bluuebunny/crossref_metadata_2025_split huggingface dataset:
FRI546 VRDN-001, A Full Antagonist Antibody To IGF-1 Receptor In Development For Thyroid Eye Disease (TED): Pharmacodynamic Responses In Healthy Volunteers And Patients With Active TED
Authors: Foster Kelly , Dickinson Brent A , Summerfelt Rochelle M , She Angela , Bedian Vahe , Katz Barrett 
Published: October 2023

Abstract
Disclosure: K. Foster: Employee; Self; Viridian Therapeutics Inc. B.A. Dickinson: Employee; Self; Viridian Therapeutics Inc. R.M. Summerfelt: Employee; Self; Viridian Therapeutics Inc. A. She: Employee; Self; Viridian Therapeutics Inc. V. Bedian: Employee; Self; Viridian Therapeutics Inc. B. Katz: Employee; Self; Viridian Therapeutics Inc.
Introduction: VRDN-001, a full antagonist antibody to IGF-1 receptor (IGF-1R), is in development for the treatment of thyroid eye disease (TED). Clinical and preclinical evidence demonstrate IGF-1R antagonism reduces the inflammation and proptosis that occur in TED. We provide pharmacodynamic (PD) results in healthy volunteers and TED patients from our ongoing phase 1/2/3 clinical trial (NCT05176639) evaluating VRDN-001. Methods: Healthy volunteers (HVs) and patients with active, moderate-to-severe TED were randomized 3:1 to receive 2 intravenous infusions 3 weeks apart (i.e., at week 0 and week 3) of either VRDN-001 (at 3-20 mg/kg) or placebo. PD parameters (IGF-1 serum levels) were assessed through 7 weeks. Results: Thirteen HVs received either placebo (n=3) or VRDN-001, 3 mg/kg (n=3), 10 mg/kg (n=3), or 20 mg/kg (n=4). Additionally, 16 TED patients received either placebo (n=4), 10 mg/kg of VRDN-001 (n=6), or 20 mg/kg of VRDN-001 (n=6). Baseline characteristics were similar across all TED cohorts. All VRDN-001 doses (3-20 mg/kg) elicited rapid, sustained, and similar increases in IGF-1 serum levels, a biomarker for target engagement and IGF-1R inhibition. In HVs receiving VRDN-001 (n=10), IGF-1 serum levels increased within a day of the first infusion for all doses, reaching 4-6-fold above baseline; levels continued to increase after the second infusion, ultimately reaching 4-9-fold above baseline. In TED patients receiving VRDN-001 (n=12), IGF-1 serum levels increased for both doses 2-6-fold above baseline after the first infusion, and further increased after the second infusion, ultimately reaching levels 4-9-fold above baseline. No increases in IGF-1 serum levels occurred for placebo. Conclusions: Two infusions of VRDN-001 in healthy volunteers as well as TED patients elicited rapid and sustained increases in IGF-1 serum levels that were similar across groups, indicating maximal target engagement at all doses tested. Results from an additional ongoing cohort of 3 mg/kg in TED patients will further inform optimal VRDN-001 dosing and potential treatment regimens to balance efficacy and safety and minimize treatment burden in TED.
Presentation: Friday, June 16, 2023
FRI195 Tuberculosis and Adrenal Glands: The Great Forgotten
Authors: Vina Isabel , Sánchez Raquel , Fernández Ivonne C , Vázquez Clotilde 
Published: October 2023

Abstract
Disclosure: I. Vina: None. R. Sánchez: None. I.C. Fernández: None. C. Vázquez: None.
Background: Tuberculous adrenalitis is an extremely rare cause of Addison disease in developed countries. Since more than 80% of the primary adrenal insufficiency cases in the developed world are caused by autoimmune disease, tuberculous adrenalitis often go unnoticed. The aim of this case report is to remember that, even if it is not frequent, TB cannot be overlooked as a cause of longstanding primary adrenal insufficiency, even without evidence of pulmonary or extra glandular TB disease. Herein, we reported a case of bilateral tuberculous adrenalitis, wherein the patient initially presented with gastrointestinal symptoms, hyperpigmentation, bilateral adrenal masses, and no evidence of extra-adrenal tuberculosis. Case report: A 57-year-old woman from Madrid with no medical relevant history, was admitted to our hospital with 4 months of evolution of asthenia, weight loss (-8kg) and nausea that in recent days has been accompanied by fever and anorexia. He also refers progressive hyperpigmentation for the past 3 years. Denies recent travel abroad. On physical examination hypotension (80/53 mmHg) and generalized hyperpigmentation predominantly in the oral mucosa stand out. Blood test: Glu: 41 mg/dL, Na+: 122 mmol/L, K+: 4.8 mmol/L, ACTH: 922 pg/mL, Cortisol: 4.63 ug/dL, Anti-Hydroxylase Ab and Anti-Adrenal glands Ab: negative
A computed tomography scan of the abdomen with intravenous contrast revealed bilaterally enlarged adrenal glands with small bilateral calcifications (12-18mm). TB QuantiFERON test: positive. She was initially treated with saline serum and intravenous hydrocortisone causing her symptoms to improve significantly in a few days and was subsequently discharged on hydrocortisone and fludrocortisone and proper treatment for TB Adrenalitis and follow-up in outpatient clinics. Conclusions: Although not frequent, infectious causes should always be kept in mind, such as the etiology of adrenal insufficiency in a patient with long-term compatible symptoms, even though it is a developed country, given world globalization, which makes infectious diseases highly transmissible between countries and continents.
Presentation: Friday, June 16, 2023
SAT450 High Diagnostic Yield Of NGS Analysis In Congenital Hypothyroidism With Thyorid Dyshormongenesis
Authors: Joo Eunyoung , Kim Sujin , Lee Ji-Eun 
Published: October 2023

Abstract
Disclosure: E. Joo: None. S. Kim: None. J. Lee: None.
Introduction: Congenital hypothyroidism is the most common neonatal metabolic disorder and detected at a rate of 1 in 3000 to 4000 live births. 10-15 % of congenital hypothyroidism is caused by thyroid dyshormonogenesis. And Its clinical manifestations are individually different. Thus, to evaluate exact causes and predict clinical course for congenital thyroid dyshormonogenesis and establish precise strategies for treatment, we conduct Next-Generation Sequencing (NGS) to patients who diagnosed congenital hypothyroidism with normal thyroid gland and analysis the results. Methods: We conducted NGS to 31 patients patients who were diagnosed congenital hypothyroidism with normal contour of thyroid gland in ultrasonography from Jan. 2018 to April. 2022 in a single university hospital. We also analyzed their thyroid function test results, dose of levothyroxine and clinical manifestations. Result: Among the 31 patients, 25patients were detected from NGS. 4patients have oligogenic mutations. 7 DUOX2 variants were detected in 7 patients (22.6%), 3 DUOXA2 variants were detected in 4 patients (12.9%), 4 TSHR variants were detected in 7 patients (22.6%) 5 TG variants were detected in 4 patients (12.9%), 2 GLIS3 variants in 2 patients (6.5%), 1 TPO variants in 1 patient, 1 THRB variants in 1 patient, 1 NKX2-1 variants in 1 patient, 1 TRH variants in 1 patient, 1 SLC5A5 variants in 1 patient. The patients with GLIS3 stop levothyroxine at 3years old and have remission. The patients with DUOX2 variants and DUOXA2 variants showed low remission rate. DUOXA2 variants has high association with goiter. None of the patients with TSHR c.1349G&gt;A mutation to stop medicine. But patients with other mutation of TSHR stop levothyroxine at 3 years old and have remission. None of the patients with TG variants showed remission. The patients with GLIS3 have remission at 3 years old. Conclusions: We cautiously recommend that using the NGS to strategize treatment plan for CH based on the clinical manifestations and genetic analysis of the family members of the index patients.
Presentation: Saturday, June 17, 2023
SAT451 High-throughput Measurement Procedure Of Free Thyroid Hormones In Serum Based On Equilibrium Dialysis ID-LC/MS/MS
Authors: Zhang Li , Ribera Ashley , D'Zio Zachary , Doty Alex , Sugahara Otoe , Ying Tse Chui , Danilenko Uliana , Vesper Hubert W 
Published: October 2023

Abstract
Disclosure: L. Zhang: None. A. Ribera: None. Z. D'Zio: None. A. Doty: None. O. Sugahara: None. C. Tse: None. U. Danilenko: None. H.W. Vesper: None.
A Reliable and accurate measurement of serum free thyroxine (FT4) is critical for diagnosis and treatment of thyroid disorders. Immunoassays (IAs) are most popularly used for FT4 measurements in-patient care. However, there are concerns about the accuracy of FT4 IAs. A reference measurement procedure (RMP) for FT4 based on well-defined equilibrium dialysis (ED) of serum has been established for standardization of routine FT4 IAs. FT4 RMP is highly accurate and precise, while it is labor-intensive and time-consuming which is not intended for routine clinical application. In the current study, we aim to develop a high-throughput FT4 method based on ED ID-LC/MS/MS that can be traceable to the RMP. FT4 in dialysate was isolated from protein-bound T4 in serum by using a commercially available micro-ED plate after 18-hours ED. The 13C6 labeled T4 was spiked into collected dialysate as an internal standard. FT4 in dialysate was extracted by using 96-well C18 SPE plate. FT4 in the samples was quantitated by using LC/MS/MS. The certified primary reference material was used to for assay calibration. T4, T3, reverse triiodothyronine (rT3), and other interferences in the dialysate were resolved on a C18 UPLC column within 4 min. The linear range of the routine FT4 assay covered 1-100 pg/mL. The assay sensitivity allowed detection of 0.3 pg/mL FT4 in serum, which is sufficient for FT4 measurement covering clinically relevant ranges including hypothyroid patient samples. Method comparison showed good agreement between our high-throughput method and RMP in Deming regression analysis with slope close to 1, while there was significant bias of IA from RMP. The intra and inter-day CV% of the assay was 6.96 and 3.38 %, respectively. The use of a micro-ED plate together with automation system could improve the throughput of the procedure. The accuracy, precision, and sensitivity of our method are suitable for the high-throughput FT4 measurements in clinical laboratories and large epidemiologic studies. The traceability of the described FT4 method to RMP can support the standardized FT4 measurements in patient care.
Presentation: Saturday, June 17, 2023
SAT465 Spectral Doppler Ultrasound in Thyrotoxicosis, a Valuable Bedside Tool
Authors: Morkos Michael , Raju Karishma , Ibrahim Katherine 
Published: October 2023

Abstract
Disclosure: M. Morkos: None. K. Raju: None. K. Ibrahim: None.
Objective: To assess the utility of spectral Doppler ultrasound as a bedside tool in the differentiation of various etiologies of thyrotoxicosis Research and Design Methods: This is a retrospective cross-sectional study of patients diagnosed with thyrotoxicosis at an academic outpatient endocrinology clinic from August 2019 to November 2022. The peak systolic velocities (PSV) were measured using spectral Doppler ultrasound at the superior and inferior thyroid arteries bilaterally. PSV ≥40 cm/sec in at least a single thyroid artery was considered a specific cut-off for Graves’ disease and PSV of peri-nodular artery ≥ 25 cm/sec was considered a specific cut-off for toxic adenoma. Thyroid antibodies (thyroid stimulating immunoglobulin and thyroid receptor antibody) and occasionally thyroid scan were used to confirm the diagnosis. Descriptive statistics, Chi square, and t-test were utilized to describe and compare data. Results: We identified 73 patients who presented for evaluation and management of thyrotoxicosis, mean age ± standard deviation 45.2 ± 16.4 years, 54 (74.0%) were female, 49 (67.1%) Caucasian, 23 (31.5%) African American, and one (1.4%) was Asian. The confirmed diagnoses were 48 (65.8%) Graves’ disease, 13 (17.8%) thyroiditis, 4 (5.5%) toxic adenoma, 4 (5.5%) amiodarone-induced thyroiditis type 2, 1 (1.4%) toxic multinodular goiter, 1 (1.4%) had a normal repeat thyroid function testing, and 2 (2.7%) were unconfirmed. Diagnosis based on the initial assessment including the spectral Doppler was accurate in 65 (89.0%) of the patients and it was conclusive and confirmatory during the initial encounter in 55 (75.3%) of the patients before additional testing. Thyroid scan was obtained in 9 (12.3%) patients. Incorrectly diagnosed patients included Graves’ disease, thyroiditis, toxic adenoma, and unconfirmed diagnoses, two patients each, a total of eight patients. Conclusion: Spectral Doppler ultrasound can be an effective bedside tool in the clinical assessment of thyrotoxicosis.
Presentation Date: Saturday, June 17, 2023
SAT470 Outcomes Of Radiofrequency Ablation For Autonomously Functioning Thyroid Adenoma- Mayo Clinic Experience
Authors: Dhanasekaran Maheswaran , Rajwani Aadil A , Castro M Regina , Morris John C , Schmitz John , Alan Lee Robert , Callstrom Matthew R , Stan Marius 
Published: October 2023

Abstract
Disclosure: M. Dhanasekaran: None. A.A. Rajwani: None. M.R. Castro: None. J.C. Morris: None. J. Schmitz: None. R.A. Lee: None. M. Callstrom: None. M. Stan: None.
Context: Autonomously functioning thyroid nodules (AFTNs) constitutes 5% of thyroid nodules and is the second most common cause of hyperthyroidism following Graves’ Disease. Untreated hyperthyroidism is associated with adverse cardiovascular and skeletal complications. Currently, radioactive iodine (RAI) and surgery are the standard treatment options for AFTNs, and both incur a risk of post-procedural hypothyroidism. To overcome this and other surgery/radiation-related complications, radiofrequency ablation (RFA) has been utilized in multiple countries (for both toxic and non-toxic thyroid nodules). It has been shown to induce significant nodule volume reduction along with restoration of normal thyroid function in many AFTNs. Methods: We present a single-center experience using RFA as an alternative treatment modality for AFTNs. The study's primary aim was to assess the efficacy of RFA in normalizing thyroid hormone concentration and restoring the euthyroid state. In addition, we analyzed the efficacy of RFA in nodule volume rate reduction (VRR) and its associated adverse events. Results: A total of 22 consecutive patients (17 F and 5 M) underwent RFA for a solitary AFTN (hot nodule in thyroid uptake and scan) under variable degrees of general anesthesia. 72% (n=16) had subclinical hyperthyroidism, 9% (n=2) had overt hyperthyroidism, and 18% (n=4) were biochemically euthyroid on anti-thyroid drugs (ATD). The mean age at the time of ablation was 52.09 years (SD= 14.6), with a mean BMI of 27.36 kg/m2 (SD= 4.67). Average pre-treatment TSH was 0.41 mIU/L (SD= 0.980) and free T4 1.29 ng/dl (SD= 0.33). The thyroid function was assessed after a single RFA session. TSH normalized in all patients within 3-6 months following the ablation. All four patients on ATD pre-treatment discontinued therapy within three months following the procedure. The average VRR (62.54%) was achieved within 3-6 months following the RFA, and importantly, none of the nodules grew back during the follow-up period (up to 24 months). Two patients (9%) developed transient tachycardia requiring short-term beta-blocker therapy, and two (9%) developed mild hypothyroidism requiring levothyroxine therapy. One patient, euthyroid post RFA, developed recurrent hyperthyroidism 45 months later and elected to undergo lobectomy. No serious adverse effects were noted in this cohort. Conclusions - RAI and/or surgery represent the standard of care for toxic adenomas but RFA shows excellent efficacy along with an excellent safety profile. Therefore at centers with RFA expertise it should be considered an alternative treatment strategy, avoiding radiation and surgery-related complications.
Presentation Date: Saturday, June 17, 2023
SAT474 A Case Report Of Moyamoya Disease Associated With Uncontrolled Graves' Disease
Authors: Tan Zi , Briggie Erin , Correia Marcelo 
Published: October 2023

Abstract
Disclosure: Z. Tan: None. E. Briggie: None. M. Correia: None.
Background: Moyamoya disease is an uncommon cerebrovascular disease that is featured by narrowing of large intracranial arteries and the development of prominent small-vessel collaterals. The etiology of Moyamoya disease is unknown, but it can be associated with multiple conditions including atherosclerosis, sickle cell disease, and Protein S deficiency. It is rarely associated with uncontrolled Graves’ disease. Clinical Case: A 37-year-old female with a history of Graves’ disease and type 1 diabetes presented with sudden onset of slurred speech and right-sided weakness. A CTA of the head and neck showed a small hypodensity in the left basal ganglia without corresponding perfusion deficit and narrowed left internal carotid arteries without focal stenosis. In addition, a brain MRI showed patchy infarcts in the left middle cerebral artery territory. A cervical and cerebral angiogram showed multiple areas of stenosis which was concerning for Moyamoya disease. She ultimately underwent balloon angioplasty of the left internal carotid artery with improvement in perfusion. During the workup for secondary causes of Moyamoya disease, her TSH was &lt; 0.01 µIU/mL (0.270-4.20 µIU/mL), with elevated T4 at 3.84 ng/dl (0.80-1.80 ng/dl) and elevated TSI at 15.5 IU/L (&lt; 0.54 IU/L). Importantly, she was diagnosed with Graves’ disease 2 years before admission, and this condition has never been well controlled due to poor compliance with methimazole. A TSH measured 5 months before admission was also undetectable with elevated T4 at 2.8 ng/dl. Her other workups for Moyamoya disease were negative including HIV antigen/antibody, syphilis IgG antibody, Lyme disease IgG & IgM antibodies, hepatitis panel antibodies, ANA, ANCA, free protein S, dsDNA antibody, factor 5 Leiden mutation, vascular endothelial growth factor-D and urine drug screening test. She started methimazole 20 mg daily and was discharged to acute rehabilitation. After rehabilitation, her Graves’ disease is slowly improving with most recent TSH &lt; 0.008 µIU/mL and free T4 at 2.39 ng/dl. She is almost back to her baseline with significant improvement in speech and strength. Conclusion: Uncontrolled Graves’ disease should be considered in the differential diagnosis of Moyamoya disease in young subjects who present with stroke-like symptoms.
Reference: Ischemic Stroke and Intraventricular Hemorrhage in Moyamoya Syndrome Associated With Graves' Disease: A Case Report. Neurologist 2022
Presentation Date: Saturday, June 17, 2023
FRI201 A Rare Case Of Severe Ectopic ACTH Syndrome Presenting With Thrombocytopenia And Hemolytic Anemia
Authors: Mohammad Nazar , Scott Alyssa , Raja-Khan Nazia 
Published: October 2023

Abstract
Disclosure: N. Mohammad: None. A. Scott: None. N. Raja-Khan: None.
Background: Ectopic ACTH syndrome (EAS) is a rare but serious endocrine emergency requiring urgent diagnostic and therapeutic intervention due to the severity of hypercortisolism induced by ACTH-secreting tumors. Here we present an unusual case of EAS associated with hemolytic anemia and thrombocytopenia. Case Presentation: A 64-year-old female with a history of COPD presented with ongoing fatigue, weakness, and bruising of the extremities. The patient was lethargic, then became hypotensive and encephalopathic. Physical exam revealed diffuse ecchymoses. Patient otherwise had no symptoms or physical stigmata of Cushing’s. Labs were significant for hypokalemia, hemolytic anemia, thrombocytopenia, and lactic acidosis. CT demonstrated consolidation in the right hilum, right posterior lung pleural thickening, hypodense lesion in the right hepatic lobe, and bilateral adrenal hyperplasia. Treatment with antibiotics and plasmapheresis was initiated due to suspicion for thrombotic thrombocytopenic purpura and sepsis. Further workup revealed elevated ACTH 1819pg/mL and AM cortisol 102.4ug/dL. Pituitary MRI was normal. Treatment with etomidate infusion was recommended given the severity of hypercortisolism which was refractory to ketoconazole. However, due to clinical deterioration comfort care was initiated. Autopsy revealed metastatic small cell lung cancer. Conclusion: To our knowledge, this is the first report of EAS presenting with thrombocytopenia and hemolytic anemia. Urgent diagnosis and treatment of hypercortisolism is needed to reduce morbidity and mortality in EAS. While surgical excision of the ACTH-secreting tumor is the mainstay of treatment, cortisol levels should be decreased with medication prior to surgery. In severe cases that are refractory to ketoconazole, etomidate infusion can be considered.
Presentation: Friday, June 16, 2023
SAT511 High Intensity Focused Ultrasound (HIFU) Ablation for Benign Thyroid Nodules: A Single-Center Cohort
Authors: Mavromati Maria , Meyer Patrick , Vermeulen François , Demarchi Marco , Saiji Essia , De Vito Claudio , Jornayvaz Francois , Leboulleux Sophie , Wolff Adriana , Triponez Frédéric 
Published: October 2023

Abstract
Disclosure: M. Mavromati: None. P. Meyer: None. F. Vermeulen: None. M. Demarchi: None. E. Saiji: None. C. De Vito: None. F. Jornayvaz: None. S. Leboulleux: None. A. Wolff: None. F. Triponez: None.
Introduction:Benign thyroid nodules may increase in size over time and cause local compressive symptoms. Current guidelines suggest surgery for benign symptomatic nodules, however, complications such as hypothyroidism, bleeding, infection and recurrent laryngeal nerve injury are of concern for a growing number of patients. Minimally invasive techniques may therefore be an alternative to surgical resection. The objective of our study was to evaluate the efficacy and safety of high intensity focused ultrasound (HIFU) ablation in a single-center cohort of benign symptomatic thyroid nodules.Materials and methods:Between February 2021 and May 2022, 13 patients were treated by HIFU for a single benign solid symptomatic thyroid nodule. Benign nature of thyroid nodules was confirmed by a Bethesda II result in fine-needle aspiration, before HIFU. Treatment was performed under hypnosis, carried out by an experienced anesthesiologist. Patients were evaluated by clinical examination and ultrasound at 6 and 12 months after treatment. Results: A total of 13 patients (12 female and 1 male) were treated with HIFU for a single solid symptomatic benign thyroid nodule. Mean age was 57 years (range: 48-67 years). Thyroid nodules had an mean maximum diameter of 48 mm (range: 31-66 mm) and a meanvolume of 28.4 mL (range: 8.5-53 mL). At 12 months after HIFU, 4 patients underwent surgical ablation (31%) because of nodule growth (n=2, 15.4%) or persistent local compression (n=2, 15.4%). Those nodules were benign on final histology. Among non-operated nodules, mean decrease of volume at 6 months was 35% (range: 20-46%) and smaller nodules showed a better response to treatment. Altogether, 8 patients (61.5%) reported a clinical improvement 6 months after treatment, while 4 patients (31%) underwent surgery. Treatment was well tolerated in the majority of patients and had to be stopped because of pain in only one case (7.7%). There were no treatment-related local complications. Conclusion:High-intensity focused ultrasound (HIFU) ablation for benign symptomatic thyroid nodules is a safe minimally invasive technique but volume reduction was only 20-46% at 6 months, while 31% of patients required surgery after all. This could be attributed to the large initial volume of nodules included in our cohort. Clinical hypnosis is a useful alterative for pain management.
Presentation Date: Saturday, June 17, 2023