bluuebunny/crossref_metadata_2025_split huggingface dataset:
THU576 Anabolic Androgenic Steroid Abuse In Cis-gender Female Bodybuilder
Authors: Marta Niedzialkowska Ewelina , Shelden Daniel 
Published: October 2023

Abstract
Disclosure: E.M. Niedzialkowska: None. D. Shelden: None.
Introduction: Anabolic androgenic steroids (AAS) are used in bodybuilders to increase muscle mass. Abuse has surged as they are regarded as potent image enhancement drugs. There are a variety of illegal AAS available. Their true content is often unknown and dosing regimens frequently include concurrent use of multiple hormonally active agents. Use among female body builders is rarely reported. Having significantly lower levels of natural testosterone, females may be more susceptible to side effects and toxicity associated with AAS abuse. Clinical case: 36 year old cis-gender female presented to the Endocrinology clinic for evaluation of fatigue. The patient worked as a personal trainer at a gym and began participating in bodybuilding competitions. A year prior to the visit the patient was started on a steroid regimen by a friend at the gym. The patient’s regimen included testosterone cypionate (250mg-350mg a week) and trenbolone acetate. Anastozole was added to limit conversion to estrogen but was not administered on a regular basis. The patient reported no gender dysphoria. She has not had a menstrual period since she started the AAS. The patient was also diagnosed with acute kidney injury at the time of AAS initiation and further work up showed negative ANA, C3, C4, normal UA and protein/creatinine ratio. Her kidney injury was deemed to be related to NSAID and testosterone use. At the time of the visit laboratory results were significant for testosterone of &gt;1500 ng/dl (N 240-1080), IGF-1 359 ng/ml (N 63-223), LH &lt;0.1 mUI/ml (N&gt;0.6), FSH &lt;0.5 mUI/ml (N&gt;1.4), estradiol 47 pg/ml (N 21-251), prolactin 10.8 ng/ml (N 3-30), hemoglobin 17.4 g/dl (N 12-15.1), platelets 416 bil/L (150-400), TSH 0.75 uIU/ml (N 0.4-4.5), creatinine 1.33 mg/dl (N 0.5-1.1), eGFR 53 ml/min/1.73m2. The patient's testosterone regimen was gradually decreased to 100 mg weekly with plans to further decrease the dose and with close follow up and monitoring of gonadotropins. Treatment to stimulate endogenous estrogen production may be necessary despite her current value being within normal limits as this may be a function of peripheral conversion of exogenous testosterone. Conclusion: AAS abuse is infrequent among cis-gender females. Its use in female bodybuilders increases muscle strength and athletic performance. Exogenous administration of synthetic testosterone results in negative feedback on the hypothalamic-pituitary axis, inhibiting GnRH, leading to inhibition of FSH and LH production leading to amenorrhea in females. AAS has also been associated with kidney injury with reports from animal studies suggesting testosterone induced podocyte damage and apoptosis. The steroid regimens used by bodybuilders differ and include multiple hormonally active agents. Its abuse among cis-gender women is uncommon and further research is needed to evaluate its toxicity among this group.
Presentation Date: Thursday, June 15, 2023
SAT016 Small Compounds Modulate Glucocorticoid Receptor Function By Binding To A Novel Allosteric Pocket
Authors: Jimenez-Panizo Alba , Alegre Andrea , Fuentes-Prior Pablo , Hager Gordon L , Estebanez-Perpina Eva 
Published: October 2023

Abstract
Disclosure: A. Jimenez-Panizo: None.
The glucocorticoid receptor (GR) is a ubiquitously expressed transcription factor that controls metabolic and homeostatic processes essential for life. This receptor exerts its functions by binding to corticosteroids through its ligand-binding domain (LBD), which harbors a hydrophobic pocket where ligands are encapsulated. Synthetic glucocorticoids, as Dexamethasone, are widely used in the clinic for the treatment of chronic inflammatory diseases. Unfortunately, their prolonged use is associated with critical side effects and most of the mechanisms underlying these collateral issues are still unknown. In this work, we present a deep biochemical and biophysical analysis showing how small molecules are able to bind a new allosteric pocket in solution and how these compounds can modulate GR transcriptional activity in cells. These findings can be essential to further understand GR signaling and how to better design synthetic corticosteroids to avoid side effects.
Presentation: Saturday, June 17, 2023
SAT021 Development Of Niclosamide Analogs For Treatment Of Androgen Receptor Positive Hepatocellular Carcinoma
Authors: Jordan Montgomery Emma , Xing Enming , Dauki Anees , Radomska Hanna , Kiyota Kulp Samuel , Granchie Lauren , Li Pui-Kai , Charles Coss Christopher 
Published: October 2023

Abstract
Disclosure: E.J. Montgomery: None. E. Xing: None. A. Dauki: None. H. Radomska: None. S.K. Kulp: None. L. Granchie: None. P. Li: None. C.C. Coss: None.
Introduction: Hepatocellular carcinoma (HCC) is the predominant form of liver cancer and a leading cause of cancer death worldwide. HCC is also highly sexually dimorphic with males having a 2-4 times higher risk of HCC occurrence than females regardless of the disease etiology. Based upon the discrepancy in HCC incidence between the sexes, the role of sex hormone receptors, such as the androgen receptor (AR), in HCC progression has been investigated. Despite the evidence behind AR’s role in HCC lethality, clinical trials of anti-androgen therapy in HCC showed no significant clinical benefit. We recently reported the presence of abundant ligand-independent AR splice variants (AR-SVs) in HCC. Niclosamide is an anthelmintic drug that was identified in drugs screens for AR-V7 degrading and anti-HCC properties making it well-positioned as a potential therapeutic for AR/AR-SV positive HCC. Despite these features, niclosamide suffers from poor bioavailability by design resulting in dose limiting toxicities. Objective: 1) Identify and understand key functional groups of niclosamide for development of niclosamide analogs. 2) Develop niclosamide analogs towards improving bioavailability and limiting first pass metabolism. Methods: HCC cell lines were treated with niclosamide to determine impacts on AR expression, cell proliferation, and cell invasion. Mouse pharmacokinetics studies to evaluate drug parameters were conducted through Charles River Laboratories. Toxicity studies on a valine conjugate of niclosamide were carried out in mice over a two-week span using a range of drug concentrations. Results: Numerous niclosamide analogs were evaluated resulting in a valine conjugated niclosamide with improved bioavailability, a niclosamide analog with improved first pass metabolism, and its valine conjugate. Valine conjugated niclosamide showed improved oral exposure without resulting in toxicities. Conclusions: Niclosamide is a drug showing key activity against AR and HCC that lends itself to treatment of AR/AR-SV positive HCC. Niclosamide analogs improve upon the parental drug by overcoming its limited bioavailability and its dose limiting GI toxicity while shedding light on additional pathways for further improvement.
Presentation: Saturday, June 17, 2023
OR22-04 The Oncogenic Action Of Glucocorticoid Receptor In Prostate Cancer
Authors: Paakinaho Ville 
Published: October 2023

Abstract
Disclosure: V. Paakinaho: None.
Steroid receptors, such as androgen (AR), and glucocorticoid receptor (GR), are hormone-controlled transcription factors (TFs) that regulate transcription in multiple central cellular systems. The action of steroid receptors has a major role in the development and progression diseases, especially endocrine-related cancers, such as prostate cancer. Since AR is the key oncogenic TF driving the development and progression of prostate cancer, the receptor is the major precision drug target in the disease. Therefore, antiandrogen treatment, i.e., the inhibition of AR activity, is a common form of cancer therapy. Despite the initial effectiveness of the therapy, antiandrogen resistance often occurs and there is no curable treatment in many cases. In contrast to AR, GR has been thought to possess tumor suppressive properties in therapy-naïve prostate cancer. Nonetheless, GR can hijack the oncogenic role of AR in prostate cancer by replacing the antiandrogen inactivated AR thus mediating antiandrogen-resistance and becoming the driver of the disease. Yet, the genome-wide effects of GR in prostate cancer have largely remained elusive. The tumor suppressive versus the oncogenic consequences of GR activation are important to acknowledge since prostate cancer patients regularly receive glucocorticoids to reduce inflammation and alleviate therapy-related side effects. To unveil these issues, we integrated ChIP-seq, RNA-seq, ATAC-seq data and uncover several pivotal features of GR action in prostate cancer cells. We detected that the replacement of AR by GR in antiandrogen-exposed prostate cancer cells occurs almost exclusively at pre-accessible chromatin sites displaying the occupancy of FOXA1. Counterintuitively to the classical pioneer factor model, the silencing of FOXA1 potentiated the chromatin binding and transcriptional activity of GR. This was attributed to FOXA1-mediated repression of the NR3C1 (gene encoding GR) expression via the corepressor TLE3. Additionally, we discovered that the chromatin binding of GR as well as transcriptional regulation by the receptor differs between different prostate cancer subtypes. Moreover, GR activity in normal prostate cells diverges drastically from that of the cancer cells. In sum, our data highlight the impact FOXA1 harbors in GR-mediated antiandrogen-resistant prostate cancer. Furthermore, the distinct GR transcriptional activity in prostate cancer subtypes could potentially be used to determine if glucocorticoid exposure possess potential harm for the prostate cancer patient.
Presentation: Saturday, June 17, 2023
OR33-06 Pioneer Factor Foxa2 Mediates Chromatin Conformation Changes In Ligand-dependent Activation Of FXR
Authors: Hao Yi , Han Lu , Wu Carol , Bochkis Irina 
Published: October 2023

Abstract
Disclosure: Y. Hao: None. L. Han: None. C. Wu: None. I. Bochkis: None.
Activation of nuclear receptors, a family of ligand-dependent transcription factors, is used extensively in pharmacology to develop drug targets for diverse medical conditions, including metabolic disease and cancer. We have previously shown that pioneer factor Foxa2 opens chromatin for binding of nuclear receptors FXR and LXRα during acute ligand activation (Kain et al., Molecular Metabolism, 2021). FXR is activated by bile acids and we have demonstrated that Foxa2 plays an important role in bile acid metabolism, as deletion of Foxa2 in the liver results in intrahepatic cholestasis (Bochkis et al., Nature Medicine, 2008). We hypothesized that in addition to increasing chromatin accessibility, Foxa2 also enables chromatin conformational changes during ligand activation. We performed Foxa2 HiChIP (chromatin conformation capture, Hi-C, combined with chromatin immunoprecipitation, ChIP) assay to assess Foxa2-dependent long-range interactions in mouse livers treated with vehicle and FXR agonist GW4064. HiChIP contact analysis shows that global chromatin interactions are dramatically increased during FXR activation. In addition, ligand-treated livers have more Foxa2-anchored loops, suggesting Foxa2 is involved in dynamic chromatin conformational changes in ligand-dependent FXR activation. We show that chromatin conformation, including genome-wide interactions, intra-chromosomal and inter-chromosomal loops, drastically changes upon addition of FXR agonist. Hence, Foxa2 enables these conformational changes and plays an extended role in bile acid metabolism.
Presentation: Sunday, June 18, 2023
THU657 Racing Hearts: A Closer Look At The Connection Between Hyperthyroidism And Coronary Vasospasm
Authors: Elahi Amna , Isidro Mateo Roselyn Cristelle 
Published: October 2023

Abstract
Disclosure: A. Elahi: None. R.I. Mateo: None.
The cardiovascular system is a major target of thyroid hormone action in which subtle changes in thyroid function can lead to cardiac complications such as coronary vasospasm. There are many proposed mechanisms in how this occurs, but further studies are needed to understand the specific pathophysiology. This case illustrates the clinical relevance of encountering a hyperthyroid patient complaining of chest pain and how to address it in real work practice. A 62 year old African American male with history of Graves hyperthyroidism, type 2 diabetes, hypertension, peripheral artery disease, and stroke with residual aphasia presented with acute onset chest pain, shortness of breath, and palpitations. He was noncompliant with his methimazole (MMI) and subsequent labs were significant for free T4 of 2.5 ng/dL, undetectable TSH, and free T3 of 11.53 pg/mL. His high sensitivity troponins were elevated at 29,569 ng/dL. EKG showed sinus tachycardia with T-wave inversions in leads II, III, and AVF with a bedside echo showing inferior lateral wall motion abnormality. He was started on MMI 20mg daily and admitted to the intensive care unit for non-ST elevation myocardial infarction management. Left heart catheterization (LHC) was done after 1 dose of MMI with findings suggestive of vasospasm; specifically, decreased blood flow of the right coronary artery which improved when the catheter was withdrawn and significant dampening of the arterial wave form of the left main coronary artery. Given the unclear differentiation between true coronary artery disease and vasospasm he needed a repeat LHC once his hyperthyroidism was more controlled. His free T3 levels were monitored every 1-2 days with administration of escalating doses of MMI up to 40mg daily. By day 7 of admission, his free T3 level was 4.54 pg/mL, free T4 was 2 ng/dL and repeat LHC was performed showing open vessel lumens with multiple occlusions requiring 2 stents in the right coronary artery and 1 stent in the left circumflex artery. Given that thyroid hormone receptors are present in the myocardium and vascular tissue, alterations in thyroid hormone concentration can affect cardiovascular function. The documentation of coronary spasm, however, is rare and to date, there are only a few limited cases describing the underlying pathophysiology. This case illustrates via cardiac catheterization images and corresponding labs, the positive correlation of coronary vasospasm with thyroid hormone levels in hyperthyroidism.
Presentation: Thursday, June 15, 2023
THU658 My Giant Calves Gave Up My Diagnosis: An Extreme Manifestation Of A Very Rare Syndrome With A Severe Elevation Of Tsh Levels
Authors: Castro Feliu Edgar Emanuel , De Freitas Angelica Ludena , Torres Rodríguez Alexis , Irizarry Gabriel 
Published: October 2023

Abstract
Disclosure: E.E. Castro Feliu: None. A. Ludena De Freitas: None. A. Torres Rodríguez: None. G. Irizarry: None.
Hoffmann’s Syndrome is a rare type of hypothyroidism myopathy in adults that classically presents with muscle cramps, weakness, muscle stiffness, hyporeflexia, delay deep tendon reflexes and pseudohypertrophy. This is the case of a 55-year-old male with history of poorly controlled hypothyroidism and medication non-compliance who was admitted to our institution for non-purulent cellulitis. Vital signs were within normal limits and Body Mass Index was 41.1. Upon physical examination flat affect, periorbital edema, moon facies features and macroglossia were distinguished. Skin had a doughy texture with areas of ichthyosis at upper and lower extremities. Goiter was absent. The most remarkable finding was bilateral calf hypertrophy, with measurements of 56 cm and 55.5 cm in diameter of right and left calves respectively. There was no tenderness to calf palpation and Homan’s sign was absent. Laboratories revealed dyslipidemia with a cholesterol of 308 mg/dL, triglycerides of 782 mg/dL, HDL of 26 mg/dL and LDL of 216 mg/dL with elevated inflammatory markers including sedimentation rate of 77 mm/hr and C-reactive protein of 6.45 mg/dL. Hypothyroidism was suspected therefore thyroid studies were ordered, which was compatible with severe hypothyroidism demonstrated by a record level TSH of 523 lU/ml. Other reported levels were Free T3 0.94pg/ml, total T3 0.5 ng/ml, free thyroxine &lt;0.07 ng/dL, thyroid peroxidase &lt;4, and thyroglobulin AB 19 IU/ml. Hoffmann’s Panel was confirmatory for this diagnosis reporting elevated levels of CPK 1509 U/L, LDH serum of 383 U/L and aldolase of 9.2 u/L. Ultrasound of the neck was non-contributory. Patient received antibiotic therapy for his skin infection and was also treated with IV Levothyroxine, which was prescribed orally upon discharge. Myopathy may be present in patients with longstanding untreated hypothyroidism in which pseudohypertrophy may occur, sometimes involving calf muscles (gastrocnemius). Hoffmann’s Syndrome is associated with changes in muscle fiber type from fast twitch type II to slow twitch type I and alteration of oxidative muscle enzyme activity with deceased calcium ATPase activity of fast twitch type II fibers leading to delayed relaxation. Biopsy of the affected muscle may reveal fiber necrosis, atrophy, hypertrophy with increased number of nuclei and increased connective tissue. Most cases of Hoffmann’s Syndrome improve after treatment with Levothyroxine, therefore, implementing this management on time can be curative. This case highlights the importance of considering this diagnosis when muscle dystrophies are studied and myopathic disorders are suspected, even in the absence of overt manifestations of hypothyroidism.
Presentation: Thursday, June 15, 2023
THU666 Should We Think About Thyroid Disease In A Patient With Thymoma Related Myasthenia Gravis?
Authors: Wintermyer Gelareh , Villanueva Erika 
Published: October 2023

Abstract
Disclosure: G. Wintermyer: None. E. Villanueva: None.
Oftentimes, Graves and Myasthenia Gravis present with very similar symptoms. This can complicate diagnoses of either. At the same time, Graves can cause thymic hyperplasia, and there is a link between Myasthenia Gravis and thymoma. In the following, we discuss a case that presented all three: 59-year-old female with PMHx of hyperlipidemia, GERD, hoarseness, and anxiety developed a sudden diplopia, unintentional weight loss, tremor, palpitation, and ptosis for approximately one week. She had an eye exam and was recommended to have an MRI/MRA of brain and new blood work including CBC, CMP, TSH, Free T4, T3, Acetylcholine receptor antibody, and ANA. TSH came back suppressed and undetectable, Free T4 6.4ug/dL and T3 40 ug/dL. ANA and Acetylcholine receptor antibody were both high. Later, Anti-TPO and TSI measured 235 IU/mL and 34.5 IU/L respectively. Also, due to high concern for stroke given her symptoms, patient had ED visit. While having stroke workup in ED, her CTA of the neck revealed incidental finding of mediastinal mass that was concerning for possible thymoma. Stroke was ruled out. Patient was referred to our endocrinology clinic for her thyrotoxicosis. She was started on Methimazole 30 mg daily and Propranolol 60 mg daily. In the meantime, patient started to see neurologist for her Myasthenia Gravis. The neurologist started her on Prednisone 5 mg daily and Pyridostigmine60 mg daily. She was also referred to thoracic surgery for mediastinal mass resection. She received lugol 7 days prior to surgery to prevent intraoperative thyroid storm. Patient successfully had the surgery, and the mass was removed. The result was thymic hyperplasia. She was clinically well after surgery, though her ocular symptoms worsened by tapering steroids. Patient also had trial of plasma exchange which helped with her ocular symptoms. Her hyperthyroidism symptoms and thyroid function improved. She gradually was able to take a lower dose of methimazole. Patient currently is on Methimazole 5 mg without any complications. Clinicians are advised to always rule out any possibility of thyroid disease in patients that are suspicious for Myasthenia Gravis especially if Myasthenia Gravis is secondary to thymoma. Neglecting thyroid diseases in this group can cause serious consequences including intraoperative thyroid storm. Also, by early diagnosis of both Myasthenia Gravis and hyperthyroidism, there will be a better and faster resolution in patients’ symptoms.
Presentation: Thursday, June 15, 2023
THU676 Real-time Assessment Of The Beneficial Role Of Computer-Aided Diagnosis In The Diagnosis Of Thyroid Nodules On Ultrasound
Authors: Kim Youngsook , Shin Sungjae , Lee Eunjung , Kim Daham , Young Kwak Jin 
Published: October 2023

Abstract
Disclosure: Y. Kim: None. S. Shin: None. E. Lee: None. D. Kim: None. J. Kwak: None.
Objective: Computer-aided Diagnosis (CAD) has been applied in various medical fields. SERA (SEveRance Artificial intelligence program) is a deep convolutional neural network algorithm. We conducted this study to evaluate whether CAD-SERA helps diagnose the malignancy when the ultrasound was used by physicians with low levels of experience and to compare with the experienced radiologist. Methods: In real-time, an inexperienced physician and a radiologist simultaneously assessed the same thyroid nodules to determine malignancy and performed CAD. The diagnosis was changed if it was necessary to correct it by referring to the CAD results, and this was compared with the surgical pathology or biopsy pathology. Results: We evaluated 191 thyroid nodules in 179 patients. Area Under the Receiver Operating Characteristics (AUROC) was analyzed with the diagnoses with/without CAD assistance and pathology results. The AUROC of the inexperienced physician was 0.716, and when assisted by CAD that increased to 0.740 (Accuracy 73.82 -&gt; 76.44%). In the case of the radiologist, AUROC without CAD assist was 0.868 and 0.880 with the assist of CAD (Accuracy 84.29 -&gt; 85.86%). Conclusion: CAD improves diagnostic performance in the diagnosis of thyroid nodules in various experienced physicians in ultrasound. In particular, the extent of this is greater in physicians with less experience in ultrasound.
Presentation: Thursday, June 15, 2023