bluuebunny/crossref_metadata_2025_split huggingface dataset:
THU554 Unconventional Estrogen Receptor Antagonists Reveal Cryptic Therapeutic Anti-breast Cancer Transcriptional Pathways
Authors: Hancock Govinda , Young Kristen , Greene Geoffrey L , Fanning Sean William 
Published: October 2023

Abstract
Disclosure: G. Hancock: None. K. Young: None. G.L. Greene: None. S.W. Fanning: Advisory Board Member; Self; Olema Oncology. Grant Recipient; Self; Olema Oncology.
Breast cancer is the most diagnosed cancer and 2nd leading cause of cancer-related death in women worldwide. The luminal subtype accounts for ∼70% of this heterogeneous disease. Standard of care for these estrogen receptor alpha (ERα) positive diseases includes 5 years of adjuvant endocrine therapy in the form of aromatase inhibitors (AIs), selective estrogen receptor modulators (SERMs) or selective estrogen receptor degraders (SERDs). Despite therapeutic advances, approximately half of ERα+ patients develop resistance to these endocrine therapies. In this study, x-ray crystallography of SERMs and SERDs link structural characteristics to transcriptional activity in order to understand mechanisms of antiestrogen efficacy in ER+ drug resistant breast cancers. A new class of antiestrogen based on a tetrahydro-6-isoquinoline (T6I) scaffold was developed to antagonize ERα by adopting unique binding poses to inhibit coactivator binding to the ligand binding domain (LBD). Optimization of structure-activity relationships produced unique antiestrogenic activities and a lead compound that induces transcriptional programs similar to fulvestrant despite its SERM-like accumulation of ERα in the breast cancer cell. Like fulvestrant, this T6I uniquely induces the expression of small ubiquitin-like modifier-1 (SUMO1), in opposition to 17β-estradiol. Together, this study uses structurally unique antiestrogens to further the understanding of key functional components of estrogen therapies.
Presentation: Thursday, June 15, 2023
FRI225 Clinical Course Of Late-onset Adrenal Insufficiency Due To Treatment Of Childhood Acute Lymphoblastic Leukemia
Authors: Iwabuchi Masayasu 
Published: October 2023

Abstract
Disclosure: M. Iwabuchi: None.
Background: Some people who were treated for cancer during childhood may develop endocrine problems as because of changes in the function of endocrine system. Acute lymphoblastic leukemia is the most common type of cancer and leukemia in children and components of ALL treatment are induction, consolidation, maintenance, and central nervous system prophylaxis. It is recommended that people who had irradiation in a dose of 40 Gy or higher to the central area of the hypothalamic-pituitary axis should have a blood test done to check the cortisol level and should be done yearly for at least 15 years since this complication can occur many years after irradiation. Clinical Case: A man in his 40s was admitted with symptoms of diarrhea, low-grade fever, and drowsiness. The serum sodium level that caused his symptoms decreased to 100 mEq/L and was adequately corrected. Endocrinological examination confirmed the diagnosis of central adrenal insufficiency. Soon after starting hormonal replacement therapy with hydrocortisone, his general conditions improved. After establishing our relationship, he confessed to having a history of ALL in childhood. According to his medical records at the time, he underwent induction therapy with vincristine-prednisone in 1977, maintenance therapy with 6-mercaptopurine, and radiation therapy to the central nervous system of 25 Gy in 1983. In 2023, 40 years have passed since radiation therapy. He was able to lead a normal life on oral hydrocortisone 20 mg/day without recurrence of adrenal insufficiency. Clinical Lesson: A 40-old male survivor of ALL developed adrenal insufficiency in 30 years after cranial irradiation during childhood. Undiagnosed adrenal insufficiency is often the cause of death. We should consider childhood cancer survivors have the risk of a central adrenal insufficiency. The Children’s Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers (COG LTFU Guidelines) are a resource for healthcare professionals who provide ongoing care to survivors of pediatric malignancies. The screening recommendations in these guidelines are appropriate for asymptomatic survivors of childhood, adolescent, or young adult cancer presenting for routine exposure-based medical follow-up. It is recommended that people who had irradiation in a dose of 40 Gy or higher to the central area of the hypothalamic-pituitary axis should have a blood test done to check the cortisol level and should be done yearly for at least 15 years since this complication can occur many years after irradiation. This case highlights the importance of long-term follow-up of cancer survivors after irradiation and the delayed presentation of adrenal insufficiency. This is the first report of the subsequent treatment course of late-onset adrenal insufficiency that developed 30 years after irradiation for childhood central nervous system ALL.
Presentation: Friday, June 16, 2023
OR27-06 Identification And Functional Analyses Of Therapeutic Targets For Testicular Germ Cell Tumors
Authors: Horie Kuniko , Kitayama Sachi , Ikeda Kazuhiro , Suzuki Takashi , Kawakami Satoru , Inoue Satoshi 
Published: October 2023

Abstract
Disclosure: K. Horie: None. S. Kitayama: None. K. Ikeda: None. T. Suzuki: None. S. Kawakami: None. S. Inoue: None.
Testicular germ cell tumor (TGCT) is the most common cancer among adolescent and young adult males. While cisplatin is a key drug that efficiently reduces TGCT growth, the acquisition of drug resistance is often life-threatening. To elucidate molecular mechanisms underlying the pathophysiology of TGCT, we established patient-derived TGCT spheroid cultures from nonseminomatous tumors, in which cancer stem cell population can be preferentially enriched. The TGCT spheroid cultures can be applied to the generation of in vivo xenograft models, which successfully recapitulated the pathological features of patient tumors with microenvironment. Transcriptomic analysis revealed that hypoxia-related genes were upregulated in TGCT spheroid cultures, and HIF1α inhibitor 2-methoxyestradiol could substantially repress the in vivo tumor formation. We further generated cisplatin-resistant TGCT models from embryonic cancer patient-derived spheroids and cell line, and found that transcription-related gene high mobility group nucleosome binding domain 5 (HMGN5) and meiosis-related gene testis-expressed 11 (TEX11) were remarkably upregulated in cisplatin-resistant TGCT cells compared with their parental cells. Either HMGN5 or TEX11 knockdown could reduce the viability of cisplatin-resistant TGCT cells in the presence of cisplatin. Of note, TEX11 knockdown increased cleaved PARP1 protein expression and the percentage of double-strand break marker γH2AX-positive cells in cisplatin-resistant TGCT cells. We demonstrated that siRNA-mediated TEX11 inhibition is a promising therapeutic option for cisplatin-resistant TGCT as we showed the efficacy in in vivo xenograft models generated from cisplatin-resistant patient-derived TGCT spheroids. Furthermore, chromatin immunoprecipitation sequencing for histone H3K27 acetylation status in the TGCT spheroid cultures revealed that the enrichment of “super-enhancers”, identified by the Rank Ordering of Super-enhancers algorithm [http://younglab.wi.mit.edu/super_enhancer_code.html], was well observed at chromosome 12p, where copy number gains are often observed in the tumors, and genes in the vicinity of super-enhancers identified in patient-derived TGCT models can be potential diagnostic and therapeutic targets for the advanced disease. Overall, the present study provides useful insights into the biology and chemoresistance of TGCT.
Presentation: Saturday, June 17, 2023
FRI236 Primary Adrenal Insufficiency Due To Coccidiomycosis
Authors: Duro Teodor 
Published: October 2023

Abstract
Disclosure: T. Duro: None.
Introduction: Primary adrenal insufficiency due to infectious adrenalitis is not common in the United States. When it occurs, the most common culprits are tuberculosis, histoplasmosis, and HIV-related manifestations. We present a rare case of disseminated coccidiomycosis presenting with hypercalcemia, adrenal insufficiency, and a right adrenal mass. Case Report: A 73-year-old Hispanic man living in New Mexico with history of paraesophageal hernia and a thoracic aortic aneurysm was admitted in the hospital during a COVID-19 infection due to severe weakness, poor oral intake, and abdominal pain. His labs on admission showed: mild eosinophilia, serum calcium corrected for albumin 13.8 mg/dL (n 8.4 - 10.4 mg/dL), PTH &lt;6 pg/mL(n 18 - 84 pg/mL), PTH-rp 4.4 pmol/L (n 0.0 - 2.3 pmol/L), Vitamin D25-OH 18 ng/mL (n &gt;29 ng/mL), Calcitriol 8.1 ng/mL (n 19.9 - 73.9 ng/mL), serum kappa/lambda light chain ratio 2.09 (n 0.29 - 1.65), SPEP and UPEP no M-spike, normal pattern, 8AM serum cortisol 0.9 ug/dL (n5.27 - 22.45 ug/dL), ACTH &gt;1250 pg/mL (n 0 - 46 pg/mL), DHEA-S 20ug/dL (n 80 - 560 ug/dL), plasma normetanephrine 3.29 nmol/L (n 0.00 -0.89 nmol/L), plasma metanephrine &lt;0.10 nmol/L (n 0.00 - 0.49 nmol/L). Abdominal CT scan showed a right hypodense adrenal mass measuring4.8 x 2.4 x 3.7 cm, with small areas of calcification. His left adrenal gland showed thickening and nodularity. Primary adrenal insufficiency was diagnosed based on labs above. He was given high dose IV hydrocortisone which was tapered to PO Hydrocortisone 15mg QAM and 5mg QPM. Fludrocortisone 0.1mg PO daily was also added. His presenting symptoms resolved. Work up for HIV, tuberculosis, and syphilis was negative. His hypercalcemia was thought to be due to acute adrenal insufficiency and less likely related to malignancy or other causes. His mildly elevated PTH-rp was thought to be due to his renal dysfunction, and his mildly elevated kappa/lambda ratio was thought to be non-specific by the oncology consultants after the patient had a negative nuclear bone scan. He was treated with IV fluids and his hypercalcemia resolved. Due to elevated plasma normetanephrines a pheochromocytoma could not be excluded. CT adrenal protocol imaging showed a 4.2 cm right adrenal mass with unenhanced attenuation: 40.6 HU. Absolute washout: 4.0 %, suggestive of hemorrhage. The left adrenal gland was unremarkable on this scan.Alpha and beta blockade were instituted, and the patient underwent aright adrenalectomy. Pathology showed: Necrotizing granulomatous inflammation and coccidioides-like organisms on GMS stain. His coccidioides serum antibodies were positive. He was referred to infectious diseases and was started on fluconazole 400mg daily. He is doing well. Clinical Lessons: Disseminated coccidiomycosis is a rare cause of infectious adrenalitis, but it should remain on the differential diagnosis of primary adrenal insufficiency, especially in endemic areas.
Presentation: Friday, June 16, 2023
FRI239 Oncocytic Adrenocortical Neoplasm Of Uncertain Malignant Potential
Authors: Barnett Katherine , Sandhu Ariel , Hasan Farhad 
Published: October 2023

Abstract
Disclosure: K. Barnett: None. A. Sandhu: None. F. Hasan: None.
Introduction: Oncocytic adrenocortical neoplasms are a rare histological subtype of adrenal mass, characterized by their abundant eosinophilic cytoplasm. Like other adrenal masses, they can be functional, or hormone-producing, and present on a spectrum from benign to malignant. Case: Our patient is a 31 year old female with a past medical history of anxiety who presented to the ER for right upper quadrant abdominal pain. She described it as a colicky, aching pain, lasting for several minutes at a time. She could identify no known trigger. A CT abdomen with contrast showed cholelithiasis and a hypodense lesion on the right adrenal gland. Her primary care physician (PCP) ordered a follow-up MRI abdomen with contrast that showed an indeterminate, 2.9 cm x 2 cm mass on the right adrenal gland without evidence of microscopic fat. After consultation with an oncologist, her PCP then recommended a PET scan, which showed that the mass was mildly hypermetabolic. She presented to the endocrinology office for further evaluation shortly thereafter. Though her abdominal pain had subsided, she did endorse a 7 lb weight loss, attributed to decreased appetite from anxiety. Additional review of systems was grossly negative. Hormonal work-up, including DHEA, renin, AM cortisol, ACTH, aldosterone, and plasma metanephrines was normal. CT-guided biopsy was deferred in favor of a repeat CT abdomen with adrenal protocol, which showed the adrenal nodule measured 40 HU on unenhanced images, with an absolute contrast washout of 50%. As this was less than the 60% threshold typically utilized to indicate a lipid-poor adenoma, the nodule was deemed indeterminate. Given the concerning features of the mass: its lipid-poor nature on unenhanced CT, metabolic activity on PET scan, and washout that was below the threshold for an adenoma, adrenalectomy was recommended. She underwent a laparoscopic right adrenalectomy, with final pathology showing oncocytic adrenocortical neoplasm of uncertain malignant potential, based on Lin-Weiss-Bisceglia criteria. She was seen by oncology, and they recommended no adjuvant treatment at this time. A repeat CTAP abdomen with adrenal protocol is planned for 1 year after this procedure. Discussion: Given the rarity of oncocytic adrenocortical neoplasms, their classification into benign, uncertain malignant potential, or malignant using Lin-Weiss-Bisceglia criteria is essential to determining appropriate treatment and surveillance. A recent retrospective cohort study showed oncocytic neoplasms with uncertain malignant potential have favorable outcomes, however, patients require continued radiographic surveillance due to the risk of late recurrence. Reference: Shirali AS, et al. Differences in Clinicopathologic Behavior of Oncocytic Adrenocortical Neoplasms and Conventional Adrenocortical Carcinomas. Ann Surg Oncol. 2022;29(9):5555-5563. doi:10.1245/s10434-022-11626-w
Presentation: Friday, June 16, 2023
FRI247 Case Of Metabolic Resolution Of Non-classic Congenital Adrenal Hyperplasia Post Roux-En-Y Gastric Bypass
Authors: Romo Karina G , Shu Sharon , Gabriel Mary , Bhamre Sneha , Iqbal Qasim Z , Noor Abdulla A , Uwaifo Gabriel I 
Published: October 2023

Abstract
Disclosure: K.G. Romo: None. S. Shu: None. M. Gabriel: None. S. Bhamre: None. Q.Z. Iqbal: None. A.A. Noor: None. G.I. Uwaifo: None.
Background: Non-classic congenital adrenal hyperplasia (NCCAH) is an autosomal recessive disorder resulting from loss of function mutations of the 21-hydroxylase gene. It is characterized by mild cortisol deficiency, excess ACTH production, and androgen excess, often with various features of dysmetabolic syndrome. Elective bariatric surgery is one of the most effective long-term management strategies for morbid and complicated obesity. This case presents a woman with NCCAH and complicated morbid obesity who s/p Roux-en-Y Gastric Bypass (RYGB) had metabolic resolution of NCCAH and no longer required glucocorticoid (GC) therapy. Clinical Case: A 34-year-old G1P1 woman with NCCAH on glucocorticoid therapy, treated hypothyroidism with thyroid nodular disease, dyslipidemia, and morbid obesity (pre-RYGB BMI 60-69.9) initially presented to endocrinology on account of hirsutism and secondary amenorrhea attributed to PCOS. Work-up then confirmed diagnosis of NCCAH with 21-hydroxylase genetic testing showing deletion of one copy of CYP21A2 and the pathogenic variant p.V282L in the remaining copy. Outside the peripartum period, she was managed with OCP therapy, spironolactone, and metformin. She was additionally prescribed GC therapy of hydrocortisone 10mg TID following her diagnosis of NCCAH. She subsequently became pregnant unexpectedly. Post-partum course was complicated by significant weight gain, which led her to seek elective bariatric surgery for long-term weight management. At 5 months post-op, she had a weight deficit of ∼100lbs. Although she self-discontinued GC therapy due to fear of weight gain, her amenorrhea resolved, her hirsutism significantly improved, and lab testing revealed normalization of all NCCAH markers, including ACTH, 17-OHP, and androstenedione. Thus, GC therapy was not restarted. At 11 months post-op and still off GC therapy, she had a total weight deficit of ∼160lbs and continued metabolic resolution of NCCAH markers. Conclusions: This case presents a patient with NCCAH and morbid obesity who no longer required GC therapy post-RYGB. Presently, GC therapy remains the only available treatment for CAH; however, long-term GC therapy has the potential for myriad possible complications and side effects. Our case presents elective bariatric surgery as a potential and unique treatment option for patients with classic or non-classic CAH who have associated morbid obesity. The exact pathophysiologic basis for this effect and its potential role in long-term management of appropriate CAH patients requires further in-depth study.
Presentation: Friday, June 16, 2023
FRI261 A Case Of Cushing Syndrome And Hyperandrogenism Secondary To An Adrenal Cortical Oncocytoma
Authors: Hall Elizabeth , Gupta Suruchi , Lee Jennifer 
Published: October 2023

Abstract
Disclosure: E. Hall: None. S. Gupta: None. J. Lee: None.
Background: Adrenal cortical oncocytomas are rare neoplasms that are often non-functional, but there have been case reports of associated hypercortisolism, hyperandrogenism, and in even rarer cases, multiple hormonal excesses. Clinical Case: A 30 year old woman with history of hypertension, prediabetes and obesity presented with 3 years of oligomenorrhea, hirsutism, weight gain, and voice deepening. She did not take any medications and had no family history of endocrine diseases. Labs revealed hyperandrogenism: elevated total testosterone of 390 ng/dL and 435 ng/dL (nl 6-82), suppressed FSH of 0.2 mIU/mL (nl 1.7-21.5) and LH of &lt;0.1 mIU/mL (nl 1.0-95.6), normal DHEA-S of 290 ug/dL (nl 98.8-340). Morning 17-hydroxyprogesterone was elevated to 944 ng/dL and increased to 1031 ng/dL (nl 23-431) on ACTH stimulation test, which did not meet diagnostic criteria for non-classical congenital adrenal hyperplasia. Also, genetic testing for CYP21A2 gene mutations was negative. Pelvic ultrasound was unremarkable. CT of the adrenal glands showed a 4.6 x 3.8 x 4.4 cm mildly heterogeneous left adrenal mass that measured 35 HU on non-contrast images with absolute washout of 50% and relative washout of 31%. The mass was concerning for malignancy based on HU &gt;20, size &gt;4cm, and 50% contrast washout (borderline). Overnight 1mg dexamethasone suppression test showed non-suppressed morning cortisol of 7.1 ug/dL (nl &lt;1.8), with dexamethasone level of 246 ng/dL (nl 180-550) and ACTH of &lt;5 pg/ml (nl 6-50). Twenty four hour urinary free cortisol level was slightly elevated to 52.3 mcg/24h (nl 4-50). Plasma metanephrines and aldosterone/renin ratio were normal. The patient underwent left laparoscopic adrenalectomy without complications. Pathology was consistent with adrenal cortical oncocytoma. Post-operatively, morning cortisol was &lt;0.3 ug/dL, so she was started on hydrocortisone replacement twice daily but was tapered off within three months. Three weeks after surgery, total testosterone was &lt;8 ng/dL. Two months after surgery, her menstrual cycles resumed. Fifteen months after surgery, she had regular menstrual cycles, 20 lb weight loss, resolution of hirsutism, hypertension and prediabetes. Conclusions: Adrenal cortical oncocytomas are rare tumors of the adrenal glands that should be considered in the differential for large adrenal tumors that appear suspicious for malignancy on imaging. They may or may not be functional, and in this case, the tumor secreted both androgens and cortisol. Although androgen-secreting tumors are frequently malignant, such as adrenocortical carcinomas, androgen-secreting oncocytomas are generally considered benign. However, there have been rare reports of malignant oncocytomas and oncocytomas of uncertain malignant potential.
Presentation: Friday, June 16, 2023
FRI270 A Rare Case Of Giant Benign Pheochromocytoma
Authors: Hossain Md Shajjad , Gautam Bharat , Mandal Kaushik , Liao Huijuan , Rosenthal David S , Kumar Salini Chellappan 
Published: October 2023

Abstract
Disclosure: M.S. Hossain: None. B. Gautam: None. K. Mandal: None. H. Liao: None. D.S. Rosenthal: None. S.C. Kumar: None.
Background: Pheochromocytomas are Catecholamine-secreting tumors that arise from the adrenal medulla. These tumors are rare however giant pheochromocytomas (&gt;7 cm) are even rarer entities, which are thought to be more aggressive and malignant. Here we present a case of incidentally found giant but benign pheochromocytoma. Case Report: A 40-year-old female with no PMH presented to the hospital with fever & cough for 1 month which was associated with weight loss (10lb). Patient was started on antibiotics and CT revealed right-sided adrenal incidentaloma while searching for sources of infection. CT & MRI abdomen were done for better characterization, showed a round circumscribed right adrenal mass measuring 11.3 x 11.4 x 12.8 cm. Mass had irregular central necrosis, peripheral enhancement & neovascularization. Patient denied headache, sweating & palpitation; no personal or family history of pheochromocytoma. On physical examination BP: 103/70, HR: 98, Temp: 98F, BMI:25.9, unremarkable for cushingoid features, virilization & hirsutism. Hormonal workup showed elevated free normetanephrine 185 (&lt;148pg/ml) & chromogranin A 801 (&lt;311ng/ml), but normal free metanephrine &lt;25 (&lt;57pg/ml) & total metanephrines 185 (&lt;205pg/ml). 24hr Urine study: elevated total metanephrines 1661 (182-739mcg/24h) & normetanephrine 1482 (88-649mcg/24h) but normal metanephrine 179(58-203mcg/24h), urine volume 2360ml/24h, urine creatinine 0.87(0.50-2.15g/24h). Patient Cortisol, ACTH, Aldosterone, Renin activity, DHEA-S, Androstenedione was normal. Patient was started on alpha-blockers. Patient underwent successful right-sided adrenalectomy & nephrectomy with IVC resection. Pathology reported pheochromocytoma stage II T2Nx, Ki 67 &lt;5%. No vascular and extracapsular invasion & no mitosis. Post operative outpatient follow up showed elevated plasma free normetanephrine 199(&lt;148pg/ml) & normal free metanephrine &lt;25 (&lt;57pg/ml) & total metanephrine 199 (&lt;205pg/ml). 24hr urine study: normal metanephrine 61 (58-203mcg/24h), Normetanephrine 268 (88-649mcg/24h) & total metanephrines 329 (182-739mcg/24h). Patient was advised for Ga68 DOTATE/PET scan, genetic counseling & lifelong follow-up with endocrinology for surveillance. Discussion: Pheochromocytoma symptoms may vary regardless of tumor size. Giant pheochromocytoma may not have high secretory potential due to central necrosis resulting in reduced chromaffin cells or catecholamines that are restricted to capsular mass which may release into the bloodstream intraoperatively1. Therefore, initiating alpha-blockers before surgery in these cases may prevent perioperative complications.1. Minei S, Yamashita H, Koh H, Satoh T, Kobayashi S, Furuhata M, et al. Giant cystic pheochromocytoma A case report. Hinyokika Kiyo. 2001;47:561-3.
Presentation: Friday, June 16, 2023