bluuebunny/crossref_metadata_2025_split huggingface dataset:
OR08-06 Adjuvant Radiation Therapy Is Not Associated With A Survival Benefit After R0 Resection In Non-Metastatic Adrenocortical Carcinoma
Authors: Lee-Saxton Yeon Joo , Egan Caitlin E , Marshall Teagan E , Tumati Abhinay , Beninato Toni , Zarnegar Rasa , Fahey Thomas J , Finnerty Brendan M 
Published: October 2023

Abstract
Disclosure: Y.J. Lee-Saxton: None. C.E. Egan: None. T.E. Marshall: None. A. Tumati: None. T. Beninato: None. R. Zarnegar: None. T.J. Fahey: None. B.M. Finnerty: None.
Introduction: The benefit of adjuvant radiation therapy (RT) in adrenocortical carcinoma (ACC) is not well characterized, particularly for those who undergo initial R0 surgical resection without evidence of metastatic disease. We aimed to identify factors associated with administration of adjuvant RT in these patients, and to determine the association between adjuvant RT and overall survival in patients with non-metastatic ACC who underwent R0 surgical resection. Methods: The National Cancer Database was queried for histologic codes denoting ACC from 2004-2018. Patients who underwent R0 resection without evidence of metastatic disease were included and placed into two cohorts - those who underwent adjuvant RT and those who did not. Patients with incomplete or unknown data regarding clinically relevant variables were excluded from analysis. A multivariable logistic regression was performed to identify predictors of adjuvant RT administration. A multivariable Cox regression was performed to identify factors associated with overall survival (OS). Kaplan-Meier survival estimates and log-rank test were also performed to assess the impact of adjuvant RT on OS. Results: 388 patients were identified: 51 (13.1%) patients received adjuvant RT, while 337 (86.9%) did not. Adjuvant chemotherapy administration was the only factor associated with administration of adjuvant RT (OR 6.45, 95% CI 3.02 - 13.8, p&lt;0.001). No significant difference was observed between the Kaplan-Meier survival estimates of the two cohorts (p=0.54). After adjusting for patient characteristics including age, sex, co-morbidity index, race, receipt of chemotherapy, and tumor characteristics including tumor size, tumor grade, pathologic tumor stage, and pathologic nodal stage, adjuvant RT was not associated with improved OS in patients who underwent R0 resection (HR 1.01, 95% CI 0.63 - 1.60, p=0.98). However, tumor size &gt;6cm (HR 1.54, 95% CI 1.03 - 2.32, p=0.04), high tumor grade (HR 3.46, 95% CI 1.83 - 6.55, p&lt;0.001), and pathologic N1 stage (HR 2.30, 95% CI 1.06 - 4.94, p=0.03) were associated with worse OS in patients who underwent R0 resection. Conclusions: Treatment with adjuvant RT in patients with ACC who underwent R0 resection was not associated with an OS benefit. Further studies assessing optimal treatment for large and high-grade tumors with lymph node metastases are warranted.
Presentation: Friday, June 16, 2023
FRI410 ESR1 Variants Reduce Estrogen Receptor Alpha Expression In Women With Unexplained Infertility
Authors: Roman Robert A , Liu Haitao , Chorich Lynn Parson , Li Yin , Hall Janet Elizabeth , Diamond Michael P , Korach Kenneth Steven , Layman Lawrence Clarke 
Published: October 2023

Abstract
Disclosure: R.A. Roman: None. H. Liu: None. L.P. Chorich: None. Y. Li: None. J.E. Hall: None. M.P. Diamond: None. K.S. Korach: None. L.C. Layman: None.
Objective: Estrogen receptor alpha (ERα), encoded by ESR1, is vital to human reproduction. DNA sequencing previously identified four ESR1 missense variants of uncertain significance in 197 cisgender women with well-characterized unexplained infertility, including a p.Thr313Met variant with impaired estrogen signaling in vitro. The p.His6Tyr, p.Ser118Pro, and p.Arg269Cys ESR1 variants did not affect estrogen signaling. We hypothesize that milder ESR1 variants could decrease ERα expression in women with unexplained infertility.
Methods: Clinically identified ESR1 variant plasmids were constructed using site-directed mutagenesis and confirmed by Sanger sequencing. HepG2 cells were transiently transfected with either empty vector, wild type (WT) ESR1, p.His6Tyr, p.Ser118Pro, p.Arg269Cys, p.Thr313Met, or p.Gln375His (ESR1 missense variant control) estrogen receptor variant expression plasmids using Lipofectamine 3000 transfection reagent. Cell lysis was isolated from HepG2 cells 24 hours after transfection using RIPA lysis buffer. ERα expression was assessed by western blot fluorescence imaging and normalized to β-actin on LI-COR Odyssey DLx. Quantitative analysis was performed using Empiria Studio Software v.2.
Results: Western blot analysis showed that the ESR1 p.His6Tyr variant had 87% decreased and the p.Ser118Pro variant had 75.6% decreased expression compared to WT ERα in vitro. The p.Arg269Cys, p.Thr313Met, and p.Gln375His variants had comparable expression to WT.
Conclusion: Although the p.His6Tyr and p.Ser118Pro variant receptors have conserved estrogen signaling, our preliminary data show that they decrease ERα expression in vitro. This could be an underlying pathophysiologic mechanism affecting some women with unexplained infertility. Additional in vitro and in vivo analyses can further characterize their pathogenicity.
Presentation: Friday, June 16, 2023
FRI438 A Unique Case Of Secondary Hypogonadism And The Covid Booster Vaccine
Authors: Syed Omar Zia , Shakir Muhammad , Sajid Khadijah , Sood Aayushi , Bansal Nidhi 
Published: October 2023

Abstract
Disclosure: O.Z. Syed: None. M. Shakir: None. K. Sajid: None. A. Sood: None. N. Bansal: None.
38-year-old male with no past medical or surgical history presented for an evaluation of his low testosterone. The patient transports patients in the hospital, he denies any medication use, including steroids, opioids, and antibiotics. He has a biological 8-year-old son and denied any history of viral infection recently and denied any history of testicular trauma, mumps, or radiation therapy. He started having fatigue, chronic mild headache, and generalized weakness after receiving his third dose of covid vaccine in January, however, he denied any diplopia, galactorrhea, hirsutism, or sexual dysfunction. He did not report any side effects with the previous 2 covid vaccines. After a couple of months of persistent symptoms accompanied by 40 pounds of weight loss( half of which he regained in a few months without intervention), he went to his PCP for evaluation. On physical examination, there were no abnormalities seen and as per the patient, there was no change in testicular size either. The patient was found to have mildly elevated prolactin of 17.8 with low free and total testosterone of 134 accompanied by FSH of less than 1.0 and LH of 1.4. The remaining labs include but are not limited to CBC, CMP, TSH, Vitamin D, CK, Sex hormone-binding globulin, and cortisol. The autoimmune panel, Hepatitis, HIV, and tick panels were negative. While he was being worked up he tested himself multiple times for covid and was negative. The patient had an MRI done which did not show any mass or lesions. Furthermore, he also had a Chest x-ray and CT of his abdomen/pelvis along with an Ultrasound of the abdomen, which did not show any concerning findings. The patient was started on testosterone gel at the endocrinology clinic with regular follow-ups to assess for response and side effects.As per the currently available literature, there have been multiple associations made between Covid 19 infection and hypogonadism. There have been reports of low testosterone following covid 19 infections and conversely there have been worse outcomes of covid 19 related to men with lower levels of testosterone. This could possibly be due to ACE 2 expression on testicular cells or due to secondary inflammation and oxidative stress inhbitiing steroidogenesis. However no literature was found linking the covid 19 vaccine to secondary hypogonadim other than a case of pituitary apoplexy. These findings in light of our case warrant further research into possible association between the covid vaccine and hypogonadism. In patients presenting with generalized weakness and similar vague symptoms, we need to consider a history of covid vaccination as it could potentially be a cause of secondary hypogonadism. Furthermore, more detailed and larger-scale studies need to be done concerning the covid booster vaccines and hypogonadism.
Presentation: Friday, June 16, 2023
FRI439 Spermatogenesis Induction For Hypogonadotrophic Hypogonadism In An Australian Tertiary Hospital Andrology Service
Authors: Sarlos Stella , Herath Madhuni , Sim Ie-Wen , Upreti Rita , McLachlan Robert Ian , Allan Carolyn A 
Published: October 2023

Abstract
Disclosure: S. Sarlos: None. M. Herath: None. I. Sim: None. R. Upreti: None. R.I. McLachlan: None. C.A. Allan: None.
Infertility affects 8-12% of couples with male factors contributing to 50% and solely responsible in 20-30% of cases. Male infertility due to hypogonadotrophic hypogonadism (HH) is amenable to medical treatment. We report a series of 23 men treated for infertility from HH (congenital n=13, acquired n=10) with a median age of 33 years. Causes included panhypopituitarism (n=11) [empty sella (n=2), adenoma (n=3), craniopharyngioma (n=1), pituitary hypoplasia (n=3), CHARGE syndrome (n=1), cranial radiotherapy (n=1)], Kallmann syndrome (n=1), thalassaemia major (n=1) and idiopathic (n=10). Urinary or recombinant human chorionic gonadotrophin (hCG) as an LH substitute was used based on established protocols. Commencing doses were 1500 IU or 62.5mcg s/cut twice weekly respectively and titrated to achieve normal serum total testosterone. Recombinant FSH was added after 6 months for persisting azoospermia. Wherever possible, men previously treated with long-acting injectable testosterone undecanoate were transitioned to transdermal testosterone for a minimum of 6 months prior to initiation of gonadotrophin therapy. There was wide variability in time to first appearance of sperm (median 16 months, range 4 - 42). In androgen treatment-naive men with acquired HH in adulthood (n=9), sperm was detected at a median 8 months (range 3 - 21 months) and for 4 men, hCG monotherapy was sufficient. For men with congenital causes of HH (n=13), time to first sperm detection was longer (median 17 months, range 12 - 42) and all required addition of FSH. In men previously treated with intramuscular testosterone (n=8), the median time to sperm appearance was 17 months (range 12-24) as compared to 13 months (5-42) in men treated with transdermal testosterone (n=6). To date, 11 of the 16 men actively seeking fertility have had children, with 7 requiring assisted reproduction. Gonadotrophin therapy is an effective fertility treatment for most men with HH. Clinicians can anticipate a longer time to spermatogenesis in men pre-treated with intramuscular androgens and those with congenital HH. Couples often move to assisted reproductive therapy, likely due to considerations such as semen quality, co-existing female factors and/or desire for prompt conception.
Presentation: Friday, June 16, 2023
FRI454 The Effect Of Growth Hormone Treatment According To Karyotype Classification In Turner Syndrome Patients
Authors: Choi Jung Eun , Yu Jeesuk , Kim Hae Soon 
Published: October 2023

Abstract
Disclosure: J. Choi: None. J. Yu: None. H. Kim: None.
OBJECTIVES Short stature is the main characteristics for Turner syndrome (TS) patients, and growth hormone (GH) therapy has been used as an essential treatment for developing final adult height. However, there are only a few studies on the difference responsiveness to GH therapy according to the karyotype of Turner syndrome in Korea. The aim of this study was to analyze the effect of different types of TS karyotype abnormality on the response of GH therapy. METHODS The clinical parameters of 194 TS patients registered in the LG Growth Study, who received rhGH therapy (Eutropin inj.,LG Chem Ltd.,Korea) between February 2001 and October 2021, were retrospectively reviewed. Data for four group of subjects were obtained as follow: Monosomy X (n=56); Mosaicism without X structural abnormality (n=41); Mosaicism with X structural abnormality (n=71); X Structural abnormality (n=26). Parameters of biochemical characteristics and growth responses were compared during 3-year GH treatment. RESULTS The baseline height standard deviation score (SDS) was -2.85±0.86 in total TS patients. The growth velocity (cm/year) in the second year was higher in the Mosaicism without X structural abnormality compared to the monosomy X patients. However, the change of Hight SDS over three years was not statistically different between karyotypes. The growth rate was the highest in the first year, and it showed a decreasing trend over time. There was an increase in Height SDS due to growth hormone treatment for three years. The variables affecting the 0-3rd Δ height SDS were not found in the regression analysis CONCLUSIONS Our results indicate that there are no difference in response to three years of growth hormone therapy according to karyotype of TS. It was found that the initial height SDS was the lowest in monosomy compared to the others group. Further studies should be performed on other factors influencing the efficacy of the therapy.
Presentation Date: Friday, June 16, 2023
SAT361 A Rare Case of Ovarian Steroid Cell Tumor in a Patient With Known Polycystic Ovarian Syndrome
Authors: Aluko Oluwatomisin A , Patel Shivani , Graul Ashley , Deshmukh Mrunalini 
Published: October 2023

Abstract
Disclosure: O.A. Aluko: None. S. Patel: None. A. Graul: None. M. Deshmukh: None.
Introduction.Sex cord stromal cell tumors are rare tumors of the ovary that usually occur inthe first twotothreedecades of life. Specifically, steroid cell tumors of the ovary account for 0.1% of all ovariantumors.Testosterone productionis typical, with hirsutism and virilizationbeing the most commonsymptoms. Amarkedly elevated testosterone level &gt;200ng/dl is animportant diagnostic threshold for discriminatingandrogen- secreting tumors from non-neoplastic lesions.We report acase of ovariansteroid cell tumor inapatient with knownPCOS.Case ReportA 28-year old female with past medical history of PCOS and infertility was referred tothe Endocrinologyoffice for evaluationof worsening hirsutism and elevated testosterone level.She reported increased facial hair especially onher upper lipand chin, abdomenand inner thighs. Shehad ahistory of irregular periods and had beenonoral contraceptives as aresult. She was started onspironolactone 50mg daily by her PCP with noimprovement insymptoms.Bloodwork done prior tovisit showed elevated total testosterone of 312ng/dL (n13-71ng/dL) withelevated free testosterone of 5.8pg/dL (n0.0- 4.2pg/dL). Pelvic ultrasound showed peripherally orientedfollicles inkeeping with knowndiagnosis of PCOS with nosuspicious adnexal mass or loculatedcollections. Repeat bloodwork done three weeks after discontinuing spironolactone showed worsening elevatedserum testosterone of 561ng/dL with elevated free testosterone of 7.7pg/dL. Further workuptorule outother underlying causes returned negative. DHEA-S, Androstenedione, 24hr urinary cortisol, salivarycortisol X3, ACTH, InhibinB, LDH, Ca-125, betaHCG, were all withinnormal limits.CT abdomenand pelvis showed anenhancing nodule inthe right ovary with normal adrenal glands.Repeat pelvic ultrasound showed anew 2.9cm right ovariansolid isoechoic hyperemic nodule O-RADScategory 5(50% risk of malignancy) similar toMRI findings.She underwent aright laparoscopic ovariancystectomy with pathology diagnosis of sex cord steroidal celltumor with noevidence of increased mitotic activity or necrosis. Immuno-histochemistry supported thediagnosis with positive steroidogenic factor-1(SF-1) gene. Repeat total testosterone and freetestosterone levels six weeks after surgery were 44ng/dl and 2.4ng/dl respectively, both withinnormallimits.ConclusionInthe setting of rapid onset hirsutism with significantly elevated testosterone levels, there should be ahigh clinical suspicionfor anandrogensecreting tumor which must be excluded, irrespective of knowndiagnosis of PCOS. Repeat imaging after non-neoplastic processes are ruled out should be consideredas surgical resectionis the primary treatment for ovariansteroid cell tumors and should not be missed.
Presentation Date: Saturday, June 17, 2023
SAT446 Association of Polychlorinated Biphenyls With the Hormonal Parameters of the Normal Menstrual Cycle May Contribute to Unexplained Infertility
Authors: Butler Alexandra E , Brennan Edwina , Sathyapalan Thozhukat , Lawrence Atkin Stephen 
Published: October 2023

Abstract
Disclosure: A.E. Butler: None. E. Brennan: None. T. Sathyapalan: None. S.L. Atkin: None.
Introduction: Polychlorinated biphenyls (PCBs) are organic lipophilic pollutants that accumulate through the diet and increase with age and obesity. Previous research has linked PCBs with menstrual function; therefore, this study was undertaken to look at the association of PCBs with parameters of menstrual function at day 21 of the menstrual cycle in a group of women who were undergoing in vitro fertilization (IVF). Methods: 29 Caucasian women from a UK academic center aged 32.9±4.4 years, with body mass index BMI 25.4±3.6 kg/m2, who were undergoing in vitro fertilization were recruited. Five of the women had unexplained infertility and the remainder (n=24) had male factor infertility or tubal problems. Blood was withdrawn at day 21 of their menstrual cycle, at the time of mock embryo transfer. PCBs were measured using high resolution gas chromatography. Results: Only PCB118, PCB153, PCB138 and PCB180 were detected. PCB153, PCB138, PCB180 inversely correlated with estradiol (p&lt;0.05). PCB 118 and PCB138 inversely correlated with FSH (p&lt;0.05). PCB118, PCB153, PCB138 and PCB180 inversely correlated with LH (p&lt;0.05, p&lt;0.01, p&lt;0.01 and p&lt;0.01, respectively). No correlation was seen between PCBs and progesterone. Women with unexplained infertility showed higher levels of PCB118, PCB153, PCB138 and PCB180 (p&lt;0.05) compared to those with male factor infertility though other hormonal parameters did not differ other than FSH that was lower in the unexplained group (p=0.01). Conclusion: These data are in accord with an effect of PCBs on the menstrual cycle in normal women and may be involved in the mechanism of unexplained infertility.
Presentation Date: Saturday, June 17, 2023
OR35-04 Anti-Müllerian Hormone Variants identified in Patients with Polycystic Ovary Syndrome Affect Secretion and Immunoactivity
Authors: Meng Li , McLuskey Anke , Elizabeth Dunaif Andrea , Visser Jenny A 
Published: October 2023

Abstract
Disclosure: L. Meng: None. A. McLuskey: None. A.E. Dunaif: None. J.A. Visser: None.
Recently rare heterozygous AMH variants were identified in women with PCOS, causing reduced AMH signaling. However, the exact functional mechanism remains unknown. Here, we analyzed the processing, secretion and signaling of these AMH variants. Six PCOS-specific AMH variants (V12G, P151S, P270S, P352S, P362S, H506Q) and one control-specific variant (A519V) were introduced in an AMH expression vector. Signaling activity was measured using the BRE-Luc reporter in the mouse granulosa cell-line KK-1. AMH cleavage and secretion was analyzed by Western Blot, confocal microscopy and ELISA. Serum AMH levels in PCOS cases harboring these variants were measured by ELISA. hAMH-151S and hAMH-506Q have ∼90% decreased AMH signaling (P&lt;0.001). The other five variants were comparable to wild-type (wt)-AMH signaling. Coexpression of hAMH-151S or hAMH-506Q with wt-hAMH at equal amounts inhibited wt-hAMH signaling by ∼30% (P&lt;0.001). Western blot analysis revealed that hAMH-151S and hAMH-506Q proteins were only detected in the cell lysate but not in the supernatant, while wt-hAMH and the hAMH-352S and hAMH-362S variants were detected in both the cell lysate and the supernatant. Confocal analysis showed that cells expressing hAMH-151S and hAMH-506Q had higher cellular AMH protein levels with ER retention compared to cells expressing wt-hAMH and hAMH-352S. In agreement, using two commercial AMH ELISA’s, hAMH-151S was readily detected in the cell lysate, while only very low levels were detected in the supernatant. Both hAMH-362S and hAMH-519V were detectable using the Fujirebio-AMH ELISA, but showed severely reduced immunoactivity measured by the pico-AMH ELISA. Surprisingly, hAMH-506Q was undetectable in both the cell lysate and supernatant by both ELISA’s. However, in PCOS cases, heterozygous carriers of the P151S and H506Q variants still had detectable AMH in both assays. In conclusion, our results show that P151S and H506Q disrupt normal processing and secretion of AMH, leading to hampered secretion of wt-AMH. Additionally, AMH variants impair the AMH immunoactivity with (H506Q) or without (P362S and A519V) influencing their bioactivities.
Presentation Date: Sunday, June 18, 2023
THU573 Paxillin Regulates Androgen Receptor In Granulosa Cells
Authors: Weidner Adelaide , Roy Anna , Candidate B S , Vann Kenji , Astapova Olga 
Published: October 2023

Abstract
Disclosure: A. Weidner: None. A. Roy: None. K. Vann: None. O. Astapova: None.
Paxillin is a ubiquitously-expressed adaptor protein that is integral in focal adhesions and plays an active role in the regulation of cell motility and apoptosis. Recently, paxillin was shown to mediate pro-tumorigenic androgen signaling in prostate cancer cells, where it is necessary for rapid cytoplasmic kinase signaling triggered by activation of membrane-bound androgen receptor. We sought to investigate the relationship between paxillin and androgen receptor (AR) in granulosa cells, where androgen actions, apoptosis and focal adhesions are of known importance, but the role of paxillin is understudied. When paxillin expression was silenced using siRNA in human granulosa-derived KGN cells, AR protein expression was significantly reduced, while its RNA expression was unaffected. Similarly, in granulosa cell-specific paxillin knockout mice, AR protein expression in granulosa cells was reduced. Further, we found that AR and paxillin co-localize in focal adhesions in mouse primary granulosa cells and in KGN cells, and their interaction requires the activity of focal adhesion kinase. Disruption of focal adhesion with a focal adhesion kinase inhibitor also leads to reduced AR protein levels. To further explore the mechanisms by which paxillin regulates AR expression, we created paxillin-null KGN cell lines using CRISPR-Cas9 gene editing. While paxillin loss resulted in reduced AR protein expression early (days) in the gene-editing process, this effect disappeared after weeks of clonal expansion from selected single cells. Expanded paxillin-null KGN clones showed normal AR protein expression, but increased AR mRNA expression, suggesting an adaptive increase in AR gene transcription to compensate for reduced AR protein levels in cells that survived paxillin deletion. Studies of AR protein degradation using cycloheximide to block protein synthesis showed that the half-life of AR was reduced from 6.7 to 4.5 hours (approximately 33%) by paxillin deletion, indicating accelerated AR protein degradation in cells lacking paxillin. Based on our results, we hypothesize that paxillin brings AR into focal adhesions in granulosa cells, thereby sequestering it from proteasomal degradation in the cytoplasm. Thus, paxillin may be a novel target in the management of androgen-related disorders in women, such as polycystic ovary syndrome.
Presentation Date: Thursday, June 15, 2023