone density. It has a very rare side effect of severe hypocalcemia (1) and a patient should take supplemental Vitamin D and calcium for prevention. There is debate among experts on when denosumab should be discontinued and if so, whether an alternative therapy should be started (2).
Case Report: A female in her 8th decade of life presented to the ED with a complaint of intermittent and diffuse numbness and confusion. She had a history of MGUS and osteoporosis; however, her most recent SPEP did not detect MGUS and her most recent bone scan showed a T score indicating osteopenia. She had been receiving denosumab for the past four years with her last injection three weeks prior. Physical exam revealed 5/5 strength and intact sensation in all four extremities. Her serum calcium level on presentation was 4.3 mg/dL (8.5-10.1), ionized calcium was 3.9 mg/dL (4.6-5.4), 25 Hydroxy Vitamin D 8.8 ng/ML (30-100), and intact PTH was appropriately elevated at 702.7 pg/mL (14.0-72.0). Her phosphorus level was also appropriately low at 2.1mg/dL (2.5/4.9). She had a serum creatinine level of 0.9 mg/dL (0.6-1.0) and an eGFR 63 mL/min. ECG showed normal sinus rhythm without any QT changes. She received 4 grams of calcium gluconate intravenously over the next 24 hours without improvement in her calcium, as trending chemistries continually showed a calcium level less than 5.0. She was started on a calcium gluconate continuous infusion along with calcitriol, Vitamin D3 5,000 IU per day, and oral calcium 500 mg with Vitamin D 600 IU three times daily. Her calcium levels improved, albeit still low, to 6.5 mg/dL and the calcium continuous infusion was stopped. A 1, 25-Dihydroxy Vitamin D level showed improvement as well resulting at 82 pg/mL (20-79). Her numbness and confusion symptoms resolved, and she was discharged on the aforementioned oral calcium and vitamin D regimen with instructions to follow up and discontinue use of denosumab.
Conclusion: There are two primary takeaways from this clinical case. The first is to ensure a patient receiving denosumab is also taking supplemental Vitamin D and calcium to prevent hypocalcemia and to periodically measure serum levels to rule out deficiency. The second is the emphasis on having a provider-patient discussion on alternative therapies when the patient may no longer be a candidate for denosumab while considering the patient’s risk for fracture.
References:
Bone, Henry G. et al. 10 years of denosumab treatment in postmenopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trail and open-label extension. Lancet Diabetes Endocrinology. 2017. 5: 513-23
Tsourdi, E. et al. Discontinuation of Denosumab therapy for osteoporosis: A systematic review and position statement by ECTS. Bone 2017. 105: 1-17.
SUN-424 Treatment of Antithyroid Drug-Induced Agranulocytosis with Granulocyte Colony-Stimulating Factor: A Meta-Analysis
Authors: Santos Maria Regina C , Lim Christian Emmanuel T , Javier Ramon Jason M , Calavera Alma R 
Published: May 2020

Abstract
BACKGROUND: Hyperthyroidism, a common condition seen by physicians, is predominantly treated with antithyroid drugs. Agranulocytosis, a potentially fatal complication, is their most serious side effect. Conflicting studies are present between the risks and benefits of the use of exogenous granulocyte colony-stimulating factor (G-CSF) in its treatment, since its pathogenesis has not been established. The objective of this study is to determine the benefit of G-CSF in antithyroid drug-induced (ATD) agranulocytosis, through a meta-analysis.
Methods: Studies were included after extensive literature search in five electronic databases; all met the inclusion and exclusion criteria, and were critically appraised. The primary outcome was days to hematologic recovery, defined as neutrophilic rise to &gt;0.5 x 109/L. Data were treated as continuous data, obtaining the standard mean difference through a Forrest Plot using the Review Manager 5.3 application.
Results: Five of the studies were non-concurrent cohort, while one was a randomized clinical trial. The duration of the studies was from 1970s to 2014. Age range of the population was from 8 to 87 years old, with more females. G-CSF dose ranged from 75 to 300ug/day, injected subcutaneously or intramuscularly. Primary outcome measured common to all the studies included hematologic recovery. Five of the six studies showed shorter number of days to hematologic recovery for the treatment group compared to the control group (with a standardized mean difference of 1 day, confidence interval (CI) of 0.45 to 1.54).
Conclusion: Exogenous G-CSF administration in ATD agranulocytosis contributed to faster hematologic recovery in terms of days, shortening recovery by a mean of 1 day.
References:
1. Tamai, H., et al. Treatment of methimazole-induced agranulocytosis using recombinant human granulocyte colony-stimulating factor (rhG-CSF). J Clin Endocrinol Metab.
1993;77(5):1356-1360.
2. Andres, E., et al. Haematopoietic growth factor in antithyroid-drug-induced agranulocytosis. Q J Med. 2001;94:423-428.
3. Fukata, S., Kuma, K., Sugawara, M. Granulocyte colony-stimulating factor (G-CSF) does not improve recovery from antithyroid drug-induced agranulocytosis: a prospective study. Thyroid. 1999;9(1):29-31.
4. Tajiri, J., Noguchi, S. Antithyroid drug-induced agranulocytosis: how has granulocyte colony-stimulating factor changed therapy? Thyroid. 2005;15(3):292-297.
5. Watanabe, N., et al. Antithyroid drug-induced hematopoietic damage: a retrospective cohort study of agranulocytosis and pancytopenia involving 50,385 patients with Graves’ disease. J Clin Endocrinol Metab. 2012;97(1):E49-E53.
6. Clauna-Lumanta, M.M., Yao, C., Bolinao, J.F. The effects of GCSF on the recovery time and duration of hospitalization in patients with anti-thyroid drug-induced agranulocytosis in a tertiary hospital. JAFES. 2016;31(2):131-136.
SUN-091 Change in Sex of Rearing in Individuals with Disorders of Sex Development
Authors: Knoll Michele , Egan Anna , Strickland Julie , Gatti John , Koenig Joel , Jacobson Jill Diane 
Published: May 2020

Abstract
Introduction: Differences of Sex Development (DSDs) encompass variations in formation of internal or external sex characteristics. Historically, sex assignment in children with DSDs depended on phenotype, and gender was thought to be malleable. Attention in DSD has recently shifted toward reducing gender dysphoria and preserving fertility potential. Our multidisciplinary DSD clinic was formed in 2008 with these goals and includes specialists from Endocrinology, Gynecology, Urology, Psychology, Social Work, Genetics, and Chaplaincy.
Subjects: A chart review was done on all patients seen in our DSD clinic between April 2008 and June 2019 to determine rates of sex reassignment and gender dysphoria. Two hundred patients were seen: 23 were found to not have DSDs; 61 were 46,XX; 66 were 46,XY; 31 had a sex chromosome DSD; 5 had gonadal dysgenesis without known chromosome mosaicism; and 14 had syndromic genital atypia. Mean age of follow-up is 8.77 years.
Results: Only 2 patients underwent sex reassignment at our institution. One was assigned male at birth, but was found to be 46,XX with 21-hydroxylase deficiency and was reassigned female at 1 month of age. The second was assigned male at birth and was found to be 46,XY with an NR5A1 variant. Sex was reassigned female at two months of age. Two additional patients had a sex reassignment outside our institution. One was born abroad and assigned male at birth. The patient was found to be 46,XY with an NR5A1 variant, and was reassigned female. The second patient was assigned male at birth, but was found to be 46,XX with P450 oxidoreductase deficiency. The parents changed the sex of rearing to female at 19 months of age. To date, none has signs of gender dysphoria.
A total of three patients experienced gender dysphoria and underwent transition. The first had genital ambiguity with sex chromosome mosaicism in the gonads and was assigned female at birth. We held care conferences with the family and discussed the possibility of gender dysphoria. At age 3, the patient declared that he was male, and parents socially transitioned him at that time. Two were assigned female after receiving the diagnosis of 46,XX 21-hydroxylase deficiency. Both declared male gender identity later, one at 12.5 years of age, and one at 20.5 years of age.
Conclusion: Whereas our patient population is still relatively young, it is reassuring that the overall rate of gender dysphoria is low. The rate in patients with CAH is similar to previous reports in the literature. Careful attention to sex assignment in early childhood may reduce the rates of gender dysphoria in children with DSDs.
SUN-222 Pre- and Post-Pubertal Reference Ranges for Oxygenated Androgens in Saliva
Authors: Adaway Joanne , Eisenhofer Graeme , Huebner Angela , Krone Nils , McTaggart Malcolm , Peitzsch Mirko , Keevil Brian George 
Published: May 2020

Abstract
Oxygenated androgens such as 11 β-hydroxyandrostenedione (11OHA4) and 11-ketotestosterone (11KT) contribute significantly to the androgen pool in humans and their measurement has been shown to be useful in diagnosing disorders such as polycystic ovarian syndrome or premature adrenarche and also in monitoring treatment of congenital adrenal hyperplasia, alongside the classical androgens. Their measurement in saliva is particularly advantageous due to the non-invasive nature of sampling, meaning samples can easily be taken regularly to monitor treatment; however reference range data is not currently available for 11OHA4 and 11KT, limiting their clinical use. These analytes were measured in saliva samples from pre and post-pubertal males and females to inform reference ranges for these analytes. Samples collected into salivettes as part of the PRIMMS study (Technische Universität Dresden) were used for this work. A total of 130 samples (35 from pre-pubertal females, 43 from post-pubertal females, 42 from pre-pubertal males and 20 from post-pubertal males) were analysed for 11OHA4 and 11KT by LC-MS/MS. The ages of the participants ranged from 3.77 to 14.0 years in the pre-pubertal samples and 13.9-17.9 years in the post-pubertal samples. Pubertal status was determined clinically. The upper cut-off of the reference interval for 11OHA4 was 560 pmol/L in pre-pubertal females and 590 pmol/L in males, whilst 11KT had an upper limit of 216 pmol/L in females and 205 pmol/L in males. The upper limits of the ranges were higher in post-pubertal samples, with ranges of up to 1542 pmol/L in females and 1775 pmol/L in males for 11OHA4; the ranges for 11KT were up to 654 pmol/L for post pubertal females and 585 pmol/L for post-pubertal males. The data shows, as expected, a rise in the 11 oxygenated androgens post puberty. The upper limits of reference intervals for both analytes were very similar in males and females both pre- and post pubertally. These data can be used to inform clinical interpretation of the 11-oxygenated androgens; further work is required with larger cohorts of samples to develop more robust reference ranges.
SUN-208 The Intra-Individual Variability of 11-Ketotestosterone and 11β-Hydroxyandrostenedione
Authors: Hawley James , Keevil Brian George 
Published: May 2020

Abstract
Background
Emerging evidence has suggested the 11-oxygenated steroids may be important in the diagnosis and monitoring of hyperandrogenism. Two in particular, 11-ketotestosterone (11KT) and 11β-hydroxyandrostenedione (11OHA4) have been implicated in polycystic ovary syndrome, congenital adrenal hyperplasia, precocious puberty and castration resistant prostate cancer. Despite the interest in these analytes, some of their more fundamental properties have yet to be determined. At present, no data is available that quantifies the biological variation of 11KT and 11OHA4 within individuals over time, this may be important as we look to establish normative reference ranges for these potentially useful analytes.
Objective
Here we sought to define the intra-individual variability of 11KT and 11OHA4 in serum using LC-MS/MS.
Method
Blood was collected from 18 healthy volunteers (8 males, 10 females) on the same day each week over a 10 week period using standard venepuncture technique. After collection, the samples were centrifuged within 1 hour, aliquoted and stored at -20°C (-4°F) prior to analysis. All samples from individual volunteers were analysed by LC-MS/MS in triplicate within the same batch so as to limit analytical variability.
Results
The mean analytical coefficient of variation (CV%) for the triplicate analysis was 3.2% for 11KT and 3.7% for 11OHA4. No significant difference was observed between the variability of 11KT concentrations in the male and female cohorts; total intra-individual variation for 11KT was 18.0%. Concentrations of 11OHA4 were more variable in the male cohort when compared to the female cohort. This was reflected by differences in their respective intra-individual variations of 32.5% vs 24.8%.
Summary
Intra-individual variation is an important consideration when interpreting patient results. Concentrations of 11KT were tightly regulated in both the male and female cohorts with no clear demarcation between the two groups. Although concentrations of 11OHA4 were prone to greater variation over the 10 week period, considerable overlap was observed between the male and female subjects. Our data suggests that 11KT and 11OHA4 concentrations are not significantly affected by the menstrual cycle.
SUN-052 Effects of Cross-Sex Hormone Therapy on Lipid Metabolism in Transgender Women and Men
Authors: Kelley Carly , Coviello Andrea D 
Published: May 2020

Abstract
Sex hormone therapy in cisgender persons (i.e. postmenopausal women and hypogonadal men and women) leads to changes in lipid metabolism and weight, but it is unclear to what extent this occurs in transgender persons receiving higher doses of cross-sex hormone therapy (CSHT) for the purpose of gender transition.Objective: To determine changes in lipid metabolism among transgender women (TW) and transgender men (TM) on CSHT.Methods: We conducted a retrospective chart review of patients identified at a transgender-specific clinic within an academic medical center. Data were collected on age, ethnicity, hormone therapies, lipid lowering therapy (LLT), surgical status, lipid panel, A1C, LFTs, BMI, and weight before and after initiation of HT. Patients on stable LLT were included but those with LLT initiated after baseline observation were excluded. Changes from baseline to post CSHT in TW and TM groups were evaluated with paired t-tests.Results: We identified 18 TW and 22 TM for whom laboratory data were available. Mean±SD age of TW was 33±13 years and for TM was 28±12 years; the majority (78%) were Caucasian. Mean±SD duration of HT in TW was 10.1±4.5 months and in TM 6.7±4.4 months. No patients had undergone gonadectomy at any time prior to or during the data collection period. One TW and one TM were on stable LLT during the observation period. All TW were treated with estradiol (78% oral, 11% patch) and spironolactone. In TW, there was a significant 10% increase in HDL from 48±17 mg/dl to 53±15 mg/dl (p=0.02) but there were no significant changes in other lipid fractions, A1c, or weight/BMI. The majority of TM (82%) were treated with weekly intramuscular testosterone-esters injections and the remainder with daily testosterone gel. More substantial and unfavorable metabolic changes occurred in the TM with a 15% decrease in HDL from 55±15 mg/dl to 47±10 mg/dl (p=0.004), increase in A1c from 5.07±0.45% to 5.22 ± 0.39%(p=0.04), increase in BMI from 29±10 kg/m2 to 31±10 kg/m2 (p=0.002), and a trend toward increased triglycerides (96±64 mg/dl to 110±80 mg/dl, p=0.07). Hemoglobin and hematocrit significantly increased in TM but there was no significant change in LFT in either group. Limitations include lack of data on body composition to determine relative changes in adipose tissue or muscle mass in relation to weight changes and small sample size.Conclusion: Our study suggests that CSHT has a neutral to slightly favorable impact on lipid metabolism in TW and a negative impact on lipids and glucose in TM. Larger, prospective studies are needed to determine whether these changes persist over the longer duration of CSHT and whether this translates to an increased risk of cardiovascular disease and mortality. Clinicians should inform TM patients about these potential negative effects of CSHT on lipid metabolism so that their patients can adopt healthy lifestyle interventions early on to optimize their cardiovascular risk.
SUN-651 Murine Cecal Ligation and Puncture (CLP) Perturbs Phosphorylation of Insulin Receptor Substrate 2 (IRS-2)
Authors: Mathew Deepa , Barillas Julia , Fernandes Tiago , Kelly Alexander , Yaipen Omar , Abraham Mabel , Deutschman Clifford 
Published: May 2020

Abstract
Hyperglycemia is a characteristic finding in sepsis, and its presence worsens outcome (1). Patients with sepsis need larger doses of insulin to reduce glucose levels. This abnormality has been termed “insulin resistance” but the molecular mechanism by which sepsis attenuates the insulin signaling pathway is unknown. Previous work has shown impairment of phosphorylation in several intracellular signaling pathways following CLP, a well-validated murine model of sepsis (2). Phosphorylation of tyrosine in IRS-2 is essential for functional insulin signaling in hepatocytes (3). Therefore the aim of this study was to investigate the effects of CLP on IRS-2 phosphorylation.
Hypothesis: CLP attenuates phosphorylation of IRS-2.
Methods: All studies were approved by the Feinstein IACUC and conformed to ARRIVE guidelines. CLP was performed on C57Bl6 mice. Before CLP, animals were identified for sacrifice at specific post-procedure time points. To stimulate phosphorylation of IRS-2, insulin was injected in control and CLP mice at 24 and 48 hours post CLP. Following sacrifice, protein was isolated from liver tissue. Protein abundance was determined using immunoblotting. The detection of the phosphorylated form of these proteins was determined by enzyme-linked immunosorbent assay (ELISA) with a phospho-insulin receptor antibody. Statistical significance was determined using ANOVA for repeated measures with a Sidak post-hoc correction.
Results: Relative to the control, tyrosine phosphorylation of IRS-2 was significantly (p&lt;0.05) reduced at 24 and 48 hours following CLP.
Conclusions: Tyrosine phosphorylation of hepatic IRS2 is attenuated at early time points following CLP. These results are consistent with other studies examining the effects of CLP on intra-cellular signal transduction pathways (1). Further, these results provide evidence that changes in the insulin signaling transduction underlie CLP-induced “insulin resistance”.
References: (1) Abcejo et al., Crit Care Med. 2009;37(5):1729-1734. (2) van den Berghe et al, NEngl J Med. 2001;345(19):1359-1367. (3) Valverde et al., Diabetes 2003 Sep; 52(9): 2239-2248.
OR09-06 HNRNPA2B1 Mediates Endocrine-Sensitivity and Alters PSAT1 in Breast Cancer Cells
Authors: Klinge Carolyn M , Piell Kellianne M , Clem Bran F , Petri Belinda J 
Published: May 2020

Abstract
Higher expression of the RNA binding protein HNRNPA2B1 (Heterogeneous Nuclear Ribonucleoprotein A2/B1), a reader of the N(6)-methyladenosine (m6A) mark in transcribed RNA, is found in endocrine-resistant, estrogen receptor (ERα)+ LCC9 and LY2 breast cancer cells derived from MCF-7 endocrine-sensitive luminal A cells (1). HNRNPA2B1 interacts with DGCR8 in the DROSHA complex to promote processing of pri-miRNAs to pre-miRNAs. We identified HNRNPA2B1-regulated miRNAs by RNA seq and target pathways, including serine family amino acid metabolic processes, TGFβ signaling, response to estrogen, and cell junction by MetaCore enrichment pathway analysis (1). Stable 4.5-fold overexpression of HNRNPA2B1 in MCF-7 cells (MCF-7-A2B1 cells) results in ablation of growth inhibition by 4-hydroxytamoxifen (4-OHT) and fulvestrant. This was not due to loss or decrease of ERα; in fact, ERα was increased ~ 1.6-fold. Conversely, transient knockdown of HNRNPA2B1 expression in LCC9 and LY2 cells sensitized the cells to growth inhibition by 4-OHT and fulvestrant, without changing ESR1 expression. MCF-7-A2B1 cells showed increased migration, reduced E-cadherin and increased vimentin, suggestive of EMT; however, they exhibited reduced clonogenic survival. Follow-up on the identification of HNRNPA2B1-miRNA regulation of the serine pathway revealed higher expression of phosphoglycerate dehydrogenase (PHGDH) and phosphoserine aminotransferase (PSAT1) transcripts and proteins in LCC9, LY2, and MCF-7-A2B1 compared to MCF-7 cells. We identified two miRNAs, miR-424-5p and miR-145-5p downregulated in MCF-7-A2B1 cells that directly targeted the PSAT1 3’UTR in dual luciferase assays. Lower miR-424-5p and miR-145-5p in endocrine-resistant LCC9 and LY2 correlate with increased PSAT1 and higher PSAT1 is associated with reduced overall and metastasis-free survival in breast cancer patients. Overall, our data suggest a role for increased HNRNPA2B1 in tamoxifen-resistance. Reference: (1) Klinge CM, Piell KM, Tooley CS, Rouchka EC. HNRNPA2/B1 is upregulated in endocrine-resistant LCC9 breast cancer cells and alters the miRNA transcriptome when overexpressed in MCF-7 cells. Sci. Rep. 2019; 9:9430.
SAT-162 Potential Diagnostic Use of a Steroid Profile in Patients with Poorly Controlled Diabetes Mellitus
Authors: Fecteau Kellie , Giori Luca , Esteller-Vico Alex , Eiler Hugo 
Published: May 2020

Abstract
Cushing’s syndrome may contribute to insulin resistance and impaired insulin secretion in patients with diabetes mellitus. The prevalence of Cushing’s syndrome in human patients with type II diabetes mellitus has been reported as high as 9.4% (1), and prevalence of diabetes mellitus as a complication of Cushing’s syndrome has been reported as high as 50% (2). In our laboratory, evaluation of steroid profiles (analysis of cortisol, progesterone, 17-hydroxyprogesterone, androstenedione, estradiol, testosterone, and aldosterone at baseline and post-ACTH) in 3,600 dogs over 2 years revealed 2% to 8% of dogs with diabetes mellitus had concurrent hyperadrenocorticism. These steroid profiles in dogs with uncontrolled diabetes mellitus, despite insulin therapy, implicated elevated estradiol, progesterone, and 17-hydroxyprogesterone concentrations, with or without elevated cortisol, as probable contributors to poor control of glycemia. It has been reported that high doses of estradiol can decrease expression of insulin receptors in target tissues (3) and progesterone can decrease GLUT 4 expression in target tissues and modulate beta cell proliferation in the pancreas (4), thereby contributing to insulin resistance and possibly insulin secretion. In human patients, decreasing cortisol concentration in Cushing’s syndrome improves the glycemic state in many, but not all gain normoglycemia (5). It is suspected, that for some human patients, cortisol is not the only steroid involved in hyperglycemia and a steroid profile may be a useful diagnostic tool for investigating other steroids contributing to insulin resistance. References: (1) Nieman, Endocrinol Metab Clin N Am. 2018; 47:259-273. (2) Giordano et al., Eur J Endocrinol. 2014; 170:311-319. (3) Gonzalez et al., Steroids. 2002; 67:993-1005. (4) Branisteanu et al., TRENDS Endocrinol Metab. 2003; 14:54-56. (5) Rogowicz-Frontczak et al., Endokrynol Pol. 2017; 68:334-342.