bluuebunny/crossref_metadata_2025_split huggingface dataset:
PSAT379 Performance of a Raman Fingerprint in Thyroid Nodules with Indeterminate Cytology: A Prospective Blinded Monocentric Study
Authors: Palermo Andrea , Sodo Armida , Naciu Anda Mihaela , Gioacchino Michael D , Paolucci Alessio , Masi Alessandra D , Maggi Daria , Crucitti Pierfilippo , Longo Filippo , Perrella Eleonora , Taffon Chiara , Verri Martina , Ricci Maria Antonietta , Crescenzi Anna 
Published: November 2022

Abstract

Background
Molecular analysis of thyroid fine-needle aspiration biopsy (FNA) was proposed to improve indeterminate nodules management. However, sensibility and specificity as well as the cost of molecular diagnostics require to be improved to increase their cost-effectiveness for medical practice setting. Raman spectroscopy (RS) demonstrated ability in separating benign from malignant thyroid lesions in surgically removed tissues, based on specific RS profile. This study aimed to investigate the diagnostic performance of RS on cytological samples obtained by thyroid FNA.

Methods
In this prospective, blinded monocentric study, we enrolled 123 patients with indeterminate or worse cytological diagnosis, candidate to surgery according to international guidelines, and submitted to RS analysis of FNA samples. Cytology specimens were evaluated in agreement to Italian Reporting System for Thyroid Cytology1 as follows: TIR1 (non-diagnostic), TIR1C (non-diagnostic-cystic), TIR 2 non-malignant/benign, TIR3A (low-risk indeterminate lesion), TIR3B (high-risk indeterminate lesion), TIR 4 (suspicious of malignancy), or TIR 5 (malignant). As previously published2, the two diagnostic subcategories referred to indeterminate nodules with low (TIR3A) and high risk (TIR3B) of malignancy, may be respectively compared to the class III and Class IV of The Bethesda System for Reporting Thyroid Cytopathology.
We compared RS, cytology and final histology, as reference standard, using various statistical approaches.
Findings: Our study population included 37 TIR3A, 32 TIR3B, 16 TIR4 and 38 TIR5; the 30.9% of patients had benign histological diagnosis after surgery. In particular, 72.9% of patients classified TIR3A and 31.3% TIR3B had benign histological diagnosis. RS analysis of FNA samples had overall specificity of 86.8% in predicting thyroid malignancy. In indeterminate cytological categories, RS specificity was 86.5%. In patients with TI-RADS score four or five, the specificity of RS increased to 87.5% for TIR3A and reached 100% in TIR3B.; if considering RS positive test, unnecessary surgery was reduced to 7.4% in the whole sample, 33.3% in TIR3A, and 6.7% in TIR 3B.
Interpretation: We demonstrated for the first time that RS represents a valuable tool for thyroid cytology and a valid alternative to molecular analyses, able to improve management and reduce unnecessary surgery in indeterminate nodules.
Funding: This study was supported by Ministero della Salute, through TIRAMA project (RF-2018-12366568).
1 J Endocrinol Invest. 2014;37(6): 593-599. doi: 10.1007/s40618-014-0062-0
2Cytopathology. 2021;32(6): 714-717.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT381 Rising Preoperative TPO Titers Decrease the Risk for Differentiated Thyroid Cancer in a Linear Fashion: A Retrospective Analysis of 1620 Consecutive Thyroid Surgeries
Authors: Paparodis Rodis , Livadas Sarantis , Karvounis Evangelos , Bantouna Dimitra , Zoupas Ioannis , Imam Shanawaz , Jaume Juan 
Published: November 2022

Abstract

Introduction
Chronic lymphocytic thyroiditis is an important risk factor for differentiated thyroid cancer (DTC) in surgical series, but the role of thyroid peroxidase antibodies (TPO) seems less clear in that regard. We designed the present study to evaluate that effect in our large patient population.

Methods
We recruited subjects operated with total thyroidectomy in 4 sites (USA: 1, Greece: 3) during a period of 14 consecutive years. We gathered data on TPO antibodies titers measured with commercially available radioimmunoassays, and reviewed data on surgical pathology. TPO≥34IU/ml was deemed high (TPO+). Odds ratios (OR) for DTC were calculated with Fischer's exact test. p&lt;0.05 was deemed significant.

Results
We reviewed data on 8,425 thyroid surgeries, and TPO titers were available for 1,620 subjects: DTC n=702 (43.3%), benign pathology (BEN) n=918 (56.7%), TPO+ n=524 (32.3%) and TPO- (&lt;34IU/ml) n=1096 (67.7%). DTC was found with a lower frequency in TPO+ (183/524, 34.9%) compared to TPO- (519/1096, 47.4%) subjects, OR 0.60 (0.48-0.74, p&lt;0.0001). Subjects with the lowest TPO titers had the highest rate of DTC: TPO&lt; 10IU/ml n=338/635 (49.3%), TPO 34-100IU/ml n=69/162 (42.6%), TPO 100-500IU/ml n=70/168 (41.7%), TPO 500-1000IU/ml n=16/50 (32.0%), TPO &gt;1000IU/ml n=28/144 (19.4%), p&lt;0.0001.

Conclusions
High TPO Antibodies appear protective against DTC in our large multicentre cohort of patients operated with a total thyroidectomy. Rising preoperative TPO titers confer linearly increasing protection against DTC in the surgical specimen. More research is needed to fully understand the role of thyroid autoimmunity in the genesis of DTC.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSAT384 Familial Non-Medullary Thyroid Cancer — Does The Number Of Alanine Residues In The FOXE1 Gene Play A Role?
Authors: Trofimiuk-Muldner Malgorzata , Domagala Bartosz , Koziara Michal , Skalniak Anna , Hubalewska-Dydejczyk Alicja 
Published: November 2022

Abstract

Familial non-medullary thyroid cancer (FNMTC) constitutes about 3–9% of all thyroid cancers. One of the genes believed to predispose to non-syndromic FNMTC is FOXE1. It contains a polyalanine tract (polyAla) with a variable number (11–22) of alanine residues. This length polymorphism could lead to changes in the FOXE1-encoded protein (FOXE1 transcription factor) structure and predispose to papillary thyroid cancer (PTC).
The aim of the study was to investigate the relationship between the length of the polyAla tract and the stage of PTC at diagnosis (according to AJCC 8th edition) in patients with FNMTC.
The study included 27 patients (from twenty families) with familial PTC (at least two family members were diagnosed with the disease). The length of the polyAla tract of the FOXE1 gene was analyzed. The following numbers of polyAla variants were detected: 11-Ala – 2, 12-Ala – 1, 14-Ala – 23, 16-Ala – 28 alleles. The staging at diagnosis was compared in two groups: less than 16-Ala and at least 16-Ala. The stages of pT1a and pT1a (m) were found in 20 alleles in the less than 16-Ala group, whereas in 16 alleles of the at least 16-Ala group, pT1b-pT2(m) was the most common (p = 0.039). Lymph node metastases were found more frequently in the less than 16-Ala group than in the at least 16-Ala group but this difference was not statistically significant (10 vs. 3 respectively; p = 0.680).

Conclusions
The analysis of the length of the polyAla tract may be a useful diagnostic tool in predicting the course of PTC in patients with a positive family history.
The research was funded by the Jagiellonian University Medical College grant No N41/DBS/000087.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
PSUN36 Subacute Thyroiditis Following mRNA Vaccine for COVID-19 in a 40-Year-Old Male Patient
Authors: Munir Kashif , Ahmed Amiya , Kim Yoon Kook , Siddiqi Muhammad , Malek Rana 
Published: November 2022

Abstract

Background
Subacute thyroiditis typically occurs a few weeks after a viral infection and is the most common cause of painful thyrotoxicosis. Cases of subacute thyroiditis have been reported following both inactivated and live-attenuated vaccines, such as the influenza vaccine. We describe a case of subacute thyroiditis in the setting of the Pfizer-BioNTech mRNA COVID-19 vaccination.

Clinical Case
A 40-year-old man with no significant medical history presented with signs and symptoms of thyrotoxicosis after receiving the Pfizer COVID-19 vaccine. Symptoms began 3 days after receiving the second vaccine dose and included 9 kg unintentional weight loss, arthralgia in both knees, palpitations, fatigue, bilateral thigh weakness, and diffuse neck swelling, pain, and tenderness. Initial treatment with antibiotics for presumed upper respiratory infection did not improve symptoms, and PCR testing for COVID-19 infection was negative. Thyroid ultrasound obtained 15 days after symptoms onset revealed a 4 cm nodule in the left lobe of the thyroid gland. Testing 30 days after onset of symptoms demonstrated TSH&lt;0.005 uIU/mL (ref: 0.45-4.50 uIU/mL), elevated free T4 of 2.53 ng/dL (ref: 0.82-1.77 ng/dL), and elevated erythrocyte sedimentation rate of 42 mm/hr (ref: 0-15 mm/hr). Repeat labs and imaging 9 days later demonstrated improvement with a TSH of 0.071 uIU/mL and free T4 of 1.04 ng/dL as well as decreased nodule size (2.5 cm). At this time, the patient reported resolution of all symptoms and return to baseline weight. Thyroid ultrasound obtained 3 months after symptoms onset demonstrated normal thyroid without detectable nodules or enlargement, and complete normalization of TSH and free T4 levels to 4.250 uIU/mL and 1.22 ng/dL, respectively.

Conclusion
This is the second documented case of subacute thyroiditis following the Pfizer-BioNTech vaccine for COVID-19 in a male patient. A literature review demonstrates 12 other cases of subacute thyroiditis following the Pfizer-BioNTech mRNA COVID-19 vaccine, 3 cases following the Moderna mRNA COVID-19 vaccine, 8 cases following the AstraZeneca recombinant COVID-19 vaccine (one male patient), 4 cases following the CoronaVac inactivated SARS-CoV-2 COVID-19 vaccine, 1 case following the Covaxin inactivated SARS-CoV-2 COVID-19 vaccine, and 3 cases following the Janssen viral vector SARS-CoV-2 COVID-19 vaccine. Albeit uncommon, providers should be aware that transient thyrotoxicosis following COVID-19 vaccination may occur. Similar to subacute thyroiditis due to viral infection, the clinical course is generally self-limited with patients returning to a euthyroid state within a few months. Usual management of subacute thyroiditis with symptomatic management and watchful waiting is appropriate.
Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
PSUN39 A rare presentation of autoimmune thyroid diseases and myasthenia gravis: A clinical case report
Authors: Udorji Ogochukwu , Trikudanathan Subbulaxmi , Desantis Anthony 
Published: November 2022

Abstract

We report a case of a 37-years-old female that presented with a three-week history of diplopia, ptosis, muscle weakness, difficulty chewing, tachycardia, and fatigue; these clinical symptoms were concerning for acute myasthenia gravis crisis. The diagnosis of Myasthenia gravis was further confirmed by a positive immunology workup. Chest CT imaging during her assessment showed anterior mediastinal mass/enlarged thymus indicative of thymic hyperplasia. Medical therapy with intravenous immune globulin, pyridostigmine and further treatment with high-dose steroid. She had a positive response to treatment but still reported persistent symptoms of fatigue, tachycardia, and intermittent diplopia, raising suspicions for underlying Graves’ thyrotoxicosis. Thyroid function testing was performed which showed a very suppressed thyroid-stimulating hormone (TSH) and elevated Free t4 levels. Further workup for Graves thyroid autoimmune antibodies indicative of extremely elevated thyroid stimulating hormone receptor autoantibodies consistent with Graves’ disease. We initiated medical therapy for Graves’ disease with a beta-blocker and thioamide (methimazole). She endorsed progressive improvement in her symptoms following treatment for Grave's disease. She was discharged with high dose steroids, pyridostigmine, and appropriate therapy for Graves’ disease. She did well after her discharge from the hospital and six months afterwards she returned to the hospital for a robot-assisted right thymectomy. Final pathology report indicative of non-thymomatous myasthenia gravis. She continued to follow up with us in the endocrinology outpatient clinic. Her steroid therapy was tapered off and medical therapy for Graves’ disease was continued accordingly. She demonstrated a positive response to medical therapy with remarkable improvement in the remaining of her symptoms, especially her neurological and ocular symptoms after initiation of treatment for Graves’ disease.

Conclusion
we report two rare concomitant autoimmune diseases, myasthenia gravis, and Graves’ disease. Both conditions have similar overlapping clinical features making diagnosis and treatment challenging in clinical practice. It is well reported in clinical literature and studies that hyperthyroidism may worsen symptoms of MG and management of hyperthyroidism in the setting of MG may lead to worsening of myasthenia symptoms; hence, certain precautions should be taken to avoid worsening symptoms of myasthenia gravis. Therefore, we call for more case-control, case series and clinical trials to explore more clinical knowledge about the association between the two conditions and formulate better management strategies.
Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
RF11 | PSAT368 The role of thyroid peroxidase antibodies on the risk of thyroid cancer: a systematic review and meta-analysis of surgical cohort studies.
Authors: Anagnostis Panagiotis , Imam Shahnawaz , Jaume Juan , Paparodis Rodis , Livadas Sarantis , Karvounis Evangelos , Bantouna Dimitra 
Published: November 2022

Abstract

Introduction
Hashimoto's thyroiditis raises the risk for differentiated thyroid cancer (DTC) in surgical series, but the role of thyroid peroxidase antibodies (TPO) remains controversial in that regard. We designed the present study to evaluate the effect of preoperative TPO titers in the risk of DTC.

Methods
A comprehensive search was conducted in PubMed, CENTRAL and Scopus databases in November 2021 for the terms "thyroid cancer" and "TPO" or "peroxidase antibodies". We characterized the differential risk found in patients with high titers of TPO (TPO+), as compared to those with low or undetectable titers (TPO-) with regard to DTC. Data are expressed as odds ratio (OR) with 95% confidence interval (CI).

Results
We retrieved and reviewed 408 records; 21 retrospective cohort studies (2006-2022) from 7 countries and n=30,5536 subjects, fulfilled the eligibility criteria: 15 studies in East Asia with n=25,125 subjects (82.2%) and 6 studies in the Western world with n=5,428 subjects (17.8%)]. These comprised n=17,684 subjects with benign disease (57.9%) and n=12,869 with DTC (42.1%). The reference used for TPO+ was 23.6±18.8 (Range 5.1-60.0 IU/ml); n=6,307 patients were TPO+ (20.6%) and n=24,246 were TPO- (79.4%). DTC was present in n=2,960 TPO+ patients (46.9%) and n=9,909 TPO- patients (40.9), OR 1.28, (95%CI 1.21-1.35), p&lt;0.001.
A high titer of TPO was associated with increased risk for DTC in both Asian cohorts, [OR 1.36 (1.28-1.45, p&lt;0.001)] and Western world alike, [OR 1.15 (1.02-1.31), p=0.025]. That risk was statistically significantly higher in the Asian world cohorts as compared to the Western World cohorts, p&lt;0.001.

Conclusions
Thyroid peroxidase antibodies are an integral part of Hashimoto's thyroiditis, which is a well characterized risk factor for thyroid cancer and seem to increase that risk as well. That effect seems significantly higher in East Asia as compared to the Western World region. Further studies are needed to characterize the effects of the immune response, with regard to thyroid cancer risk.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Saturday, June 11, 2022 1:24 p.m. - 1:29 p.m.
RF11 | PSAT369 CDK7 and CDK9 Inhibition Induces RNA Polymerase II Ubiquitination and Proteasome Degradation in Thyroid Cancer Cells
Authors: Rajan Neel , Khanal Tilak , Adik Amy , Porter Kyle , Ringel Matthew 
Published: November 2022

Abstract
"Superhenhanced" transcription of specific oncogenes by aberrant looping of upstream enhancer elements to marked transcriptional regulatory regions is a mechanism of oncogene overexpression. Therefore, compounds that target key positive regulators of RNA polymerase II (RNAPII) activity, such as CDK7 and CDK9, can relatively selectively reduce expression of such superenhanced oncogenes and are in clinical trials. We have previously reported activity of the CDK7 inhibitor THZ1 in medullary thyroid cancer (MTC) along with identification of a superenhancer in RET. CDK7 inhibitors also are reported to be active in anaplastic thyroid cancer cell lines. In the present study, we extend this work to both CDK7 and CDK9 inhibitors, and to a more extensive set of thyroid cancer cell lines. We selected 8 thyroid cancer cell lines (TPC1, FTC133, BCPAP, SW1376; K1, THJ-16T, C643, and 8505C) from a variety of histological subtypes with different driver mutations for treatment with a CDK7 (THZ1) or CDK9 (AZD4573) inhibitors. Cell viability assays were performed to determine IC50 and Western blots were performed for target validation. IC50 values ranged from 5-100 nM for both compounds for all cell lines demonstrating broad activity and robust activity. Unexpectedly, both compounds inhibited both CDK7 RNAPII phosphorylation (Ser5) and CDK9 RNAPII phosphorylation (Ser2) due to a loss of total RNAPII protein levels in all cell lines. Further time course studies two cell lines, 8505C (BRAFV600E) and TPC1 (RET/PTC) showed the loss off RNAPII occurred rapidly (1-3 hours) with stable RNAPII mRNA levels by qRTPCR. We therefore hypothesized that RNAPII stalling induced by inhibition of CDK7 may cause loss of RNAPII protein stability through ubiquitination and proteasome-mediated degradation. Immunoprecipitation-Western blots demonstrated variable baseline levels of RNAPII ubiquitination in 8505C (low) and TPC1 (high) cells. THZ1 treatment induced ubiquitination of RNAPII in 8505C cells signficantly, while a modest increase beyond the higher baseline occurred in TPC1. Bortezomib (proteasome inhibitor) treatment rescued THZ1-reduced RNAPII protein levels in both cell lines. In summary, human thyroid cancer cell lines are broadly sensitive to CDK7 and CDK9 inhibitors. CDK 7 and 9 inhibitors reduce RNAPII levels and THZ1 induces RNAPII ubiquitination and proteasome degradation demonstrating a new mode of action for the reduced RNAPII activity induced by these inhibitors.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Saturday, June 11, 2022 1:42 p.m. - 1:47 p.m.
RF11 | PSAT370 I-PET Score: Combining Whole Body Iodine Scan and 18 Fluorodeoxyglucose Positron Emission Topography to Predict Progression in Thyroid Cancer
Authors: Wijewardene Ayanthi , Hoang Jeremy , Maw Aung Min , Gild Matti , Tacon Lyndal , Roach Paul , Schembri Geoffrey , Chan David , Clifton-Bligh Roderick 
Published: November 2022

Abstract

Introduction
A well-known 'flip flop' phenomenon exists between whole-body scans (WBS) and 18FFDG PET imaging in differentiated thyroid cancer (DTC) such that cancer progression is typically associated with reduced iodine uptake and increased FDG avidity. Patients with FDG avidity have a poor clinical outcome while those with iodine avid lesions are more responsive to radioactive iodine therapy (RAI) and have a better prognosis. A spectrum however exists, as thyroid cancers become less well differentiated, when they will be both iodine and FDG avid. Current scoring systems in thyroid cancer are limited to a single imaging data set. We propose a new scoring system (I-PET) combining WBS and FDG findings to identify patients more likely to be refractory to RAI, and who may be ideal candidates for 're-differentiation' before RAI treatment.

Methods
Retrospective analysis of 142 patients age &gt; 18 with differentiated thyroid cancer who had a 18FFDG PET and WBS within a 6 month period of each other between 2010 and 2020. Initial pair of 18F FDG PET and WBS were reviewed by two independent nuclear medicine physicians and an IPET score was assigned: IPET [0]: Iodine –ve, FDG –ve, IPET [1]: Iodine +ve, FDG –ve, IPET [2]: Iodine +ve, FDG +ve and IPET [3]: Iodine –ve, FDG +ve. Patients with FDG +ve lesions (I-PET 2 and I-PET 3) were further classified into group 'a' and 'b' if SUVmax was less than or greater than 5 respectively. Follow-up data was obtained by chart review. Progression was defined as either structural recurrence as per RECIST 1.1 or equivalent clinical assessment, or biochemical incomplete response with an unstimulated Tg &gt; 1ug/L. The study was approved by IRB (ETH00674/ STE01494).

Results
Of the 142 patients included in the study 121 patients had follow up data available for review. At baseline, 49 patients were classified as IPET [0], 10 as IPET [1], 16 as IPET [2] and 46 as IPET [3]. Progression was identified in 49% (59/121) patients; of which 54 were structural and 5 biochemical. Patients classified as [2b] and [3b] had a recurrence rate of 88% (7/8) and 78% (25/32) respectively, while IPET [0] patients had 22% (11/49) recurrence (p &lt; 0.001). Patients classified as IPET [3b] were 10.4 times more likely to commence on tyrosine kinase inhibitor therapy (p=0.005) and had a 8.1 times greater mortality rate (p=0.02) than patients in the other IPET groups.

Conclusion
IPET score is a novel scoring system incorporating WBS and 18FFDG PET imaging which predicts progression and death in patients with FDG avid thyroid cancer.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Saturday, June 11, 2022 1:48 p.m. - 1:53 p.m.
RF23 | PSAT365 An Open-Label Therapeutic Efficacy Study of Tirosint (Levothyroxine Sodium) Capsules in Thyroidectomized Patients Taking Proton Pump Inhibitors
Authors: Sachmechi Issac , Burman Kenneth D , Mautone Giuseppe , Lanzi Gabriele , Moriarty Patricia L , Scarsi Claudia , Wartofsky Leonard 
Published: November 2022

Abstract
Levothyroxine sodium (LT4) absorption is known to be affected by proton pump inhibitors (PPIs). Normal gastric acid secretion is important for the subsequent intestinal absorption of LT4. A reduced gastric acidity may diminish the dissolution of the LT4 tablet in the stomach and the release of LT4 to the gut. The dissolution profile of LT4 soft capsules has been reported to be less affected by pH than that of tablets. Previous studies in healthy subjects administered with LT4 and PPIs, as well as in hypothyroid patients with atrophic gastritis confirmed little or no impact of increased gastric pH on LT4 absorption when administered in soft capsule formulation. The present study was aimed at evaluating whether LT4 soft capsules may provide better control of thyroid stimulating hormone (TSH) in thyroidectomized patients undergoing chronic replacement therapy with LT4, who were also on chronic use of PPIs.Forty-seven (47) patients were enrolled in this multicenter study. Upon switching to Tirosint capsules at the same previous dose of LT4 tablets and while maintaining the same dose of PPI, TSH (when measured on week 12 of treatment) was significantly reduced from a mean±SD of 1.34±1.51 mIU/L to 0.75±1.08 mIU/L (p&lt;0.0001) in the Intention-To-Treat population analysis on original data. No significant changes were detected in the level of free and total thyroxine (T4), while slight but significant (p&lt;0.05) increases were measured in free and total triiodothyronine (T3). The measured extent of TSH decrease is consonant with the extent of TSH increase previously reported by other authors upon start of PPI therapy in hypothyroid patients treated with LT4 tablets.In conclusion, these data confirm previous reports that LT4 soft capsules absorption is not affected by increased gastric pH due to PPIs. This may be relevant to improve TSH stabilization in patients who take PPIs intermittently or those with gastric pH altered by concomitant pathologies.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Sunday, June 12, 2022 1:00 p.m. - 1:05 p.m.