bluuebunny/crossref_metadata_2025 huggingface dataset:
THU569 Steroid Receptor Coactivator 3 Is Required To Prevent Early Pregnancy Loss In The Mouse
Authors: Kumar Maurya Vineet , Hai Lan , Szwarc Maria M , San-Pin Wu , DeMayo Francesco J , Lydon John P
Published: October 2023

Disclosure: V. Maurya: None. L. Hai: None. M.M. Szwarc: None. W. San-Pin: None. F.J. DeMayo: None. J.P. Lydon: None.

Members of the Steroid Receptor Coactivator (SRC) family enact distinct transcriptional coregulator functions within a broad spectrum of physiologies and pathologies. We previously demonstrated that endometrial SRC-3 is critical for in vitro human endometrial stromal cell decidualization, a critical cellular process in the establishment of the maternofetal interface. To address SRC-3’s in vivo role in endometrial periimplantation biology, we recently generated a SRC-3 conditional knockout mouse model (SRC-3d/d) in which SRC-3 is selectively ablated in cells that express the progesterone receptor. A six-month breeding trial with wild type proven stud males demonstrated that the SRC-3d/d female fails to produce litters (n>10 per genotype). Unlike the SRC-2d/d female, however, both embryo attachment and implantation into the stromal compartment of the SRC-3d/d endometrium are not impaired at gestation day (GD) 5 or 6. While endometrial stromal decidualization initiates with embryo invasion, pregnant SRC-3d/d mice exhibit early pregnancy loss (EPL) by GD-7.5 (before placentation). At GD-6, the SRC-3d/d decidua is significantly smaller than those of sibling controls. Histological analyses reveal extensive decidual cell death in the SRC-3d/d decidua by GD-7, which results in the sudden demise of the embryo. These histological findings are supported by recent genome-wide RNA profiling studies that show a pro-survival role for SRC-3 in this tissue. Based on these results, we conclude that endometrial SRC-3 is critical for maintaining the functionality and survival of the decidual stromal cell and embryo developmental progression to placentation. Therefore, endometrial SRC-3 (and its downstream signaling networks) are predicted to represent new molecular determinants of non-aneuploid EPL, a poorly understood pregnancy complication for which diagnostic and treatment options are limited.

Presentation Date: Thursday, June 15, 2023
THU575 The Canonical Wnt/β-catenin Pathway Is Not Involved In Estrogen-induced Skeletal Muscle Fibrosis In A Mouse Model Of Inguinal Hernia
Authors: You Tianming , Zhao Hong , Potluri Tanvi , Yin Ping , Ekrem Bulun Serdar
Published: October 2023

Disclosure: T. You: None. H. Zhao: None. T. Potluri: None. P. Yin: None. S.E. Bulun: None.

Inguinal hernias affect up to 27% of elderly men, with approximately 800,000 inguinal hernia repair surgeries performed annually. While these procedures are often effective, a significant subset of hernias are refractory to treatment, resulting in high mortality, high recurrence, and chronic pain. Until recently, little research has been done examining the molecular mechanisms that drive hernia-associated lower abdominal wall weakening. Our lab previously created a transgenic mouse model expressing the human aromatase gene (Aromhum) and showed that male Aromhum mice produced high levels of estrogen in the lower abdominal muscle (LAM) tissue, leading to extensive LAM fibrosis, muscle atrophy, and hernia formation. Single-cell analysis of fibrotic LAM tissue in these mice showed high expression of estrogen receptor alpha (ERα) in LAM fibroblasts as well as upregulation of Wnt signaling pathways in these ERα-positive fibroblasts. The canonical Wnt/β-catenin signaling pathway has been implicated in fibroblast activation and fibrosis in multiple organs, including the lung, heart, and skin. Thus, we hypothesized that canonical Wnt/β-catenin signaling acts as a downstream mediator of ERα to cause LAM fibroblast activation, tissue fibrosis, and hernia. To test our hypothesis, we cultured primary ERα-positive LAM fibroblasts from Aromhum mice in the presence of estrogen with or without siRNA knockdown (KD) of β-catenin. However, KD of β-catenin under these conditions did not alter fibroblast proliferation as measured by EdU assay, nor did it alter expression of genes involved in fibroblast activation or extracellular matrix formation. Furthermore, administration of LGK974, a Wnt signaling inhibitor, in male Aromhum mice did not prevent hernia development, decrease hernia size, or decrease the extent of LAM fibrosis and muscle atrophy. Thus, we concluded that the canonical Wnt/β-catenin signaling pathway does not serve as a downstream mediator of estrogen-induced skeletal muscle fibrosis in our Aromhum mouse model of inguinal hernia. Further studies are needed to evaluate the role of Wnt/β-catenin signaling in other inguinal hernia models or in humans.

Presentation Date: Thursday, June 15, 2023
SAT017 Investigating The Spatial Regulation Mediated By Constitutive Androstane Receptor
Authors: Asokakumar Anjana , Anakk Sayeepriyadarshini
Published: October 2023

Disclosure: A. Asokakumar: None. S. Anakk: None.

Xenobiotic nuclear receptor, Constitutive Androstane Receptor (CAR/NR1i3), is extensively studied in the liver for its detoxification functions. In addition, CAR is also involved in controlling metabolic processes, protein synthesis, immune functions, and cellular proliferation. We examined if CAR achieves these wide ranges of functions by the spatial distribution of labor within the liver. Although previous studies have shown that CAR transcriptionally regulates many genes involved in these pathways, their spatial control is yet to be examined. For instance, the liver is divided into three zones (pericentral, periportal and midzonal) and whether CAR is expressed equally in these zones remains unknown. However, CAR has not been studied at the protein levels due to the lack of reliable antibody. We generated a Flag-tagged CAR mouse model using CRISPR Cas that will enable us to investigate CAR protein expression, localization and its interactions with other proteins. The transgenic FLAG-CAR model will also allow us to monitor its transition between the cytoplasm and nucleus or between different liver zones upon activation. Further, we have generated single-cell RNA sequencing data from individual liver cells in both sexes of WT mice with and without CAR activation. We classified the hepatocytes, the major liver cell population, into different zones based on known biomarkers. Currently, we are investigating if these hepatocytes from different zone activate different CAR target genes. Our initial analysis revealed that CAR target genes are highly expressed in the central and midzonal regions. Next, we will examine the CAR target genes expression in different liver zones based on their functions. In the future, we aim to visualize the CAR protein and its target protein expression based on zonation. Overall, this study will help us to understand CAR localization and its target regulation both at transcriptional and translational levels.

Presentation: Saturday, June 17, 2023
SAT022 A Mechanism Of Resistance To Novel Inhibitors Of The N-Terminal Domain Of Androgen Receptor
Authors: Setiawan Josie , Mawji Nasrin R , Tien Amy H , Andersen Raymond J , Sadar Marianne D
Published: October 2023

Disclosure: J. Setiawan: None. N.R. Mawji: None. A.H. Tien: None. R.J. Andersen: Stock Owner; Self; ESSA Pharma. M.D. Sadar: Stock Owner; Self; ESSA Pharma.

Background: Androgen receptor (AR) is a steroid hormone receptor and a major therapeutic target in prostate cancer. Antiandrogen therapies directed at the AR C-terminal ligand-binding domain (LBD) provide initial benefit to patients with advanced prostate cancer, but they eventually progress to lethal metastatic castration-resistant prostate cancer (CRPC). AR N-terminal domain (NTD) inhibitors are a novel class of antagonists that were developed to overcome resistance mechanisms related to the AR-LBD, including splice variants lacking the LBD (AR-V7). While mutations in the AR-LBD have been well-characterized, the impact of NTD mutations on AR transcriptional activity and drug efficacy remains unclear. The mutation W435L was discovered from clinical samples of prostate cancer from patients treated with antiandrogens. This mutation stabilizes interaction between the AR’s NTD and LBD (N/C interaction) to increase AR transcriptional activity. Tryptophan residues W435 and W397 in AR NTD are essential in the binding site for the AR-NTD inhibitor EPI-7386 that is currently in clinical trials. We hypothesize that tryptophan mutations within the EPI-7386 binding site of AR are a potential mechanism of resistance. Methods: Site-directed mutagenesis was used to create expression vectors with W435 and W397 point mutations in AR. Plasmids were transfected into AR-negative CV-1 cells to compare the transcriptional activity of wild-type (WT) versus mutant ARs. IC50s for each inhibitor were generated for androgen-induced reporter gene constructs. A mammalian two-hybrid system assay was used to assess the impact of inhibitors and AR mutations on N/C interaction. Results: The AR-W435L mutation led to higher IC50s to inhibit androgen-induced MMTV-luciferase activity by NTD inhibitors and antiandrogens. Differences in N/C interaction were observed between WT and mutant ARs treated with EPI-7386. Importantly, the ability of another EPI analog, EPI-7170, to decrease AR-N/C interaction was not significantly impacted by W435L. These data support that loss of efficacy with EPI-7386 is not across the entire class of EPI analogs and may be specific to EPI-7386. Conclusion: Tryptophan mutations in the EPI-7386 binding site are predictive of resistance to this specific antagonist and do not broadly apply to the entire class of EPI analogs. Key differences were revealed between AR-LBD and AR-NTD inhibitors that support the recruitment of different tau regions in the NTD.

Presentation: Saturday, June 17, 2023
FRI182 Cardiometabolic Risk And Outcomes In Patient With Adrenal Adenomas
Authors: Lam Han , Han Hye Jeong , Athimulam Shobana
Published: October 2023

Disclosure: H. Lam: None. H. Han: None. S. Athimulam: None.

Background: Approximately 5% of adults undergoing cross-sectional imaging are reported to have an adrenal adenoma. Although most adenomas are considered non-functioning (NFAT), up to 48% can present with mild autonomous cortisol secretion (MACS). Published studies have reported an increased prevalence of cardiometabolic risk factors, cardiac and cerebrovascular events in MACS patients. Objective: To determine the prevalence of cardiometabolic disease and outcomes in a population-based cohort of patients with adrenal adenomas. Design: Retrospective cross-sectional study of patients with adrenal adenomas over a 10-year period (Jan 2012 – Dec 2021). Setting: Academic primary and tertiary care setting. Main outcomes measured: Prevalence of cardiometabolic disease, cardiovascular events requiring procedure (percutaneous coronary intervention, PCI or coronary artery bypass graft, CABG) and cerebrovascular events. MACS was diagnosed based on cortisol level ≥ 1.8cmg/dL after overnight 1mg dexamethasone suppression testing (DST) and NFAT if cortisol < 1.8mcg/dL. Patients who did not undergo 1mg DST were categorized as unknown cortisol status (UCS). Results: Preliminary results include 198 patients with adrenal adenomas [(135 women (67%) with a median age of 67y, 106 Black (54%), 83 White (42%) and 9 other races (4%)]. 74 (37%) were diagnosed with NFAT, 42 (21%) with MACS, and 82 (41%) with UCS. Hypertension (n=163,83%; MACS vs NFAT vs UCS: 23% vs 34% vs 43%) is the most prevalent cardiometabolic risk factor, followed by hyperlipidemia (n=146, 75%; MACS vs NFAT vs UCS: 21% vs 38% vs 41%), prediabetes (n=94, 50%; MACS vs NFAT vs UCS: 18% vs 43% vs 39%) and type 2 diabetes mellitus (n=82,43%; MACS vs NFAT vs UCS: 22% vs 35% vs 43%), respectively. 14% of patients with adrenal adenomas underwent procedures (PCI or CABG) for cardiovascular events (MACS vs NFAT vs UCS: 33% vs 26% vs 41%) and 11% were diagnosed with cerebrovascular events (MACS vs NFAT vs UCS: 29% vs 19% vs 52%). Conclusions: Patients with adrenal adenomas and mild autonomous cortisol secretion (MACS) are at increased risk of cardiovascular events requiring intervention and cerebrovascular events, compared to non-functioning adrenal tumors. 41% (n=82, 61% Blacks, 30% White, 2% Others) of patient population was classified as unknown cortisol status indicating further need to educate health care professionals on evaluation of adrenal adenomas to improve health care outcomes and disparities in management.

Presentation: Friday, June 16, 2023
THU669 Time To Achieve Euthyroidism In Graves Disease Using Methimazole In An Urban Population
Authors: Sultana Habbsa Samima , Yunasan Elvina , Krishnan Adityanarayan , M Kashif
Published: October 2023

Disclosure: S.S. Habbsa: None. E. Yunasan: None. A. Krishnan: None. K.M. Munir: None.

Context: Previous studies of treatment response in Graves disease have shown that that the mean time to reach euthyroidism with methimazole (MMI) was several weeks to months. In 1987 Okamura et al. concluded that the average period was 6-7 weeks with MMI 30mg daily. Nakamura et al. showed similar data in 2007 (5.8 +/- 4 weeks). These studies were performed in Japanese hospitals over 15 years ago. Limited data exists regarding treatment response times with different doses in a diverse urban population, which may vary with regards to typical dietary patterns, thyroid hormone metabolism and thionamide pharmacokinetics. Objective: The objective of this retrospective chart review was to determine the mean time to achieve euthyroidism with MMI in patients with newly diagnosed Graves disease in Baltimore City. Methods: Patients with Graves hyperthyroidism newly diagnosed in the last 5 years were identified from outpatient endocrine and primary care clinics within the University of Maryland Medical Center healthcare system. Time to achieve euthyroidism (from the start of thionamide therapy to date of euthyroid labs, defined as normal free T4 level) was assessed. Results: 128 patients with recently diagnosed Graves hyperthyroidism were identified (126 patients treated with MMI only and 2 with PTU only). 78% of subjects were female and the mean age at diagnosis was 47 years. The average daily dose of MMI ranged from 2.5mg to 60mg. On average, Free T4 decreased by 0.47 ng/dL per week. The mean time to achieve euthyroidism was 10.1 weeks (8.6, 11.6) overall, similar in males and females. On sub analysis, time to achieve euthyroidism was lower in younger males (age < 40 years) [6.6 weeks (3.9, 9.3)] and older females (age > 40 years) [8.3 (6.9, 9.7)]. Conclusion: The above data may inform expectations for treatment response for newly diagnosed Graves disease, specifically in an urban population on a Westernized diet. Patient forums have shown increasing interest in therapeutic alternatives to thionamides, including specialized diets. This data may help to determine whether other proposed therapies for initial treatment of Graves hyperthyroidism are more or less efficacious.

Presentation: Thursday, June 15, 2023
THU680 Cytologic And Molecular Assessment Of Isthmus Thyroid Nodules
Authors: Jasim Sina , Chen Yang , Jiang Rouchen , Hao Yangyang , Huang Jing , Klopper Joshua P , Kloos Richard T , Brown Taylor C
Published: October 2023

Disclosure: S. Jasim: None. Y. Chen: Employee; Self; Veracyte, Inc. Stock Owner; Self; Veracyte, Inc. R. Jiang: Employee; Self; Veracyte, Inc. Stock Owner; Self; Veracyte, Inc. Y. Hao: Employee; Self; Veracyte, Inc. Stock Owner; Self; Veracyte, Inc. J. Huang: Employee; Self; Veracyte, Inc. Stock Owner; Self; Veracyte, Inc. J.P. Klopper: Employee; Self; Veracyte, Inc. Stock Owner; Self; Veracyte, Inc. R.T. Kloos: Employee; Self; Veracyte, Inc. Stock Owner; Self; Veracyte, Inc. T.C. Brown: None.

Thyroid nodules arising in the isthmus are more likely to be malignant and demonstrate more aggressive behavior relative to thyroid nodules from either thyroid lobe. Preliminary studies of papillary thyroid cancers (PTC) studied in The Cancer Genome Atlas (TCGA) indicate molecular profiles that may explain the more aggressive phenotype of isthmic PTC, including an increased ERK signaling molecular profile. The goal of this study was to interrogate the Veracyte Afirma thyroid nodule database and assess cytologic and molecular differences of thyroid aspirates sent for Afirma Genomic Sequencing (GSC) testing from isthmus nodules relative to lobar nodules. Samples from isthmus nodules represented 4.8% of all samples. Most Afirma nodules had indeterminate cytology (ITN, Bethesda III or IV) and there were more ITN samples from the thyroid lobes (95.7%) compared to the isthmus (91.8%). For Bethesda V or VI nodules, the proportion from the isthmus was almost double that from the lobes (8.2% vs 4.3%). There were no significant differences observed in the Afirma benign or suspicious result of ITN samples comparing isthmus versus lobar location. Analysis of molecular alterations in Afirma suspicious nodules from ITN and Bethesda V-VI nodules showed that isthmus nodules had twice the frequency of BRAFV600E mutations compared to lobar nodules (21% vs 10%), an increased frequency of ALK/NTRK/RET fusions (4.6% vs 2.5%), and a lower frequency of NRAS (7.7% vs 13%) and HRAS (4.5% vs 8.2%) variants (all comparisons significant (p < 0.001)). Additionally, isthmus nodules had significantly higher BRAF-like signature, ERK signaling, and follicular-mesenchymal transition scores compared to lobar nodules (p < 0.01). In summary, thyroid nodules sent for Afirma molecular testing arising from the isthmus are more likely to have Bethesda V and VI cytology and, amongst Afirma suspicious ITN and Bethesda V and VI lesions, have higher levels of molecular markers of aggressiveness relative to lobar nodules. This study expands upon the data seen in PTCs from the TCGA as most thyroid tumors referred for molecular testing have Bethesda III and IV cytology and thus are enriched for follicular lesions including follicular variants of PTC and follicular carcinomas. Future studies should investigate the final histopathology of these molecularly tested isthmus nodules as well as oncologic outcomes.

Presentation: Thursday, June 15, 2023
FRI463 A Case Of Post COVID-19 Subacute Thyroiditis: A Thyroid Equivalent Of Long COVID?
Authors: Shiraliyeva Naila , Rios Chen Ana , Azimi-Nekoo Elham , Kishore Preeti
Published: October 2023

Disclosure: N. Shiraliyeva: None. A. Rios Chen: None. E. Azimi-Nekoo: None. P. Kishore: None.

Background: The thyroid can be affected by COVID-19 either directly through viral infection or indirectly through abnormal immune regulation (1). We report a case of subacute thyroiditis (SAT) induced by COVID-19 in which thyroid function (TFT) abnormalities lasted for over a year. Case Presentation: A 36 year old woman with a history of T2DM presented to the clinic with tachycardia, chills, tremors, and subjective fever. On exam, she had mild diffuse non-tender thyromegaly. History was significant for COVID-19 infection one month prior and she denied taking any supplement, including biotin. Laboratory data revealed TSH of 0.064 (0.270-4.2 uIU/mL), prior 0.3 in 2017, FT4 of 1.24 (0.75 – 2.0 ng/dL), TT3 129 (60 - 181.0 ng/dL ), negative TSI, TRAb, and TPO antibodies. Thyroid ultrasound demonstrated normal vascularity and no evidence of thyroid enlargement or nodules. Nuclear medicine uptake scan exhibited low thyroid uptake of 5.9 %. A diagnosis of COVID-19-related SAT (COVID-SAT) was made and she was treated with propranolol. She continued to have palpitations and TSH remained low for 15 months. TSH normalized at 17 months and repeat thyroid uptake scan demonstrated a normal uptake at 15.5%. Conclusion: SAT is a self-limited inflammatory thyroid disorder usually preceded by a viral upper respiratory tract infection. COVID-SAT has been described in multiple patients. Like typical SAT, COVID-SAT can present with neck pain, asthenia, fever and palpitations (1). COVID-19 infection can cause SAT either directly through ACE-2 mediated viral invasion of cells or indirectly through abnormal immune regulation leading to cytokine storm (1). Our literature search found 20 patients with COVID-SAT. The vast majority were middle-aged females with no history of thyroid issues. In most cases of COVID-SAT, TFT abnormalities lasted 4 to 8 weeks (1). Our patient is unique in that her TFT abnormalities lasted for over a year, which is different from the usual course of SAT or COVID-SAT. Prospective studies on patients with long COVID without associated thyroid disorders demonstrated that TFT and anti-thyroid antibodies did not play a significant role in long COVID (2). We speculate that the suppression of TSH and low thyroid uptake for >1 year, may represent a form of long COVID of the thyroid. More studies are needed to elucidate the mechanism of long term effects of COVID infection on the thyroid and thyroid function.

References: 1. Ruggeri RM et al. SARS-COV-2-related immune-inflammatory thyroid disorders: facts and perspectives. Expert Review of Clinical Immunology. 2021 Jul;17(7):737-759. 2. Lui DTW et al. A prospective follow-up on thyroid function, thyroid autoimmunity and long COVID among 250 COVID-19 survivors. Endocrine. 2023 Jan 3:1–12. doi: 10.1007/s12020-022-03281-8. Epub ahead of print. PMID: 36596904; PMCID: PMC9810240.

Presentation: Friday, June 16, 2023
FRI481 Clinical Characteristics Of Neutropenic Patients Under Anti-thyroid Drug: A Retrospective Cohort Study In Taiwan
Authors: Tseng Chih-Hsueh , Tseng Chi-Lung , Chen Harn-Shen , Chen Pei-Lung , Jui Huang Chun
Published: October 2023

Disclosure: C. Tseng: None. C. Tseng: None. H. Chen: None. P. Chen: None. C. Huang: None.

Background: Thionamide-induced agranulocytosis (TiA), is a rare adverse event with a reported incidence of around 0.1-1.75%. To reduce mortality, prompt recognition is critical but the differential diagnosis of TiA cases from non-TiA neutropenia can be challenging as other causes of neutropenia, such as concomitant chemotherapy, liver dysfunction or infection, may simultaneously exist. The present study aimed at investigating the possible factors associated with the development of TiA. Method: This is a retrospective cohort study of patients treated with anti-thyroid drugs (ATDs) in Taipei Veterans General Hospital from 2006-2018. Patients who developed a neutropenic event under treatment of ATDs were identified from the medical records. TiA was defined as (1) development of neutropenia under treatment or within 7 days of previous exposure to the same ATDs; (2) total recovery of neutropenia within one month after discontinuation of the culprit drug with absolute neutrophil count > 1500/μL; (3) exclusion of other causes for neutropenia. The incidence and risk factors for developing TiA were analyzed and compared to those with non-TiA neutropenia. Results: Among 6644 patients treated with ATDs, 66 (mean age, 53±15 years; 16.2% men) developed a neutropenic event and 20 were diagnosed with TiA (incidence: 0.3%). In univariate analysis, TiA was associated with shorter treatment duration, lesser cumulative ATD dosage, higher ATDs dosage, higher absolute neutrophil count and higher free T4 level at the time of the neutropenic event, compared to non-TiA neutropenia. After accounting for age, gender and time to neutropenia, ATDs dosage at the time of neutropenic event [odds ratio (OR) and 95% confident intervals (CIs): 635.47, 1.88-214562.36], free T4 level (OR and 95% CIs: 17.23, 1.02-290.58), and absolute neutrophil count (OR and 95% CIs: 1.00, 1.00-1.01) were still independently associated with TiA in multivariable logistic regression. Conclusions: TiA patients were more likely to have higher free T4 level, higher absolute neutrophil count at the time of neutropenic event and had received higher dosage of ATDs, compared to non-TiA cases.

Presentation: Friday, June 16, 2023
FRI491 The Impact Of Insulin Resistance On Thyroid Function In Pregnancy
Authors: Trofimiuk-Muldner Malgorzata , Jerzy Nowak Andrzej , Podlewski Jacek , Hubalewska-Dydejczyk Alicja
Published: October 2023

Disclosure: M. Trofimiuk-Muldner: None. A.J. Nowak: None. J. Podlewski: None. A. Hubalewska-Dydejczyk: None.

The influence of hyperinsulinemia on thyroid function is debatable. Insulin as an anabolic hormone may be responsible for thyroid hypertrophy and nodular development. The interplay between insulin and the function of the pituitary-thyroid axis may influence thyroid tests’ results and their interpretation. This study evaluated the association between thyroid hormones and insulin resistance in pregnant women. The study group was recruited from the Polish National Program for Elimination of Iodine Deficiency, conducted between 2007-2017. We assessed the fasting glucose, insulin levels, thyroid hormones (TSH, FT4, FT3), and ATPO antibodies in 1069 pregnant women (median age 29 years, IQR 6 years). Based on calculated HOMA-IR, participants were stratified into three subgroups HOMA1 (324 women with HOMA-IR < 1), HOMA 2 (570 women with HOMA-IR ≥1& <2.5) and HOMA3 (175 women with HOMA-IR ≥ 2.5). Results: Median (IQR) TSH concentrations were 1.42 (1.33) mIU/L, 1.65 (1.31) mIU/L, and 1.77 (1.29) mIU/L in HOMA1, HOMA2, and HOMA3 subgroups, respectively. Median (IQR) FT4 concentrations were 12.9 (3.0) pmol/L, 12.48 (2.85) pmol/L, and 11.38 (2.8) pmol/L in HOMA1, HOMA2, and HOMA3 subgroups, respectively. Median (IQR) FT3 concentrations were 4.79 (1.75) pmol/L, 4.6 (1.02) pmol/L, and 4.47 (0.88) pmol/L in HOMA1, HOMA2, and HOMA3 subgroups, respectively. Median (IQR) aTPO concentrations were 10 (11.34) IU/L, 11.59 (8.54) IU/L, and 10.15 (7.5) mIU/L in HOMA1, HOMA2, and HOMA3 subgroups, respectively. HOMA1 and HOMA2 subgroups differed significantly in TSH (p=0.026) and FT3concentrations (p=0.001). HOMA2 and HOMA3 subgroups differed significantly in FT4 (p<0.001) and aTPO concentrations (p=0.045). HOMA1 and HOMA3 patients differed in TSH (p=0.001), FT4 (p<0.001), and FT3 (p=0.001) concentrations. aTPO-positivity was not related to HOMA-IR values (mean HOMA-IR in aTPO-positive andaTPO-negative women were 1.63 and 1.80 respectively, p=0.32). Conclusions: Insulin resistance may impact thyroid function in pregnancy independently of thyroid autoimmunity, with higher TSH and lower thyroid hormones concentrations in pregnant women with higher HOMA-IR indices.

Presentation: Friday, June 16, 2023
FRI495 Analytical Validation Of An Inductively Coupled Plasma Mass Spectrometry Method For Measuring Iodine Content In Breast Milk
Authors: Li Jia-Zhen , Lee Lin-Hsuan , Wang Fan-Fen , Yang Chen-Chang , Jui Huang Chun
Published: October 2023

Disclosure: J. Li: None. L. Lee: None. F. Wang: None. C. Yang: None. C. Huang: None.

Background: Adequate iodine status in lactating women is defined by a maternal median urinary iodine concentration above 100 μg/L. However, the current standard does not account for the secretion of iodine into breastmilk and could not truly reflect the amount of iodine delivered to the infants. Measuring breastmilk median iodine concentration (BMIC) is of crucial importance but the method to measure BMIC has not been developed and validated in Taiwan. Method: We adopted the ammonia dilution method without prior sample digestion to measure BMIC by inductively coupled plasma mass spectrometry (ICP-MS). Samples and iodine calibrators were prepared into an aqueous solution containing Triton X-100, 0.5% ammonia solution and tellurium (128Te) as the internal standard. Precision, accuracy, serial dilution, and recovery tests were performed for method validation. Results: The intra-assay and inter-assay coefﬁcient of variation for the four human breast milk samples with different iodine concentrations ranged from 3.2% to 4.7% and 2.3% to 5.5%, respectively. The standard NIST 1549 milk powder was prepared into three different concentrations of 50 μg/L, 100 μg/L and 200 μg/L to assess accuracy and the biases were <5%. A recovery of 95-105% was achieved for four human breast milk samples spiked with sodium iodide solution. The serial dilution test confirmed linearity up to 500 μg/L. The limit for detection and quantification was 0.73 μg/L and 2.19 μg/L, respectively. Conclusion: The results of the current study conﬁrmed that this ICP-MS method is accurate and reliable in measuring BMIC.

Presentation: Friday, June 16, 2023
FRI548 A Case Of Periureteric Myxedema
Authors: Ferris Jaclyn M , Merrimen Jennifer , Kaiser Stephanie M
Published: October 2023

Disclosure: J.M. Ferris: None. J. Merrimen: None. S.M. Kaiser: Advisory Board Member; Self; Amgen Inc. Speaker; Self; Amgen Inc.

Background: Graves’ disease is the most common cause of hyperthyroidism. Classic extrathyroidal manifestations include Graves orbitopathy and pretibial myxedema (also known as thyroid dermopathy). Both involve cytokine-induced hyaluronic acid secretion by fibroblasts, likely related to TSH-receptor antibodies. Pretibial myxedema is now rare, but nearly always coexists with orbitopathy. It classically involves the shins, but has been described in other locations. Here we present a case of myxedema changes affecting the periureteric soft tissue of a patient with Graves’ disease. Case: A 46-year-old male was seen by endocrinology for symptomatic hyperthyroidism. His clinical presentation was consistent with Graves’ disease and the diagnosis was confirmed with a strongly positive TSH receptor antibody of 25 IU/L (normal <1 IU/L). He had findings of moderate thyroid eye disease and had bilateral skin changes suspicious for pretibial myxedema. The skin findings preceded his hyperthyroidism by a few years. Dermatology was consulted and a skin biopsy confirmed pretibial myxedema, which was treated with triamcinolone injections with good effect. His thyroid function normalized with methimazole. Coincidentally, while being treated for Graves’ disease he altruistically donated a kidney to a transplant recipient. During the nephrectomy, it was noted that part of the periureteric tissue appeared thickened and firm, and further dissection revealed a soft tissue, lipoma-like mass surrounding the ureter. A frozen section sent from the operating room was found to contain myxomatous adipose tissue with very little cellularity. The final pathology reported adipose tissue with myxoid degeneration and reactive lymphoid aggregates. The histomorphology was consistent with a reactive process and there was no evidence of malignancy. In the context of the patient’s history the findings were concluded to be related to his Graves’ disease. Discussion: While pretibial myxedema most commonly affects the shins, it has also been described at other dermatologic sites, often associated with areas of trauma. Our patient, who had biopsy proven thyroid dermopathy, was also found to have myxedema affecting the ureter. To our knowledge this is only the third reported case of ureteral myxedema, and the first in a kidney donor. The patient’s renal function before surgery was normal, and post-nephrectomy his eGFR is mildly decreased, but stable. His thyroid function remains normal on methimazole.

Presentation: Friday, June 16, 2023
SAT452 Efficacy Of I-131 Treatment Dosage For Hyperthyroidism With Current Institution Formula
Authors: Salam Sanna , Nso Nso , Nassar Mahmoud , Kondaveeti Ravali , chings Scotti
Published: October 2023

Disclosure: S. Salam: None. N. Nso: None. M. Nassar: None. R. Kondaveeti: None. S. chings: None.

-131 (radioactive iodine) therapy effectively targets overactivity of the thyroid gland; however, literature provides conflicting outcomes regarding dosage optimization of I-131 for patients with hyperthyroidism and associated clinical complications. This retrospective study aimed to validate the therapeutic efficacy of an empirically derived I-131 institution formula in resolving hyperthyroidism by establishing a euthyroid or a hypothyroid state. Methods: This retrospective chart review was undertaken for 89 adult patients (>18 years) who received I-131 therapy from 2016 to 2020 at H&H/Queens, New York. The I-131 dose range was determined in accordance with their thyroid gland weight and thyroid uptake percentages; however, the follow-up assessment was performed for the duration of 6 months. The primary endpoint (i.e., treatment success) was defined by the interim development of a euthyroid state, or hypothyroidism, or subclinical/questionable/suspected hypothyroidism, or questionable euthyroid state. The secondary endpoints included the frequency of repeat RAI doses and post-ablation thyroid function tests (TFTs). Results: The univariate and multivariate analysis of patient data indicated an 83% I-131 treatment success rate defined by the achievement of a euthyroid state and hypothyroidism in 6.7% and 70.8% of patients along with the attainment of questionable euthyroid status, questionable hypothyroidism, subclinical hypothyroidism, and suspected hypothyroidism in 1.1%, 1.1%, 2.2%, and 1.1% of patients, respectively. In addition, a low number (i.e., 9%) of patients with hyperthyroidism required repeat I-131 treatment dosages to achieve a hypothyroid or euthyroid state. The results indicated a clinically significant impact of I-131 treatment dosages on post-ablation TSH, T3, and FT4 levels. Conclusion: The results of this study testified to the therapeutic efficacy of the current institution formula for I-131 treatment dosages in treating hyperthyroidism. In addition, 83% treatment success and a low retreatment requirement strengthened current evidence favoring the optimization of RAI therapy for hyperthyroidism.

Presentation: Saturday, June 17, 2023
SAT457 Ethanol Ablation For The Treatment Of Cystic Thyroid Nodules: The First Ecuadorian Prospective Cohort
Authors: Solis Pazmiño Andrea Paola , Carrion Felipe , Mesias Joseph , Pilatuna Eduardo , Godoy Richard , Garcia Cristhian
Published: October 2023

Disclosure: A.P. Solis Pazmiño: None. F. Carrion: None. J. Mesias: None. E. Pilatuna: None. R. Godoy: None. C. Garcia: None.

Introduction: Percutaneous ethanol injection (PEI) has been adopted to treat benign cystic nodules in the last decade. For this study, we aimed to investigate the change in nodule volumes and cosmetic scores before and after EA in benign thyroid nodules and the effectiveness of treatment. Method: This prospective study, conducted at ITECC, included adults who underwent PEI for benign thyroid nodules (TN) with cystic content, between February 2021 and October 2022. The technique first consists of providing anesthesia using 10 ml of 2% solution. lidocaine. We then injected 75% ethanol into 1/3 of the volume of the TN. Nodule size and volume, thyroid function, and complications were evaluated before and after UPEA. Initial volume and change in TN volume were calculated with the ATA calculator and the independent-samples T-test. Results: A total of 13 patients with purely cystic single nodules with non-functioning and graded as Bethesda II were included. The mean age at the time of PEI was 52.46 years, and most of the patients were female (76.9%), euthyroid (77%), and symptomatic (69%). The median largest diameter of the thyroid cyst was 4.0 cm (interquartile range [IQR], 3.2 -4.5 cm; range, 1.7-5.9 cm); the median volume pre-PEI was 15.06 mL (IQR, 3.63-22.07 mL; range, 0.6-44.8 mL). The median amount of cystic fluid drained before PEI was 20 mL, and the median amount of ethanol administered was 3,85 mL (IQR, 3-5.25 mL; range, 1.5-6 mL). After a month’s follow-up, of 10 patients with available imaging on follow-up, 8 (80%) had a 50% or greater reduction in nodule volume. The median volume post-PEI was 1.5 (IQR, 0.6-8.1) ml decrease, 80.44% [IQR, 31.88%-95%]). We did not have any adverse effects. Prior to ablation, there were 46% of patients with cosmetic problems and symptomatic scores. At the 12-month follow-up, the overall cosmetic score improved from 2 to 0 (p< 0.001), as well as the overall symptomatic score improved from 3.2 to 0.5. Conclusions: Percutaneous ethanol injection seems to be a safe and effective alternative to surgical resection for patients with purely or predominantly cystic thyroid nodules and compressive symptoms who decline surgery or are not good surgical candidates. ITECC is the first center in Ecuador to perform this procedure, having encouraging results with a considerable reduction in TN in the first month with symptomatic relief and improvement in cosmetic score.

Presentation: Saturday, June 17, 2023
SAT472 A Case of Contrast Induced Thyrotoxicosis in a Patient Newly Diagnosed with Hyperthyroidism
Authors: Askar Esraa , Reddy Bharrathi
Published: October 2023

Disclosure: E. Askar: None. B. Reddy: None.

Background: It is quite uncommon for thyrotoxicosis to manifest itself after the administration of iodinated contrast. Although the actual prevalence has not yet been identified, estimates showed that the prevalence in areas with iodine deficiency is 0.25 to 0.5% and 0.025% in non-iodine-deficient areas with higher risk in elderly patients. Clinical Case: A 68-year-old female presented to the emergency department for 2 weeks of intermittent substernal chest pain associated with diaphoresis. She was diagnosed with hyperthyroidism by an outside clinic approximately one week prior to her presentation and was prescribed methimazole but did not start it. Her physical examination was significant for mild exophthalmos. EKG showed ST depression in anterolateral leads. Laboratory data showed a troponin of 0.328 ng/ml (0.0.015-0.45) which trended up to 4.830 after 3 hours and TSH of <0.005 mIU/L (0.358-3.74), otherwise BMP and CBC were within normal limits. Patient was started on aspirin, statin and heparin infusion along with methimazole. Patient was transferred to tertiary hospital for urgent cardiac catheterization that showed 90 % stenosis of left anterior descending artery (LAD) and 95 % stenosis in distal right coronary artery (RCA). A successful drug eluting stent was deployed in LAD with a plan of staged PCI in RCA. An hour after the procedure, Patient complained of palpitations and diaphoresis. Laboratory findings at that time revealed Free T4 of 17.5 ng/dl (0.9-1.8), Free T3 of 12.3 pg/ml (1.8-4.6) with positive Thyroperoxidase antibody, TSI and TSH Receptor Antibody. Thyroid ultrasound revealed diffusely heterogeneous thyroid gland with increased vascularity, consistent with Graves’ disease. The patient was diagnosed with thyrotoxicosis secondary to contrast administration. She was treated with methimazole 20 mg TID, metoprolol tartrate 25mg BID and hydrocortisone 25 mg BID. Decision was made to postpone the second procedure until trending down of thyroid hormones and improvement of symptoms. A successful staged RCA PCI was performed eight days later and patient did not experience any complications despite exposure to the same dose of iodinated contrast. Conclusion: Rarely, hyperthyroid patients may experience chest discomfort and EKG abnormalities that are consistent with cardiac ischemia. This usually happens in older patients with known underlying coronary artery disease in response to the rise in cardiac contractility and strain caused by thyrotoxicosis. Our case did not have any history or risk factors of coronary artery disease other than hyperthyroidism. This case highlights how recognition of hyperthyroidism may alter management, because the use of some procedures or treatments may acutely exacerbate the condition of the patient.

Presentation Date: Saturday, June 17, 2023
SAT541 Pleural Effusion As First Manifestation Of Recurrent Follicular Thyroid Cancer
Authors: Kadakia Natasha S , Poku Caroline A
Published: October 2023

Disclosure: N.S. Kadakia: None. C.A. Poku: None.

Pleural effusions are a rare presentation of Follicular Thyroid Cancer (FTC). We portray a case of a patient with a remote history of FTC who presented with pleural effusion 57 years later as the first sign of recurrence. A 80 year old male presented to the hospital 8/2021 with shortness of breath and was found to have a pleural effusion. He had a history of FTC diagnosed at age 23 status post total thyroidectomy, external beam radiation and radioactive iodine. He was started on thyroid hormone replacement and was subsequently lost to follow up. Chart review showed unremarkable neck ultrasounds completed in 2004 and 2006. During admission 8/2021, a malignant pleural effusion was diagnosed after the effusion tested positive for TTF-1 and thyroglobulin (Tg). He was diagnosed with recurrent metastatic thyroid cancer. A CT scan of the neck showed a small paratracheal nodule while a PET scan revealed hypermetabolic activity in the left pleura. A neck ultrasound reported a 2 cm cervical lymph node on the right with preserved fatty hilum and an ovoid 1 cm isoechoic solid nodule in the left surgical bed. There was evidence of bulky calcified lymph nodes on CT. The pleural lesion was not accessible however biopsy of a supraclavicular lymph node was consistent with metastatic follicular carcinoma. After a delay due to iodine contrast exposure, a whole body scan with radioactive iodine was completed in 1/2022 and showed multiple foci of uptake in the right neck, right thyroid, left clavicular region, and lung bases. He was treated with 250 mCi I-131 sodium iodide in 1/2022 and levothyroxine dose was increased with a target TSH of less than 0.1. His Tg level was mildly increased. Thyroglobulin antibodies (Tg ab) were positive but have continued to trend down after treatment. A follow up CT chest done 7/2022 had persistent pleural thickening but significant improvement in pleural effusion and thus thyroxine kinase inhibitors (TKI) chemotherapy has not been initiated. Malignant pleural effusion is a rare presentation of FTC metastasis with a reported median survival of 11 months (Kazushige). Pleural effusion is a poor prognostic sign in patients with FTC and distant metastases (Broome). This affirms that prompt recognition is of essence however it also raises the question of how effective current therapies are. A retrospective study evaluated 20 patients who received RAI for pulmonary metastasis from FTC, and found the efficacy rate was relatively low (40%). There is insufficient data to determine the effectiveness of RAI as treatment for metastatic FTC to the pleura. This case adds to the limited literature on recurrence of FTC with pleural effusion and highlights limitations of current management. If the response to RAI is deemed inadequate then consideration should be given to the use of TKI.

Presentation Date: Saturday, June 17, 2023
SAT395 Gender Dysphoria In A Patient With Ovotesticular Disorder Of Sex Development
Authors: Moreno Telma , Rodrigues Pedro , Ribeiro Sara , Carvalho Davide M
Published: October 2023

Disclosure: T. Moreno: None. P. Rodrigues: None. S. Ribeiro: None. D.M. Carvalho: None.

Introduction: Ovotesticular disorder of sex development (OT-DSD) is a rare condition characterized by the presence of both ovarian and testicular tissue in the gonads. Management and sex designation of these patients depend on several factors and an underlying potential for gender dysphoria should be acknowledged.Clinical Case: A 12-month-old patient from Guinea-Bissau, born from consanguineous parents, was referred to Pediatric Surgery due to atypical genitalia. Karyotype was 46,XX and SRY gene analysis was negative. Genitoscopy showed absence of a vagina and a uterus was not found on magnetic resonance imaging. An exploratory laparotomy and biopsy of the gonads was performed. The pathology report confirmed the presence of gonadal ovarian and testicular tissue, establishing the diagnosis of OT-DSD. Surgical removal of both gonads and clitoroplasty was performed and a female sex designation was attributed. Endocrinology follow-up was started at the age of 8 and the first physical examination revealed weight 48.6 kg (> P97), height 135.5 cm (P90–97); Tanner stage I (P1A1M0) and a blind vagina with normal clitoris size. Blood tests showed FSH 12.53 mUI/L, LH 1.07 mUI/L, estradiol 5.8 pg/mL and total testosterone 0.04 ng/mL. Reconstructive surgery for a neovagina was performed at 13-years-old and, two years later, the patient was started on hormone replacement therapy with transdermic estradiol. At the age of 16, the patient manifested gender dysphoria issues, decided to stop estradiol and was referred for psychiatric evaluation. Two years later, intramuscular testosterone enanthate was initiated but treatment was stopped after a six-month trial, as the patient claims to identify as male but is not interested in seeking hormone treatment at this point.Conclusion: OT-DSD is an uncommon condition, raising issues of gender assignment that are dependent on factors such as age at diagnosis, phenotype, internal structures and reproductive potential. Scarce data exists on long-term outcomes in OT-DSD, including the frequency of gender dysphoria in these patients. Gender identity is an important factor to consider on long-term follow-up of OT-DSD patients.

Presentation: Saturday, June 17, 2023
SAT400 Evaluation Of Lipid Profile Of Transgender Women On Long-Term Estrogen Therapy
Authors: Mobilia Alvares Leonardo Azevedo , Santos Lívia Marcela , Mendonça Berenice Bilharinho , Frade Costa Elaine Maria , Domenice Sorahia
Published: October 2023

Disclosure: L.A. Alvares: None. L.M. Santos: None. B.B. Mendonça: None. E.M. Costa: None. S. Domenice: None.

Introduction: For transgender women (TW), previous exposed to male puberty, on long-term estrogen therapy, the knowledge about the lipid profile is important since it impacts on cardiovascular risk. Methods: A cross-sectional study was carried out with 15 TW (34.2 +/- years old), 14 CW and 13 CM. The TW received hormone therapy for 14.4 +/- 3.5 years. The IPAQ was used to measure the level of physical activity. Body composition was assessed by an InBody 720 device. The subjects (TW, CW and CM) were classified into five categories (sedentary, insufficiently active A and B, active and very active) according to IPAQ recommendations. Results: Age (years) TW: 34.2 SD +/- 5.2; CW: 35.6 SD +/- 4.1 and CM: 36.7 SD +/- 3.8. BMI (kg/m2) TW 25.5 SD +/- 2.8, CW 23.1 SD +/- 3.3 and CM 26.3 SD +/- 3,0. Total testosterone (ng/dL) TW 18.0 (range 12-637), CW 19 (range 12-40.1) and CM 524 (SD+/- 169). Median total cholesterol analysis (mg/dL): TW 154 SD +/- 33.0, CW 177 SD +/- 18.7 and CM 173 SD +/- 23.0 (p>0.05 in all subanalyses), HDL (mg/dL) TW: 46.5 SD +/- 10.9; CW:67.0 SD +/- 15.6 and CM: 46.5 SD +/- 9.8 p value <0.05; significant difference between TW and CW; between CW and CM; LDL (mg/dL) TW: 93 SD +/- 30.4; CW 94.5 SD +/- 14.2 and CM 104 SD +/- 22.0. The % FAt mass of TW was lower than that of CW (29.5±5.7 vs 32.9±5.7; p>0.05) and higher than that of CM (20.2±5.7; p<0.001). There was no significant difference in the level of physical activity between the groups (TW vs CW, p>0.05; TW vs CM, p>0.05; CW vs CM, p>0.05), with most participants being active or very active in all groups. Discussion: studies show that in the first few months of estrogen therapy HDLc increases about 10%. Conclusion: after long term on estrogen therapy, TW present HDLc pattern similar to CM, different of the usually observed in the first months analyses.

Presentation: Saturday, June 17, 2023