bluuebunny/crossref_metadata_2025 huggingface dataset:
SAT414 Gender Identity And Sexual Orientation Among Patients Evaluated By Psychiatric In A Pediatric ED
Authors: Alejandro Diaz , Martinez Andrea , Escudero Carolina , Rieger Gina
Published: October 2023

Disclosure: D. Alejandro: None. A. Martinez: None. C. Escudero: None. G. Rieger: None.

Background: Over the two decades the number of transgender and Gender Non-Conforming (GNC) youth has increased significantly. The prevalence of depression, anxiety, and other psychiatric conditions has been reported to be high among this population. In this report we explore gender identity and sexual orientation among patients evaluated by psychiatry in an emergency room of a pediatric hospital.

Methods: We reviewed the charts of 220 patients who were evaluated by a psychiatric social worker in the emergency department between August and October 2022. Gender identity and sexual orientation were documented in 118 of these patients.

Results: Of 118 patients, ranging in age from 10 to 21 years, whose gender identity and sexual orientation were evaluated, 78 (66%) were Assigned Female at Birth (AFAB) and 40 (33%) were Assigned Male at Birth (AMAB). Hispanic ethnicity was represented in 78% (93) of our population followed by Non-Hispanic White in 13% (16).Of AFAB, 12 patients (15%) identified as trans-male and 10 (13%) identified as non-binary. Of AMAB, one (2.5%) was identified as non-binary and three (7%) were unsure. Regarding sexual orientation, 26 (33%) of AFAB reported being heterosexual, 23(29%) bisexual, 5 (6.4%) pansexual and 9 (11.5%) were unsure/exploring. Among trans-males, 4(33%) identified as bisexual, 3 (25%) as gay, 2(16%) as pansexual, 2(16%) were unsure and one (8%) did not respond. Twenty-eight (70%) of AMAB reported to be heterosexual, 4 (10%) bisexual, one (2.5%) gay, 4 (10%) were unsure/exploring. The only trans-female reported to be bisexual. Regarding identified psychiatric diagnoses, major depressive disorder was reported in 83% of our population, being AFAB the most affected in 67%.

Conclusions: The prevalence of transgender/GNC among pediatric patients evaluated by a psychiatric social worker at a children’s hospital emergency department is significantly higher than in the general population. Non-heterosexual sexual orientation is also higher than in the cisgender population. Emergency department providers in pediatric emergency facilities should receive formal training in the evaluation and management of LGBTQ youth.

Presentation: Saturday, June 17, 2023
SAT420 Bone Health In Transgender People
Authors: Grande Giuseppe , Ceolin Chiara , Vescovi Beatrice , Dall'Agnol Martina , Ziliotto Chiara , Pasqualini Sara , Petre Gabriel Cosmin , Scala Alberto , Giannini Sandro , Camozzi Valentina , Bertocco Anna , Sergi Giuseppe , Ferlin Alberto , Garolla Andrea
Published: October 2023

Disclosure: G. Grande: None. C. Ceolin: None. B. Vescovi: None. M. Dall’Agnol: None. C. Ziliotto: None. S. Pasqualini: None. G. Petre: None. A. Scala: None. S. Giannini: None. V. Camozzi: None. A. Bertocco: None. G. Sergi: None. A. Ferlin: None. A. Garolla: None.

In transgender subjects, worse Bone Mineral Density (BMD) values were observed when compared to cisgender controls before initiating Gender-Affirming Hormonal Therapy (GAHT). The reasons have not yet been fully clarified. In this study we analyzed bone metabolism and body composition in a population of transgender people before initiating GAHT, and their possible correlation with endocrine profile, mental health, and lifestyle habits. Medical data, phosphocalcic metabolism and hormonal parameters, lumbar and femoral bone mineral density, body composition, strength and psychological well-being (by Patient Health Questionnaire-9-PHQ-9 and Perceived Stress Scale-PSS questionnaires), were collected in a sample of 32 transgender people before GAHT initiation and 32 cisgender controls. Assigned Female At Birth (AFAB) transgender people presented worse Z-score values at total hip and neck femoral sites (-0.52±0.94 vs 0.15±0.82, and -0.37±0.79 vs 0.19±0.66, p=0.04 respectively), while in Assigned Male At Birth (AMAB) transgender people also lumbar sites were compromised in comparison to cisgender controls. No significant difference in phospho-calcium metabolism (calcium, phosphate, PTH and vitamin D) or hormonal profile (Testosterone, estradiol, LH, FSH) was found between the transgender and the cisgender group. PHQ-9 (a questionnaire to screen for depression) scores were higher in the transgender population than cisgender controls (9.35±7.41 vs 4.08±3.14, p=0.03 in AFAB and 9.54±5.45 vs 4.46±3.59, p=0.02 in AMAB transgender people). Multiple regression analysis identified PSS (a tool to assess stress levels and identify which situations are perceived as stressful) score as an independent predictor of total femur BMD, explaining about 54% of the variance. Transgender people before GAHT have worse bone health than cisgender subjects. In particular, BMD was reduced at the hip and in AMAB even at lumbar site. The reduction in bone mass before GAHT seems independent by hormonal and phospho-calcic profile and associated mostly with psychological status. Further study will clarify the specific pathogenetic mechanisms involved in bone growth in transgender people. However, according to our evidences, the psychological stress might influence negatively lifestyle habits therefore being involved in reduced bone health. Early lifestyle and psychological interventions might so be beneficial also for bone health in the transgender population.

Presentation: Saturday, June 17, 2023
OR31-01 The Dose-dependent Effect Of Estrogen On Bone Mineral Density In Trans Girls
Authors: Boogers Lidewij S , van der Loos Marianne A T C , Wiepjes Chantal M , van Trotsenburg A S Paul , den Heijer Martin , Hannema Sabine E
Published: October 2023

Disclosure: L.S. Boogers: None. M.A. van der Loos: None. C.M. Wiepjes: None. A. van Trotsenburg: None. M. den Heijer: None. S.E. Hannema: None.

Introduction: Treatment in transgender girls can consist of puberty suppression with Gonadotrophin-releasing hormone agonists (GnRHa) followed by estrogen treatment. A decrease in bone mineral density (BMD) Z-scores is a known effect of GnRHa. After initiation of estradiol BMD Z-scores remain relatively low, even after several years of treatment. It has been hypothesized that the estradiol dosage may be insufficient, explaining the persistently low Z-scores. Some trans girls are treated with a higher dosage of estradiol or ethinylestradiol in order to limit growth. This provides the opportunity to evaluate if a higher estradiol dosage results in a greater increase in BMD Z-scores. Methods: Trans girls diagnosed with gender dysphoria were included if they were treated with GnRHa for a minimum of one year prior to treatment with estradiol. Estradiol was increased to the regular dosage (2 mg), or high growth-reductive dosages of estradiol (6 mg) or ethinyl estradiol (100-200 μg (EE)) before the age of 18 years. BMD was assessed using DXA scans performed regularly during GnRHa and estrogen treatment. Z-scores of the lumbar spine were adjusted for height, and the development over time was compared between the different treatment groups. Results: A total of 100 trans girls were included with a mean duration of GnRHa treatment of 2.3±0.7 years. Mean BMD Z-score of the lumbar spine at start of PS was -0.26±0.84. During PS, Z-scores decreased in all three treatment groups to a mean Z-score of -0.99±0.86. After two years of estrogen treatment, Z-scores increased by 0.15 (95% CI 0.00 to 0.30) in the 2 mg estradiol group (n=65) versus 0.35 (95%CI 0.08 to 0.62) in individuals treated with 6 mg estradiol (n=21), and 0.74 (95%CI 0.27 to 1.21) in the EE group (n=14). Compared with 2 mg estradiol, the increase in trans girls treated with EE was significantly higher (0.59, 95% 0.10 to 1.08). There was no difference in individuals treated with 2 mg or 6 mg estradiol (0.20 , 95%CI -0.11 to 0.51). After three years of estrogen treatment, only in the individuals treated with EE, Z-scores were not significantly different from start of GnRHa (-0.01, 95%CI -0.38 to 0.36). Conclusion: When compared to the regular 2 mg dosage of estradiol, a higher estradiol dose, and especially treatment with EE resulted in a greater increase in BMD Z-scores in the lumbar spine in trans girls. This might indicate that 2 mg estradiol is insufficient as a maintenance dose during adolescence and that a higher adult dose is required to optimise BMD.

Presentation: Sunday, June 18, 2023
OR31-03 Testosterone Gender-affirming Hormonal Therapy Is Associated With Decreased Cerebral Blood Flow In Transgender Teens
Authors: Cote Samantha , Fathy Karim , Lenet Stephanie , Espinosa-Bentancourt Oscar-Esteban , Lavallee Eric , Croteau Etienne , Rottembourg Diane , Lepage Jean-Francois , Whittingstall Kevin
Published: October 2023

Disclosure: S. Cote: None. K. Fathy: None. S. Lenet: None. O. Espinosa-Bentancourt: None. E. Lavallee: None. E. Croteau: None. D. Rottembourg: None. J. Lepage: None. K. Whittingstall: None.

There is increasing demand for gender-affirming hormonal therapy (GAHT) in recent years, with increased access to GAHT for transgender teenagers. While it is well documented that psychological outcomes and quality of life improve after GAHT, it remains unclear how cerebrovascular physiology changes with GAHT. Therefore, this study aimed to investigate the effects of testosterone GAHT on cerebral microvascular and macrovascular physiology in teenage transgender men receiving GAHT.

Six teenage transgender men were referred by their endocrinologist prior to the start of GAHT. Participants visited the research center before GAHT (session 1) and between 3 to 9 months into their GHAT (session 2). At each visit, participants completed a non-contrast-enhanced magnetic resonance imaging (MRI) protocol. This protocol assessed the macrovasculature using time-of-flight magnetic resonance angiography to visualize cerebral arteries and estimate diameters of the Circle of Willis and 2D-Phase Contrast to estimate large artery blood velocity. The microvasculature was assessed using pseudo-Continuous Arterial Spin Labelling, which estimates cerebral blood flow (CBF). Paired-sample t-tests were performed between sessions to determine if arterial diameters, CBF and blood velocity change with GAHT.

Whole-brain CBF significantly decreased with GAHT between session 1 and session 2 (CBFS1=69.15 +/- 5.85 ml/100g/min; CBFS2=59.30 +/- 8.11 ml/100g/min; t=3.19, p=0.02, df=5). The average percent change in CBF was -9.85%, and the largest decrease experienced by a participant was -20.44%. Note that even though CBF decreased, average whole-brain CBF for all participants remained in a healthy range. We observed no significant change in large artery blood velocity or arterial lumen diameters of the Circle of Willis after starting GAHT.

Our results suggest that GAHT influences the brain’s microvasculature. As women tend to have higher CBF than men, the reduction in CBF likely reflects a masculinization of the brain with GAHT. Without EEG to probe neuronal activity, it is difficult to determine if the change is due to decreased neuronal activity or a structural and/or functional change in the microvasculature. Considering that little is known about the long-term effects of GAHT on the brain, these results highlight the need to better understand how hormonal states impact human cerebrovascular physiology and how it may relate to risk for cerebrovascular disease and neurological disorders.

Presentation: Sunday, June 18, 2023
THU476 Role Of Mitochondrial Sirtuins 3 And 5 On Glutamine Addiction In Prostate Cancer Cell
Authors: Hasan Kamrul M , Friedman Theodore C , Chen Wenyong
Published: October 2023

Disclosure: K.M. Hasan: None. T.C. Friedman: None. W. Chen: None.

Myc-transformed and hypoxic cancer cells are sensitive to glutamine deprivation. Reprogramming to glutamine addiction helps to maintain the TCA cycle pool and anaplerosis that provide cancer cells energy and various macromolecules critical for rapid proliferation. However, the mechanism of glutamine addiction has yet to be fully understood. Here we explore the effect of mitochondrial sirtuins (Sirt3 and Sirt5) on glutamine metabolism in prostate cancer (PCa) cell. We used lentiviral-based knockdown or overexpression methods to examine the effect of Sirt3 and Sirt5 on the growth and proliferation of PC3 and LnCap cells. Cells were grown in both regular or glutamine-free liquid and soft agar media to investigate the effect of Sirt3 and Sirt5 on anchorage-dependent or independent growth, respectively. Cells after the knockdown of Sirt3 and Sirt5 were also grown in media supplemented with cell permeable dimethyl ketoglutarate (DMK), an alternative to ketoglutarate to continue the TCA cycle in the absence of active glutamine metabolism. We showed that anchorage-independent growth (AIG) of PCa cells relied on mitochondrial sirtuins (mtSirts). Inhibition of Sirt3 and Sirt5 activity impaired AIG, and the inhibitory effect was rescued by supplying DMK, suggesting the impact of mtSirts on glutamine metabolism. Most intriguing, our results demonstrated that Sirt3 overexpression enhanced AIG, which can be suppressed by knockdown glutamate dehydrogenase (GDH), suggesting that Sirt3 upregulated glutamine metabolism through GDH activation. Indeed, we found that silencing of Sirt3 and Sirt5 induced the acetylation of GDH and decreased the GDH activity. In agreement, we further observed that glutamine was essential for AIG of prostate cancer cells, and the addition of DMK in a glutamine-free medium rescued the growth, implying that PCa cells are addicted to glutamine. Finally, we showed that the knockdown of Sirt3 and Sirt5 impaired the tumorigenicity of PC3 cells in vivo mouse xenograft model. Thus, we concluded that sirtuins-mediated GDH regulation is a crucial process in the metabolic adaptation of PCa cells that can be a therapeutic target.

Presentation: Thursday, June 15, 2023
THU487 Xenograft of VHL-deficient Pancreatic Neuroendocrine Neoplasm Cells - A Novel Low-grade PNEN In Vivo Model
Authors: Telerman Alona , Yossef Yuval , Chmelnik Adiel , Tirosh Amit
Published: October 2023

Disclosure: A. Telerman: None. Y. Yossef: None. A. Chmelnik: None. A. Tirosh: None.

Background: Von Hippel-Lindau (VHL) disease is a familial cancer syndrome caused by a germline mutation in the VHL tumor suppressor gene. Although VHL-related pancreatic neuroendocrine neoplasms (vPNEN) have been studied, their molecular pathogenesis is not fully understood. Aims: To generate a mouse model for studying the mechanisms that promote vPNEN development in vivo. Methods: We induced a frameshift mutation in VHL using the CRISPR/Cas9 technique in the BON1 cell line, originating from high-grade PNEN (FS-BON1). We validated the pseudohypoxic nature of the cells by real-time polymerase chain reaction of VEGF and EPO in FS-BON1 compared to VHL wild-type BON1 (WT-BON1). We compared cell line-derived xenografts (CDXs) growth in athymic Nude-Foxn1nu female mice injected with WT-BON1 (n=9), FS-BON1 (n=9) and media (purified bovine serum, n=5). Tumor diameter and calculated volume and mice weight were recorded weekly. Plasma chromogranin A (CgA) levels were measured in mice sera by ELISA. Results: FS-BON1 showed upregulation of VEGF and EPO compared with WT-BON1, confirming their pseudohypoxic microenvironment. At 14 weeks, 0/9 FS-BON1 CDX reached a volume of 1 cm3 compared with 5/9 of the WT-BON1 group (p=0.03). In time-dependent analysis, FS-BON1-derived xenografts grew significantly slower than WT-BON1 xenografts (p=0.02). No significant differences in CgA serum levels were found between the mice groups. Conclusions: We report a new pseudohypoxic in vivo PNEN model. The pVHL-deficient cells show an unexpected indolent course, suggesting it as a new model for low-grade PNEN. This CDX mouse model can be utilized in further studies to evaluate the mechanism responsible for vPNEN development and for evaluating interventions in low-grade PNEN.

Presentation: Thursday, June 15, 2023
THU491 GRHL2 Overexpression In Breast Cancer Progression
Authors: Zheng Christy , Allen Kaelyn O , Reese Rebecca , Solodin Natalia M , Vera Jessica , Mcilwain Sean , Liu Tianrui , Alarid Elaine T
Published: October 2023

Disclosure: C. Zheng: None. K.O. Allen: None. R. Reese: None. N.M. Solodin: None. J. Vera: None. S. Mcilwain: None. T. Liu: None. E.T. Alarid: None.

Metastasis constitutes the permissive migration and growth of cancerous cells from the primary tumor to a distant location in the body. Epithelial to mesenchymal transition (EMT) is implicated in metastasis as it allows for cells to abandon an epithelial identity, adopt a mesenchymal phenotype, become migratory, and promote tumor progression. Grainyhead-like protein 2 (GRHL2) is a nuclear transcription factor responsible for driving epithelial cell fate. By regulating epithelial differentiation and integrity in estrogen receptor (ER) positive breast cancer, GRHL2 suppresses EMT, and as such, it was long thought to act primarily as a tumor suppressor. However, clinical evidence contradicts its tumor suppressive role in that patients expressing high levels of GRHL2 have a significantly lower probability of long-term recurrence free survival compared to low levels of GRHL2, and high levels of GRHL2 are also associated with high grade tumors. To better understand this discrepancy, a tetracycline (tet) inducible GRHL2 overexpression model in the ER-positive breast cancer MCF7 cell line was developed to assess cancer associated phenotypes and the transition between epithelial and mesenchymal states. Dose response and time course studies were performed to determine optimal GRHL2 induction in our tet-inducible model using immunofluorescent microscopy and Western blot analysis. Gene expression analyses was performed to assess representative genes associated with epithelial and mesenchymal states, and the intermediates between them known as hybrid or partial EMT. Interestingly, immunocytochemistry identified that the overexpression of GRHL2 induces the late EMT marker, vimentin, despite the inhibition of migration in the epithelial dominant MCF7 cell line. Together, these data indicates that GRHL2 overexpression leads to a complex phenotype that cannot be defined by a binary epithelial or mesenchymal state. Further analyses are aimed at understanding the pleiotropic roles GRHL2 plays in ER+ tumor progression.

Presentation: Thursday, June 15, 2023
THU493 The Role Of Liver Receptor Homolog1 (LRH-1) In Regulating Breast Cancer Progression By Modulating The Immune Response
Authors: Wang Yu , Krawczynska Natalia , Bendre Shruti , Duong Bryan , Vidana Gamage Hashni Epa , Nelczyk Adam , Gupta Anasuya Das , Nelson Erik Russell
Published: October 2023

Disclosure: Y. Wang: None. N. Krawczynska: None. S. Bendre: None. H. Vidana Gamage: None. A. Nelczyk: None. A. Das Gupta: None. E.R. Nelson: None.

Breast cancer is the most common type of cancer and the second leading cause of death among American women. While immunotherapy holds much promise, the current FDA-approved immunotherapies are effective for only a subset of patients lacking expression of estrogen receptor, progesterone receptor and HER2, but positive for PD-L1. Thus, there is strong impetus to develop novel ways to engage the immune system.

We have demonstrated that cholesterol metabolism and homeostasis within myeloid cells can either promote or suppress anti-cancer immunity. One of the regulators of cholesterol homeostasis is Liver Receptor Homolog 1 (LRH-1/NR5A2). We have found that elevated LRH-1 expression in breast tumors is associated with an increased survival. LRH-1 is highly expressed in myeloid cells, particularly neutrophils, a major immune population of the tumor microenvironment. Therefore, we hypothesized that LRH-1 plays modulatory roles in myeloid cells, that subsequently impacts breast cancer progression. Specifically, we evaluated the impact of LRH-1 on myeloid cell biology, including NETosis and phagocytosis.

Treatment of neutrophils with an agonist of LRH-1, DLPC, resulted in decreased NETosis, a function of neutrophils previously implicated in recurrence and metastasis. Treatment with an antagonist resulted in increased NETosis. Both the agonist and antagonist exhibited dose-depended effects, strongly suggesting that LRH-1 regulates the process of NETosis.

Macrophage phagocytosis is an important initial step towards antigen presentation and activation of T cells. Bone marrow derived macrophages treated with the LRH-1 antagonist exhibited decreased phagocytosis activity, in a dose dependent manner. Treatment with the agonist (DLPC) did not alter phagocytosis, but this may be because basal phagocytosis was already very high.

Collectively, our data indicate that LRH-1 plays important roles in the regulation of myeloid cell function, including NETosis in neutrophils and phagocytosis in macrophages. Overall, these findings suggest that LRH-1 activity would be beneficial for an anti-cancer immune response, and therefore position LRH-1 as a therapeutic target. Our ongoing studies will assess the role of LRH-1 in other myeloid cell-related functions including efferocytosis, T-cell expansion and differentiation.

Presentation: Thursday, June 15, 2023
THU522 Symptomatic Hypoglycemia As The First Manifestation Of Multiple Endocrine Neoplasia Type 1 (MEN-1): Case Report
Authors: Oliveira Vitória Dupas , Tormin Stephanie Corradini , Dias Bruna Vieira , Scalissi Nilza , Cunha Scalco Renata Da , Olivati Caroline , de Moricz Andre , Szutan Luiz Arnaldo , Lima Jose Viana
Published: October 2023

Disclosure: V.D. Oliveira: None. S.C. Tormin: None. B.V. Dias: None. N. Scalissi: None. R.D. Scalco: None. C. Olivati: None. A. de Moricz: None. L.A. Szutan: None. J.V. Lima: None.

Introduction: MEN-1 is a rare, autosomal dominant syndrome that occurs due to a pathogenic variant of MEN1. The incidence of insulinoma in MEN-1 is relatively rare. 4-6% of patients with insulinoma will develop MEN-1. Unlike sporadic insulinomas that usually develop after the age of 40, MEN-associated insulinoma usually occur before 40 years of age and even sometimes before 20. CASE REPORT: A 26-year-old male patient had a 3-year history of Whipple's triad associated with significant weight gain with a body mass index (BMI) of 33 kg/m² to 58 kg/m² during this period. His father has a metastatic carcinoid tumor, being treated with palliative chemotherapy. Laboratory tests at the time of hypoglycemia were: blood glucose 42mg/dL (RV 75-99), insulin 39 mU/L (RV < 3) and C-peptide 11.6 ng/dL (RV < 0.2). Magnetic resonance imaging (MRI) of pancreas showed 3 hypervascular nodules, the largest in the tail, measuring 3.3 cm, with neuroendocrine characteristics. Distal pancreatectomy, splenectomy and lymphadenectomy were indicated. After surgery, the episodes of hypoglycemia disappeared, with a weight loss of 25 kg. He required postoperative metformin, with satisfactory glycemic control. During the investigation, a prolactinoma was diagnosed (pituitary MRI, which showed a 4 mm adenoma, prolactin 56ng/mL (LR < 25) and hypogonadotrophic hypogonadism), and cabergoline 0.25 mg/week was started. In addition, diagnosis of mild primary hyperparathyroidism (PTH 188 pg/mL and calcium 10.4mg/dL). Parathyroid scintigraphy with 99mTc-MIBI showed increased uptake in the right lower parathyroid. Genetic testing was performed by Next Generation Sequence (NGS) of the MEN1 gene, which was positive for the pathogenic variant c.825-2A>G in heterozygosis in intron 5. A molecular study was performed on the patient's father and sister, which identified the same pathogenic allelic variant in both. Conclusion: We described a rare case of MEN-1 whose first manifestation was insulinoma.

Presentation: Thursday, June 15, 2023
THU524 Combination Of Mustardé Cheek Advancement Flap And Paramedian Forehead Flap As A Reconstructive Option In Basal Cell Carcinoma Of The Nose: A Functional And Aesthetic Alternative
Authors: Solis Pazmiño Andrea Paola , Rocha Carla , Pilatuna Eduardo , Godoy Richard , Garcia Cristhian
Published: October 2023

Disclosure: A.P. Solis Pazmiño: None. C. Rocha: None. E. Pilatuna: None. R. Godoy: None. C. Garcia: None.

Background: Defects resulting from the surgical procedure due to basal cell carcinoma (BCC) may be challenging to reconstruct depending on the size and location. In moderate to large-sized defects, especially in face lesions, a combination of more than one type of flap might be necessary. We present a patient with a large BCC in the nasal region which was successfully closed using a combination of rotation and advancement flaps. The patient showed excellent functional and cosmetic outcomes. Clinical Case: An elderly woman presented to our center with a five-year history of a persistent nasal vestibular lesion. It was treated with multiple cauterizations without a total improvement, until then. There was no associated pain, bleeding, or drainage. She denied family history, risk factors, or systemic diseases associated with this skin pathology. Physical examination revealed a 4 cm x 3 cm desquamated plaque with multiple pustules and a small deep ulcered area on the left nasal vestibule and overlying telangiectasia. A skin biopsy confirmed the clinical suspicion that this patient had nodular basal cell carcinoma (BCC), also known as rodent ulcer. The patient underwent surgery and we sent an intraoperative frozen section (IFS), 6 margins were taken in 10 mm strips each, and two of the seven tissue samples were reported positive. Made do with a double scalpel blade numbered by segments following clockwise order.Meanwhile, the defect reconstruction was done after histopathological examination confirmed tumor-free margins. A local skin flap, a paramedian forehead flap, transferred full-thickness skin and subcutaneous tissue into the surgical defect, which maintained the local blood supply via a vascular pedicle that remained connected to the donor site. Then, the advancement bilateral flap (Mustardé) was slid into the defect where the incisions were made tangentially to the defect to free neighboring tissue, with the wound edge acting as the free margin of the flap. Finally, for the frontal opening graft tissue, we used a pressure dressing on cutaneous grafts using a gauze wad (Brown Curative). Clinical lessons: This case exposes basal cell carcinoma (BCC), the most common skin malignancy with a predilection on sun-exposed areas such as the face. The surgical technical selected was a combination of skin flap techniques such as paramedian forehead flap, and the cheek rotational (Mustardé) flap showed excellent functional and cosmetic outcomes. Also, the oncological accepted margins depend on the risk group and the tumor size. For primary well-demarcated BCCs smaller than 2 cm, in the low-risk group, a safety margin of 3 mm gives satisfactory results.

Presentation: Thursday, June 15, 2023
THU529 Challenges In The Management Of Biochemically Silent Paraganglioma
Authors: Dewan Sandesh , Farooqi Aneeba , Jun John
Published: October 2023

Disclosure: S. Dewan: None. A. Farooqi: None. J. Jun: None.

Biochemically silent Pheochromocytoma and Paraganglioma (PPGL) are rare neuro-endocrine tumors because of which there is low quality evidence and insufficient guidelines for their management. 74-year-old Female was referred to our Endocrine clinic for incidentally discovered Retroperitoneal mass on MRI. On evaluation patient reported having concerns of escalating anxiety, difficult to control HTN and episodic flushing after physical activity in the last one year. A CT abdomen and pelvis with contrast was ordered which showed 1.7 x 1.8 cm mass anterior to the L5 vertebral body just caudal to the aortic bifurcation. The biochemical work up including 24-hour urine Metanephrines (104 ug/24 hr; n 52-341), Normetanephrines (479 ug/24 hr; n 88-444), Total Metanephrines (583 ug/24 hr; n 88-444), 3 Methoxytyramine (166 mcg/24 hr; n <242) was inconclusive. For further evaluation PET CT DOTATATE scan was ordered which showed the lesion to be DOTATAE somatostatin analogue avid, consistent with somatostatin receptor positive neuroendocrine tumor. Patient was scheduled for surgery in 2 weeks and was started on Terazosin in addition to her anti HTN medications Amlodipine, Losartan and HCTZ. The surgery had to be rescheduled due to inadequate blood pressure control. Her amlodipine and Terazosin dosage were gradually increased while the procedure was rescheduled. Eventually she underwent Laparotomy exploration and resection of the lesion. Patient tolerated the procedure well and had no major intra or post operative fluctuations in her blood pressure, heart rate or blood glucose. According to the Endocrine Surgery team, the tumor could not be sufficiently removed since it was immovable during surgery and could not be delineated from the spine. The post-operative CT scan showed nodular lesion at aortic bifurcation slightly increased in soft tissue component from prior CT scan. After discussions with surgery and oncology team, patient opted for imaging surveillance for now and will consider genetic counseling and/or radiation therapy if the tumor increases in size. Untreated PPGL carries a high risk of cardiovascular morbidity and mortality, and some may also be malignant with a propensity to cause mass effects and metastasis. Currently, there are scarce evidence-based studies comparing treatment options in biochemically silent PPGL, and there is no consensus for the most appropriate peri-operative management of biochemically silent PPGL. This case adds to the literature on how a combination of calcium channel blocker and alpha blocker can be used to achieve peri-operative blood pressure and heart rate control with no major side effects. It also demonstrates the importance of functional imaging, especially in clinically or radiologically suspected PPGL, even with a normal biochemical work up. We suggest multi-disciplinary evaluation and individualized management to ensure positive outcomes.

Presentation: Thursday, June 15, 2023
FRI221 A Case Of Pulmonary Embolism Presenting As Adrenal Crisis
Authors: Guntaka Shilpa , Barron Carly , Zhou Ping
Published: October 2023

Disclosure: S. Guntaka: None. C. Barron: None. P. Zhou: None.

Introduction: Adrenal crisis is not a typical presentation for iatrogenic adrenal insufficiency. We present a case of pulmonary embolism (PE) with a history of steroid use, to show the complexity of diagnosing adrenal crisis caused by iatrogenic adrenal insufficiency. Case Presentation: A 19-year-old woman with a history of severe atopic dermatitis, was treated with high dose prednisone for three weeks. One month after completing the course, she presented to the ED with rash, mid-sternal chest pain, dizziness and shortness of breath. Vitals were significant for tachycardia and hypotension. BMP showed Na 129 mEq/L (135-145), K 6.1 mEq/L (3.5-5), glucose 140 mg/dl, BUN 22mg/dL (5-20), and Creatinine 1.25 mg/dl (< 1.2). EKG showed peaked T waves and chest X-ray was normal. Adrenal crisis was the initial impression due to the history of steroid use and electrolyte abnormalities. She received hydrocortisone 100 mg IV for 2 doses. Hyperkalemia was treated with a calcium gluconate bolus, albuterol, insulin and glucose. She continued to endorse difficulty breathing, and chest pain, and so other etiologies were considered. A V/Q scan demonstrated multiple v/q mismatched defects in bilateral lung fields, suggestive of PE. She was admitted for anti-coagulation therapy and showed clinical improvement, without additional steroid use. An ACTH stimulation test demonstrated adequate function of the hypothalamic-pituitary-adrenal axis with normal cortisol response. Baseline and post-stimulation androstenedione and 17OHP, aldosterone, plasma renin activity, DHEAS and TFTs were also normal. Extensive work-up for coagulative and autoimmune disorders was unremarkable. The patient was subsequently restarted on oral prednisone for worsening skin disease. Conclusion: Steroid use has been associated with the development of PE. Hyponatremia can be seen among patients with PE, occurring at rates of 21 to 26%.1 In contrast, secondary adrenal insufficiency presents with euvolemic hyponatremia, and uncommonly hypoglycemia. Hyperkalemia is not typically seen. Salt craving, postural dizziness, dehydration are also not common in secondary adrenal insufficiency as mineralocorticoid function is preserved. This case demonstrates the importance of evaluating for additional etiologies in the setting of hyponatremia with electrolyte abnormalities that are not usually seen with secondary adrenal insufficiency. This patient’s initial presentation is more consistent with PE and acute renal insufficiency. Understanding the presentation of iatrogenic adrenal insufficiency is necessary to make the correct diagnosis, and to ensure patients receive appropriate care.

References: 1. Xiao-Yu Zhou, Song-Shi Ni, et, al. Hyponatremia and short-term prognosis of patients with acute pulmonary embolism: A meta-analysis. International Journal of Cardiology. Vol 227, p251-256, January 15, 2017

Presentation: Friday, June 16, 2023
THU533 Cowden Syndrome: A Rare Disease With A Lasting Impact
Authors: Hastings Camden S , Patrick Stephanie A , James Deirdre
Published: October 2023

Disclosure: C.S. Hastings: None. S.A. Patrick: None. D. James: None.

Introduction: Cowden Syndrome (CS) is a genetic condition caused by an autosomal dominant mutation in the phosphatase and tensin homolog (PTEN) tumor suppressor gene. The prevalence of CS is approximately one in 200,000 and onset is typically in the second decade of life. It is characterized by multiple benign or malignant skin tumors, non-medullary thyroid cancer, breast carcinoma, endometrial carcinoma, gastrointestinal hamartomas, renal cell carcinoma, and/or developmental delay. CS is typically underdiagnosed due to the variety of phenotypic presentations. Case Description: We present a case series of Cowden Syndrome. The first patient was a 51-year-old male with follicular thyroid cancer status post radiation and thyroidectomy, multiple gastrointestinal polyps, trichilemmomas, and an extensive family history of cancer. These factors led to an increased suspicion for CS. The patient underwent genetic testing for PTEN mutations in 2022 and was heterozygous for the c.723dupT pathogenic PTEN mutation as well as p.S598L mutation. The second patient was an 18-year-old female with developmental delay, autoimmune hypothyroidism, multinodular goiter who presented with an increasing number of thyroid nodules on annual thyroid ultrasounds. Her thyroid nodule biopsy revealed follicular and papillary thyroid carcinoma requiring total thyroidectomy. Her mother had a known history of CS. Genetic testing revealed she was heterozygous for the p.S1701 pathogenic mutation in the PTEN gene. Diagnosis of CS involves a combination of family history, presence of mucocutaneous lesions, and either thyroid, breast, or endometrial carcinoma. Given the higher likelihood of cancers in these patients, routine screening for thyroid, breast, kidney, and colon cancers should begin at an earlier age. Treatment includes topical agents such as fluorouracil or excision surgery for skin lesions. Treatment of malignancy is similar to sporadic counterparts and involves systemic immunosuppressants, chemotherapy, or surgery. Conclusion: Cowden Syndrome is a rare genetic condition resulting in tumors in a variety of organ systems, placing patients at a higher risk of malignancy. A strong family history of malignancy, as well as skin, breast, GI, or thyroid findings should prompt further investigation. Collaboration between dermatology, oncology, gastroenterology, endocrinology, and neurology is essential for successful treatment. Routine screening for these patients includes thyroid studies every 3-4 months, thyroid ultrasound yearly, colonoscopy every two years, and renal CT or MRI yearly. Early diagnosis of the condition is pivotal for close cancer surveillance and management.

Presentation: Thursday, June 15, 2023
THU534 Humoral Hypercalcemia Of Malignancy As Initial Presentation Of Hepatocellular Carcinoma And Monoclonal Gammopathy Of Undetermined Significance
Authors: Jovanovic Filip , Raghavan Aravind , Sudhakar Aboorva
Published: October 2023

Disclosure: F. Jovanovic: None. A. Raghavan: None. A. Sudhakar: None.

Background: Humoral hypercalcemia of malignancy can be initial metabolic manifestation of different neoplasms, and it is exceedingly rare in hepatocellular carcinoma (HCC).1 In this case report, we present a patient with humoral hypercalcemia secondary to HCC and monoclonal gammopathy of undetermined significance (MGUS) in the context of nonalcoholic steatohepatitis. Case Report: A 73-year-old Caucasian male with liver cirrhosis secondary to nonalcoholic steatohepatitis presented to the emergency department with a two-week history of constipation and progressive confusion. The patient was jaundiced on exam and tender to palpation in left and right middle abdominal quadrants. Laboratory findings on admission showed serum calcium 12.7 mg/dL (7.9–10.6), albumin 2.6 g/dL (3.5–5), platelets 85x103/µL (138–338), alkaline phosphatase 349 unit/L (50–136), alanine aminotransferase 234 unit/L (15-53), aspartate aminotransferase 133 unit/L (15–37), alpha-fetoprotein 1912.7 ng/mL (0–8), parathyroid hormone <3 pg/mL (14–72), and ammonia 40 mmol/L (11–32). The patient’s altered mental status improved with lactulose and rifaximin. Serum calcium levels persisted despite lactated Ringer’s solution, but improved with zoledronic acid 5 mg infusion to a nadir of 9.1 mg/dL during the hospital stay. The patient was administered repeat zoledronic acid before discharge, but was readmitted 5 days later with worsening mental status and corrected serum calcium 13.1 mg/dL. The CT abdomen and pelvis showed a mass (4.2 x 3.7 cm) in the lower right hepatic lobe. The send out labs returned with PTH-related peptide 48 pg/mL (11–20), 1,25 hydroxyvitamin D 20 pg/mL (20–45), and serum protein electrophoresis with a monoclonal M spike 1.33 g/dL in the gamma globulin region. The patient’s hypercalcemia was found to be PTH–independent and with the new hepatic mass on CT imaging, he was diagnosed with MGUS and humoral hypercalcemia secondary to HCC. The literature review shows only one case report with alcoholic cirrhosis and similar clinical presentation, which is in contrast to nonalcoholic steatohepatitis as seen in our patient.2 The patient’s family refused further treatment and opted for hospice care. Conclusion: We recommend that the patients with HCC and resistant hypercalcemia undergo diagnostic evaluation for monoclonal paraprotein as part of humoral hypercalcemia workup.

References:

(1) Luo JC, Hwang SJ, Wu JC, Li CP, Hsiao LT, Lai CR, Chiang JH, Lui WY, Chang FY, Lee SD. Paraneoplastic syndromes in patients with hepatocellular carcinoma in Taiwan. Cancer. 1999 Sep 1;86(5):799-804.

(2) Gentric A, Pennec Y, Jouquan J, et al. [Hepatoma manifesting monoclonal gammapathy and hypercalcemia]. Ann Gastroenterol Hepatol (Paris). 1984 Jul-Sep;20(4): 211-2.

Presentation: Thursday, June 15, 2023
THU546 A Lasofoxifene/Elacestrant Hybrid Antiestrogen Shows Effective Anti-tumoral Activities In Y537S ESR1 Breast Cancer Xenografts
Authors: Young Kristen S , Hancock Govinda R , Kregel Steven , Fanning Sean William
Published: October 2023

Disclosure: K.S. Young: None. G.R. Hancock: None. S. Kregel: None. S.W. Fanning: Advisory Board Member; Self; Olema Oncology. Grant Recipient; Self; Olema Oncology.

In the United States, breast cancer is the second leading cause of cancer related deaths among women. Over 70 percent of these breast cancer cases are classified as overexpressing Estrogen Receptor alpha (ERα), denoting that the hormone estrogen fuels the cancer growth. In ER+ breast cancer patients, a distinct tyrosine to serine missense mutation at position 537 (Y537S) leads to hormone- independent ERα activity, causing drug resistance and increased metastatic potential. By favoring the active conformation of ERα, the Y537S mutation reduces binding affinity of small molecule drugs by 5-10 fold. Additionally, this mutation adversely effects the allosteric rearrangement of the receptor that is needed to achieve therapeutic efficacy. Recently, we identified a common structural interaction that distinguishes effective versus ineffective therapeutic antagonists in Y537S breast cancer cells. Based on this relationship, we have developed a new isoquinoline- based antiestrogen (T6I-29-1A) to aid in interpretation of the relationship between ligand binding pose and antagonistic efficacy. Our data suggest that this novel pose effectively antagonizes mutant ERα in breast cancer cells by significantly blunting cell proliferation and downregulating transcriptional activity. Importantly, T6I-29-1A shows potent anti-tumoral activity in ectopic murine xenografts of Y537S ESR1 MCF7 cells, is orally available, and shows a favorable DMPK and ADME profile. Additionally, mice treated with T6I-29-1A exhibited decreased distant metastases compared to hormone-only control. Collectively, these studies point to a distinct relationship between ERα ligand binding pose and novel anti-metastatic activities in drug resistant Y537S ESR1 breast cancer cells.

Presentation: Thursday, June 15, 2023
FRI227 Functional Transformation Of An Initially Non-functional Paraganglioma In A Patient With Cyanotic Congenital Heart Disease
Authors: McConnell Megan , Kanin Maralee , Auerbach Martin S , Yu Run
Published: October 2023

Disclosure: M. McConnell: None. M. Kanin: None. M.S. Auerbach: None. R. Yu: None.

Background: Most pheochromocytomas and about half of paragangliomas (P-PGLs) are functional in that they produce catecholamines. Transformation of non-functional to functional P-PGLs is exceedingly rare. We present a case of such transformation in a young male with cyanotic congenital heart disease (CCHD), resulting in catecholamine-induced cardiomyopathy. Clinical Case: A 27-year-old male with CCHD presented to the hospital with tachycardia, hypertension, and hypoxia. He had a newly depressed ejection fraction of <20% and was in florid heart failure. Despite intervention, he decompensated rapidly, requiring extracorporeal membrane oxygenation (ECMO). Five years prior to this presentation, he had had normal 24-hour urine fractionated metanephrines, vanillylmandelic acid (VMA), and homovanillic acid (HVA) levels; on imaging, he had been incidentally found to harbor a 3.3 x 1.6 x 2.5-cm nodule in the upper aortocaval space which could represent a paraganglioma. Subsequent imaging showed slow growth of this mass. Given this pertinent history, urine and plasma free metanephrine studies were repeated during the hospitalization while he was not on vasopressors. 24-hour urine normetanephrines were elevated at 2,644 mcg/d (81-667 mcg/d), metanephrines at 405 mcg/d (55-320 mcg/d) while plasma free metanephrines were elevated at 0.92 nmol/L (0-0.49 nmol/L) and normetanephrines at 11.85 nmol/L (0-0.89 nmol/L). DOTATATE PET/CT revealed a soft tissue mass measuring 4.3 x 3.1 x 4.9 cm with intense DOTATATE activity in the right paravertebral space between the aorta and cava. He was treated with alpha-adrenergic blockade with improvement in blood pressure. Two months later, he underwent resection of the mass with pathology confirming a 4.9 cm paraganglioma. Conclusion: It is very rare for a paraganglioma to undergo transformation from non-functional to functional status although it is reported in the literature. This scenario is supported by our patient’s normal 24-hour urine metanephrines, VMA, and HVA results on initial presentation followed by marked elevation in urine and plasma metanephrines 5 years later when he presented with heart failure. The functional transformation in this patient was accompanied by significant growth of the paraganglioma. We surmise that alterations in gene expression during tumor growth may be responsible for the functional transformation. It is crucial to reassess the functionality of a paraganglioma if the clinical condition suggests catecholamine excess.

Presentation: Friday, June 16, 2023
FRI228 Primary Adrenal T-cell Lymphoma: A Case Report
Authors: Tabassum Humera , Xu Shiming , Manavalan Anjali
Published: October 2023

Disclosure: H. Tabassum: None. S. Xu: None. A. Manavalan: None.

Introduction: Primary T-cell adrenal lymphoma (PAL) is exceedingly rare. Adrenal insufficiency (AI) is common in these cases. Here we describe a patient with bilateral, large, T-cell PAL with rapid progression, without adrenal insufficiency. Clinical Case: A 62-year-old male, with coronary artery disease and recent coronary intervention, hyperlipidemia and hypertension presented to the hospital with abdominal pain, fever, night sweats and weight loss for a month. Work up revealed a 5.8 cm left adrenal mass with 14% absolute washout, measuring 34 Hounsfield Units (HU) pre-contrast, 68 HU postcontrast, and 63 HU on delayed images, and a 5.2 cm right adrenal mass with 42% absolute washout, measuring 35 HU pre-contrast, 81 HU postcontrast, and 62 HU on the delayed images with no other suspicious lesions or lymphadenopathy. The patient demonstrated no clinical symptoms or signs of adrenal hormone excess or deficiency. Levels of renin, aldosterone, serum cortisol, ACTH, 24-hour urine free cortisol, serum metanephrines, and thyroid function were normal. Additional tests to rule out adrenal cortical carcinoma (ACC) revealed normal levels of androstenedione, 17-hydroxyprogesterone, dehydroepiandrosterone sulfate, and estradiol. Persistent non-significant elevation of 11-deoxycortisol was observed at 51 ng/dL and 63ng/dL (Ref < 42 ng/dL). Adrenal biopsy was suggested but deferred due to the increased risk of hemorrhage given recent coronary revascularization and use of dual antiplatelet therapy. Follow up imaging in a few weeks revealed diffuse, retroperitoneal lymphadenopathy with unchanged adrenal masses. A lymph node biopsy confirmed a diagnosis of peripheral T-cell lymphoma. The left adrenal gland demonstrated an uptake SUV of 22.7 and the right, 19.17 on FDG PET. The patient was initiated on chemotherapy with etoposide, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin. Imaging three months later revealed a marked decrease in FDG activity SUV 6.98 g/mL on the left and SUV up to 3.32 g/mL on the right. Adrenal function remained intact on follow up. Conclusion: Peripheral T-cell lymphoma with adrenal involvement is an extremely rare and aggressive disease with rapid progression. Mostly seen in males over the age of 50, it may present with abdominal pain, B symptoms or both. While ACC is usually unilateral, lymphoma and metastatic disease may present bilaterally, however, other imaging features can be similar. AI is expected when 90% of the adrenal glands are destroyed by tumor infiltration, however, this does not always correlate with tumor size. In our patient, AI was not observed on presentation or follow up. As adrenal insufficiency can occur at any time in the disease course and may mimic symptoms of cancer or chemotherapy, the clinician should always be vigilant for its development in these cases.

Presentation: Friday, June 16, 2023