bluuebunny/crossref_metadata_2025_split huggingface dataset:
7012 Genetic Defects Involved in the Progression from Differentiated to Anaplastic Thyroid Cancer
Authors: Gill Simranpreet , Chavez Luis F 
Published: October 2024

Abstract
Disclosure: S. Gill: None. L.F. Chavez: None.
Although much more invasive and with a disease specific mortality approaching almost one hundred percent, anaplastic thyroid cancers (ATC) are not mutually exclusive from their differentiated counterparts. Almost one third of patients diagnosed with ATC have a coexisting synchronous differentiated thyroid carcinoma (DTC). We describe a case of a 59 year old male with a 20 pack year smoking history who presented to the hospital for dysphagia and dyspnea after a recent diagnosis of papillary thyroid carcinoma (PTC) one month earlier after workup for an enlarged thyroid. Patient was unfortunately lost to follow up after initial diagnosis. Notably, immunohistochemistry (IHC) was positive for PAX8, TTF1, and BRAF V600E at that time. On arrival to the emergency department, patient described the dysphagia as progressively worsening from solids to liquids associated with a 20 pound weight loss since initial diagnosis of PTC. He had also been experiencing hoarseness of voice, intermittent fevers, night sweats, and hemoptysis. Physical exam revealed an enlarged thyroid mass with discrete nodularity. Labs were largely unremarkable but CT imaging of the neck and chest revealed a heterogeneous mass 6.3 cm in diameter centered within the upper esophagus causing mass effect on the upper airway and scattered bilateral pulmonary nodules. The thyroid was also heterogeneous appearing and had multiple peripheral calcified masses along with a 4.2 cm hypodense nodule in the left lobe. Patient underwent tracheostomy to secure the airway along with laryngoscopy, thyroid biopsy, and esophagoscopy with biopsies. The results of the thyroid biopsy once again showed PTC while the results of the esophageal biopsies showed ATC. Given extensive metastases, the patient was deemed to have stage IVC ATC and he was started on palliative chemotherapy and radiation therapy. Treatment was switched to BRAF inhibition in the outpatient setting after documentation of BRAF V600E mutation in the ATC component. IHC also revealed expression of PAX8, p53, CAM 5.2, and vimentin within the ATC component. And so, just one month after initial diagnosis of PTC, the patient developed ATC in the surrounding thyroid. This case highlights how DTC can serve as a stepping stone for the development of ATC. The mechanism at play may be due to genetic defects such as those in BRAF V600E and PAX8 that could be seen in both the DTC and ATC possibly signifying an underlying unifying pathway.
Presentation: 6/1/2024
6644 Glycosylation Patterns of the IgG Variable Region in Thyroglobulin Antibodies and Their Impact on Antigen Binding Affinity
Authors: Wang Shuaihang , Cao Yedi , Zhao Chenxu , Huang Chuncui , Zhao Keli , Li Yan , Huang Youyuan , Ying Zhang , Zhang Yang , Gao Ying 
Published: October 2024

Abstract
Disclosure: S. Wang: None. Y. Cao: None. C. Zhao: None. C. Huang: None. K. Zhao: None. Y. Li: None. Y. Huang: None. Z. Ying: None. Y. Zhang: None. Y. Gao: None.
Objective: Thyroglobulin antibodies (TgAb), key serological markers in Hashimoto's thyroiditis (HT) patients, are predominantly in immunoglobulin G (IgG) form. Prior research has highlighted the importance of increased glycosylation in TgAb IgG from HT patients. This study investigates the unique glycosylation patterns of F(ab')₂ fragments in TgAb IgG in HT patients, compared to healthy individuals. It focuses on how these patterns differ and their impact on binding to thyroglobulin (Tg). Exploring the role of N-glycosylation in the F(ab')₂ segment of TgAb IgG is crucial for understanding its effect on immune responses in HT, potentially unveiling key mechanisms of the disease. Methods: To assess serum TgAb levels in HT patients (n≥28), we used an electrochemiluminescence immunoassay, dividing patients into medium-level (mHT, n≥14) and high-level (hHT, n≥14) groups. TgAb IgG was isolated from serum of both HT and control groups (n = 14) using affinity chromatography. TgAb IgG was then cleaved with Ides enzyme to yield TgAb IgG F(ab’)2 and Fc fragments. The F(ab')2 fragment of TgAb IgG underwent MALDI-QIT-TOF-MS mass spectrometry for glycosylation profiling. Additionally, mixed TgAb IgG was separated using columns that recognize mannose and terminal sialic acid, yielding high mannose and high terminal sialic acid TgAb IgG. Different TgAb IgG glycoforms were prepared through enzymatic treatment with peptide-N-glycosidase F, β1-4 galactosidase, and α2-3,6,8 neuraminidase. The binding affinity of these TgAb IgG to Tg antigen was measured using Tg specific ELISA and surface plasmon resonance (SPR). Results: Using MALDI-TOF MS, we identified 22 IgG glycan types in both HT and control (Con) groups. In the hHT group, six glycan types (G0F, G1F, G2F, M5A1, A3G1F, A3F) were upregulated compared to Con, with statistical significance (p &lt; 0.05). The mHT group showed increased levels of G1F and G2F compared to Con (p &lt; 0.05). Between hHT and mHT, only A3F was significantly elevated (p &lt; 0.05). Removal of N-glycosylation from IgG TgAb F(ab)2 reduced binding to Tg antigen. Presence of both mannose and terminal sialic acid in TgAb enhanced the binding to Tg. Conclusions: Most TgAb IgG in the variable region of HT patients contain N-glycans. The glycosylation patterns of TgAb IgG F(ab)2 in HT differ significantly from healthy controls, affecting antibody binding affinity. Our findings reveal the complex role of glycosylation patterns in TgAb IgG, providing new insights into HT pathogenesis and potential research directions.
Presentation: 6/1/2024
8373 High suspicion for thyroid cancer in patient with thyroid Hemiagenesis
Authors: Aoun Laurence , Almardini Shaza , Anise Marina , Haddadin Fadi , Saliba Fares , Zaidan Julie 
Published: October 2024

Abstract
Disclosure: L. Aoun: None. S. Almardini: None. M. Anise: None. F. Haddadin: None. F. Saliba: None. J. Zaidan: None.
Background: Thyroid Hemiagenesis (THA) is a rare condition characterized by congenital absence of one lobe of the thyroid gland. Notably, THA is more prevalent in females and the left lobe is more likely to be absent with or without the isthmus. Most patients are euthyroid, and diagnosis is usually incidental, so the true prevalence of THA is uncertain as there are certainly undiagnosed cases. Studies have shown a link between THA, thyroid cancer, and hyperparathyroidism. We present a case of THA and high suspicion for thyroid cancer. Case Presentation: 54-year-old female with history of Rheumatoid arthritis who presented for evaluation of incidental thyroid nodules, occasional palpitations, tremors, and mild change in her voice. She denied abnormal weight loss or diarrhea. No history of radiation to the neck and no family history of thyroid disease or thyroid cancer. The thyroid exam showed an enlarged left palpable nodule. Labs significant for TSH 1.6 mIU/L (normal: 0.4-4 mIU/L), FT4 0.8 ng/dl (normal 0.7-1.9 ng/dL) and T3 77ng/dL (normal: 60-180 ng/dL). Thyroid U/S showed left hemiagenesis and right sided nodules biggest is 1.1 cm solid, hypoechoic with coarse calcifications, FNA was recommended and showed follicular lesion of undetermined significance, molecular testing was done and Thyroseq came back intermediate to high risk RAS and EIF1AX positive reflecting a 70 % probability of cancer. Based on these results, surgery was recommended, and the patient underwent right thyroidectomy. Surgery was uncomplicated and despite reported higher risk of hyperparathyroidism patient’s calcium and PTH were normal, and no parathyroid adenomas were identified intraoperatively. The pathology from the thyroidectomy showed follicular adenoma of 1 cm and no malignancy. She was started on Synthroid 100mcg daily post op. Discussion: This case demonstrates a case of a benign thyroid nodule and preserved parathyroid levels in the setting of thyroid hemiagenesis. Usually in THA, the contralateral lobe is at an increased risk for pathology of compensatory hypertrophy or hyperplasia. According to available studies, cancer association with THA was more common in left hemiagenesis and parathyroid adenomas more common ipsilateral to hemiagenesis . Despite Our patient’s FNA revealed atypical findings, molecular testing revealed RAS and EIF1AX positive, marking intermediate to high cancer risk. However, the thyroidectomy pathology report unveiled no evidence of malignancy, contraindicating the anticipated high cancer risk in those with left THA. This case highlights the rarity of THA and different possible presentations and cancer risks.
Presentation: 6/2/2024
7209 Immune Check Point Inhibitors And Periodic Thyroid Function Assessment
Authors: Farooqi A , Dewan S , Jun J Y , Farooqi S 
Published: October 2024

Abstract
Disclosure: A. Farooqi: None. S. Dewan: None. J.Y. Jun: None. S. Farooqi: None.
Introduction: Immune checkpoint inhibitors, namely anti-cytotoxic T-lymphocyte-associated antigen 4 (anti-CTLA-4), anti-programmed death 1 (anti-PD-1) and anti-programmed death-ligand 1 (anti-PD-L1) monoclonal antibodies, have emerged in the last decade as a novel form of cancer treatment, promoting increased survival in patients. As they modify the immune system and destroy the immune cells, an array of immune related adverse effects has been noticed, with strong predilection to endocrine organs. Among endocrinopathies, thyroid dysfunction occurs frequently ∼5% especially with the use of anti-PD-L1. While the majority have been cases with destructive thyroiditis leading to transient thyrotoxic phase often followed by transient or permanent hypothyroid phase, the occurrence of hyperthyroidism or Basedow’s disease after the administration of anti CTLA-4 has also been reported. Case Presentation: We present a case of 66-year-old male with past medical history of ischemic cardiomyopathy, atrial fibrillation and metastatic cholangiocarcinoma diagnosed in August 2023. He was initially treated with combined chemotherapy and immunotherapy with duravulamab, anti PD-L1., and then later with duravulamab alone. Three weeks after the second cycle of duravulamab, he was admitted due to episodes of ventricular tachycardia with shock administered through his implantable cardioverter defibrillator. Further evaluation revealed thyroid stimulating hormone (TSH) of &lt;0.01 (0.49-4.67 uIU/L), free T4 of 4.39 (0.61-1.60 ng/dL), total T3 of 160 [87-178 ng/dL], negative thyroid stimulating immunoglobulin and TSH receptor antibody. Of note, three months prior to immunotherapy, TSH was 6.52 uIU/L with normal free T4, pointing to subclinical hypothyroidism. Ultrasound of thyroid revealed enlarged heterogeneous thyroid gland related to thyroiditis. Prednisone 20 mg twice a day was prescribed for presumptive diagnosis of immunotherapy-induced thyroiditis. Patient continued prednisone for 14 days (about 2 weeks) until he ran out. Repeat TSH &lt; 0.01 uIU/L and free T4 5.51 ng/dL with total T3 266 ng/dL confirming ongoing thyrotoxicosis and prednisone was further extended for 2-week period. Conclusion: Thyroid dysfunction is frequently observed during treatment with immune check point inhibitors. While increased body weight and elevated inflammatory markers at baseline are associated with development of thyroid dysfunction, there is no definite predictor identified. This case highlights the importance of periodic assessment of thyroid function test to identify and manage thyroid dysfunction in a timely fashion to avoid potential development of life-threatening consequences of thyroid dysfunction including thyroid storm.
Presentation: 6/3/2024
8390 It's not Cancer: Establishing the Diagnosis of Hyaline Trabecular Tumor
Authors: Zielinski R A , Khalifa M , Dillon M , Kaur M 
Published: October 2024

Abstract
Disclosure: R.A. Zielinski: None. M. Khalifa: None. M. Dillon: None. M. Kaur: None.
Background: Hyaline trabecular tumor (HTT) is a rare benign follicular thyroid neoplasm characterized by extensive intra-trabecular hyaline stromal material. Resemblances to other follicular neoplasms create difficulty in distinguishing HTT from its more nefarious counterparts such as medullary thyroid cancer (MTC) and papillary thyroid cancer (PTC).Clinical Case:Our patient is a 56-year-old female with Hashimoto’s thyroiditis diagnosed in her twenties who has been on different strengths of levothyroxine based on her fluctuating TSH. A thyroid ultrasound done to evaluate left-sided neck fullness on physical exam showed a solid, hypoechoic 2.3 cm x 1.4 x 0.9 cm left middle thyroid nodule without calcifications (TI-RADS 4) and benign-appearing lymph nodes, the largest of which was 1.5 cm at level 1B. Cytology from a thyroid FNA biopsy was suspicious for PTC, Bethesda category IV. A thyrosure genetic panel was negative for genetic mutations. FNA biopsy of the 1.5 cm lymph node was negative for malignancy. The patient was referred for thyroid lobectomy but instead elected to undergo total thyroidectomy with level VI lymph node dissection. Pathology revealed a 2.2 cm HTT in the left lobe, scattered psammoma bodies in adjacent soft tissue, and a 0.2 cm multifocal papillary microcarcinoma in the right lobe. The microcarcinoma had negative margins, no lymphatic or vascular invasion, and 7/7 benign level VI lymph nodes; staging it as pT1aN0. Immunohistochemistry staining was positive for TTF-1 and thyroglobulin and negative for calcitonin, chromogranin, and synaptophysin. Post-thyroidectomy she was started on Tirosint 175 mcg daily with good response. No I-131 treatment was pursued due to the microcarcinoma being categorized as low risk.Discussion and Conclusion: HTT is a benign neoplasm and management is usually conservative with surgical excision. The diagnosis of HTT by cytology alone is challenging due to the presence of nuclear clearing, grooves and intranuclear pseudo-inclusions that may be mistaken for PTC or MTC. Cell membrane immunoreactivity of MIB1 monoclonal to Ki67 and the molecular identification of the novel PAX8-GLIS1 or PAX8-GLIS3 fusions may aid in making the correct diagnosis.References:Rossi ED, et al. The Diagnosis of Hyalinizing Trabecular Tumor: A Difficult and Controversial Thyroid Entity. Head Neck Pathol. 2020 Sep;14(3):778-784. doi: 10.1007/s12105-019-01083-5. Epub 2019 Sep 30. PMID: 31571046; PMCID: PMC7413943.
Presentation: 6/2/2024
12556 Medullary Thyroid Cancer With Persistent Elevation Of Carcinoembryonic Antigen: Case Report
Authors: Campana Mario S , Vodopivec Danica , McCammon Susan , Heatherly Alexis 
Published: October 2024

Abstract
Disclosure: M.S. Campana: None.
Introduction: Medullary thyroid Cancer (MTC) is a rare neuroendocrine tumor that originates from thyroid parafollicular C-cells and represents 5 % of all thyroid cancers. MTC can be sporadic (75%) or hereditary (25%) associated with multiple endocrine neoplasia type 2 syndrome (MEN2). Serum calcitonin (Ctn) and carcinoembryonic antigen (CEA) are its tumor markers. We report a case of persistently elevated CEA levels despite an undetectable Ctn in a patient with MTC after initial thyroid lobectomy. Description of the case: A 42-year-old woman self-identified a neck lump after intentional weight loss. A neck US showed a right lobe thyroid nodule which resulted as suspicious for malignancy (Bethesda V) with subsequent right lobectomy. Pathology reported a 2.6 cm unexpected MTC with negative surgical margins, extrathyroidal extension, angioinvasion, and lymphatic invasion. No cervical lymph nodes (LNs) were removed. Immunohistochemistry was positive for CEA, chromogranin A, synaptophysin, and Ctn. T2 Nx. One month after lobectomy, the Ctn was 10.5 (0-3.0 pg/mL) and CEA 205.2 (0-3.0 ng/mL Non-smoker; 0-5.0 ng/mL smoker). The patient was then referred to our clinic for further management. Laboratories showed normal serum calcium, PTH, and fractionated plasma metanephrine/normetanephrine. A 2-month post-operative Ctn was undetectable, but CEA was elevated at 24.5. Subsequently, we broaden imaging studies to include neck US, CT neck /chest with contrast, and MRI abdomen pelvis with contrast. The only remarkable finding was a 6.7 cm pelvic mass with normal Ca-125. Genetic testing was negative for germline RET, ruling out MEN2. Patient underwent completion left lobectomy with prophylactic bilateral central neck dissection. Pathology showed benign thyroid parenchyma with multinodular hyperplasia and 0/12 LNs. Because of concerning pelvic mass, the patient was referred to OB/GYN. She underwent a laparoscopic bilateral salpingo-oophorectomy. Pathology showed a follicular ovarian cyst, negative for malignancy. A year post-completion total thyroidectomy Ctn remains undetectable, and a CEA is normal at 1.3. Discussion: Because Ctn was already undetectable 1 month after lobectomy with persistent elevated CEA a complete total thyroidectomy with prophylactic bilateral central neck dissection was indicated to achieve operative cure. Ctn is specific to MTC but variable. CEA is more reproducible with less variability; however, it is not specific to MTC and can also be elevated in smokers, benign breast and genitourinary disease, emphysema, cirrhosis, and cancer of colon, rectum, liver, genitourinary, and lung. If residual disease is present, Ctn tends to be proportionally more elevated than CEA. When the opposite occurs, poorly differentiated MTC with possibility of distant metastases vs. a second primary malignancy vs. a distant benign neoplasm known to elevate CEA need to be ruled out.
Presentation: 6/2/2024
6472 Methimazole Induced Agranulocytosis: Uncommon Complication of a Common Medication
Authors: Kaur Ravleen , Kaur Lavleen , Sridhar Archana , Chaudhary Taibah , Patel Nirali 
Published: October 2024

Abstract
Disclosure: R. Kaur: None. L. Kaur: None. A. Sridhar: None. T. Chaudhary: None. N. Patel: None.
Methimazole (MMI) induced agranulocytosis is a rare and life threatening adverse effect that usually occurs within 3 months of drug initiation and can rapidly lead to overwhelming infection. It is reported in 0.1 to 0.5 % of patients on treatment with methimazole. MMI is a standard drug used in graves disease and toxic multinodular goiter. We report a case of MMI induced agranulocytosis in an elderly female with recently diagnosed toxic multinodular goiter. A 66 year old female with past medical history of recently diagnosed toxic multinodular goiter for which she was started on methimazole 80mg/day two months ago presented to the emergency department with chief complaint of severe sore throat associated with rapidly increasing pharyngeal pain and fever over the past 24 hours. She was lethargic, febrile with temperature of 102 F, tachycardic with heart rate of 115/minute and hypotensive with blood pressure of 108/64 mm Hg. Physical examination revealed diffuse pharyngeal and tonsillar erythema with bilateral purulent exudate with tender anterior cervical lymphadenopathy. Thyroid was enlarged, firm, irregular and nontender. Pulmonary, cardiac and abdominal exam was unremarkable. Lab work showed severe leukopenia with WBC count of 1,600/mm3, neutropenia with absolute neutrophil count of 0.0 x 1000/ul (normal range 1.8-7.3 x 1000/ul) and erythrocyte sedimentation rate and C reactive protein were both elevated. Blood cultures and fungal cultures showed no growth. Urinalysis and urine culture were both unremarkable. She had an extensive haematological, rheumatological and infectious disease workup for neutropenia, which was largely unrevealing. Rapid streptococcal testing was negative but throat cultures grew beta haemolytic streptococci. Treatment included suspending methimazole, administering antimicrobial therapy with piperacillin - tazobactam, acyclovir and fluconazole. She was also started on a granulocyte colony stimulating factor. Patient presented satisfactory evolution with progressive increase in leukocyte count and remission of symptoms by day 5 of treatment, rendering further bone marrow testing unnecessary. Antibiotics were changed to oral amoxicillin-clavulanic acid after throat culture results were available and the patient was discharged in stable condition. One month after discharge she underwent total thyroidectomy for definitive cure and is currently followed up as an outpatient by endocrinology. The objective of this case report is to present an uncommon case of agranulocytosis secondary to use of methimazole and to increase awareness among the physicians about the need to consider this diagnosis in patients on this medication. It is also advised that these patients be educated about the drugs side effects, a practice that may avert suffering and unnecessary costs.
Presentation: 6/3/2024
12264 Myxedema Coma And The Impact Of Treatment Noncompliance
Authors: Subramani Rashmi , Marasandra Ramesh Harshita , Yavuz Sahzene 
Published: October 2024

Abstract
Disclosure: R. Subramani: None. H. Marasandra Ramesh: None. S. Yavuz: None.
Introduction: Myxedema coma represents a critical medical condition marked by a heightened risk of both morbidity and mortality. It manifests as severe hypothyroidism, typically presenting with symptoms like lethargy, altered mental status, or potential obtundation. Various triggering factors, including infections, hypothermia, metabolic imbalances, surgery, and specific medications like amiodarone, lithium, and anesthetics, can precipitate this emergency. Here we outline a classic instance of myxedema coma stemming from non-adherence to levothyroxine treatment in the context of primary hypothyroidism. Case Summary: A 56-year-old woman with a medical history significant for primary hypothyroidism, hyperlipidemia, and mood disorder presented to the hospital exhibiting symptoms suggestive of a stroke. Upon arrival, she had a seizure episode and eventual unresponsiveness. Emergency intubation was performed due to a low Glasgow Coma Scale score and concern for airway protection. Further history revealed non-compliance with levothyroxine therapy. Laboratory findings included TSH of 150 uIu/ml, T4 of 1.1 ng/dl, T3 of 1.17 ng/dl, and cortisol of 21.9 ug/dl. Chest x-ray revealed complete atelectasis of the left lung with mediastinal shift initially before intubation. CT head and neck were unremarkable. A diagnosis of myxedema coma was made based on clinical presentation and a myxedema score of 75. Treatment included IV levothyroxine 50 mcg, increased to 100 mcg, nor-epinephrine drip for hypotension and 1000 mg of levetiracetam for seizures management. Pulmonary edema resolved following levothyroxine initiation. The patient was successfully extubated on day 3, weaned off oxygen, and discharged home after 8 days with counseling on medication adherence. Discussion: While encountering a case of myxedema coma is rare, it is crucial to maintain a low threshold for diagnosing this potentially fatal emergency. Early recognition, facilitated by a comprehensive history, physical examination, and prompt initiation of treatment, is essential for effective management. Despite early intervention, the mortality rate remains high, ranging from 50% to 60%. Wartofsky et al. advocate for the primary treatment approach with T4 alone, emphasizing its efficacy. Supportive measures such as warming, fluid resuscitation, mechanical ventilation, administration of antibiotics, vasopressors, and corticosteroids are also integral components of management. This case report underscores the considerable morbidity and mortality associated with myxedema coma. The most common trigger precipitating myxedema coma is non-compliance with levothyroxine therapy, particularly in elderly females with longstanding hypothyroidism. Therefore, counseling regarding strict adherence to levothyroxine is of paramount importance.
Presentation: 6/1/2024