Abstract
Late Breaking Oral Abstracts
Oral 0004
Thyroid Hormone Action, Metabolism and Regulation, Basic, Oral
Thyroidal function of the endoplasmic reticulum molecular chaperone, GRP170
Xiaohan Zhang*1, Crystal Young1,2, Xiao-Hui Liao3, Samuel Refetoff3,4, Stephanie Michelle Mutchler5, Hao Zhang1, Dennis Larkin1, Jeffrey Brodsky5, Teresa Buck5, Peter Arvan1, 1Division of Metabolism, Endocrinology & Diabetes, University of Michigan, USA, 2Department of Molecular & Integrative Physiology, University of Michigan, USA, 3Department of Medicine, University of Chicago, USA, 4Pediatrics and Committee on Genetics, University of Chicago, USA, 5Department of Biological Sciences, University of Pittsburgh, USA
Thyroxine synthesis involves the coordination of multiple thyroid-specific proteins delivered via the secretory pathway to the apical and basolateral cell surface of thyrocytes. The endoplasmic reticulum (ER) provides the infrastructural environment necessary for delivery of these proteins to the plasma membrane. Specifically, ER luminal folding of most of newly-synthesized proteins delivered to the thyroid plasma membrane is supported by ER molecular chaperones such as GRP170, which has both hsp70-like activity as well as function as a nucleotide exchange factor, and has been reported to physically interact with thyroglobulin (Tg). Here we have examined the role of GRP170 in thyroid protein trafficking and hormonogenesis in vivo, and in vitro.
We generated an inducible, Pax8 promoter-driven thyroidal-GRP170-KO mouse and examined thyroid status after 21 days of induced deletion. We also performed siRNA-mediated knockdown of GRP170 in PCCL3 (rat thyrocyte) cells for protein trafficking studies.
Adult mice with 21 day-induced thyroidal-GRP170-KO exhibited primary hypothyroidism (decreased serum T4; increased circulating TSH) with a dramatic decrease of T4 formed within Tg. We obtained no direct or indirect evidence of defective Tg folding or trafficking, as there was no apparent increase of ER stress (e.g., BiP, CHOP or spliced XBP1 mRNAs) and there was no induced defect in Tg delivery to the thyroid follicle lumen. TPO protein also appeared normal in induced thyroidal-GRP170-KO mice, but we observed a ∼30% and ∼50% decrease in TSHR and NIS protein, respectively. After 21 days of induced thyroidal-GRP170-KO, no thyroid gland growth or change in the size of thyroid follicles was detected, suggesting under-responsiveness to the increased circulating TSH.
GRP170-KD in PCCL3 cells also did not impair Tg trafficking, but instead revealed abnormalities including increased misfolding, protein aggregation, and diminished export from the ER of TSHR-GFP, as well as an alteration of NIS N-linked glycosylation (suggesting a post-translational effect on NIS).
These studies suggest that GRP170 is not required for Tg trafficking but instead supports the folding and trafficking of TSHR, resulting in primary hypothyroidism under conditions of thyroidal GRP170 deficiency.
Oral 0007
Thyroid Nodules and Goiter, Clinical, Oral
Clinical feasibility study using nanosecond pulsed field ablation (nsPFA) to treat benign thyroid nodules
STEFANO SPIEZIA*1, CHIARA OFFI1, CLAUDIA MISSO1, GIOVANNI ANTONELLI1, RALPH TUFANO2, WILLIAM KNAPE3, 1Department of Endocrine and Ultrasound‐Guided Surgery, Ospedale del Mare, Italy, 2Department of Head and Neck Endocrine Surgery, USA, 3pulse bioscences, USA
Thermal ablation can be effective in reducing symptomatic thyroid nodules but is subject to risk of major complications such as nerve injury and nodule rupture. Nanosecond Pulsed Field Ablation (nsPFA) is a novel, cell-specific, nonthermal modality utilizing ultrashort pulses of electrical energy to ablate cells while sparing acellular tissue, by taking advantage of natural regulated cell death processes (e.g., apoptosis). This study aims to assess the ability of nsPFA energy to safely reduce the volume of symptomatic, benign thyroid nodules.
An nsPFA percutaneous electrode was used to ablate benign thyroid nodules under ultrasound guidance in a single-center study. In Cohort 1 (5 patients), ablations were created prior to a thyroidectomy procedure (treat-and-resect), so that initial safety and ablation zone characterization could be assessed. In Cohort 2 (20 patients), up to 4 isolated ablations were created in the in situ thyroid, to allow for estimation of ablation zone volume. In Cohort 3 (5 patients), the nodule was treated with therapeutic intent with multiple, overlapping ablations.
For Cohort 1, the average ablation zone measured 1.7 cm long by 0.7 cm wide (hypoechoic via ultrasound) immediately post ablation. For Cohort 2, the average ablation zone was estimated to be 2.7 mL in volume at 90 days post ablation (based on comparison of nodule size to baseline). Transient dysphonia (<24 hours) was seen in two subjects treated at the highest ablation setting. For Cohort 3, treated nodules had an average volume reduction of 65% which persisted to 90 days. There was no transient dysphonia in this group. Noticeable volume reduction was seen as early as 2 weeks. No fibrosis or scarring were seen on follow-up ultrasounds. No serious adverse events (SAEs) were reported for any Cohorts.
This first-in-human study supports the initial safety/efficacy profile of the nsPFA electrode in treating and reducing the volume of benign thyroid nodules. The nonthermal nature of nsPFA energy has the potential to reduce risk of major complications in minimally invasive treatment of benign thyroid nodules, and improve healing through rapid reduction of ablated areas and lack of post-procedure fibrosis. Further studies are needed to further explore the potential for improved outcomes.
Oral 0008
Thyroid Cancer, Translational, Oral
Hereditary thyroid cancer in the United States population
Nikita Pozdeyev*1,2,3, Samantha White1, Christopher Gignoux1,2, Bryan Haugen3, 1Department of Biomedical Informatics, University of Colorado Anschutz Medical Campus, USA, 2Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, USA, 3Division of Endocrinology, Diabetes and Metabolism, University of Colorado Anschutz Medical Campus, USA
Oral 0016
Pediatrics, Clinical, Oral
Incidence trends and the influence of puberty on pediatric thyroid cancer
Simo Kraguljac*1, Konda Reddy2, Krystal Irizarry2, Fouad Hajjar2, Richard Wong3, Jatin Shah3, Joseph Lopez2, 1University of Central Florida College of Medicine, USA, 2AdventHealth for Children, USA, 3Memorial Sloan Kettering Cancer Center, USA
Pediatric thyroid malignancies have increased rapidly in recent years. Studies have not distinguished between presentation in young children vs adolescents to this point. We aim to evaluate the epidemiological trends for pediatric thyroid cancer in the United States and whether pre- and post-pubescent patients differ in presentation.
We conducted a cross-sectional study analyzing pediatric thyroid cancer data from the National Cancer Institute’s Surveillance Epidemiology and End Results (SEER) database. Inclusion criteria included those aged 0–21, malignant tumors, primary site of thyroid, and diagnosis from 2000–2019. We stratified data by sex, year of diagnosis, age, and histology. Pre-pubescent patients were defined as those aged 0–12 while post-puberty included ages 13–21. Statistical analysis between these groups was performed using chi-square tests.
We identified 11,219 pediatric thyroid tumors from 2000–2019, comprising 38.4% of all pediatric head and neck tumors. There were 9,169 (81.7%) tumors in females and 2,050 (18.3%) in males. There were 9,712 (86.6%) papillary carcinomas, 769 (6.9%) follicular carcinomas, and 311 (2.8%) medullary carcinomas. We identified 957 tumors in pre-pubescent patients and 10,099 in post-pubescent patients. Papillary carcinoma was isolated more frequently in post-pubescent patients, with 9,014 (89.3%) tumors while there were 698 (72.9%) tumors in pre-pubescent patients (p < 0.0001). Medullary carcinoma was more common in pre-pubescent patients where there were 140 (14.6%) tumors while there were 171 (1.69%) tumors in post-pubescent patients (p < 0.0001). There were also 39 (4.08%) cases of Nonencapsulating sclerosing carcinoma found in pre-pubescent patients vs. 133 (1.32%) in post-pubescent patients (p < 0.0001).
Overall incidence was 1.26 [1.24, 1.29] per 100,000 person-years. The incidence from 2000–2004 was 0.90 [0.86,0.94] which increased to 1.61 [1.55, 1.66] from 2015–2019. Notably, papillary carcinoma rose from 0.75 [0.72, 0.79] cases per 100,000 person-years to 1.42 [1.37, 1.47] while follicular and medullary carcinoma both did not change significantly.
The incidence of pediatric thyroid cancer is increasing, due to large increases in papillary carcinoma in just the last 20 years. There were significant differences in papillary carcinoma, medullary carcinoma, and Nonencapsulating sclerosing carcinoma between younger patients and adolescent patients. Future studies are necessary to determine the cause of these trends.
Oral 0019
Pregnancy and Development, Clinical, Oral
Discordance of TSI and TRAb assays used in pregnancy to predict risk of fetal and newborn graves’ disease
Nelson Nelson*1, Kelly Doyle1, Linda Barbour2, Joely Straseski1, 1University of Utah, USA, 2University of Colorado, Anschutz Medical Campus, USA
Background/Objective: Patients with a history of Graves’ disease may transfer Graves’ antibodies to the fetus, resulting in fetal/neonatal hyperthyroidism. Serious fetal complications include tachycardia, goiter, growth restriction, cardiac failure, and fetal demise. Early identification and treatment in-utero improves fetal and newborn outcomes. ATA guidelines recommend TSH Receptor (TRAb) or Thyroid Stimulating Immunoglobulin (TSI) be tested at 20–22 weeks gestation. Values ≥3X the upper limit of normal (ULN) predict sufficient risk, thereby warranting intensive surveillance with fetal ultrasounds every 4-weeks and twice weekly non-stress tests (NSTs). However, the commonly used TRAb competitive assay (Roche) detecting both stimulating and blocking antibodies and the newer automated TSI “Bridge” immunoassay (Siemens) detecting only stimulating IgG antibodies have never been directly compared. Due to our recognition of a discordance in our pregnant population with Graves’, we investigated concordance of TRAb and TSI results in the same samples from pregnant and non-pregnant patients.
Methods: A retrospective evaluation of concordance between TRAb and TSI values from 17,447 results were examined. Values ≥3X ULN for each assay were assigned “positive” while values <3X ULN were designated “negative”, using recommended cut-offs to initiate fetal surveillance.
Results: We observed discordance in the ≥3X ULN cut-off between TRAb and TSI in 1,727 (10%) of samples. A total of 12,550 (72%) results were negative by both methods and 3,170 (18%) were positive by both methods. Of the discordant samples, 1,578 (91%) were positive by TSI but negative by TRAb, whereas 149 (9%) were negative by TSI but positive by TRAb. Defining the TRAb assay as the reference method, the newer TSI Bridge assay has a negative predictive value of 99%, but a positive predictive value of only 67%.
Conclusion: Our results demonstrate that when the Siemens TSI results are ≥3X ULN, TRAb results are similarly elevated only ∼2/3 of the time, potentially resulting in unnecessary ultrasound or NST orders 1/3 of the time. The discordance observed between assays challenges the validity of “universal” cutoffs in guideline recommendations. Large prospective trials are critical to establish the predictive values of automated assays for fetal/neonatal Graves’ and to determine if assay specific cutoffs are warranted.
Oral 0020
Autoimmunity, Clinical, Oral
Efficacy and safety of the FcRn inhibitor, batoclimab, in graves’ thyroidal and extrathyroidal disease: a proof-of-concept study
George Kahaly*1, Jan Wolf1, Anna-Lena Ganz1, Maximilian Luffy1, Katherine Albert2, Maria Alba2, E Lin2, William Macias2, 1Johannes Gutenberg University Medical Center, Germany, 2Immunovant, Inc., USA
Oral 0027
Thyroid Nodules and Goiter, Clinical, Oral
The utilization of radiofrequency ablation in the management of thyroid nodules and factors influencing its efficacy
Dana Hamadi*1, John Schmitz2, Marius Stan2, 1Hennepin Healthcare, USA, 2Mayo Clinic, USA
Oral 0031
Thyroid Cancer, Translational, Oral
Anaplastic thyroid cancer bone metastasis: Mechanistic insight from mouse models
Shiyu Yuan*, Xinhai Wan, Ali Dadbin, Marie-Claude Hofmann, Theresa Guise, Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, USA
Oral 0033
Thyroid Cancer, Clinical, Oral
Re-differentiation therapy clinical trial using dabrafenib & trametinib in RAI-Refractory BRAF/RAS-Mutant thyroid cancer applying a novel Time-Dependent concept
Samantha, Peiling Yang*1,2,3, Kelvin, Siu Hoong Loke4,5, Wei Ming Chua4,5, Wan Qin Chong6,2, Jun Ting Teo3, Belinda Loh6, Lingzhi Wang3, David, Chee Eng Ng4,5, Li Ren Kong3,7, Azhar Ali3, Boon Cher Goh6,2,3,7, 1Endocrinology Division, Department of Medicine, National University Hospital, Singapore, 2Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 3Cancer Science Institute of Singapore (CSI), National University of Singapore, Singapore, 4Department of Nuclear Medicine and Molecular Imaging, Singapore General Hospital, Singapore, 5Duke-NUS Medical School, Singapore, 6Department of Hematology-Oncology, National University Cancer Institute, Singapore, 7Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Current re-differentiation therapy strategies in MAPK-driven radioactive iodine (RAI)-refractory thyroid cancer deploy BRAF/ MEK inhibition +/- HER3 inhibition for 4–6 weeks, with 35–67% of patients attaining dosimetry threshold for RAI treatment, and partial response rate of 20–63%. We hypothesize that a shorter course of BRAF/MEK inhibition could enhance NIS expression in BRAF/RAS-mutant thyroid cancers, leading to improved patient treatment response.
We conducted a phase II clinical trial using dabrafenib & trametinib to examine the kinetics of NIS upregulation in RAI-refractory metastatic thyroid cancer with BRAFV600E or RAS mutation. Iodide uptake was assessed with I-124 PET-CT scan at baseline, 1–2 weeks, and at 4 weeks if needed. If there was adequate tumoral iodide retention with at least 1 tumour lesion attaining lesional dosimetry of ≥2000 cGy using I-131 dose of ≤300 mCi, RAI was administered (ClinicalTrials.gov ID: NCT04554680).
We recruited 12 patients with papillary, follicular, & poorly differentiated thyroid cancer with BRAFV600E or RAS mutations. Primary outcome of attaining dosimetry was reached in 8/12 patients (67%). Five patients (63%) were early responders (1–2 weeks); 3 patients needed 4 weeks to attain RAI treatment threshold (late responders). The proportion of RAS-mutant thyroid cancer was 60% (3/5) in early responders, 0% (0/3) in late responders, and 25% (1/4) in non-responders (p >0.05).
At 6 months, 7/8 RAI-treated patients had partial response (87.5%), and 1 patient had non-evaluable disease (bone metastases without measurable component) as per RECIST criteria. The median reduction in non-stimulated thyroglobulin (TG) at 3–6 months post-RAI in 5 patients who received RAI was 72% (+/- IQR 48%). Two patients had elevated TG antibody with inaccurate TG assessment. One patient had TG reduction at 2 months post-RAI but TG increased at 5 months post-RAI. The proportion of patients with treatment-related adverse events as assessed by CTCAE v4.0 is 91%, with onset within the first week.
We showed that 63% of re-differentiation therapy response occurred within 1–2 weeks. Work is ongoing to identify predictors of early response.
Oral 0034
Thyroid Cancer, Clinical, Oral
Effect of PI3K pathway activating mutations (PI3Kpath-mutation) on response to BRAF/MEK inhibitor (BRAF/MEKi) therapy in BRAFV600E mutated anaplastic thyroid cancer (BRAFV600Em-ATC)
Trisha Cubb*, Sarah Hamidi, Maria Gule-Monroe, Naifa Busaidy, Pryanka Iyer, Kenna Shaw, Sinchita Roy Chowdhuri, Gloria Sura, Mark Zafereo, Jennifer Wang, Victoria Banuchi, Anastasios Maniakas, Maria Cabanillas,University of Texas MD Anderson Cancer Center, USA
Oral 0035
Thyroid Cancer, Clinical, Oral
Adjuvant pembrolizumab (pembro) after multimodal therapy for anaplastic thyroid cancer (ATC)
Maria Cabanillas*, Naifa Busaidy, Priyanka Iyer, Maria Gule-Monroe, Gary Gunn, Michael Spiotto, Neal Akhave, Luana Sousa, Renata Ferrarotto, Mark Zafereo, Jennifer Wang, Anastasios Maniakas, Michelle Williams, Suyu Liu, Bryan Fellman, Sarah Hamidi, Ramona Dadu, The University of Texas MD Anderson Cancer Center, USA
Thursday, October 31, 2024
Poster 0500
Autoimmunity, Case Study, Poster
Potassium iodide for the chronic management of graves disease: a case series
Oyunbileg Magvanjav*, Ryan MacLeod, Priya Balasubramanian, Kavya Mekala, Silvio Inzucchi, Sachin Majumdar, Section of Endocrinology and Metabolism, Yale University School of Medicine, USA
The mainstays of pharmacotherapy for Graves disease are methimazole and propylthiouracil (PTU). Few options exist for patients who cannot tolerate thioamides and do not want thyroidectomy or radioactive iodine (RAI). Potassium iodide (KI) is an option, though not widely used due to concerns of transient effectiveness.
Six patients with Graves disease were treated with KI (SSKI 1 g/ml; 1 drop = 50 mg KI) at our institution. Patients’ age ranges were 24–77 years (mean 51.2 ± 21.9 years); 66% female. Four patients started KI for methimazole-associated transaminitis, one for pancytopenia during chemotherapy, and another for uncontrolled hyperthyroidism. The latter patient was on high-dose PTU with KI add-on. Mean initial free T4 (FT4) level prior to switching to KI was 2.4 ± 1.1 ng/dL (normal: 0.8–1.7 ng/dL). One patient had a normal FT4 level (1.4 ng/dL) due to methimazole pretreatment, another patient’s FT4 was not being followed (only T3 was elevated and being followed), and a third patient had normalized FT4 and T3 levels but suppressed TSH. Initial KI doses ranged from 100 mg/day to 750 mg/day (mean 516.7 ± 254.4 mg/d). Average time from KI initiation to FT4 normalization was 18.0 ± 7.3 days (median 20 days) in the three patients with elevated FT4. Among the other three patients, two already had normal FT4 on a thioamide; of these, one had a suppressed TSH that normalized with the addition of KI, while the third had an elevated T3 that normalized after switching to KI. KI treatment duration ranged 20–402 days (mean 126.0 ± 133.9 days), ending with five patients undergoing a thyroidectomy. One patient with acute myeloid leukemia was treated for 39 days then transitioned to hospice.
In this series, treatment response to KI ranged from 20 days to >1 year. In total, 67% (4/6) had normal thyroid hormone levels at the end of KI treatment, while 23% (2/6) had hyperthyroidism recurrence. In 3/6 patients, FT4 levels were normal before KI; however, one had elevated T3 and another had suppressed TSH despite high-dose PTU (both levels normalized after KI). Larger observational studies from Japan show response durations to KI of up to several years [1].
In summary, chronic KI therapy may even serve as a bridge to surgery and may be a longer-term option for patients who cannot or will not accept thioamides, surgery or RAI.
Poster 0501
Surgery, Case Study, Poster
Thyroid paraganglioma with SDHA mutation: Tumor recurrence, surgical cure, and long-term follow-up
Oyunbileg Magvanjav*1, Alexander Ladenheim2, Saral Mehra3, Olga Sakharova1, 1Section of Endocrinology, Yale University School of Medicine, USA, 2Department of Pathology, Yale University School of Medicine, USA, 3Department of Otolaryngology, Yale University School of Medicine, USA
Thyroid paraganglioma is a rare, benign, neuroendocrine tumor arising from paratracheal ganglia, located within or adjacent to the thyroid gland. The diagnosis is often missed pre-operatively. Successful treatment depends on complete surgical removal, which is challenging due to the tumor’s anatomical location, proximity to the thyroid cartilage and tracheal rings, and infiltrative growth pattern. Current evidence primarily consists of case reports with limited genetic information and short-term follow-up. Here, we describe a patient with a thyroid paraganglioma associated with an SDHA mutation who experienced disease recurrence. The recurrence necessitated a tracheal-segmental resection, resulting in a complete response to treatment and no evidence of disease 8 years later.
A 31-year-old woman presented with dyspnea, revealing a palpable neck mass on examination. Thyroid ultrasound disclosed a 3.9 cm solid, isoechoic, and hypervascular isthmic nodule. FNA biopsy indicated atypia of undetermined significance with cellular features seen in medullary cancer; Thyroseq® was infeasible due to inadequate thyroid epithelial cells. The patient opted for total thyroidectomy. Immunohistochemistry confirmed a 2.9 cm thyroid paraganglioma, marked by positive staining for synaptophysin, chromogranin, CD56, and S-100, with a low Ki-67 index (<1%), and negative staining for other neuroendocrine tumors. Microscopic infiltration into peri-thyroidal tissue and skeletal muscles was noted, with positive inked margins on the right. Post-surgical observation was recommended. Genetic screening uncovered paraganglioma-pheochromocytoma syndrome (PGL-PCC), attributed to an SDHA mutation (p.Q185*; c.553C>T). A year later, recurrence of dyspnea prompted repeat imaging, which identified a 1.4 cm tracheal mass obstructing the subglottic airway. Tracheal-segmental resection was successfully performed and revealed a 1.5 cm paraganglioma with tracheal extension. Since then, serial imaging showed no evidence of residual/recurrent local disease, multifocality, or secondary tumors. Annual testing for a hormone-secreting paraganglioma is negative. Eight years later, the patient remains free of detectable disease.
Local tumor extension is common in thyroid paragangliomas due to their proximity to the trachea and their infiltrative pattern of growth. However, aggressive behavior is not typical. Longitudinal surveillance is pivotal for detecting residual disease and early recurrence, despite the benign nature of paragangliomas. Our case underscores the challenges and importance of complete surgical resection for treatment success. Notably, to our knowledge, this is the first documented instance of a thyroid paraganglioma linked to a deletion mutation in the SDHA gene.
Poster 0502
Autoimmunity, Case Study, Poster
Pembrolizumab and immune-related adverse events: a case report
Diana Sadaieva*, Jaeun Ahn, Sami Tahhan, EVMS, USA
Immune checkpoint inhibitors (ICIs) like Pembrolizumab have been revolutionary in treating cancer, but they can cause severe side effects. In this case report, we will discuss immune-related adverse events (irAEs) due to ICIs.
Our patient is a 61-year-old man with a history of RCC with pancreatic metastases. The patient presented to the ER with fatigue, polyuria, polydipsia, and poor oral intake two days after completing his third monthly infusion of Pembrolizumab.
The exam revealed new onset Atrial Fibrillation with rapid ventricular response.
His labs were significant for a blood sugar of 780 mg/dl (normal range 70-99mg/dl), moderate Acetone levels in the blood, glucosuria, and ketonuria. He had a low TSH (<0.01 mcU/mL) and high FT4 (>2.0 ng/dl). TSIs were elevated.
Diabetic ketoacidosis resolved with fluids and an insulin drip, and he was transitioned to a basal-bolus insulin regimen, which controlled his glucose well. His tachycardia was controlled with a beta-blocker. He was discharged on propranolol, apixaban, and methimazole.
His final diagnoses were Pembrolizumab-induced new onset Type 1 Diabetes Mellitus and Pembrolizumab-induced Graves’ Disease.
Immune checkpoint inhibitors (ICIs) have substantially improved the prognosis of patients with advanced malignancies.
Despite clinical benefits, ICIs are associated with a unique spectrum of side effects known as immune-related adverse events (irAEs). IrAEs include dermatologic, gastrointestinal, hepatic, endocrine, and other less common inflammatory events. IrAEs are believed to arise from general immunological enhancement. Temporary immunosuppression with glucocorticoids and other immunosuppressants is effective in treating irAEs in most cases. Although rare, fulminant and even fatal toxicities may occur. Therefore, prompt recognition and management is essential.
The incidence rate for Pembrolizumab-induced hyperthyroidism is 0.6 %. Autoimmune thyroid disease due to ICIs can manifest as primary hypothyroidism secondary to destructive thyroiditis or rarely as hyperthyroidism associated with Graves’ disease.
ICI-related Graves’ disease is treated similarly to non-ICIs-related Graves’ disease, and thyroid function should be monitored before each dose of an ICI for early detection of thyroid dysfunction.
Treatment with ICIs has also been associated with acute onset of type 1 diabetes mellitus in approximately 0.2 to 0.9 % of cases. Patients who develop it are typically treated with insulin and will remain Insulin-dependent. In contrast to other irAEs, treatment with immunosuppressive agents is not effective in these patients due to the near-complete destruction of the pancreatic beta-cells.
A brief literature review did not show other cases of Pembrolizumab-related combined new-onset Diabetes and Graves’ disease.
Poster 0503
Disorders of Thyroid Function, Case Study, Poster
Paraneoplastic Beta-HCG induced hyperthyroidism
Harrison Kaufman*, Melissa Lechner, Shira Grock, Megan McConnell, UCLA, USA
Introduction
Here, we will discuss the case of a 50 year old women with paraneoplastic secretion of Beta-HCG (bHCG) and subsequent bHCG-induced hyperthyroidism. We will discuss management, as well as implications for treatment.
Description of Case
The patient is a 50 yo female with no medical history, who presented to the hospital with seizures. She was noted to have a large lung mass with metastatic disease in the brain. Subsequent biopsy of the mass was consistent with squamous cell carcinoma of the lung. She was noted to have a positive pregnancy test, with workup eventually demonstrating paraneoplastic secretion of bHCG. bHCG at that time was 132,737. Of note, TSH was 0.03 with a free T4 of 1.70, thought to be thyroiditis. She was later started on pembrolizumab and discharged to rehab. While at rehab, she was noted to be severely tachycardic at rest. She was brought to the hospital, vitals demonstrating a heart rate of 158 and a temperature of 101.4 degrees Fahrenheit. She denied any with heat intolerance, diarrhea, or abnormal behavior. Exam demonstrated a mild tremor, otherwise with normal reflexes. TSH was noted to be <0.02 with a free T4 of >7.00 and free T3 of 1,690. bHCG was >1,000,000. She was diagnosed with bHCG-induced hyperthyroidism and treated with methimazole and propranolol. Steroids were held so that she could undergo a second round of pembrolizumab. She was eventually discharged on methimazole, which was tapered off as bHCG eventually fell 19,981. Unfortunately, bHCG has recently begun to rise with blood work now again indicating hyperthyroidism.
Discussion
bHCG-induced hyperthyroidism is a rare entity, typically seen in trophoblastic disease and germ cell tumors. Due to the weak affinity of the bHCG subunit for the TSH receptor, a high level of bHCG is required to result in clinical hyperthyroidism. While paraneoplastic bHCG secretion has been reported in many other cancers, these levels are typically mild and do not result in clinical hyperthyroidism. Literature review for cases such as ours are exceedingly rare, and as such this case highlights the unique approaches that are being taken to manage her complex disease.
Poster 0504
Disorders of Thyroid Function, Case Study, Poster
Acute heart failure due to thyroid storm reversed by therapeutic plasma exchange
Ji Ae Yoon*1, Charit Taneja2, Avani Sinha2, Rifka Schulman-Rosenbaum3, 1Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, USA, 2Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, USA, 3Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Long Island Jewish Medical Center, USA
Therapeutic plasma exchange (TPE) can play a crucial role in the treatment of severe thyroid storm. We present a case of potentially fatal heart failure due to thyroid storm successfully treated with TPE.
A 24-year-old otherwise healthy male presented to the emergency department for new-onset psychosis. Labs revealed severe hyperthyroidism with TSH <0.01mIU/L, free T4 > 5.0 ng/dL, total T3 651 ng/dL and positive antibodies for Graves’ disease. He had fever, tachycardia and severe agitation; Burch-Wartofsky score was 55, indicating severe thyroid storm. On initial assessment there was no cardiac dysfunction on point-of-care ultrasound (POCUS) or clinical evidence of heart failure. He was admitted to the ICU, and required sedation and intubation given severe agitation and inability to take oral medications. Treatment for thyroid storm was initiated with methimazole, hydrocortisone, iodine solution and esmolol infusion. Cholestyramine was added when initial therapies did not yield clinical improvement after 24 hours. Despite maximal medical therapy for 3 days, the patient developed shock associated with persistent tachycardia and fevers up to 102 °F. POCUS revealed new right ventricular (RV) dilation, tricuspid regurgitation and elevated pulmonary artery systolic pressure up to 60 mmHg. Transthoracic echocardiogram confirmed acute RV failure and pulmonary hypertension, which was attributed to thyroid storm after ruling out pulmonary embolism or myocardial infarction. Within 24 hours of detecting RV failure, left ventricular failure was also discovered. Given this severe clinical deterioration, TPE was initiated. A three-session course of TPE resulted in normalization of cardiac function and resolution of hypotension. The patient made excellent clinical recovery and was discharged uneventfully from the hospital. His hyperthyroidism remained well-controlled with methimazole on outpatient follow-up.
Current guidelines recommend that TPE be reserved for patients with thyroid storm when first-line therapies fail or cannot be used (1, 2), however the exact decision-making around identification of suitable candidates and timing of TPE being initiated is left to the treating clinician. This case demonstrates the importance of recognizing acute heart failure as a complication of thyroid storm and the efficacy of prompt TPE in managing patients refractory to first-line therapies.
Poster 0505
Disorders of Thyroid Function, Case Study, Poster
Management of T3 thyrotoxicosis during pregnancy
Aanu Sihota*1,2,3, Christina Hirner1,2,3, Dragana Lovre1,2,3, Robert Galagan1,2,3, 1Tulane University, USA, 2University Medical Center, USA, 3Veterans Affairs Southeast Louisiana, USA
Hyperthyroidism during pregnancy is uncommon with ∼95% of cases due to Graves’ disease and <1% toxic multinodular goiter (MNG).
A 34-year-old female at 9 weeks gestation was referred to endocrinology for hyperthyroidism evaluation. She reported palpitations, heat intolerance and hand tremors. Her medical history included asthma, opiate addiction disorder, and depression. She was a nonsmoker.
Examination: weight 85 kg, (BMI of 36.6 kg/m2), HR 102 bpm, BP 145/66 mm Hg and enlarged thyroid gland with a palpable left lobe nodule, no exophthalmopathy. Labs: T3 419 ng/dL (71–180 ng/dL), T4 17 mcg/dL (4.8–13.9 mcg/dL), TSH <0.005 mIU/mL (0.358–3.74 mIU/mL), and TSI <0.10 IU/L (<0.54 IU/L). Ultrasound identified enlarged thyroid gland with multiple nodules, including a significant left lobe hypo-echoic nodule (5.0 × 3.2 × 2.4 cm).
A diagnosis of hyperthyroidism due to a toxic MNG was established. Propylthiouracil (PTU) was prescribed but not initiated due to fear of side effects. By gestational week 14, her symptoms had worsened, and T4 was 17 mcg/dL, FT4 2.1 ng/dL, T3 363 ng/dL, TSH <0.002 mIU/mL. Methimazole (MMZ) 5 mg daily and propranolol 10 mg TID were prescribed.
By week 22, her symptoms improved, with a normal FT4 and elevated T3 (FT4 1.05 ng/dL, T3 404 ng/dL, TSH <0.02 mIU/mL). MMZ was increased to 10 mg daily. By week 32, FT4 was mid-normal, and T3 level was mildly elevated. At 36 weeks, she underwent a cesarean section, delivering a healthy infant weighing 3.66 kg with Apgar score of 9. The postpartum course was uncomplicated.
1. Serum TSH may decrease in the first trimester of pregnancy due to the stimulating effect of hCG on the TSH receptor, peaking between 7 and 11 weeks.1 Overt hyperthyroidism is confirmed with suppressed TSH and elevated TT4/FT4 or T3 levels.1,2
2. In pregnant patients with T3 thyrotoxicosis, the goal is to lower T3 to 1.5 x ULN.2 Caution should be paid to prevention of fetal hypothyroidism since T3 doesn’t cross the placenta.
3. Our unique case emphasizes the balance between effective maternal treatment of T3 thyrotoxicosis and fetal safety where treatment guidelines are limited.
Poster 0506
Disorders of Thyroid Function, Case Study, Poster
Myxedema coma: an endocrine emergency case study
Maitri Acharekar*, John Godke,Baton Rouge General medical center, USA
Introduction:
Myxedema coma is a rare but potentially fatal complication of severe hypothyroidism with hemodynamic impairment caused by untreated or undiagnosed hypothyroidism. The mortality rate is significant, reaching 25–60%. Female sex, advanced age, cold, exposure, or a triggering event such as infection, trauma, are all risk factors for myxedema coma.
Case Description:
This 49-year-old female with a past medical history of hypothyroidism who presented to the emergency department [ED] with generalized weakness and progressive shortness of breath for the past 2 to 3 weeks. On arrival at the ED, the patient was somnolent, confused and demonstrated delayed cognitive responses. She was severely hypothermic, with bradycardia and hypotension. Initially, a blood gas analysis revealed hypoxemia with acute hypercapnic respiratory failure. On examination, she had a swollen face, generalized thickened nonpitting, edema over the skin, and delayed relaxation of deep tendon reflexes. Laboratory investigations revealed a highly raised thyroid stimulating hormone- TSH [24.5 uIU/ml] and a decreased free thyroxine- T4 [0.13 ng/ml], and a diagnosis of myxedema coma was established. Considering the severity of the illness, patient was admitted to the critical care unit, where she was intubated and treated with IV hydrocortisone, IV levothyroxine, and liothyronine. She recovered successfully with the above treatment and ICU supportive care.
Discussion:
Myxedema coma is characterized as diminished mental status, hypothermia, and other symptoms associated with the slowing of multiple organ functions caused by severe hypothyroidism, and should be considered in patients, particularly elderly females with a history of hypothyroidism or thyroidectomy. In our patient medication non compliance precipitated this condition. This case serves as a reminder that myxedema coma is a true endocrine emergency that requires immediate recognition and appropriate care.
Poster 0507
Disorders of Thyroid Function, Case Study, Poster
The thyroid paradox: Hypothyroidism in the face of normal TSH
Vikram Jeet Singh Gill*1, Suha Soni2, Hongxiu Luo1, 1Saint Peters University Hospital, USA, 2UTHealth Houston School of Public Health, USA
Central hypothyroidism (CH) is rare, particularly when isolated, and usually presents with detectable but biologically inactive serum TSH. CH results from a disorder in the pituitary, hypothalamus, or hypothalamic-pituitary portal circulation, leading to diminished levels of TSH and/or thyrotropin-releasing hormone (TRH). Although TSH levels may appear normal, their biological activity is often reduced. We present two cases highlighting the presentation and treatment of this rare condition, which has an incidence rate of 1 in 100,000.
We will discuss two middle-aged female patients who presented to our outpatient Endocrinology clinic with clinical features of hypothyroidism but without other symptoms of pituitary dysfunction.
On laboratory workup, both patients had normal TSH levels but below-normal free T4 (fT4) and total T3 levels. They tested negative for anti-TPO and anti-Tg antibodies. Further investigation with MRI revealed a partially empty sella turcica without pituitary adenoma in one patient, and a large pituitary macroadenoma with necrosis in the other. Weight-based levothyroxine (LT4) treatment was initiated after testing pituitary-adrenal function to rule out acute adrenal insufficiency.
It is imperative to check fT4 in clinical scenarios suggestive of CH, as it can often be missed, leading to delayed diagnosis. Once CH is confirmed, other pituitary hormonal deficiencies must be ruled out before starting LT4 treatment to avoid precipitating an adrenal crisis. Therapy adequacy should be monitored with serial serum T4 and T3 levels, aiming to maintain them in the upper normal range.
Poster 0508
Iodine Uptake and Metabolism, Case Study, Poster
A rare cause of radiation thyroiditis requiring plasma apheresis
Edward Echevarria*, Amber Champion, Emily Ahner, Kirk Kerkorian at UNLV, USA
Radioactive iodine (RAI) has been well established in the United States for the definitive treatment of Graves’ disease. Adverse events from RAI are uncommon. About 1–5% of patients who receive RAI develop radiation thyroiditis, and only around 0.3% of these patients develop severe symptoms of thyrotoxicosis requiring inpatient admission. I herein report a patient with radiation thyroiditis that required plasma apheresis as an inpatient.
A 41-year-old female with a history of Graves’ disease presented to the emergency department with signs and symptoms of thyrotoxicosis. Three weeks prior to admission, the patient received 22 mCi of I-131 as definitive treatment for Graves’ disease. She had stopped methimazole one week prior to the procedure. This was the third visit post-radioiodine ablation that the patient presented with symptoms of thyrotoxicosis despite treatment with thioamides and steroids. Thyroid function tests prior to RAI showed a TSH of <0.008, FT4 of 1.37, and FT3 of 3.32. Three weeks after RAI, thyroid function tests showed a TSH of <0.008, FT4 of 3.00, and FT3 of 8.23. The decision was made to start the patient on plasmapheresis. She received a total of 11 sessions of plasmapheresis. Upon re-checking thyroid function tests, FT4 improved to 1.50 and FT3 improved to 2.48. The patient was eventually discharged and evaluated as an outpatient, where she was found to have biochemical hypothyroidism.
Discussion:
The mechanism for radiation thyroiditis has been postulated to involve thyroid follicular cell injury secondary to RAI. This causes a release of thyroid hormones into the circulation, resulting in signs and symptoms of thyrotoxicosis. Most of the time, these patients are asymptomatic, but in rare instances, like in this case, patients may require inpatient admission in a critical setting. Management of this rare condition is mostly focused on symptomatic relief, but sometimes, the use of plasmapheresis is warranted for patients who develop resistance to treatment. We present this case of radiation thyroiditis to create awareness of the presentation of this rare adverse event, to enhance timely diagnosis and intervention, and to provide evidence of different treatment modalities.
Poster 0509
Surgery, Case Study, Poster
Prophylactic extracorporeal membrane oxygenation cannulation in extreme airway compromising thyroid goiters
Thomas Szabo Yamashita*, Anee Jackson, Adil Malek, Neil Saunders, Jyotirmay Sharma, Collin Weber, Snehal Patel, Emory, USA
Poster 0510
Surgery, Case Study, Poster
Recurrent laryngeal nerve repair with anastomosis of ansa cervicalis in thyroid surgery in two cases
Takashi Hirano*, Munehito Moriyama, Kaori Shinomura, Masashi Suzuki, Department of Otolaryngology, Faculty of Medicine, Oita Unversity, Japan
Recurrent laryngeal nerve (RLN) injury in thyroid surgery is the most common postoperative complication, causing breathy hoarseness and decreasing phonation time, and significantly impairing the patient’s quality of life in daily conversation. In this study, we experienced two cases of immediate intraoperative repair of the recurrent nerve include ansa cervicalis to RLN anastomosis. Case 1 was a 75-year-old woman whose chief complaint was a right cervical mass without preoperative hoarseness. She was diagnosed with papillary thyroid carcinoma (cT2N1bM0, Stage II), and the total thyroidectomy with right lymph nodes dissection (D2a) were performed. During the cervical dissection, the right recurrent nerve was resected along with the lymph nodes because it was firmly attached to the metastatic lymph nodes. At that time, anastomosis of ansa cervicalis and RLN was performed. Case 2 was a 66-year-old woman whose chief complaint was hoarseness. She was diagnosed with papillary thyroid cancer (cT4aN0M0, Stage III) and underwent left thyroid lobectomy and left cervical dissection (D1). During thyroid tumor resection, the left RLN was tightly attached to the tumor and resected, so the ansa cervicalis and RLN were anastomosed immediately. Case 1 had a maximal vocalization time of 29 seconds at 4 months after the surgery, and Case 2 had a maximal vocalization time of 30 seconds at 4 months after the surgery. Immediate nerve repair of the RLN by ansa cervicalis is simple and effective in improving the prognosis of voice function.
Poster 0511
Thyroid Cancer, Case Study, Poster
Use of selpercatinib before iodine ablation in a child with RET-Fusion+ papillary thyroid cancer with advanced neck and pulmonary disease
Hilary Seeley*, Crystal Wang, Helen Nadel, Kara Meister, Stanford University School of Medicine, USA
INTRODUCTION
In a pediatric patient with RET-fusion positive papillary thyroid cancer (PTC) and cervical lymph node and pulmonary metastases, we report significant reduction of disease burden with Selpercatinib (RET inhibitor) after thyroidectomy.
DESCRIPTION OF THE CASE
Twelve-year-old male presented with 1 month of bilateral cervical lymphadenopathy. Ultrasound revealed four thyroid nodules, chest x-ray demonstrated nodular opacities in a miliary pattern, and chest CT showed innumerable miliary papillary thyroid cancer pulmonary metastases. TSH and free T4 were normal. Thyroglobulin level was greater than 4500 mg/ml (ref range <50) and thyroglobulin antibody was 75 IU/mL (ref range <4).
Fine needle aspiration (FNA) of bilateral thyroid nodules was suspicious for PTC. After total thyroidectomy with bilateral central and lateral neck dissection, surgical pathology confirmed multi-focal PTC, classical subtype, Stage T4a N1b M1, 25/80 lymph nodes positive, ATA pediatric high risk for recurrent/residual disease. Thyroseq (Sonic Healthcare USA, Rye Brook, NY) from FNA and Stanford actionable mutation panel for solid tumors were positive for RET/PTC3 (NCOA4/RET) fusion. I-123 uptake scan noted innumerable subcentimeter pulmonary nodules bilaterally.
1 month post-operatively, oral selpercatinib was initiated. His course was complicated by pneumonitis and tumor lysis syndrome, which required a dose reduction from 120 mg to 80 mg BID. He developed drug-induced hyperphosphatemia and low T3 requiring liothyronine. After 3 months, CT scans demonstrated significant radiographical improvement in pulmonary metastases. After 4 months, his oxygen requirement with sleep and exercise resolved. After 5 months, thyroglobulin level decreased to 987 ng/mL and thyroglobulin antibody improved to 53 IU/ml. At 6 months, we will consider radioactive iodine ablation (RAI) pending continued response to selpercatinib.
DISCUSSION
Studies on distant metastases in pediatric PTC are limited, and patients have persistent disease despite multiple RAI courses. We describe a patient with RET-fusion positive PTC with cervical and neck metastases who demonstrated significant biochemical and radiographical response to Selpercatinib. Selpercatinib is approved by the FDA for children and adults. The use of kinase inhibitors as neoadjuvant therapy in children with thyroid cancers is evolving and may be a useful tool in mitigating long term sequelae of both surgical and nuclear medicine therapies.
Poster 0512
Thyroid Cancer, Case Study, Poster
Unexplained hyperthyroglobulinemia in a pathologically unique case of differentiated thyroid cancer
Lina Pedraza*, Samantha Newman, Memorial Sloan Kettering, USA
A 49 year old male noted a rapidly enlarging neck lump. After multiple FNAs were non-diagnostic. He underwent diagnostic lobectomy, revealing a 9 cm left sided tall cell variant papillary thyroid carcinoma (TCV-PTC) with oncocytic features and extensive vascular and lymphatic invasion. He then underwent completion thyroidectomy with evidence of two foci of the same pathology and positive margins. He was treated with adjuvant RAI (100 mCi), after which thyroglobulin (TG) was 18 ng/dl. Subsequent TG rose to 200 ng/dl with imaging showing bulky cervical lymphadenopathy. In the subsequent year, he underwent two neck dissections revealing low volume lymph node disease, without resolution of thyroglobulin. 18 months later, brain MRI, PET/CT, thyroid ultrasound all are negative for recurrent or metastatic disease. His thyroglobulin remains in 80 ng/dl despite full TSH suppression.
Few data are available to guide the management of unexplained hyperthyroglobulinemia in patients with differentiated thyroid cancer. Traditionally, patients such as these are given repeat doses of RAI, but there is minimal evidence to support this. Elevated thyroglobulin after total thyroidectomy and RAI without evidence of iodine avidity on imaging can be due to inadequate TSH stimulation, iodine contamination, loss of iodine uptake through tumor de-differentiation, or a disease volume too small to be detected by standard imaging techniques. While repeat doses of RAI sometimes result in diminution of serum TG, there is no evidence which suggests this strategy impacts prognosis.
In the case of TCV-PTC described above, our inability to detect a focus of disease may be related to tumor de-differentiation. This tumor expressed both features of TCV-PTC as well as oncocytic carcinoma (OC) of the thyroid — the latter of which tends toward high thyroglobulin production even in the setting of small (often undetectable) volume of disease. Iodine uptake for both TCV-PTC and OC are poor, ranging from 10–20%. As generally TCV-PTC and OC are considered pathologically distinct, this case is highly unusual. The behavior of this patient’s cancer over time features core elements of both pathologies. This case highlights the need for specialized pathological evaluation and an individualized approach in the care of patients with complex thyroid tumors.
Poster 0513
Thyroid Cancer, Case Study, Poster
Redifferentiation of metastatic RET-Rearranged papillary thyroid cancer with selpercatinib
Aurelie Forget-Renaud*1, Marielle Bily2, Marie Nicod-Lalonde3, Julien Dagher4, Peter Kopp1, 1Division of Endocrinology, Diabetes and Metabolism, University Hospital of Lausanne and University of Lausanne, Switzerland, 2Endocrinology, Hospital Network Neuchâtel, Switzerland, 3Division of Nuclear Medicine, University Hospital of Lausanne and University of Lausanne, Switzerland, 4Translational Onco-Pathology Unit, University Institute of Pathology, University Hospital of Lausanne and University of Lausanne, Switzerland
Poster 0514
Thyroid Cancer, Case Study, Poster
Thyroglossal duct cyst papillary thyroid cancer: a case report
Jessica Khoury*1, Katherine Mann1, Arjun Joshi2, Chelsey Baldwin1, 1The George Washington University School of Medicine and Health Sciences, Department of Endocrinology, USA, 2The George Washington University School of Medicine and Health Sciences, Department of Otolaryngology, USA
Introduction:
Thyroglossal duct cyst (TGDC) is a remnant of thyroid development and presents as an anterior midline neck mass. Carcinoma of TGDC occurs in only 1–2% of TGDC cases. Definitive surgical management of a TGDC is the Sistrunk procedure. If a cancer diagnosis is made on pathology, management is debated. We report a case of papillary thyroid cancer (PTC) of TGDC with nodal metastasis that was managed with Sistrunk procedure and surveillance as opposed to total thyroidectomy with radioiodine ablation.
Case Presentation:
A 45-year-old male patient presented with a history of a midline neck mass at the level of the hyoid that elevated while swallowing. Neck ultrasound (US) demonstrated a 1.5 × 2.0 × 2.2 cm well defined oval mixed solid- cystic mass in the midline anterior neck with adjacent two suspicious level VI lymph nodes. Midline mass biopsy was consistent with PTC. Patient underwent central compartment neck dissection with Sistrunk operation. Pathology showed a 9 mm classical variant papillary thyroid cancer with approximately 25% of cells showing tall cell features, with negative margins, and no perineural invasion. The two resected lymph nodes were consistent with PTC however with greater than 90% of cells showing tall cell features. The patient was counseled on recommendation of total thyroidectomy and radioactive iodine, but declined. Patient has been followed for 40 months without definitive evidence of recurrence.
Discussion:
The literature supports stratifying patients with PTC of the TGDC into low and high risk groups. For PTC of TGDC, low risk features include ages between 15–45 years, no radiation history, tumor size <4cm, and no nodal or distant metastases. These patients can be treated with the Sistrunk procedure alone. For patients that are high risk, it is recommended to undergo the Sistrunk procedure and a total thyroidectomy often with radioactive iodine ablation to reduce the risk of recurrence and ability to monitor with thyroglobulin. However, given that ultrasonography is likely sufficient for detecting clinically significant recurrence of PTC in the neck, patients with noninvasive primary tumors without bulky metastatic nodal disease may represent an intermediate risk category that can undergo surveillance without total thyroidectomy.
Poster 0515
Thyroid Cancer, Case Study, Poster
Differentiated high grade thyroid carcinoma arising in a malignant struma ovarri: a case report
Jessica Khoury*1, Shabnam Samankan2, Mohadese Behtaj2, Elham Arbzadeh2, Katia DaSilva3, Osereme Abulu3, Priya Sathyanarayn3, James Castro3, Nicole Chappell3, Chelsey Baldwin1, Jennifer Vaz3, 1The George Washington University School of Medicine and Health Sciences, Department of Endocrinology, USA, 2The George Washington University School of Medicine and Health Sciences, Department of Pathology, USA, 3The George Washington University School of Medicine and Health Sciences, Cancer Center, USA
Papillary thyroid cancer (PTC) arising from ovarian teratoma is rare, occurring in 0.1–0.3% of ovarian cancers. The rarity of PTC in malignant struma ovarii (MSO) makes standardized treatment challenging. To our knowledge, this case is the first case report of MSO with differentiated high grade thyroid carcinoma based off new WHO (2022) classification of endocrine and neuroendocrine tumors.
A 47-year-old, Hispanic female with Hashimoto’s thyroiditis presented to her primary gynecologist for urinary frequency and pelvic fullness. Physical exam revealed a firm, palpable, lower abdominal mass. MRI illustrated complex multicystic mass replacing right ovary measuring 9.9 × 7.3 × 10.2 cm with septations and free fluid in the cul de sac. Preoperative, cancer antigen 125 (CA125), carcinoembryonic antigen (CEA), cancer antigen 19–9 (CA19-9) and thyroid test were normal. The patient underwent exploratory laparotomy. Intraoperative findings included 12 cm cystic and solid right ovarian mass adherent to the left pelvic sidewall. A thorough exploration of her abdomen revealed no other evidence of disease. A total abdominal hysterectomy bilateral salpingo-oophorectomy, omentectomy to R-0 was performed. Histological examination revealed remnants of the ovarian cortex and residual thyroid tissue consistent with struma ovarii and differentiated papillary neoplasm with ground glass nuclei consistent with PTC. By immunohistochemical (IHC) stains both benign and malignant components expressed TTF1 and thyroglobulin. Cytomorphologically PTC was predominantly classical subtype admixed with a minor tall cell component. High mitotic activity (≥5/2 mm2) and BRAF V600E mutation were present. Based on retained architectural and nuclear features of PTC in the presence of high mitotic activity, the diagnosis of differentiated high grade PTC per 5th edition WHO guidelines for endocrine tumors was concluded. Based off these findings, the patient was diagnosed with FIGO Stage IA Ovarian MSO.
PTC arising in MSO are uncommon. Owing to the extreme rarity of these cases, there is no well-established guidance on recommended treatments. Histology subtype, mitotic figures, necrosis, and molecular analysis serve to prognosticate and guide adjuvant treatment of primary thyroid PTC. Additional research is needed to study if these histological and molecular findings have similar significance in PTC arising from MSO.
Poster 0516
Thyroid Cancer, Case Study, Poster
Largest case series of thyroid collision tumors from a single healthcare system
Sherry Liang*1,2,3, Christina Nguyen-Hirner1,2,3, Dragana Lovre1,2,3, Robert Galagan1,2,3, 1Tulane University School of Medicine, USA, 2Southeast Louisiana Veterans Health Care System, USA, 3University Medical Center, USA
Introduction
Thyroid collision tumors (TCT) account for 1% of all thyroid cancers. Papillary thyroid cancer (PTC) and medullary thyroid cancer (MTC) are the most common co-occurrence.1 TCTs consisting of PTC and follicular thyroid cancer (FTC) are reported less frequently than PTC and MTC.
Methods
We retrospectively reviewed the clinical presentations and tumor features of 24 cases of PTC and FTC co-occurrences in an urban New Orleans healthcare system. This is a retrospective cohort study from the years 2000 to 2024 of PTC and FTC collision tumors. The electronic medical record was systematically searched by ICD-10 diagnosis code for all thyroid cancers. Each chart was reviewed to confirm the diagnosis of a collision tumor based on surgical pathology.
Results
The average age at diagnosis was 49 years with 75% female, which is consistent with observations from prior literature reviews. Fifty-four percent of subjects were white and 29% were black. Forty percent of cases were discovered incidentally by imaging. All TCT cases were diagnosed as co-occurrence of PTC and FTC with a majority PTC microcarcinomas. Genetic testing of multiple mutation types was done in 11 (46%) of cases. Four of 10 PTC that were tested for BRAF were positive which is comparable to the incidence reported in isolated PTC cases. One case involved metastases to lymph node and bone with genetic testing positive for BRAF on FTC and NRAS on PTC. Ninety-two percent of cases had FTC contralateral to PTC. Fifteen of 24 cases had initial lobectomy then completion thyroidectomy. Of the 15 initial lobectomy cases 9 had only FTC, 2 only PTC and 4 had both FTC and PTC. Seven of the 9 initial FTC had contralateral PTC microcarcinoma after completion thyroidectomy.
Discussion/Conclusion
Our case series is unique as it reveals that the majority of TCT are co-occurrences of PTC and FTC in a community healthcare setting, whereas most TCT are co-occurrences of MTC and PTC in tertiary thyroid research centers. Longitudinal studies are important to understand the disease progression and prognosis of co-occurrence of PTC and FTC.
Poster 0517
Thyroid Cancer, Case Study, Poster
Coexisting medullary and papillary thyroid carcinoma: an uncommon and often underdiagnosed Entity-Case report
Alin Abreu Lomba*1, Santiago Sierra Castillo2, Maria Henao Rincon3, David Aristizabal Colorado4, David Vernaza Trujillo4, 1Imbanaco Clinic, Colombia, 2ces, Colombia, 3ces, Colombia, 4Interinstitutional Medicine Intern Group (GIMI 1), Libre University, Cali, Colombia
To present a rare instance of coexisting medullary and papillary thyroid carcinoma (MTC/PTC), highlighting the diagnostic challenges and treatment considerations associated with this uncommon presentation.
This is a case report based on the CARE guidelines.
A 59-year-old patient presented with dysphonia due to left vocal cord paralysis. Following a chest CT scan and PET-CT, thyroid cancer with mediastinal infiltration was diagnosed. Following surgical intervention and pathological assessment, a mixed medullary/papillary carcinoma was identified. The pathological report revealed poorly differentiated MTC with blue cell features, measuring 6.5 × 6.4 × 4.4 cm and a Ki-67 proliferation index of 10%. The tumor exhibited positivity for cytokeratin AE1/AE3, carcinoembryonic antigen, synaptophysin, chromogranin, TTF-1, S-100, and calcitonin. Additionally, a metastasis was found in a mediastinal lymph node, consistent with usual-type papillary thyroid carcinoma, positive for cytokeratin AE1/AE3, thyroglobulin, and TTF-1. Genetic testing was conducted with negative results for (Gencell Pharma). Due to incomplete surgical resection, treatment with radiotherapy was initiated.
The coexistence of papillary thyroid carcinoma (PTC) and medullary thyroid carcinoma (MTC) can manifest independently, as collision tumors, or as mixed tumors. The onset age ranges from 27 to 70 years, with a male predominance. Diagnosis is particularly challenging, as fine-needle aspiration (FNA) and ultrasound are limited in their ability to detect both types simultaneously. Immunohistochemistry and serum levels of calcitonin and carcinoembryonic antigen (CEA) are essential for the identification of MTC, while thyroglobulin (TG) and other markers assist in identifying PTC. In our case, lesions exhibiting characteristics of both MTC and PTC were observed in two distinct locations. Although not performed in this patient, the RET proto-oncogene is known to contribute to oncogenesis in both MTC and PTC by activating tyrosine kinase. Standard treatment for both cancer types includes total or near-total thyroidectomy, tumor resection, and lymph node dissection, with radiotherapy and chemotherapy employed in advanced cases. Prognosis is primarily dependent on the stage of MTC at the time of diagnosis.
The coexistence of papillary and medullary thyroid carcinoma presents significant diagnostic challenges due to the limitations of conventional imaging and biopsy techniques. Immunohistochemical markers and serum levels are crucial for accurate identification. Comprehensive treatment, including thyroidectomy and appropriate adjuvant therapies, is essential. Prognosis depends largely on the timely detection and staging of medullary carcinoma, underscoring the need for heightened clinical vigilance and advanced diagnostic strategies in managing these rare, mixed thyroid tumors.
Poster 0518
Thyroid Cancer, Case Study, Poster
NUT thyroid carcinoma: a case report of rare malignancy
Matthew Gonzalez*, Kim Ely, Sean All, Lindsay Bischoff, Sarah Rohde, Jennifer Choe,Vanderbilt University Medical Center, USA
Poster 0519
Thyroid Cancer, Case Study, Poster
Life-threatening cardiac tamponade as initial presentation of suspected primary tumor from thyroid and lung
Marcos Chacon Cruz*1, Margarita Ramirez Vick2, Milton Carrero Quiñonez1,1, Yaniris Garcia Cruz1, 1Mayaguez Medical Center, USA, 2University of Puerto Rico, USA
Ocasionally, pericardial effusion may be the first manifestation of malignant disease and this must be excluded in every case presenting with cardiac tamponade. Thyroid cancer very rarely metastasizes to the pericardium, especially as an initial presentation, although quite a few case reports have appeared in the literature.
Case of 67 y/o male patient, with PMHx of HTN, DM, CKD, Stroke, Dyslipidemia, and BA who was brought to the hospital c/o weakness and progressive shortness of breath, requiring intubation and vasopressors. A chest CT revealed bilateral moderate sized pericardial effusions and enlargement of both thyroid lobes predominantly involving the right side with intrathoracic extension. Thyroid U/S revealed an abnormally enlarged heterogenous thyroid gland with multiple nodules. A very large right thyroid had 2 worrisome nodules, a solid, taller-than-wide nodule with ill-defined margins measuring 3.5 × 3.3 cm (TR5) and a solid, taller-than-wide nodule of 1.5 × 2.2 cm (TR4), both without internal calcifications. In the left thyroid lobe, the 2 largest nodules described were: a solid, hypoechoic nodule with smooth margins and no calcifications measuring 1.4 × 1.2 cm (TR4) and a mixed nodule predominantly hypoechoic with ill-defined lobulated margins measuring 1.8 cm (TR3). An echochardiogram was done that revealed a large amount of pericardial effusion, evidence of cardiac tamponade and hemodynamic compromise. A cardiothoracic surgeon performed emergency drainage of the pericardial effusion and removed 800 cc of bloody fluid. Cytology was positive for malignant cells and consistent with metastatic carcinoma. The following immunohistochemical stains were found positive performed: CK-7, TTF-1, Napsin-A, CK-19, p53, CDX-2. These tumor markers are found in thyroid and lung malignancies. Patient is pending sono-guided FNA of the thyroid and bronchoscopy.
A pericardial effusion is rarely malignant but if effusions are very large and associated to cardiac tamponade, as in our patient, the prevalence of neoplasia rises significantly. However, pericardial effusion as an initial manifestation of thyroid cancer is uncommon. In our patient, the immunohistochemistry of the pericardial fluid points to both thyroid and lung malignancies, causing concern for the possibility of two primary malignancies.
Poster 0520
Thyroid Cancer, Case Study, Poster
Incidental RET gene mutation with 100% penetrance of MTC
Aisha Parihar*, Jessica Khoury, Rohit Jain, George Washington University, USA
Medullary thyroid carcinoma (MTC) accounts for 2% of all thyroid cancers with 75% of cases being sporadic, while the remainder are hereditary. The heterozygous RET gene mutation c.2410G>A (p. Val804Met) is associated with an increased risk of MTC. With patient accessible genetic testing, management of incidentally detected mutations is challenging.
Two sisters, 25-years-old (sister A) and 28-years-old (sister B), with no family history of thyroid cancer, pursued genetic health screening test that was positive for heterozygous RET gene mutation c.2410G>A (p. Val804Met). Sister A had a calcitonin level of 45.8 pg/ml (0.0–5.0 pg/mL) and negative CEA. Thyroid ultrasound showed a right 0.7 × 0.5 × 0.5 cm nodule, which was positive for MTC on biopsy. A total thyroidectomy with right central neck dissection was performed. Pathology showed 1.2 cm MTC with positive calcitonin immunostaining and negative invasion, margins, and lymph nodes. Post-op calcitonin was undetectable. Sister B had a calcitonin level of 8.6 pg/ml and negative CEA. Her thyroid ultrasound showed a 0.44 cm left thyroid nodule and 0.29 cm right thyroid nodule, too small for biopsy. She underwent total thyroidectomy and pathology showed diffuse C-cell hyperplasia, with one focus of sub-centimeter MTC with positive calcitonin immunostaining and negative invasion, margins, and lymph node. Her post-op calcitonin was undetectable. Both sisters did well post-operatively and were started on levothyroxine. They had unremarkable serum metanephrines. Sister A had a CT scan abdomen/pelvis without adrenal pathology. Annual screening with serum calcitonin, CEA, metanephrines, and PTH, and thyroid ultrasound was recommended for both patients.
Our patients’ clinical picture and RET gene mutation c.2410G>A (p. Val804Met) is consistent with familial MTC, which confers a low risk of pheochromocytoma and parathyroid hyperplasia, more commonly seen with MEN2. This mutation has a high-lifetime penetrance for MTC. In our patients, because of elevated calcitonin levels and presence of nodal disease, early surgery was felt to improve prognosis. The trajectory of MTC is unclear if patients with this gene mutation are non-surgically managed. Increased patient driven genetic self-testing and cases of incidentally detected MTC, call for updated guidelines for biochemical and nodal screening, management, and surveillance.
Poster 0521
Thyroid Imaging, Case Study, Poster
Peripheral serpiginous arrangement of punctate hyperechoic foci in thyroid nodules: Ultrasonographic aspect suggestive of papillary carcinoma
Laila Daibes*1, Stefano Spiezia2, Fernanda Aguiar Pescador3, Marianna Daibes1, Pedro Mandetta4, Marilene Filgueira do Nascimento5, Haitham Sharara6, Fernando Dias4, 1Clinica Daibes Diagnósticos, Brazil, 2Ospedale del Mare, Italy, 3Secretaria de Saúde do Estado do Rio de Janeiro, Brazil, 4Instituto Nacional de Câncer, Brazil, 5Universidade Federal Fluminense, Brazil, 6Institut de Cancérologie du Gard, France
Poster 0522
Thyroid Nodules and Goiter, Case Study, Poster
Graves’ disease diagnosed six months after microwave ablation of benign thyroid nodules: a case report
Yunru Gu*, Rui Chen, Mingling Chen, Xiaohong Jiang, Long Wang, Xiaolin Huang, Department of Endocrine and Metabolic Diseases, The First People’s Hospital of Changzhou, The Third Affliated Hospital of Soochow University, China
Objective: We report a middle-aged male patient who was diagnosed with Graves’ disease (GD) 6 months after microwave ablation of a thyroid nodule, and whose thyroid function returned to normal after 3 months of antithyroid medication. The purpose of this case report and study is to analyze the potential causes of GD after ablation and to emphasize the importance of strictly grasping the indications for ablation and standardizing the operation of ablation procedures.
Methods: This article is a case report of a descriptive study of a middle-aged male who developed hyperthyroidism secondary to Graves’ disease after microwave ablation of a thyroid nodule. We reviewed the patient’s medical history, the postoperative course of his hyperthyroidism, and collected the patient’s test parameters during his visit to our hospital.
Results: To the best of our knowledge, this is the first case report of hyperthyroidism symptoms due to GD after microwave ablation of benign thyroid nodules.We searched through the literature, and we did not search for case reports of GD after microwave ablation of thyroid nodules, but there are relevant reports of cases of GD occurring after radiofrequency ablation of thyroid nodules, as well as percutaneous ethanol ablation. We analyzed the possible causes of thyroid function abnormalities in patients, including the release and accumulation of postoperative thyrotoxins due to intraoperative thermal injury, patients with high levels of TgAb and TPOAB prior to ablation, improper surgical procedures, or failure to strictly follow guideline recommendations when evaluating a patient’s suitability for ablation, but all of these cause analyses are speculative and are not based on evidence.
Discussion/Conclusion: From this case study, we recognize that the adverse effects of microwave thyroid ablation limit its widespread use, and there is a lack of large studies on the long-term follow-up of patients undergoing microwave thyroid ablation. With the popularity of MWA, more large studies are needed in the future to assess thyroid ablation risk indicators, especially preoperative thyroid antibody indicators, to predict the incidence of postoperative thyroid abnormalities and to guide preoperative ablation protocols.
Poster 0523
Thyroid Nodules and Goiter, Case Study, Poster
Graves’ disease diagnosed six months after microwave ablation of benign thyroid nodules: a case report
Yunru Gu1, Rui Chen1, Mingming Chen2, Xiaohong Jiang1, Long Wang1, Xiaolin Huang*1, 1Department of Endocrinology, The Third Affiliated Hospital of Soochow University, China, 2Department of Urology, The third affiliated hospital of Soochow university, China
The possible mechanism of thyroid function abnormalities may be the release and accumulation of postoperative thyrotoxins due to intraoperative thermal injury, high levels of TgAb and TPOAB prior to ablation, improper surgical procedures, or failure to strictly follow guideline recommendations when evaluating a patient’s suitability for ablation.
Poster 0524
Thyroid Imaging, Clinical, Poster
Evaluation of fibroinflammatory activity in thyroid eye disease using 18F-FAPI PET/CT: a prospective study
Hui Li*1, Yi Wang1, Jichao Zhou1, Debo You1, Le Song1, Meng Wang1, Meixin Zhao1, Yansong Lin2, Huanwen Wu2, Zhaofei Liu1, Weifang Zhang1, Lingge Suo1, 1Peking University Thrid Hospital, China, 2Peking Union Medical College Hospital, China
Poster 0525
Thyroid Cancer, Clinical, Poster
After Long-Term follow-up, is there an impact of minimal extrathyroidal extension on clinical outcomes in differentiated thyroid carcinoma?
Julia M Fagundes Velloni*, Rosa Biscolla, Cleber P Camacho, Fabiano M Callegari, Federal University of São Paulo, Brazil
Introduction: One of the criteria that defines risk of recurrence in Differentiated Thyroid Cancer (DTC) is the presence of extrathyroidal extension. According to the ATA (American Thyroid Association) guideline, the presence of minimal extrathyroidal extension (mETE) is considered as an intermediate risk with about 3–9% risk for structural disease after initial treatment. However, the relationship of minimal extension and clinical outcome still presents controversies. Objective: Evaluate the impact of mETE on clinical response in patients with differentiated thyroid carcinoma. Methods: Retrospective study with 167 patients classified as having an intermediate risk of recurrence (IRR). Among them, 125 (75%) presented mETE in addition to the characteristics that defined them as intermediate risk (IRRmETE), while 42 patients (25%) did not present it (IRRwtomETE). For each patient, data evaluated were age, gender and histological tumor-related characteristics, serum stimulated thyroglobulin (sTg), treatment performed and clinical response. Univariate and multivariate logistic regression models were used to investigate the association of clinical variables with the response to treatment: acceptable (excellent and indeterminate) and unacceptable (incomplete biochemical response and structural disease). Results: Clinical response was deemed acceptable in 70 patients (42%) and unacceptable in 97 (68%). Histological aggressive subtype (odds radio [OD]: 10.8 [IC: 4.0–23.9], p = 0.001), vascular invasion (OD: 6.1, [IC: 3.5–10.9] p = 0.001), presence of lymph nodes (OD: 1.19, [IC: 1.08–1.3] p = 0.001), serum sTg (OD: 3.05, [IC: 1.7–5.2], p = 0.001) and mETE (OD:1.8, [IC:1.1–2.9] p = 0.01) were predictors of an unacceptable clinical outcome in univariate analysis. In contrast, the presence of minimal extension, as an independent criterion, was not a predictor of a worse clinical response after multivariate analysis. Conclusion: After long-term follow-up of patients with DTC, the presence of mETE was a histological finding for worse clinical outcomes only when combined with other criteria such as histological subtype, serum thyroglobulin, vascular invasion, and lymph node involvement.
Thursday, October 31, 2024
Poster 0526
Autoimmunity, Basic, Poster
The role and mechanism of gut microbiota in thyroid eye disease
Yanan Wang*, Yushu Li, Zhongyan Shan, Weiping Teng, Department of Endocrinology and Metabolism, Institute of Endocrinology, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Affiliated Hospital of China Medical University, China
Thyroid Eye Disease (TED) is a relatively rare yet serious ocular condition, the full etiology and pathogenesis of which are still not completely understood. Emerging evidence highlights the role of gut microbiota in both the onset and progression of TED. This study aims to explore the key differential microbial species and their associated metabolites, investigating their potential mechanisms in the pathophysiology of TED.
This study examines how gut dysbiosis affects TED, recruiting 33 patients with TED, 34 patients with Graves’ Disease (GD) but not TED and 33 healthy individuals to assess gut microbiota composition and metabolic features. Furthermore, we established a spontaneously developed TED mouse model using BALB/C mice, where recombinant adenovirus containing A-subunit of human TSHR (hTSHR A) was injected, thus highlighting the potential relationship between gut microbiota composition and TED progression.
Based on enrichment results, TED shows significant differences in gut microbiota and fecal metabolites compared to the other two groups. [Clostridium]_innocuum and oleamide are notably elevated in TED patients compared to the other groups, while Akkermansia muciniphila and inosine are significantly reduced. These findings are associated with TRAb levels, clinical activity score (CAS), and TGAb. Animal experiments suggest that an imbalance in gut microbiota may disrupt T cell subset equilibrium through metabolite influence, correlating with serum TT4 and TRAb levels, as well as orbital brown adipose tissue content (BAT%). Furthermore, intestinal mucosal damage, particularly the activation of NLRP3 inflammasomes, plays a crucial role in this process in TED patients.
This study underscores notable differences in gut microbiota ([Clostridium]_innocuum and Akkermansia muciniphila) and fecal metabolites (oleamide and inosine), which potentially affect T cell differentiation and thereby influence the onset and progression of TED.
Poster 0527
Autoimmunity, Basic, Poster
Plasma proteins and graves’ disease: Proteome-wide mendelian randomization and colocalization analyses
Yifei Liu*, Sisi Luan, Yinhe Chai, Jianbo Zhou, Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, China
Although Graves hyperthyroidism is relatively common, no causal treatment options are available. To identify potential therapeutic targets, we estimate the causal effects of plasma proteins on Graves’ Disease (GD) in Mendelian randomization (MR) and colocalization analyses.
Genetic data on plasma proteome are obtained from 54,219 UK Biobank participants and 35,559 Icelanders. Datasets of GD were obteined from genome-wide association study including Sakura S study (1,678 cases) and Finngen study (3,176 cases). A two-sample MR analysis was conducted to examine the potential targets for GD. The colocalization analysis was used to detect whether the potential proteins exist in the shared causal variants. To enhance the credibility of the results, external validation was conducted. Additionally, enrichment analysis, assessment of protein druggability, and the protein-protein interaction networks were used to further enrich the research findings.
Among 2,923 proteins, genetically predicted levels of 84 plasma proteins are associated with GD. Five of these proteins have strong support of colocalization and 3 of them (FCRL1, FCRL2 and FCRL3) stands out as potential drug targets (PP.H4 > 0.99). GO analysis shows that biological processes are associate with B cell function. PPI networks confirm FCRL3 play a key role in interacting with the known drug targets.
Our study reveals causal proteins (FCRL1, FCRL2 and FCRL3) for GD, which enhances the understanding of molecular etiology and development of therapeutics.
Poster 0528
Autoimmunity, Basic, Poster
Dihydroartemisinin inhibits the development of autoimmune thyroiditis by modulating oxidative stress and immune imbalance
Shuangjie zhu1, Yongqi Cui1, Huizheng Hu2, Chenxi Zhang2, Kan Chen2, Zhongyan Shan2, Weiping Teng2, Jing Li*2, 1Graduate School, Liaoning University of Traditional Chinese Medicine, China, 2Department of Endocrinology and Metabolism, Institute of Endocrinology, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, China
OBJECTIVE:
Autoimmune thyroiditis (AIT) is one of the most common autoimmune endocrine disorders, and its pathogenesis has not been clarified. With the improvement of healthcare, AIT remains highly prevalent and it is still lack of effective treatment methods. Therefore, the present study explored whether the dihydroartemisinin (DHA) had any therapeutic activity on AIT and its potential mechanisms of action with respect to oxidative stress (OS) responses and T-cell immune imbalance using network pharmacological analysis and the experimental AIT (EAT) mouse model.
METHODS:
The target genes, signaling pathways and biological processes potentially responsible for the therapeutic actions of DHA on AIT were firstly predicted by network pharmacology, and then validated using EAT model established by thyroglobulin (Tg) immunization. ELISA, HE, and immunofluorescence were used to detect thyroid autoantibodies and histological changes after DHA intervention, RT-PCR to detect mRNA expression of representative T-cell cytokines in the spleen, OS kit to detect superoxide dismutase (SOD) activity and reduced glutathione (GSH) level, and immunohistochemical staining to detect Nrf2 protein expression in thyroid tissue.
RESULTS:
Network pharmacology analysis showed that DHA potentially modulated immune and OS responses by interfering with multiple biological processes, including protein phosphorylation, reactive oxygen species (ROS) production and such intracellular signaling as toll-like receptors and HIF-1-related pathways. The in-vivo studies in EAT model revealed that serum TgAb level and the intrathyroidal infiltration of inflammatory cells were significantly reduced in the EAT mice receiving high-dose DHA as compared with that of vehicle-treated controls. The mRNA expressions of IFN-γ, IL-17A and IL-6 were markedly reduced, whereas that of IL-4 and IL-10 was significantly increased in the spleen. The SOD activity, GSH content, and Nrf2 protein expression level were pronouncedly elevated in the thyroid tissue after high-dose DHA treatment.
CONCLUSION:
The findings in this study suggest that DHA treatment may inhibit TgAb production and attenuate the intrathyroidal infiltration of inflammatory cells by correcting the imbalance of Th1/Th2 and Th17/Treg, and alleviating OS response through the Nrf2 pathway. It provides a new therapeutic strategy for DHA application in AIT.
Poster 0529
Disorders of Thyroid Function, Basic, Poster
Modeling to inform dose selection for TOUR006, a fully human anti-IL-6 antibody, for treatment of thyroid eye disease: Effect of gender and liver and kidney function on modeling the optimal dose regimen
Swati Debroy*1, Shahram Mehr1, Craig Comisar1, Stuart Seiff2, Kristine Erickson3, Yung Chyung3, Emil DeGoma3, John Walsh3, Paul Martin1, 1Certara Inc., USA, 2Department of Ophthalmology, University of California San Francisco, USA, 3Tourmaline Bio, USA
Poster 0530
Disorders of Thyroid Function, Basic, Poster
Endocrine complications secondary to combination of immune checkpoint inhibitors, amiodarone and steroids
Mounika Lakshmi Allam*1, Prathayini Subarajan2, Marriam Ali2, 1Loyola Medicine-MacNeal Hospital, USA, 2Loyola University Medical Center, USA
Introduction-
The use of Immune Checkpoint Inhibitors (ICI’s) has led to an increase in the incidence of immune-related Endocrine adverse events(irAEs) which can present as hyperthyroidism, hypothyroidism, hypophysitis, diabetes, primary adrenal insufficiency (PAI), or a combination of these conditions (1)(2). Our case is unique with the presentation of adrenal insufficiency and abnormal thyroid function testing in the setting of recent ICI therapy, high dose steroid taper, and ongoing amidarone therapy.
Case Presentation-
A 59-year-old female with a past medical history of endometrial cancer treated with pembrolizumab from September 2023 to December 2023 and new onset atrial fibrillation managed with amiodarone since October 2023 presented to the ED with a 3 week history bilateral lower extremity swelling, 10 lb weight gain, fatigue, and dyspnea on exertion. Relevant history includes the development of ICI-related colitis following pembrolizumab treatment. She was treated for the colitis with a high-dose prednisone taper over 4 months She had been off prednisone completely for 3 weeks prior to arrival to the ED.
On admission, morning cortisol was undetectable (<1.1) and ACTH was low (<5), suggestive of immune checkpoint inhibitor-mediated adrenal insufficiency versus axis suppression from steroid therapy. She was initiated on hydrocortisone 40 mg and 20 mg. Additionally, thyroid function tests indicated new onset thyrotoxicosis with a TSH (0.11), (1.8), and T3 (437). She was started on methimazole 10 mg daily to treat empirically for a hyperthyroid state secondary to AIT-1. Reviewing lab results from the prior 7 to 12 month revealed thyroid function tests with a normal to elevated TSH and normal free hormones. TPO, TRAb and TSI were negative and thyroid ultrasound was negative for nodules and increased vascularity, which supported thyroiditis rather than a hyperthyroid state. The thyroidtis was suspected to possibly be related to ICI therapy or AIT-2. This information, as well as repeat free hormones showing no further increase, prompted discontinuation of methimazole. She was discharged with plans for outpatient monitoring of TFT’s.
Discussion-
Patients, such as ours, with multiple etiologies for abnormal TFTs or thyrotoxicosis, require close monitoring for appropriate treatment. When there is concern for thyrotoxicosis related to a hyperthyroid state leading to a suppressed TSH and elevated fT4, treatment with antithyroid medications and beta blockers should be utilized.
Poster 0531
Pregnancy and Development, Basic, Poster
Development of a 3D trophoblast model
Mariana Lourenção1, Bianca Gonçalves1, Maria Sibio1, Vinicius Peghinelli1, Marna Sakalen2, Célia Nogueira*1, 1UNESP, Brazil, 2UEL, Brazil
Poster 0532
Thyroid Cancer, Basic, Poster
Small molecule targeting Voltage-Gated sodium channels reduces metastasis in a medullary thyroid cancer mouse model
Piyasuda Pukkanasut*, Jason Whitt, Shannon Lynch, Carlos Gallegos, Herbert Chen, Anna Sorace, Renata Jaskula-Sztul, Sadanandan Velu,The University of Alabama at Birmingham, USA
Poster 0533
Thyroid Cancer, Basic, Poster
Opposing effects of TRβ-LSD1/KDM1A Co-Regulatory complex in normal and anaplastic thyroid cancer cells
Jaime Boisoneau*1, Noelle Gillis2, Emily Wilson3, Sadie Lamothe1, Jennifer Tomczak1, Kathleen Bright1,4, Seth Frietze1,4, Frances Carr1, 1Larner College of Medicine, UVM Cancer Center, University of Vermont, USA, 2Masonic Cancer Center, University of Minnesota, USA, 3Huntsman Cancer Institute, University of Utah, USA, 4College of Nursing and Health Sciences, UVM Cancer Center, University of Vermont, USA
Objective: Analysis of TRβ protein interaction profiling revealed lysine-specific demethylase 1 (LSD1/KDM1A) as a co-regulator in thyroid cells. This study unveils the complex interplay of LSD1/KDM1A in modulating TRβ signaling in both normal and anaplastic thyroid cancer (ATC) cells and explores the therapeutic potential of LSD1/KDM1A inhibition to enhance TRβ-mediated tumor suppression in ATC.
Methods: Differential enrichment of proximity biotinylation data combined with protein-protein interaction network (PPIN) analysis was used to elucidate the ligand-dependent interactions of TRβ with chromatin-associated proteins. CUT&RUN was used to map differential TRβ and LSD1/KDM1A chromatin binding and histone modifications after treatment with ligand. The effect of LSD1/KDM1A knockdown on the liganded TRβ transcriptome (T3 or TRβ-selective agonist, GC-1) in thyroid cells was assessed by RNA-seq. Phenotypic changes in ATC cell lines were observed using live cell imaging, cell viability assays, and cancer stem cell growth assays. LSD1/KDM1A silencing by shRNA knockdown or allosteric inhibition with SP-2509 was performed in combination with TRβ agonists.
Results: PPIN analysis revealed TRβ and ALL-1 interaction nodes that include LSD1/KDM1A. Chromatin occupancy analysis revealed overlapping genomic binding sites of TRβ and LSD1/KDM1A with a decrease in repressive histone marks around the TSS following ligand treatment. RNA sequencing showed that LSD1/KDM1A preferentially regulates downregulated TRβ target genes. Inhibition of LSD1/KDM1A demethylase activity or knockdown of protein expression levels, in combination with TRβ agonism, inhibits the aggressive ATC phenotype in vitro by reducing cell viability, proliferation, and cancer stem cell growth. The effects of LSD1/KDM1A inhibition and TRβ agonism on cell viability are additive.
Discussion: Our data reveals that the TRβ-LSD1/KDM1A co-regulatory complex modulates the TRβ transcriptome through histone demethylation at target genes. Blunting the LSD1/KDM1A-catalyzed removal of repressive histone marks at TRβ target genes allows for cellular reprogramming and redifferentiation by maintaining these genes in an active state. The combined effects of TRβ agonism and LSD1/KDM1A inhibition may hold promising implications for the treatment of ATC. Elucidating the co-regulators and chromatin remodeling complexes in the TRβ interactome will reveal potential therapeutic targets and advance our mechanistic understanding of TRβ -mediated tumor suppression.
Poster 0534
Thyroid Cancer, Basic, Poster
TRβ agonism enhances tumor suppression by BETi in an anaplastic thyroid cancer model
John Rustad*, Jennifer Tomczak, Sadie Lamothe, Jaime Boisoneau, Ian Orsmond, Ignatius Hastomo, Kathleen Bright, Seth Frietze, Frances Carr, University of Vermont College of Medicine, USA
Poster 0535
Thyroid Cancer, Basic, Poster
Sodium selenite impacts on reinforcing therapeutic effect of radioactive-iodine in papillary thyroid cancers
JI MIN OH*, PRAKASH GANGADARAN, Ramya Lakshmi Rajendran, Chae Moon Hong, Byeong-Cheol Ahn, Kyungpook National University School of Medicine, Korea, Republic of
Radioactive-iodine (RAI) therapy is one of mainstay therapeutic option for recurrent and metastatic thyroid cancer patients. However, considerable portion of this cancer exhibits dedifferentiation characteristics along with lack of sodium iodide symporter (NIS) functionality, downregulated expression of thyroid-specific proteins for controlling iodide-metabolizing machinery, leading to poor response to the RAI therapy. Selenium is critical mineral for thyroid hormone synthesis and metabolism. Several studies suggested that application of selenium could be a therapeutic armor for thyroid cancers by promoting cell cycle arrest and apoptosis. However, there is no report about effect of the selenium administration for promoting RAI therapeutic response in thyroid cancers. In the present study, we investigated the potential for utilization of selenium for reinforcing RAI avidity by elevating differentiation degree and increasing RAI therapeutic effect in papillary thyroid cancers (PTCs).
A BHP10-3SCp, as a PTC cell line, was exposed to sodium selenite for 72 hrs. Next, change of biological characteristics, including thyroid-specific proteins, were assessed by western blots. 125I avidity in BHP10-3SCp cells was tested and cytotoxic effect of 131I after the selenium treatment was evaluated as well. Analysis of signaling pathways was investigated to understand influence of sodium selenite to BHP10-3SCp cells.
Treatment of sodium selenite induced upregulation of thyroid-specific proteins, translocation of NIS on plasma membrane and reinforcement of RAI avidity, leading to enhancing therapeutic effect of 131I. Sodium selenite strongly inhibited p-AKT and p-ERK as well as interrupting the translocation of β-catenin into nucleus which might be underlying mechanisms of the reinforcing RAI avidity in PTCs.
Sodium selenite can be a potential therapeutic agent for enhancing RAI therapeutic effect in PTCs.
Poster 0536
Thyroid Hormone Action, Metabolism and Regulation, Basic, Poster
Neuronal types that express type 3 deiodinase in brain regions for homeostatic control identified using Dio3-Cre knockin drivers
Ye Liu*, Lily Ng, Douglas Forrest, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), USA
Poster 0537
Thyroid Hormone Action, Metabolism and Regulation, Basic, Poster
Regulation of osteogenic differentiation by thyroid hormone via the transcription factor Klf9 in mice
He Liu*, Yushu Li, Yunmiao Pan, Zhongyan Shan, Weiping Teng,Department of Endocrinology and Metabolism and the institute of Endocrinology, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, China
In Klf9Osx -/- mice after L-T4 treatment: there was a significant increase in serum T3 and T4 levels; no significant differences were observed in serum bone metabolism markers and calcium ion concentrations; the maximum force of the femur decreased, with no significant differences in fracture strength and bending stiffness; histological staining and collagen fiber quantity had no significant impact, but there was a significant decrease in calcium deposition; the ratios of cortical bone volume fraction, thickness, cortical bone area, and total area all significantly decreased, although cortical bone density showed no significant change; the trabecular bone analysis parameters showed no significant changes.
Poster 0538
Thyroid Nodules and Goiter, Basic, Poster
Mutational analysis to classify thyroid nodules
Amandeep Kaur*, University of Winnipeg, Canada
Conclusion: The diagnosis methods for DTC cytology are majorly operative approaches which based on statistical data have a dangerous chance of producing false positives. This means TC patients are undergoing unnecessary surgeries causing further implications. Investigation of NMT and other related genes as a biomarker could be essential for differentiating between different thyroid cancers without operative procedures reducing risks of implication.
Poster 0539
Thyroid Cancer, Translational, Poster
RAI GuidePx: a robust predictor for radioactive iodine sensitivity status in differentiated papillary thyroid cancer leveraging thyroid differentiation genes
Jeremy Fan1, Oliver Bathe2,1, Cynthia Stretch*2,1, 1Qualisure Diagnostics Inc., Canada, 2University of Calgary, Canada
Poster 0540
Thyroid Cancer, Translational, Poster
Fusion with thyroglobulin gene as a novel mechanism of oncogenesis in thyroid cancer
Gavin Schmidt1, Ian Fornal1, William Doerfler*2, Abigail Wald1, Shannon Keating1, Marina Nikiforova1, Yuri Nikiforov1, Alyaksandr Nikitski1, 1University of Pittsburgh, USA, 2UPMC of Pittsburgh, USA
Poster 0541
Thyroid Cancer, Translational, Poster
Immune evasion as a mediator of PTC progression and the emerging role of THBS1
Emma Su*1, Amanda Garza1, Athanasios Bikas2, Jihye Park1, Laura Valderrabano1, Kevin Bi1, Jingxin Fu1, Sabrina Camp1, Himanshu Patankar3, Yutaro Tanaka1, Breanna Titchen1, Eliezer Van Allen1, Erik Alexander2, Theodora Pappa2,1, 1Dana-Farber Cancer Institute, USA, 2Brigham and Women’s Hospital, USA, 3Mass General Brigham, USA
Poster 0542
Thyroid Cancer, Translational, Poster
Transcriptomic analysis for early detection of radioactive iodine refractory disease in thyroid cancer patients
VINCENZO CONDELLO*, CARLOTTA MARCHETTINI, CATHARINA IHRE LUNDGREN, JOACHIM NILSSON, CHRISTOFER JUHLIN, Karolinska Institutet, Sweden
Poster 0543
Thyroid Cancer, Translational, Poster
Pan cancer analysis of germline POT1 variants implicates risk for PTC and CLL
Pamela Brock*1, Morgan Webster2, Sandya Liyanarachchi1, Lindsey Byrne1, Mohamed Abdel-Rahman1, Matthew Ringel1, 1The Ohio State University, USA, 2Legacy Health, USA
Poster 0544
Thyroid Cancer, Translational, Poster
Challenges and factors affecting successful patient-derived xenograft model establishment for anaplastic thyroid cancer
Ahmad Abubaker*1, Ying Henderson1, Jennifer Wang1, Mark Zafereo1, Victoria Banuchi1, Maitrayee Goswami1, Maria Cabanillas2, Naifa Busaidy2, Ramona Dadu2, Priyanka Iyer2, Sarah Hamidi2, Michelle Williams3, S. Mohsen Hosseini3, Stephen Lai1,4,5, Anastasios Maniakas1, 1Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, USA, 2Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, USA, 3Department of Pathology, The University of Texas MD Anderson Cancer Center, USA, 4Department of Radiation Oncology, Division of Radiation Oncology, The University of Texas MD Anderson Cancer Center, USA, 5Department of Molecular and Cellular Oncology, Division of Basic Science Research, The University of Texas MD Anderson Cancer, USA
Poster 0545
Thyroid Cancer, Translational, Poster
Mapping tumor endothelium in papillary thyroid carcinoma: a Patient- Controlled, transcriptomic landscape
Bradley Pearson*1, Yang Lin2, Ben Greenspun1, Teagan Marshall1, Abhinay Tumati1, Rasa Zarnegar1, Brendan Finnerty1, Thomas Fahey1, Shahin Rafii2, 1NewYork-Presbyterian/Weill Cornell Medical Center, USA, 2Weill Cornell Medicine, USA
Papillary thyroid carcinoma (PTC) is the most common thyroid cancer accounting for greater than 80% of thyroid tumors. Although largely indolent, PTCs have the potential to de-differentiate into more aggressive, lethal thyroid cancers. The exact role that the thyroid vasculature, and its critical component, the endothelial cell (EC), plays in PTC pathogenesis necessitates further exploration. Using single-cell RNA sequencing (scRNA-seq), we explored the transcriptomic landscape of PTC at single-cell resolution in an effort to better define benign from tumor endothelium.
In this study, we profiled tumor and stromal cells of ten fresh, matched samples from five patients after primary resection for biopsy-proven PTC.
Of the five PTC samples, two were classical type (one with tall cell features) and three were follicular variant. On clinical genetic testing, four of five samples had BRAF mutations, one follicular variant had a BRCA1 mutation, and the classical type (with tall cell features) had a CHEK2 mutation. Three of five tumors demonstrated focal invasion. When compared to organotypic ECs within Tabula sapiens, a human cell atlas of nearly 500,000 cells from 24 organs, normal thyroid ECs were found to be enriched in ESM1, IL3RA, KLF12, NFATC2, NME2, PDGFD, PLPP1, PRDM1, SOX5, TCF12, WNT5B, and ZEB1. Of note, thyroid ECs clustered with closest proximity to pancreas ECs. When compared to thyroid tumor EC, normal thyroid EC demonstrated significantly increased expression of genes involved in regulating inflammation/oxidative stress (JUND, KLF9, and STC1), angiogenesis (SOX5 and IL32), and shear stress and EC differentiation (ATOH8). When compared to normal thyroid EC, CDH13, COL4A1, ID2, IGFBP7, INSR, MAF, PIEZO2, SMAD1, SMAD6, UNC5B, and ZEB1 were found to be enriched in PTC. Interestingly, UNC5B expression in PTC EC correlates with expression of an alternative splicing factor NOVA2 for UNC5B, which has been found to regulate angiogenesis by promoting apoptosis.
Taken together, these findings highlight notable differences between tumor and wild-type endothelium in the context of papillary thyroid carcinoma. Further studies will aim to decipher the role of tumor EC functionality and tumor-endothelial cell crosstalk that may influence PTC progression and/or de-differentiation.
Poster 0546
Thyroid Cancer, Translational, Poster
BRAF treatment response determinants in anaplastic thyroid cancer studied through single cell DNA and RNA sequencing
Aatish Thennavan*, Maxime Tarabichi, Mark Zafereo, Michelle Williams, Chia Chin Wu, Meghan Martin, Tuan Tran, Stephen Lai, Maria Cabanillas, Priyanka Iyer, Anastasios Maniakas, Ying Henderson, Xiao Zhao, Naifa Busaidy, Ramona Dadu, Nicholas Navin, Jennifer Wang,University of Texas MD Anderson Cancer Center, USA
Poster 0547
Thyroid Cancer, Translational, Poster
Transcription factor and pathway activity inference of thyroid cancers unveils potential novel prognostic indicator and therapeutic targets
Ignatius Hastomo*, Frances Carr, Seth Frietze, University of Vemont College of Medicine, USA
Poster 0548
Thyroid Cancer, Translational, Poster
TERT promoter mutation mediates the interaction between male sex and BRAF V600E in driving aggressiveness of papillary thyroid cancer
Wu Liufeng*1, Wang Zhuo1, Yu Jinigting1, Xing Mingzhao1,2, 1Thyroid Research Institute, School of Medicine, Southern University of Science and Technology, China, 2Medicine Emeritus, Johns Hopkins University School of Medicine, USA
Poster 0549
Thyroid Cancer, Translational, Poster
Multiple targeting amorphous nanoflowers (a-BiOI@PEG) for Dual-Modality imaging and therapy in differentiated thyroid cancer
Chen Li*, Meng-Meng Zhang, Ke-Wei Jiang, Ying-Jiang Ye, Peking University People’s Hospital, China
Ultrasound (US) and computed tomography (CT) are the primary diagnostic tools for thyroid screening and detection of lymph node metastasis. The aim of this research is to utilize the tumor-targeting potential of nanoparticles, in conjunction with the iodophilic characteristics of differentiated thyroid cancer, to develop nanoparticles with passive and active targeting functionalities, resulting in improved contrast in ultrasound and CT imaging, as well as photothermal therapy (PTT) and photodynamic therapy (PDT).
The facile synthesis of amorphous BiOI was achieved by uniformly dispersing Bi(NO3)3·5H2O and KI in 1,3-propanediol. TEM, XPS, Zetasizer, ICP and other techniques were used to determine the physicochemical properties of a-BiOI@PEG. Four cell lines were chosen for in vitro experiments, and BALB/c nude mice and NCG mice were selected to establish in vivo models.
The size of a-BiOI@PEG was determined to be 60–80 nm, exhibiting a high zeta potential value of +21.5 mV in aqueous solution, which persisted well-dispersed for days. In vitro experiments found that a-BiOI@PEG could enter cancer cells and localize in the cytoplasm, which relies on the abundant coordinatively unsaturated iodine ions exposed to the surface can readily recombine with other moieties and cancer cells with iodophilic properties have a greater uptake capacity. Under the near-infrared ray (NIR) and X-ray, amorphous a-BiOI@PEG could not only product photothermal effect but also photocatalyze the generation of ROS to kill cancer cells. After that, HMGB1, CRT, IFN-α, eATP were used to confirmed that immunogenic cell death (ICD) was induced. In vivo experiments showed that BiOI@PEG has promising CT imaging potential in tumors and metastatic lymph nodes (mLNs) compared with conventional contrast agents, and ultrasound could identify the specific “spark-like” strong echo of BiOI@PEG in both tumors and mLNs. Thus, the potential of PTT/PDT were confirmed in tumor-bearing mouse model.
We report the a-BiOI@PEG nanoflowers exhibited the promising CT/US imaging and high concentration of surficial active sites which can enhance PTT/PDT-ICD effect. It could therefore be considered a potential multifunctional agent for personalized integration of diagnosis and treatment of differentiated thyroid cancer.
Poster 0550
Thyroid Cancer, Translational, Poster
Urokinase-type plasminogen activator receptor (uPAR) as a target in poorly differentiated and anaplastic thyroid cancers
Grayson Gimblet*1, Jason Whitt1, Hailey Houson1, Faith Swain1, Dezhi Wang1, John Ness1, Andrea Gillis1, Herbert Chen1, John Copland2, Diana Lin1, Suzanne Lapi1, Renata Jaskula-Sztul1, 1University of Alabama at Birmingham, USA, 2Mayo Clinic Jacksonville, USA
Poster 0551
Thyroid Cancer, Translational, Poster
Molecular subtypes in Radiation-Induced papillary thyroid cancer (PTC) using thyroid GuidePx®
Elleine Allapitan*1, Jeremy Fan2, Sara Dutton2, Oliver Bathe1,2, Cynthia Stretch1,2, 1University Of Calgary, Canada, 2Qualisure Diagnostics Inc., Canada
Friday, November 1, 2024
Poster 0552
Surgery, Basic, Poster
Initial outcomes of Gas-Insufflation One-Step Single-Port transaxillary robotic thyroidectomy: a comparative study with open thyroidectomy
Sangchun Park*, Chonnam National University Hwasun Hospital, Korea, Republic of
Poster 0553
Surgery, Clinical, Poster
The cost of thyroidectomy: a qualitative analysis of Patient-Surgeon discussions
Emily Crowley*1, Catherine Jensen2,3,4, Elizabeth Bacon2, Benjamin James5, Mary Byrnes2, Susan Pitt2, 1University of Michigan Medical School, USA, 2University of Michigan, Department of Surgery, USA, 3University of Wisconsin, Department of Surgery, USA, 4National Clinician Scholars Program, University of Michigan, USA, 5Beth Israel Deaconess Medical Center, USA
Three themes related to direct costs were identified: insurance coverage, preoperative work-up, and long-term costs. Insurance coverage was the most commonly discussed direct cost and included patient concerns about co-payments, willingness to pay out of pocket for diagnosis and treatment, and timing of surgery scheduling related to annual insurance deductible. Discussion of direct costs related to preoperative work-up focused on the costs of imaging, molecular testing, and laryngoscopy. Discussion of long-term costs focused on lifelong thyroid hormone supplementation and the need for long-term cancer surveillance.
Discussions of indirect costs focused on two main themes including disability during recovery and the timing of surgery. Most discussions related to indirect costs focused on recovery from surgery including physical work restrictions and the inability to fulfill household obligations. Timing of surgery themes related to missed days of work and previously scheduled life events.
Poster 0554
Surgery, Clinical, Poster
Changes in serum lipids profile after total thyroidectomy versus thyroid lobectomy for papillary thyroid cancer patients
LIANG ZHENG*, First Affiliated Hospital of Sun Yat-sen University, China
Poster 0555
Surgery, Clinical, Poster
Bilateral superficial cervical plexus block for conduct of thyroidectomy and parathyroidectomy surgeries: a prospective randomised clinical study
Rudrashish Haldar*1, Ashish Kannaujia2, 1SGPGIMS, India, 2SGPGIMS, India
Poster 0556
Thyroid Cancer, Clinical, Poster
Updated efficacy and safety, including overall survival, from LIBRETTO-531: a phase 3, randomized, open-label study of first-line selpercatinib in advanced RET-mutant medullary thyroid cancer (MTC)
Lori Wirth*1, Julien Hadoux2, Marcia Brose3, Ana Hoff4, Bruce Robinson5, Ming Gao6, Jolanta Krajewska7, Katerina Kopeckova8, Dagmar Führer9, Bhumsuk Keam10, Eric Sherman11, Makoto Tahara12, Mimi Hu13, Ashish Massey14, Adrienne Gilligan14, Nivedita Sharma14, Yan Lin14, Patricia Maeda14, Jaume Capdevila15, Rossella Elisei16, 1Department of Medicine, Massachusetts General Hospital, USA, 2Service d’oncologie endocrinienne, département d’imagerie, Gustave Roussy and ENDOCAN-TUTHYREF Network, France, 3Department of Medical Oncology, Sidney Kimmel Medical College, Thomas Jefferson University, USA, 4Instituto do Cancer do Estado de Sao Paulo, ICESP, Brazil, 5Kolling Institute of Medical Research, The University of Sydney, Australia, 6Department of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute & Hospital, China, 7Department of Nuclear Medicine and Endocrine Oncology, Maria Sklodowska Curie National Research Institute of Oncology, Gliwice Branch, Poland, 8Department of Oncology, 2nd Faculty of Medicine of Charles University and Motol University Hospital, Czech Republic, 9Department of Endocrinology Diabetology and Metabolism, Endocrine Tumour Center at West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Germany, 10Department of Internal Medicine, Seoul National University Hospital, Korea, Republic of, 11Department of Medical Oncology, Memorial Sloan Kettering Cancer Center, USA, 12Department of Head and Neck Medical Oncology, National Cancer Center Hospital East, Japan, 13Department of Endocrine Neoplasia and Hormonal Disorders, University of Texas M. D. Anderson Cancer Center, USA, 14Eli Lilly and Company, USA, 15Medical Oncology Department, Vall Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Spain, 16Endocrine Unit, Department of Clinical and Experimental Medicine, University Hospital of Pisa, Italy
Patients on selpercatinib reported improved PRT with less time on treatment with “high side-effect burden” compared with control (8% vs. 25%; p < 0.0001). Grade ≥3 TEAEs occurred in 62% of patients with selpercatinib versus 81% with control; dose reductions in 46% and 83%, respectively; and discontinuations due to TEAEs in 6% and 31%, respectively. The safety profile remained consistent; however, erectile dysfunction (16%) emerged as a new adverse drug reaction in RET-mutant MTC males on selpercatinib.
Poster 0557
Thyroid Cancer, Basic, Poster
Divergent evolution of BRAFV600E Papillary and Anaplastic Thyroid Cancer
Aatish Thennavan, Meghan Martin, Mark Zafereo, Jennifer Wang, Stephen Lai, Nicholas Navin, Xiao Zhao*, MD Anderson Cancer Center, USA
Poster 0558
Poster 0559
Thyroid Nodules and Goiter, Clinical, Poster
Characteristics of thyroid nodules in 153 LatinX patients
Jee Lee*1, Rowena Dsouza1, Emilia Liao1, Daniel Kuriloff2, Leonid Poretsky1, Angelica Sanchez1, Karina Ziskovich1, Tungming Leung1, Jose Sanchez1, 1Division of Endocrinology and Metabolism, Lenox Hill Hospital, Northwell Health, USA, 2Division of Otolaryngology/Head & Neck Surgery, Lenox Hill Hospital, Northwell Health, USA
Objective: There are multiple predisposing factors for thyroid nodules (TN). These include age, sex, iodine deficiency, radiation exposure, the metabolic syndrome and others. The characteristics of TN in the Hispanic-American population have not been well studied despite the rising incidence. This report describes the characteristics of TN in a registry of LatinX patients in an urban setting.
Methods: An ongoing prospective observational study currently includes a registry of 153 patients in an endocrinology faculty practice. The patients were recruited between January 2023 and June 2024. Baseline surveys included questionnaires for thyroid symptoms (Thypro39, lump score and cosmetic score) and sonographic information (number of nodules, volume, location and laterality).
Results: In this Hispanic cohort median age was 60 years, median BMI was 28.8 kg/m2, and the majority female gender (93.5%). Coexisting medical problems included hypertension (34%), diabetes (32.7%), hyperlipidemia (28.1%), pre-diabetes (12.4%) and thyroid disease (13.1%). The median levels of TSH and FT4 were 1.26 µIU/ml (IQR: 0.71–2.05) and 1.20 ng/dL (IQR: 1.10–1.40). The most common reason for referral was imaging findings (67.97%) followed by abnormal laboratory tests (5.23%) and palpable nodules (0.65%). Most patients (98.04%) had no symptoms. Thyroid nodule US-findings were as follows: a median number of 3 per patient (IQR:2.0–4.0), median total volume of 1.78 ml (IQR:0.27–6.21) and the majority bilateral (61.4%) followed by right (17%) and left laterality (11%). The number of thyroid nodules was positively correlated with age (p = 0.0005), and the total volume of nodules was positively correlated with cosmetic score (p = 0.0009).
Discussion/Conclusion: In this cohort of LatinX patients in an urban setting, the number of thyroid nodules was correlated with age and total nodular volume was positively correlated with cosmetic score. The majority of patients were asymptomatic and abnormal imaging was the most common reason for referral to endocrinology evaluation.
Poster 0560
Thyroid Cancer, Clinical, Poster
Radioactive iodine adjuvant therapy (RAI-AT) does not improve clinical outcomes in intermediate risk tall cell variant papillary thyroid carcinoma (TCV-PTC) with nodal involvement
Aya Ghosn*, Ronald Ghossein, James Flory, Mona Sabra, Memorial Sloan Kettering, USA
After complete disease resection, RAI adjuvant therapy is often advocated for patients with intermediate risk tall cell variant papillary thyroid cancer with extensive nodal involvement. These tumors are enriched with BRAF V600E driver mutations that are postulated to downregulate the sodium iodine symporter and decrease iodine incorporation.
To study the efficacy of RAI-AT on the response to therapy in patients with TCV-PTC, we retrospectively reviewed the records of patients treated with total thyroidectomy at Memorial Sloan Kettering between 2015 and 2023. We selected subjects with TCV-PTC with >10 affected nodes or any metastatic node >1 cm. We excluded those with metastatic nodes >3 cm, gross extrathyroidal extension and distant metastasis and those who received RAI after redifferentiation therapy. We studied the response to therapy 6–18 months after initial surgery and again at end of the follow up.
A total of 105 subjects were included: 79 received RAI-AT (median RAI activity 100 mCi, range 30–156) and 26 were observed. Most subjects were females (64%), with median age 42 years (range 20–85) and median tumor size 1.8 cm (range 0.2–7). The median number of metastatic nodes was 10 (range 1–31) with median size 1.6 cm (range 0.4–2.9). Median FU was 3.2 years (range 0.4–9.1). At 6–18 months, 79% had either excellent or indeterminate response, 11% had biochemical incomplete response and 10 % had structural incomplete response. At the end of the follow up, 76% had excellent or indeterminate response, 10% had biochemical incomplete response and 14% had structural incomplete response. In the observation group at the end of the follow up, 92% had excellent or indeterminate response versus 71% in the RAI-AT group (difference 21%, 95% confidence interval 4.5% to 38%). After propensity score weighting to adjust for baseline differences between the groups, the rate of excellent or indeterminate response in the observation group was 13% higher than in the RAI-AT group (95% CI — 4.5% to 31%).
In conclusion, in a cohort of selected patients for adjuvant therapy, RAI therapy is not associated with better clinical outcomes than observation in patients with intermediate risk TCV-PTC with nodal metastasis.
Poster 0561
Thyroid Cancer, Clinical, Poster
Identification of somatic events associated with anaplastic transformation in BRAF V600E-driven thyroid carcinomas: NGS profiling of 1,000 thyroid cancers
Vicente Marczyk*, Sarah Hamidi, Maria Cabanillas, Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas MD Anderson Cancer Center, USA
Poster 0562
Thyroid Cancer, Clinical, Poster
Establishing an anaplastic thyroid cancer rapid access pathway at a tertiary care Centre: Impact on time to treatment
Sana Ghaznavi*, Kiana Mahboubi, Shamir Chandarana, Moosa Khalil, Robert Hart, Debbie Lamb, Kara Hawker, Robyn Banerjee, Dean Ruether, Adrian Box, Steve Gorombey, University of Calgary, Canada
Poster 0563
Thyroid Cancer, Clinical, Poster
A pilot trial of camrelizumab plus apatinib in patients with locally advanced or metastatic, radioactive Iodine-Refractory differentiated thyroid cancer
Xin Zhang*1, Di Sun1, Cong Shi1, Ying-Qiang Zhang1, Jun Liang2, Yan-Song Lin1, 1Peking Union Medical College Hospital, China, 2Peking University International Hospital, China
Poster 0564
Thyroid Cancer, Clinical, Poster
Radiation level and safe isolation duration in thyroid cancer patients Post-Radioactive iodine therapy
Dhara Patel*, Meghana Pattipati, Sasan Fazeli, City of Hope Cancer Center, USA
Poster 0565
Thyroid Cancer, Clinical, Poster
Methionyl-tRNA synthetase 1 expression as a diagnosis and prognosis factor in papillary thyroid cancer
Jun Sung Lee*, Nam Kyung Kim, Seok Mo Kim, Yong Sang Lee, Hang Seok Chang,Thyroid Cancer Center, Gangnam Severance Hospital, Korea, Republic of
Poster 0566
Poster 0567
Thyroid Cancer, Clinical, Poster
Performance and impact of advanced molecular testing for evaluation of indeterminate thyroid nodules at a large academic safety net hospital
Nishkala Gutta*1,2, Andrew Gianoukakis1,2, Bradley Neutel1,2, Laron McPhaul1, 1Harbor UCLA, USA, 2The lundquist institute for Biomedical Innovation, USA
Of the 63 indeterminate nodules identified after implementation of ThyroSeq, repeat FNA resolved the diagnosis in 18 patients. 6 declined molecular testing, preferring surgery. Thyroseq testing was performed on 39 patients. Twelve tested positive and underwent surgery. 10 were true positives, and 2 were false positives. ThyroSeq was associated with a positive predictive value of 83.3%. Twenty-seven patients tested negative. 2 underwent surgery for compressive symptoms, one was a true negative, and the other, a false negative. Thirteen were lost to follow-up, and 12 were managed with serial clinical and ultrasound assessments without needing intervention for a median follow up of 24 months. ThyroSeq testing prevented 25 surgeries.
Poster 0568
Thyroid Cancer, Clinical, Poster
Less is more: Comparison of survival between single and multiple radioiodine (RAI) treatments in differentiated thyroid cancer with RAI-Avid distant metastases
Cong Shi, Qi-Jun Li, Di Sun, Xin Zhang, Wen-Ting Guo, Yan-Song Lin*, Peking Union Medical College Hospital, China
So far, the benefit of repeated radioactive iodine (RAI) therapy remains controversial. We aimed to investigate the risk factors for time to progression and to evaluate the benefit of repeated RAI therapy in patients with initially RAI-avid distant metastatic DTC (DM-DTC).
A total of 203 patients with RAI-avid distant metastases were retrospectively enrolled from January 2008 to December 2022, structural response to RAI therapy was evaluated as disease progression (PD) or non-PD. The time from first RAI therapy to local recurrence or progression of DM lesions was defined as time to PD. Univariate and multivariate Cox regression analysis was used to identify risk factors that may affect time to PD, propensity scoring matching (PSM) was also performed between patients who received repeated RAI therapy or not.
With a median follow-up of 71.6 months (18.5–522.5), 72 (35.5%) were PD and 131 (64.5%) were non-PD. Totally, 154 (75.9%) received repeated RAI therapy (3, 2–16) and 49 (24.1%) received once. Compared to non-PD, patients with PD had older age at diagnosis, more extensive DM sites, received more frequent, higher administered RAI activities and more often demonstrated RAI-refractory at last RAI therapy (all p < 0.01). As time to PD is critical for RAI decision making, univariate analysis was performed and showed that age at diagnosis (p < 0.001), histological type (p = 0.038), DM sites (p = 0.009) were associated with time to PD, but not times or activity of RAI therapy (p = 0.834, 0.794). Multivariate analysis suggested that age at diagnosis (HR = 1.027; 95%CI: 1.011–1.043; p < 0.001) and DM sites (HR = 1.525; 95%CI: 1.029–2.262, p = 0.036) were independent risk factors for time to PD. To minimize the potential interference, we matched age, DM sites, histological type, and follow-up time by PSM. The Kaplan-Meier analysis showed no significance in time to PD between the 45 pairs of patients who received repeated RAI therapy or not (p = 0.099), suggesting repeated RAI therapy did not improve the progression-free survival.
In patients with RAI-avid distant metastases, older age at diagnosis and more extensive metastases were independent risk factors for time to PD while further repeated RAI therapy did not confer long-term survival benefit.
Poster 0569
Thyroid Cancer, Clinical, Poster
Impact of BRAF mutation on progression-free survival in radioactive iodine refractory differentiated thyroid cancer patients receiving multi-kinase inhibitors
Di Sun1, Xin Zhang1, Xiao-Na Jin1, Cong Shi1, Yu-Qing Sun1, Ying-Qiang Zhang1, Jun Liang2, Yan-Song Lin*1, 1Peking Union Medical College Hospital, China, 2Peking University International Hospital, China
Chinese domestic multi-kinase inhibitors (MKIs) apatinib, donafenib, and anlotinib have demonstrated satisfactory efficacy on radioactive iodine refractory differentiated thyroid cancer (RAIR-DTC) in their phase II/III trials, while the potential impact factors on the progression-free survival (PFS) of these MKIs remain unclear.
We retrospectively reviewed patients enrolled in the clinical trial of apatinib (NCT02731352, NCT03048877), donafenib (NCT02870569, NCT03602495), and anlotinib (NCT05007093) in our center. Responses were assessed according to RECIST 1.1. PFS was estimated using the Kaplan-Meier method and compared using the log-rank test. The hazard ratio (HR) was calculated using the Cox proportional hazards model.
Eighty courses of MKI therapy for 71 patients were reviewed. Of the 71 patients, the average age at diagnosis was 47.9; 52.1% were female; 70.4% of the tumors were papillary, 14.1% were follicular, 15.5% were poorly differentiated; 49.3% were BRAF mutant, 32.4% were BRAF wild-type, 18.3% didn’t have BRAF mutational assessment. Of the 80 courses of MKI therapy, 25% were anlotinib, 41.3% were apatinib, 33.7% were donafenib; 71.2% were first-line, 18.8% were second-line, 10% were third-line. The median baseline thyroglobulin (Tg) level was 560.9 (IQR 127.0–2029.0) ng/mL; the median baseline neutrophil to lymphocyte ratio (NLR) was 2.9 (IQR 2.1–3.5); bone metastases were identified before 36.3% of the therapies. The median follow-up time was 46.6 (95% CI 32.8–60.4) months and the median PFS was 19.6 (95% CI 14.2–25.1) months. Patients with bone metastases had shorter PFS (median PFS, 11.1 vs. 23.0, p = 0.007) with an HR of 2.12 (95% CI 1.21–3.72), whereas patients with BRAF mutant tumors had longer PFS (median PFS, 28.8 vs. 13.5, p = 0.004) with an HR of 0.42 (95% CI 0.23–0.77). PFS did not differ by ages at diagnosis, sexes, pathologies, treatment regimens, lines of MKI, baseline Tg levels, or NLRs (p >0.05). In the multivariate Cox proportional hazards model, the influence of bone metastases on PFS was no longer statistically significant (p = 0.290), while BRAF status is the only remaining predictor, with an adjusted HR of 0.46 (95% CI 0.25–0.86).
RAIR-DTC patients whose tumors harbored BRAF mutation showed significantly longer PFS under Chinese domestic MKIs apatinib, donafenib, and anlotinib.
Poster 0570
Thyroid Cancer, Clinical, Poster
The role of genetic mutations in lymph node metastasis of papillary thyroid cancer: Insights from Whole-Exome sequencing
Hao Zhao1, Xiaoyi Li*2, 1Beijing Shijitan Hospital, China, 2Peking Union Medical College Hospital, China
Objective
Papillary thyroid cancer (PTC) generally demonstrates a favorable prognosis; however, the incidence of lymph node metastasis (LNM) is significantly high, posing a major clinical challenge. The genetic determinants contributing to LNM in PTC remain poorly understood. This study sought to identify the genetic differences between PTC cases with and without LNM.
Methods
Patients who underwent routine prophylactic lymph node (LN) dissection, with more than five LNs harvested, were included in the study. Exclusion criteria encompassed individuals with coexisting malignancies, a history of thyroid surgery, chemotherapy or radiotherapy, and those with incomplete clinical information. The included patients were subsequently stratified into lymph node metastasis (LNM) and non-LNM groups based on postoperative pathology. A 1:1 propensity score matching (PSM) was employed to match patients in the non-LNM group with those in the LNM group. Following this, whole-exome sequencing (WES) analysis was conducted on neoplastic tissues from the included patients. The downloaded sequencing data underwent subsequent quality control and variant calling procedures. Thereafter, Maftools software was utilized to summarize, visualize, and compare somatic mutations across both cohorts.
Results
A total of 88 patients were included in the study, with 44 patients in each group. There were no significant differences between the two groups in terms of age (p = 0.276), gender (p >0.999), tumor size (p = 0.342), capsular invasion (p = 0.811), chronic lymphocytic thyroiditis (p = 0.867), histological subtype (p >0.999), and TNM stage (p >0.999). The median number of harvested lymph nodes was 10.0 (IQR 8.0–13.0) for the non-LNM group and 17.5 (IQR 10.3–38.3) for the LNM group. There was no significant difference in tumor mutation burden (TMB) between the two groups (p = 0.33). The median number of variants per sample was 192. In both groups, the most frequently mutated genes were BRAF, MUC4, MUC12, TTN, FLG, MUC16, MUC17, PDE4DIP, IGFN1, and USP17L20. Notably, the mutation frequencies of 11 genes, including PDE4DIP, CACNA1H, DNAH9, and MUC17, among others, demonstrated significant differences between the LNM group and the NLNM group.
Conclusion
The identified genetic differences may contribute to the development of LNM and hold potential as biomarkers for LNM in PTCs. Nevertheless, further research is required to validate these findings.
Poster 0571
Thyroid Cancer, Clinical, Poster
Unveiling molecular mechanisms and metabolic subtypes in thyroid cancer dedifferentiation via Multi-Omics analysis
YANZHI ZHANG*, BEN MA, Fudan University Shanghai Cancer Center, China
Objective
Metabolic reprogramming is a common feature of tumorigenesis and differentiation that significantly impacts gene expression, cellular differentiation, and the tumor microenvironment. The factors driving the progression from well-differentiated to fatal undifferentiated forms remain as elusive as dark matter. Our objective is to uncover the molecular mechanisms underlying dedifferentiation and classify these into subtypes based on metabolic activities, thereby informing targeted clinical therapeutic decisions.
Methods
An integrative multi-omics analysis was conducted, incorporating transcriptomics and metabolomics data obtained from the FUSCC cohort, which consists of 39 normal thyroid, 67 papillary, 31 follicular, 27 poorly differentiated, and 16 anaplastic thyroid cancer samples.
Results
Our multi-omics results revealed abnormal activation of 18 metabolic pathways in dedifferentiated thyroid cancer. These pathways include serine, arginine, glutamine, and glycolysis, indicating a rich array of biochemical reactions within the cancer cells. Through further characterization and clustering of the metabolic subtypes of malignant tumors, we identified three distinct metabolic behaviors within differentiated tumors (DMGs). Among these, the lactate-dominant microenvironment subgroup (DMG3) exhibited the poorest prognosis. By employing multiple machine learning methods, we defined a cluster of metabolites (DMC) associated with the dedifferentiation potential of thyroid cancer, demonstrating significant predictive value for prognosis. We utilized the Recon3D database to identify transcriptional genes significantly correlated with the DMC, subsequently termed DMC-G. Using Lasso, we developed a formula to calculate the DMC-GScore, including BCAT1, LPCAT2, and ST3GAL1. DMG-GScore was validated in the GSE29265, GSE76039, and GSE65144 datasets, showing a significant association with differentiation status.
Conclusion
Our study established a formula, DMC-GScore, for calculating differentiation status based on both metabolite and transcriptome levels. This formula offers potential for rapid assessment of differentiation status and could guide clinical decision-making effectively.
Poster 0572
Thyroid Cancer, Clinical, Poster
Association between financial toxicity, radioactive iodine (RAI) symptom burden, and health-related quality of life (HRQOL) domains among patients with differentiated thyroid cancer (DTC)
Alaina Carr*1, Kristi Graves1, Victoria Lai2, Jeffrey Giguere1,3, Gary Bloom4, Jacqueline Jonklaas5, 1Georgetown University Medical Center, USA, 2MedStar-Washington Hospital Center, USA, 3School of Medicine, Georgetown University, USA, 4ThyCa: Thyroid Cancer Survivors’ Association, Inc, USA, 5Division of Endocrinology, Department of Medicine, Georgetown University, USA
Poster 0573
Thyroid Cancer, Clinical, Poster
Molecular alteration patterns, rather than tumor size, to predict tumor behavior in papillary thyroid cancer: results from an international multicenter retrospective study
Gregoire Morand*1,2, Idit Tessler3, Josh Krasner2, Marc Pusztaszeri2, Galit Avior3, Richard Payne2, 1University Hospital Zurich, Switzerland, 2McGIll University, Canada, 3Tel Aviv University, Israel
Background: Molecular testing is a well-established tool that assists in the management of thyroid nodules and allows classification in distinct molecular alteration patterns: BRAF-like, RAS-like and non-BRAF-non-RAS (NBNR). In this paper we compared tumor behavior according to molecula alteration pattern versus tumor size alone, which is still used for traditional staging.
Methods: Retrospective multicenter multinational study of thyroid nodules that underwent preoperative molecular profiling with ThyGenX/ThyGeNEXT or ThyroSeq V3 between 2015–2022.
The clinical characteristics and molecular alteration profiles of tumors were compared. Collected data included demographics, cytology results, tumor size, surgical pathology, and molecular alterations.
Results: 784 patients who had surgery were included, of which 603 (76.2%) were females. BRAF-like, RAS-like, and non-BRAF-non-RAS (NBNR) were present in 227 (29.0%), 183 (23.3%), and 76 (9.7%), respectively. Median tumor size was 16 mm (IQR 10–25). Extrathyroideal extension (ETE) was present in 7.4% (gross ETE) and 6.5% (minimal ETE) of the cases.
Tumor size (maximal dimension) was significantly smaller in patients with BRAF-like than RAS-like and/or NBNR molecular alterations (p = 0.00008 resp. 0.00009). ETE was more likely in nodules with BRAF-like molecular alterations than with RAS-like and NBNR molecular alterations (p = 1.3E-15). There was no statistically significant imbalance between ETE and tumor size.
Conclusion: Molecular testing of thyroid nodules can help determine molecular alteration pattern. The latter can be used to predict tumor behavior and was a stronger predictor than tumor size alone. Future staging systems should incorporate molecular testing into their algorithms.
Poster 0574
Thyroid Cancer, Clinical, Poster
Multi-institutional registry study of the results of the oncomine Dx target test for advanced thyroid cancer in Japan
Ken-ichi Ito*1,2, Iwao Sugitani1, Naoyoshi Onoda1, Hisato Hara1, Chie Masaki1, Norisato Mitsutake1, Shunji Takahashi1, Naomi Kiyota1, Nobuyasu Suganuma1, Makoto Tahara1, Tomoko Yamazaki1, Morimasa Kitamura1, Seigo Kinuya1, Mitsuyoshi Hirokawa1, Keisuke Enomoto1, Tetsuo Kondo1, Hideyuki Sakurai1, Mana Yoshimura1, Sadamoto Zenda1, Ichiro Horie1, Naoki Fukuda1, Noriaki Nakashima1, Mami Sato1, Kiyomi Horiuchi1, Nobuhiro Shibata1, Hiroshi Katoh1, Tatsuya Fukumori1, Katsuhiro Tanaka1, Kazuyuki Oishi1, Yoshiko Matsumoto1, Hidemitsu Tsutsui1, Yukio Koibuchi1, Yatsuka Hibi1, Satoru Noda1, Takaaki Fujii1, Kazuma Maeno1, Yasushi Shimizu1, Toru Nishikawa1, Takahiro Fukuhara1, Daisuke Kawakita1, Haruhiko Yamazaki1, Keiko Ohkuwa1, Hiroko Monobe1, Hirokazu Uemura1, Tokiko Ito1, 1Thyroid Cancer Multidisciplinary Treatment Committee, ATC Research Consortium of Japan, Japan, 2Shinshu University School of Medicine, Japan
Poster 0575
Thyroid Cancer, Clinical, Poster
Adjuvant radioactive ablation iodine in Tall-Cell papillary thyroid cancer: a systematic review and Meta-Analysis
Phillip Staibano1, Michael Gupta1, Fay Alresaini*1,2, Michael Au1, Keean Nanji1, Emily Oulousian3, Maya Senthilkumaran4, Sarah Oulousian5, Jesse Pasternak6, Tyler McKechnie1, Eric Monteiro7,8, Alex Thabane1, Han Zhang1, 1McMaster University, Canada, 2King Faisal Specialist Hospital and Research Center (KFSH-RC), Saudi Arabia, 3McGill University, Canada, 4University of Ottawa, Canada, 5University of Quebec, Canada, 6University Health Network, Canada, 7University of Toronto, Canada, 8Mount Sinai Hospital, Canada
Tall cell variant papillary thyroid cancer (TCV-PTC) is associated with aggressive disease features and worse prognosis. It remains unclear whether adjuvant radioactive ablation iodine (RAI) is associated with improved survival in TCV-PTC. The aim of our study was to assess survival benefit of adjuvant RAI in the management of TCV-PTC compared to thyroidectomy alone.
We searched OVID Medline, EMBASE, Scopus, and Cochrane CENTRAL databases. All studies that investigated survival outcomes in adult patients with TCV-PTC which compared thyroidectomy with thyroidectomy and adjuvant RAI were included. Risk of bias was evaluated using ROBINS-I and certainty of evidence was evaluated using GRADE. Sensitivity analysis was done for all survival-based outcomes. Meta-analysis was performed using a random effects model and all analyses were performed in Revman 5.3 (Cochrane, UK).
Seven non-randomized studies were included with 9611 TCV-PTC patients, of which 6296 (65.5%) underwent adjuvant RAI. All studies were at high risk of bias. Based on low certainty evidence, we found that adjuvant RAI improved overall survival in TCV-PTC (HR = 0.60, 95% CI: 0.42–0.85). This benefit was maintained in studies that performed propensity score matching, but we did not find a significant impact of tumor size. No studies investigated treatment harms or quality of life.
Adjuvant RAI may improve overall survival in TCV-PTC, but future randomized studies with risk stratification are needed. Based on very low certainty evidence, we were uncertain whether adjuvant RAI impacts cancer-specific or recurrence-free survival.
Poster 0576
Thyroid Cancer, Clinical, Poster
Molecular surveillance to monitor progression of thyroid nodules with low-risk molecular alterations
Steven Hodak1, Joel Rosenbaum2, Marina Nikiforova2, Jules Aljammal3, Abigail Wald2, Cihan Kaya4, Xiaoling-Lynn Guo4, Paolo Cotzia4, Yuri Nikiforov*2, 1NYU Langone Health, USA, 2UPMC, USA, 3The Thyroid Clinic Utah, USA, 4CBLPath/Thyroseq laboratory, Sonic Healthcare USA, USA
Poster 0577
Thyroid Cancer, Clinical, Poster
Impact of delayed diagnosis on overall survival and Disease-Free survival in medullary thyroid cancer
Andrea Cavallo1,2, Ines Califano3, Javier Roberti4, Maria Storani5, Florencia Ortiz2, Ana Voogd1,6, Maria del Carmen Negueruela1, Eduardo Faure7, Fabian Pitoia*8, 1Hospital Universitario Austral, Argentina, 2Hospital Alta Complejidad, Argentina, 3Hospital Roffo, Argentina, 4CIESP/CONICET, Argentina, 5Htal. Hospital Municipal Central de San Isidro “Dr. Melchor Ángel Posse”, Argentina, 6Sanatorio las Lomas, Argentina, 7Centro Endocrinologia Buenos Aires, Argentina, 8Hospital de Clìnicas, Argentina
Poster 0578
Thyroid Cancer, Clinical, Poster
The impact of thyroglobulin antibodies on stimulated thyroglobulin levels in differentiated thyroid carcinoma
Meghana Pattipati, Dhara Patel, Sasan Fazeli*, City of Hope Cancer Center, USA
Poster 0579
Thyroid Cancer, Clinical, Poster
microRNA profiling augments mutation status in the risk stratification of thyroid nodules with a suspicious for malignancy (bethesda V) cytology diagnosis
Venkata Arun Timmaraju, Jonathan Levine, Sydney Finkestein, Nicole Massoll*, Interpace Diagnostics, USA
Most thyroid tumors develop from thyroid follicular cells by acquiring driver mutations activating the MAPK signaling pathway. Initial diagnosis of malignancy is based on cytological analysis of ultrasound guided fine-needle aspiration (FNA) of thyroid nodules. The Bethesda system for reporting thyroid cytopathology classifies 25% of these nodules to be Indeterminate thyroid nodules (ITNs). ITNs are subclassified as BIII Atypia of Undetermined Significance, BIV Follicular Neoplasm, and BV Suspicious for Malignancy.
Thyroid nodules with a Bethesda V diagnosis are associated with a 67–83% Risk of Malignancy (ROM) and can pose a challenge in terms of surgical decision-making. Molecular testing is increasingly being used to aid in decisions regarding the extent of surgery. We assessed the utility of miRNA analysis to further augment oncogene testing results.
A retrospective analysis was conducted on a cohort of thyroid nodule samples with Bethesda V cytology (n = 425) tested from September 2022 to January 2024. Samples were evaluated using the combined ThyGeNEXT + ThyraMIRv2 testing to determine the ROM for each nodule.
The ThyGeNEXT test examines the oncogene alterations in the MAPK/PI3K pathways and TERT promotor region. The ThyraMIRv2 test utilizes a microRNA (miRNA) expression-based classifier and pair-wise profiling algorithms to further assess the malignancy risk. ThyraMIRv2 analysis was performed only on nodules that did not contain a BRAF V600E-like driver mutation.
Mutational analysis identified genomic alterations in 62% of cases, the remaining 38% tested negative. The majority of the samples (81%) had a BRAF V600E-like mutation, followed by RAS-like mutations (11%) and sporadic fusions in ALK, BRAF, NTRK3, and RET (8%).
miRNA algorithmic analysis classified 32% of the mutation-negative nodules as high risk and the miRNA pairwise expression profiling further refined the risk in a subset of RAS-positive/ algorithmic miRNA classifier-negative nodules.
miRNA pairwise expression profiling enhances the miRNA algorithmic classifier and mutation status in assessing malignancy risk and allowed for further stratification of both RAS-positive and mutation-negative Bethesda V thyroid nodules.
Poster 0580
Thyroid Cancer, Clinical, Poster
Clinical Outcomes of a Family Carrying a RET K666N Germline Mutation
Allison Yip*, Melissa Lechner, Steven Jacobsen,UCLA, USA
Medullary thyroid cancer (MTC) is a rare neuroendocrine tumor of the thyroid parafollicular C cells and is associated with calcitonin production. Although most cases are sporadic, inherited MTC is associated with multiple endocrine neoplastic type 2 (MEN2) syndrome, an autosomal dominant inherited syndrome caused by activing mutations in the RET proto-oncogene. The RET K666N germline mutation is rare and uncommonly described.
A RET K666N germline mutation was discovered incidentally following Myriad MyRisk Hereditary Cancer testing done for breast cancer risk stratification in an asymptomatic 24yo woman. Subsequent evaluation of her 60yo father, 21yo sister, and 84yo grandmother showed the same RET mutation. Serum calcium, PTH, and plasma fractionated metanephrine testing results in all individuals were within normal limits. Calcitonin levels were mildly elevated (13pg/mL) in the father so thyroid ultrasonography (US) was done and revealed 3 subcentimeter, intrathyroidal, solid and hypoechoic TIRADS-4 nodules. Thyroid FNA revealed MTC in 2 of 3 nodules with positive calcitonin staining accompanied by Bethesda III or V cytology; the third nodule was cytologically benign. He underwent total thyroidectomy with pathology demonstrating multiple, bilateral subcentimenter MTC and C-cell hyperplasia. There was no extrathyroidal extension or lymph node spread and 4-week post-operative calcitonin level was undetectable. Thyroid US of both daughters showed no nodules and undetectable serum calcitonin levels. Thyroid US done on the grandmother showed several nodules, and calcitonin levels were mildly elevated (37pg/mL). Annual surveillance thyroid US and screening calcitonin testing was recommended. Genetic counseling was recommended for first-degree relatives.
We report the clinical outcomes of a RET K666N mutation associated with MTC within a family identified with publicly available genetic testing. Carriers of RET K666N mutation present with low penetrance of isolated MTC without other features of MEN2. This mutation affects the intracellular domain of the tyrosine kinase receptor and in vitro exhibits ligand-independent phosphorylation activity and transforming potential. This mutation does not directly alter the catalytic region, which may explain its association with later onset disease. This case highlights the increasing availability of genetic risk information and the need for correlation to disease penetrance and phenotypes.
Poster 0581
Thyroid Cancer, Clinical, Poster
Health-related quality of life in patients with thyroid cancer receiving the gasless trans-subclavian approach endoscopic or open thyroidectomy: a prospective observational study
Jianhong Yu*1, Wen Pan1, Chang Liu1, Shunjin Chen1, Xiyu Yao1, Hui Liu2, Yu Wu1, 1Department of Head and Neck Surgery, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, China, 2Department of Head and Neck Surgery, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospita, China
These findings suggest that TAET may offer potential advantages in terms of cosmetic and psychological outcomes for patients with differentiated thyroid cancer (DTC) and could be considered as an alternative surgical approach.
Friday, November 1, 2024
Poster 0582
Autoimmunity, Clinical, Poster
Predictive Factors and Treatment Outcomes in Intravenous Glucocorticoid Pulse Therapy for Active Moderate-to-Severe Thyroid Eye Disease: Identifying the Need for Surgical Interventions
Anna Giannakogeorgou*1, Thomas Bobbert1, Daniel Salchow2, 1Charité - Universitätsmedizin Berlin, Department of Endocrinology and Metabolic Diseases (including Division of Lipid Metabolism), Germany, 2Department of Ophthalmology, Charité - University Medicine Berlin, Campus Virchow Clinic, Germany
Poster 0583
Autoimmunity, Clinical, Poster
THRIVE phase 3 trial of VRDN-001 in active thyroid eye disease (TED): next generation insulin-like growth factor-1 receptor blockade
Steven Leibowitz*1, Michael Yen2, Thomas Ciulla3, Abhijit Narvekar3, Cathy Michalsky3, Antonio Manuel Garrido Hermosilla4,5, 1Jules Stein Eye Insitute, UCLA, USA, 2Baylor College of Medicine, Alkek Eye Center, USA, 3Viridian Therapeutics, Inc., USA, 4Andalusian Public Health System, Spain, 5Virgen Macarena University Hospital, Spain
VRDN-001, a full antagonist antibody to the insulin-like growth factor-1 receptor (IGF-1R), is an investigational treatment for thyroid eye disease (TED) designed for fewer infusions, lower antibody dose, shorter infusion time, and reduced treatment burden. VRDN-001 was well tolerated in both phase 1 and 2 studies and showed signs of clinical activity in patients with TED. On the basis of these initial data, a double-masked, placebo-controlled phase 3 registrational trial (THRIVE) was conducted to evaluate the safety and efficacy of VRDN-001 in active TED. THRIVE has completed enrollment and topline results expected in September 2024 will be presented.
THRIVE investigated 5 intravenous (IV) infusions of VRDN-001 (10 mg/kg) vs placebo administered every 3 weeks in patients with moderate-to-severe active TED, a clinical activity score (CAS) of ≥3, and onset of signs and symptoms within 15 months of enrollment. In the U.S., the primary efficacy endpoint is the proptosis responder rate at 15 weeks (defined as the proportion of patients having ≥2-mm proptosis reduction from baseline, without a corresponding increase of ≥2-mm in the fellow eye, at 3 weeks post the fifth infusion). Secondary and exploratory endpoints include measures of diplopia, CAS, MRI/CT volumetric analyses, and quality of life.
Preclinical studies showed that VRDN-001 provides near-complete inhibition of IGF-1R signaling, as evidenced by the autophosphorylation of IGF-1R, marker of proximal signaling, and phosphorylation of AKT and ERK, markers of distal signaling. Preliminary results from a phase 2 proof-of-concept study of 2 IV infusions of VRDN-001 in patients with moderate-to-severe active TED demonstrated clinically meaningful improvements in TED symptoms (proptosis, CAS, and diplopia) at 6 weeks. The THRIVE phase 3 trial, initiated in December 2022, randomized 113 patients in a 2:1 fashion to either VRDN-001 or placebo. Topline data expected to be reported will include responder rates and mean changes for proptosis, CAS, and diplopia.
Topline results from THRIVE, a double-masked, placebo-controlled phase 3 registrational trial, will provide an initial view on the clinical safety and efficacy outcomes of a full treatment course (5 IV infusions) of VRDN-001 in active TED.
Poster 0584
Autoimmunity, Clinical, Poster
Comparison of efficacy of tocilizumab to intravenous glucocorticoids in the treatment of thyroid eye disease
Hui Xu*, MengTing Zhang, Yushun Qiao, Jianbo Zhou, Beijing Tongren Hospital, Capital Medical University, China
Subjective: Thyroid eye disease (TED) is a challenging autoimmune disorder, where some patients exhibit poor responses to steroid therapy. Tocilizumab (TCZ) has shown potential in steroid-resistant TED patients, but its efficacy in patients without prior steroid treatment remains understudied. This study aims to compare the efficacy of TCZ with intravenous glucocorticoids.
Methods: A retrospective analysis was conducted on patients treated with TCZ and steroids in our endocrinology department, with confirmed TED diagnosis and no intravenous glucocorticoid treatment in the past two months. Clinical data, laboratory results, and orbital CT/MRI (before treatment and within 2 months post-treatment) were collected and compared for efficacy and changes in various indicators. The primary evaluation criteria were a reduction in CAS score of 2 points or more, or a score reduced to 1 or less, a reduction in proptosis by at least 2 mm, and a decrease in 99mTc-diethylenetriamine-pentaacetic-acid (DTPA) uptake as measured by single photon emission computed tomography (SPECT).
Results: A total of 90 patients were included, with 50 receiving steroid treatment and 40 receiving TCZ. No significant differences were found in baseline characteristics except for gender (χ2 = 5.51, p = 0.019). After TCZ treatment, 42% of patients (17/40) achieved remission in CAS scores, 77% (27/35) showed a decrease in DTPA uptake, and 29% (9/31) had a reduction in proptosis of at least 2 mm. However, these improvements did not reach statistical significance when compared to the steroid group (p = 0.065, p = 0.466, p = 0.615). TCZ significantly reduced CAS scores and TRAb levels (p < 0.001). TCZ (1.23 ± 1.45 mm) shows a more effective reduction in proptosis compared to steroid therapy (0.60 ± 1.26 mm). (T = 2.025, p = 0.046). Additionally, univariate and multivariate regression analyses revealed a positive correlation between pre-treatment CAS scores and treatment efficacy (OR = 2.324, p = 0.027), indicating that patients with higher CAS scores may benefit more from TCZ treatment.
Conclusion: TCZ has shown potential in the treatment of TED, not only reducing CAS scores, proptosis, DTPA uptake, and TRAb levels, but also showing superior efficacy in alleviating proptosis over steroid therapy.
Poster 0585
Autoimmunity, Clinical, Poster
Proteome-wide mendelian randomization study identifies potential novel drug targets for thyroid eye disease
Ikramulhaq Patel*, Yin-He Chai, Jin-Yan Zhang, Jian-Bo Zhou,Beijing Tongren Hospital, Capital Medical University, China
Poster 0586
Autoimmunity, Clinical, Poster
Audiologic adverse effects secondary to teprotumumab: a single academic center historical cohort
Samira Takkoush, Neil Patel, Vishnu Sundaresh*, University of Utah, USA
Introduction:
Teprotumumab, an IGF-1R antagonist approved for thyroid eye disease (TED) is known to cause audiologic adverse effects. This study aimed to investigate the audiometric screening and characterize the audiologic adverse effect pattern in the real-world setting.
Methods:
This historical cohort included all consecutive adults (≥18 years) who received teprotumumab for TED between March 2020 — February 2024, at the University of Utah Health. Data on demographics were extracted electronically while audiologic symptoms and audiometry results were extracted manually.
Results:
Thirty-four patients (mean age 60 ± 2 years, 85% Caucasian, 82% females, 9% current smokers) received at least 1 infusion of teprotumumab and had follow-up medical records available for review. Five (14.7%) patients underwent baseline audiometric testing, while follow-up testing was available for 20.5% (7/34) of the patients during and 14.7% (5/34) at the end of their treatment. Fifteen (44%) patients reported adverse effects (autophony, eustachian tube dysfunction, ear fullness, hyperacusis, and ear popping) including 5 patients who reported subjective change or decrease in hearing. Among these patients, and due to their hearing symptoms, 3 had discontinued treatment with 2 of them having audiologic testing which reported worst ear pure tone average (PTA) of 49 dB HL and 35 dB HL and word recognition score (WRS) of 92% and 84%, respectively. Two other patients had serial pre-treatment to post-treatment audiometry demonstrating threshold shifts associated with new onset audiologic symptoms; both patients elected to complete 8 infusions despite symptoms. In total, ten patients reported tinnitus during treatment with varying degrees of resolution at most recent follow up. Of those with threshold shifts, there was no selective effect on the high frequency (4 kHz-8 kHz) range.
Conclusion:
While it is known that teprotumumab causes hearing loss, tinnitus, and other audiologic symptoms, audiometric patterns and monitoring recommendations have yet to be defined. Based on this case-series, hearing loss patterns do not necessarily affect the high frequency range alone, as seen in other ototoxic drugs. Serial audiometric monitoring at baseline and throughout teprotumumab treatment is recommended.
Poster 0587
Autoimmunity, Clinical, Poster
The neonatal Fc receptor and disease outcomes: a phenome-wide mendelian randomization study
Jin Yan Zhang*, Zi Qi Wang, Jian Bo Zhou, Beijing Tongren Hospital, China
Background:
The neonatal Fc receptor (FcRn) is a protein that plays a crucial role in maintaining IgG homeostasis. Consequently, employing FcRn inhibitors to block the binding of IgG to FcRn and reduce endogenous IgG levels is an emerging strategy for treating antibody-mediated autoimmune diseases like thyroid eye disease. However, its association with other diseases is still unclear. To evaluate the association between FcRn and a wide range of diseases, we conducted a phenome-wide Mendelian Randomization (MR) study on FCGRT, the gene that encodes FcRn.
Method:
Utilizing the most significant missense variant rs56709164 associated with FCGRT as a genetic instrument to characterize the effects of FCGRT overexpression, a phenome-wide MR study was conducted to explore the relationship between genetically proxied FCGRT overexpression and 1,473 disease outcomes using data from the GTEx Portal (n = 838). Subsequently, the position of rs56709164 was used to identify segments associated with FCGRT overexpression in various CRP GWAS datasets. These segments were then used for replication studies to further elucidate the relationship between FCGRT and multiple diseases across different datasets, thereby supplementing the genetic evidence.
Result:
PheWAS-MR identified that genetically proxied overexpression of FCGRT is associated with an increased risk of various vascular-related diseases, including hypertensive heart disease and hypertensive nephropathy. This finding was corroborated across different populations and CRP datasets corresponding to segments of FCGRT overexpression. Additionally, PheWAS-MR also found that FCGRT overexpression is associated with an increased risk of pregnancy complications such as gestational diabetes and hyperemesis gravidarum, as well as tumor diseases like cancer of the oropharynx. However, these associations were not confirmed in the CRP validation datasets. Therefore, while using FCGRT inhibitors to suppress FCGRT overexpression in the treatment of thyroid eye disease, we observed potential cardio-renal protective effects along with potential adverse reactions.
Conclusion:
This study supports that the expression of FCGRT has a detrimental effect on various vascular-related diseases, including hypertensive heart disease and varicose veins. Therefore, FcRn inhibitors, used in the treatment of thyroid eye disease, may concurrently offer cardio-renal protective effects. However, increased pharmacovigilance is warranted in relation to the potential adverse effects.
Poster 0588
Disorders of Thyroid Function, Clinical, Poster
Preliminary safety and efficacy of subcutaneous lonigutamab (anti–IGF-1R) from a phase 1/2 proof-of-concept study in patients with thyroid eye disease (TED)
Shoaib Ugradar*1, David Kostick2, Jane Spadaro3,4, Anita Grover5, So Jung Imm5, Sarah Chesler5, Shephard Mpofu5, Jwu Jin Khong6,7, 1Department of Orbital and Oculoplastic Surgery, Thrive Health, USA, 2Florida Eye Specialists, USA, 3Department of Ophthalmology, Corewell Health William Beaumont University Hospital, USA, 4Kahana Oculoplastic and Orbital Surgery, USA, 5ACELYRIN, INC., USA, 6Centre for Eye Research Australia, Royal Victorian Eye and Ear Hospital, Australia, 7Department of Surgery, University of Melbourne, Australia
In cohort 2, at week 6, 4/6 (67%) patients had a proptosis response; proptosis mean change (SD) from baseline was −1.8 (0.8). In patients with baseline diplopia (n = 5), 2/5 (40%) had a diplopia response. At week 6, 5/6 (83%) patients achieved a ≥2-point CAS reduction (study eye). TEAEs were reported in 5/6 (83%) patients; all were grade 1–2 with no SAEs or AESIs.
Poster 0589
Disorders of Thyroid Function, Clinical, Poster
Comparison of atypical and typical thyroid eye disease presentations based on muscular involvement and outcomes of teprotumumab therapy
Cigdem Yasar*, Andrea Kossler, Byers Eye Institute, USA
Purpose: This study aims to compare the clinical features and outcomes of teprotumumab therapy among different presentations of Thyroid Eye Disease (TED). Methods: We conducted a single-center, retrospective analysis of patients diagnosed with TED who received teprotumumab treatment. Patients were categorized into three distinct groups based on baseline orbital imaging showing specific muscles and glands involved: Group-1(atypical) with superior and/or lateral rectus and/or lacrimal gland involvement, Group-2 with medial and/or inferior rectus involvement, and Group-3 with the involvement criteria of both Group-1 and Group-2. Patient demographics, including baseline age, ethnicity, gender, and smoking status, were recorded. Baseline and follow-up (weeks-12/24 and years-1/2) measurements included proptosis, extraocular motility (EOM) score, Gorman score, and clinical activity score (CAS). The efficacy of teprotumumab was evaluated in reducing proptosis, CAS, Gorman score, and EOM scores across all groups. Restriction of EOM was assessed in the four cardinal directions, individual restrictions were summed for a total EOM score. Flare is documented. Results: A total of 41 patients were selected and analyzed: 7 in Group 1, 7 in Group-2, and 27 in Group-3. Among them, 85.8% of patients in Groups-1 and 2 and 66.7% in Group 3 were female. Mean ages were 60.5 years in Group-1, 54.1 years in Group-2, and 50.7 years in Group-3 (p = 0.323). There were no significant differences regarding age, gender, and smoking status among the groups. However, there was a statistically significant difference in terms of ethnicity (p = 0.011). All subjects in Group-1 were Asian, while 42.8% in Group 2 and 45.1% in Group 3 were white. Baseline proptosis measurements were statistically higher in Group-3 compared to Group-1 and 2 (p = 0.008). At week-24, reduction in proptosis were significantly different between the three groups (p = 0.020). Other baseline and follow-up measurements were not significantly different between the groups. Flare rates were 28.6%, none and 40.7% in group-1, 2 and 3 respectively. Group-3 showed higher flare rates ( p >0.05). Conclusion: Our findings indicate that atypical-TED presentations involving superior/lateral rectus muscles or lacrimal gland are more likely to be seen in patients of Asian ethnicity. Higher baseline proptosis may be associated with typical presentations and involvement of more than two muscles. There were no significant differences in the therapeutic response to teprotumumab overall. Involvement of atypical and/or more then two muscles may present with higher flare rates. The main limitation of the study is the small sample size.
Poster 0590
Disorders of Thyroid Function, Clinical, Poster
A randomized comparative study between liquid (tirosint®-SOL) and tablet formulations of levothyroxine in neonates and infants with congenital hypothyroidism — preliminary results
Susan Rose*1,2, Claudia Scarsi Perler3, Giuseppe Mautone3, Gabriele Lanzi3, The Tirosint-SOL Pediatric Study Investigators.4, 1Cincinnati Children’s Hospital Medical Center, USA, 2University of Cincinnati College of Medicine, USA, 3IBSA Institut Biochimique SA, Switzerland, 4various institutions, USA
Objective: Tirosint®-SOL is the first FDA-approved levothyroxine sodium (LT4) oral solution for the treatment of hypothyroidism and for thyroid stimulating hormone (TSH) suppression in adult and pediatric patients, including neonates. It is presented in unit-dose ampules at 15 strengths ranging from 13 to 200 mcg. The present study was aimed at gathering information on the use of Tirosint®-SOL as replacement therapy in neonates and infants with congenital hypothyroidism (CH) compared to conventional treatment with crushed LT4 tablets in a real-life setting. We present preliminary descriptive results at the earliest time points of treatment.
Methods: 31 (31) subjects were randomized in this multicenter study (4 neonates naïve to treatment and 27 infants already on LT4 tablets). Neonates were randomized to start treatment with LT4 tablets (1) or Tirosint®-SOL (3), while infants were switched to Tirosint®-SOL (17) or kept taking LT4 tablets (10).
Results: At screening, 1–2 weeks and 3–4 weeks upon treatment start the following TSH levels were measured in infants: 2.28 ± 1.70 mIU/L, 1.32 ± 1.43 mIU/L and 1.33 ± 1.22 mIU/L in the Tirosint®-SOL group and 5.95 ± 4.97 mIU/L, 3.29 ± 4.43 mIU/L and 4.48 ± 6.36 mIU/L in the LT4 tablets group. At the same timepoints, the following free thyroxine (FT4) levels were measured: 25.4 ± 6.5 pmol/L, 24.0 ± 6.2 pmol/L and 24.9 ± 8.9 pmol/L in the Tirosint®-SOL group and 19.7 ± 4.8 pmol/L, 19.5 ± 4.4 pmol/L and 19.3 ± 5.4 pmol/L in the LT4 tablets group.
Conclusion: These preliminary data confirm Tirosint®-SOL was able to maintain stable FT4 and TSH levels in infants affected by CH switched from LT4 tablets.
Poster 0591
Disorders of Thyroid Function, Clinical, Poster
Screening failures in a phase 2, multicenter, Non-Randomized, Open-Label, single arm, self-controlled study of once-weekly subcutaneous levothyroxine (XP-8121)
Valentina Conoscenti, James Meyer*, Dawn Harper, Robbie Huang,Xeris Pharmaceuticals, Inc., USA
Objective: This Phase 2 trial was designed to determine the comparable dose from stable oral levothyroxine to once-weekly subcutaneous (SC) levothyroxine in adults (18–65 years old) with hypothyroidism. However, the study enrollment presented challenges due to the high rate of screen failures (SF). The data for the SF are presented in this analysis.
Methods: Participants were screened based on specific criteria. Key inclusion criteria included: chronic hypothyroidism, a stable daily dose of oral levothyroxine for at least 3-months, thyroid-stimulating hormone (TSH) and free thyroxine (fT4) levels within study reference range at screening [(0.47 to 4.68 µIU/mL), (0.78 to 1.42 ng/dL), respectively], and TSH levels within reference range at least 3 months prior to screening.
Results: Among 140 participants screened, 94 (67%) were a SF. The main reason for SF [57/94 participants (61%)] was TSH and/or fT4 being out of range, despite having been on a “stable” oral dose for at least 3 months. Twenty-one/57 (37%) SF participants with TSH/fT4-out-of-range were taking concomitant medications that are known to affect levothyroxine absorption. For the remaining participants [36/57 (63%)] who were SF due to TSH/fT4 out-of-range, there is not enough information to justify the abnormal labs.
Discussion/Conclusions: Screening failures in this trial were primary due to out-of-range TSH levels, reflecting the complexities of treatment of hypothyroidism. Understanding these screening failures is crucial to optimize the treatment of participants with hypothyroidism. Future studies are needed to further define the population of participants who are over- or under-treated with oral levothyroxine.
Poster 0592
Disorders of Thyroid Function, Clinical, Poster
Is teprotumumab associated with decreasing heart rate?
Dana Hamadi*1, David Toro Tobon2, Marius Stan2, 1Hennepin Healthcare, USA, 2Mayo Clinic, USA
Objectives: Thyroid eye disease (TED) is an autoimmune condition linked to thyroid autoimmunity that significantly impairs the quality of life of affected patients. Teprotumumab, an inhibitor of the insulin-like growth factor-1 receptor (IGF-1R), has previously shown effectiveness in addressing TED. There is a paucity of data regarding the effect of Teprotumumab on heart rate. The aim of this research is to identify if there is an association between teprotumumab use and changes in heart rate.
Methods: A retrospective review was conducted on all patients that received teprotumumab at Mayo Clinic between 2020 and 2024. Patients’ heart rate and blood pressure were assessed at baseline, and before and after each teprotumumab infusion. TED severity, clinical activity score (CAS), thyroid function tests (TFTs) and thyroid antibodies were collected at baseline. Other confounding factors such as negative chronotropic agents use, history of heart disease or conduction abnormalities, and electrolyte disturbances were included.
Results: 35 patients were analyzed. Sixty-nine percent (24/35) experienced a ≥15% decrease in heart rate from baseline (prior to teprotumumab initiation) during at least one infusion. Of these, 58% (14/24) had this occur with 3 or more infusions. Additionally, 38% (9/24) maintained a lower baseline heart rate for at least three months post-teprotumumab completion. Importantly, no patient reported symptoms related to these heart rate changes.
Conclusion: A substantial number of patients experienced a significant decrease in heart rate during teprotumumab therapy. While the clinical significance of this findings in not yet clear, physicians should be aware of these findings when assessing individuals at risk of experiencing symptomatic bradycardia. Further research is needed to understand the potential causality and the clinical importance of this phenomenon.
Poster 0593
Disorders of Thyroid Function, Clinical, Poster
Effects of thyroid disease on brain biological age
H.T. Pretorius, M.D., Ph.D. *, Betsy Budke, C.N.M.T. , Nichole Bodnar, B.S., C.N.M.T. , Dennis Menke, A.A.
Objective: Report thyroid disease effect on calculated biological brain age (BA).
Methods: Patients included had thyroid diseases defined by usual laboratory parameters and had memory complaints, but without dementia or other significant neurological disease affecting cognition. Patients with acute COVID-19 were excluded but those with long COVID-19, were included. Brain biological age was calculated from analysis of FDG-PET scans using a transcendental parameter, the Brain Functional Nuclear index (BFNi), which resembles a Gompertz function, combined in linear regression with aging abnormalities of both brain grey and white matter. The oldest biological brain age was set to 122 years, the age of the oldest known person. Montreal Cognitive Assessment (MoCA) scores monitored cognition and statistical analysis used EXCEL spreadsheets.
Results: Eight near-normal patients age 69.6+−15 years had MoCA 26.8+−32.9 and BA 62.4+−9.8. Thyroid patients, 9 hyperthyroid and 8 hypothyroid, age 66.3+/−9.1 years had MoCA 22.3+−2.7 (p < .01), BA 88.6+/−8.2 (p < 0.00003). None of the patients had severe thyroid dysfunction: the lowest TSH was 0.051 in a thyroid cancer patient on TSH suppression therapy and the highest TSH was 8.21; the lowest Free T4 was 0.57 ng/dl in a patient with secondary hypothyroidism post COVID-19. A group of 62 patients with memory complaints including the 17 thyroid patients as well as diabetics and traumatic brain injured had initial brain age 23.5+−8.4 years older than their chronologic age 62.6+/−12.2 years; when 21 of these, including 5 thyroid patients, were treated for 1 to 3 years for memory loss with multiple methods, including 2 g twice daily omega 3 fish oil and autologous stem cells, their BA 71.1+/−10.1 was no longer different from their chronologic age 72.8+−7.0 years.
Discussion: Thyroid hormone, even with mild abnormalities as in this series, has pleomorphic cognitive effects. We reported previously that thyroid dysfunction decreases liver function, which compromises cognition as does hypothyroid-related low growth hormone. Hyperthyroidism exacerbates menopausal symptoms including memory loss. Both hyperthyroidism and hypothyroidism contribute to marked increases in dementia. FDG PET is often insurance-reimbursed for significant memory abnormality and the PET brain age concept we developed is readily understood by patients and providers.
Poster 0594
Disorders of Thyroid Function, Clinical, Poster
Association between Long-Term exposure to environmental fine particulate matter and the prevalence of thyroid disorders: a national Cross-Sectional study in China
Kaijie Yang, Cihang Lu, Kang Chen, Zhongyan Shan, Weiping Teng, Yongze Li*, The First Hospital of China Medical University, China
Poster 0595
Disorders of Thyroid Function, Clinical, Poster
Therapeutic plasma exchange in severe thyrotoxicosis: a Single-Center experience
Andres Calderon-Valladares*1, Maria Aguilera1, Alexsandra Drinnon1, Jawairia Shakil1,2, 1Houston Methodist Hospital, USA, 2Weill Cornell Medical College, USA
Introduction:
Thyrotoxicosis and its most severe manifestation, thyroid storm, can have devastating consequences. While medical therapy remains first-line treatment in severe cases, complications arise for patients who have minimal or delayed response to medical therapy, those who require rapid thyroid normalization such as the elderly or those with history of arrhythmias, and patients who experience adverse effects with antithyroid drug (ATD) administration. In such cases, therapeutic plasma exchange (TPE) has been proposed as a safe and effective means to rapidly decrease thyroid hormone levels.
Objective:
To evaluate the effectiveness of TPE as a bridge for definitive treatment in patients with severe thyrotoxicosis or thyroid storm who do not respond to medical therapy.
Methods:
Retrospective case analysis of patients with severe thyrotoxicosis and thyroid storm who required TPE at a single institution between April 2023 and April 2024.
Results:
Six patients were included. The mean age was 44.7 years. 66% of patients were women. Among the causes of thyrotoxicosis and thyroid storm, Graves’ disease was present in three cases (50%), Amiodarone-induced thyrotoxicosis in two cases (33%) and mixed picture between AIT and Graves’ disease in one case (17%). TPE was initiated due to severity of presentation or poor response to medical therapy. Mean fT4 before the first TPE session was 5.42 ng/dl and 4.27 ng/dl after TPE. The mean difference in fT4 before and after TPE was −1.15 ng/ml (p 0.009). Mean T3 before the first TPE session was 238 ng/dl and 149.4 ng/dl after TPE. The mean difference in T3 before and after TPE was −88.60 ng/ml (p 0.087). The relative reduction of fT4 level after the first TPE session was 20.1%, and for T3 was 39.4%. Two patients died from cardiac causes. The rest of the patients underwent thyroidectomy safely after improved fT4 and T3.
Conclusions:
In patients with severe thyrotoxicosis and thyroid storm not responding to standard medical therapy or needing rapid improvements of thyroid levels, initiation of TPE significantly improved the fT4 and T3 levels allowing for definitive treatment with thyroidectomy. The clearance rate for T3 was more pronounced compared to fT4; although not statistically significant, this data is limited by the number of patients included in the cohort.
Poster 0596
Disorders of Thyroid Function, Clinical, Poster
A system to simplify and facilitate thyroid function test interpretation
ROBERT DONS*1, Jeffrey Gustafson2, Bina Malapur1, Michael Jakoby1, 1Southern Illinois University, USA, 2Belmont University Department of Chemistry and Physics, USA
Poster 0597
Health Disparities/Health Equity, Clinical, Poster
Effect of social determinants of health care on outcomes for Well-Differentiated thyroid cancer at an urban Safety-Net hospital
Patrick Weldon*, University of Missouri-Kansas City, USA
Multiple studies have been conducted evaluating the impact of social determinants of health on survival of well differentiated thyroid cancer. Many studies utilized national databases, but few have examined the effect at an institutional level. We hypothesized that assessing survival at our urban safety-net hospital would identify disparities among gender, race, and insurance status.
We examined records from our institutional cancer registrar for patients diagnosed with thyroid cancer from 2000–2023. We obtained data regarding their demographics and cancer stage at diagnosis. A survival analysis was performed using Kaplan-Meier estimates and Cox proportional hazards regression models.
A total of 336 patients were diagnosed during this time. Most patients were female 285 (84%) and 215 (63%) under age 55. We compared survival among our white 155 (54%) and black populations 127 (45%). Insurance status was stratified into non-insured/VA insurance/other 116 (34%), Medicaid 107 (32%), private insurance 64 (19%), and Medicare 49 (15%). 5-year survival was worse in those age >55 (p < .001), white individuals (p = .019), and Medicaid beneficiaries (p = .003). Mortality risk was higher in males (p = .012, confidence interval (CI): 0.13–0.78), age >55 (p < .001, CI: 0.13–0.78), whites (p = .026, CI: 0.21–0.91), and Medicaid insured (p = .002, CI: 0.08–0.56).
Our study demonstrates there are significant factors leading to disparities in survival for thyroid cancer. Interestingly, our white population is at increased risk which is contrary to other studies at either a national or institutional level. Further investigation is required to identify how to target this group to alleviate any modifiable factors impacting outcomes.
Poster 0598
Health Disparities/Health Equity, Clinical, Poster
Socioeconomic and racial disparities in pediatric cancer outcomes in the ghanaian health sector: Challenges and strategies for equitable care
Gideon Asare*, Tamale Teaching Hospital, Ghana
Objectives
This study aims to investigate the socioeconomic and racial disparities in pediatric cancer outcomes within the Ghanaian health sector. The objectives are to identify the specific challenges faced by different socioeconomic and racial groups, assess the impact of these disparities on diagnosis and treatment outcomes, and propose strategies for achieving more equitable care for pediatric cancer patients in Ghana.
Methods
A mixed-methods approach was employed, combining quantitative analysis of patient data from national cancer registries and hospitals with qualitative interviews of healthcare providers and affected families. The quantitative component focused on variables such as socioeconomic status, race, stage of cancer at diagnosis, treatment received, and survival rates. The qualitative component explored personal experiences, barriers to care, and perceptions of the healthcare system. Data were collected from multiple regions to ensure a representative sample of the diverse population in Ghana.
Results
The study found significant disparities in pediatric cancer outcomes based on socioeconomic status and race. Children from lower socioeconomic backgrounds and minority racial groups were more likely to be diagnosed at later stages and had lower survival rates compared to their higher-income and majority-race counterparts. Key challenges identified included limited access to specialized oncology care, financial barriers, inadequate health insurance coverage, and cultural beliefs affecting treatment-seeking behavior. Additionally, there was a shortage of trained healthcare professionals and insufficient infrastructure in rural areas.
Conclusion
Socioeconomic and racial disparities significantly impact pediatric cancer outcomes in Ghana. Addressing these disparities requires a multifaceted approach, including policy interventions to improve healthcare access and affordability, targeted outreach programs to educate communities, and investment in healthcare infrastructure and workforce training. Implementing these strategies can promote more equitable care and improve survival rates for all pediatric cancer patients in Ghana. Collaboration between government, healthcare providers, and non-governmental organizations is essential to overcome these challenges and ensure that every child has the opportunity for a healthy future. Key words: Pediatric Cancer, Disparities, Socioeconomic Status, Racial Inequities, Ghanaian Health Sector, Cancer Outcomes, Healthcare Access, Diagnosis, Treatment, Equitable Care.
Poster 0599
Pediatrics, Clinical, Poster
Diverging trends between genders in the incidence of pediatric thyroid carcinoma: a SEER database analysis
JB Eyring*1, Christopher Nielson1, Michelle Meder2, Casey Mehrhoff3, J Grimmer1, 1Otolaryngology-Head & Neck Surgery, University of Utah, USA, 2Pediatric Endocrinology, University of Utah, USA, 3Pediatrics, University of Utah, USA
Poster 0600
Pregnancy and Development, Clinical, Poster
Upper airway obstruction caused by intratracheal ectopic thyroid in pregnancy
yisihak Debodina*1, Berhanu hailemariam2, Mengistu Yismie2, Tassew Jebessa2, Ayalew tadesse2, Abraham Ariaya2, 1saint paulos Hospital Millennium Medical College, Ethiopia, 2saint paulos Hospital Millennium Medical College, Ethiopia
Upper airway obstruction due to Ectopic intratracheal thyroid manifested during pregnancy is a rare event from ectopic thyroid tissue inside the trachea. It may be physiological to manifest at pregnancy.it needs high suspicion to diagnose. even though there are several options of management, Surgical excision/ resection is one of the best ways when the patient presented with obstruction. We present surgical management of our patient presented with upper air way obstruction.
Poster 0601
Thyroid Hormone Action, Metabolism and Regulation, Clinical, Poster
Effects of acarbose and metformin on thyroid function and thyroid hormone sensitivity in type 2 diabetes patients: a post-hoc analysis of the MARCH study
Chenyu Zhang*1, Wenying Yang2, Weiping Teng3, Jing Li1, Zhongyan Shan1, 1Department of Endocrinology and Metabolism, Institute of Endocrinology, NHC Key laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, China, 2Department of Endocrinology, China-Japan Friendship Hospital, China, 3Department of Endocrinology and Metabolism, Institute of Endocrinology, NHC Key Laboratory of Diagnosis and Treatment of Thyroid Diseases, The First Hospital of China Medical University, China
Poster 0602
Thyroid Hormone Action, Metabolism and Regulation, Clinical, Poster
Association between thyroid hormones and metabolic vulnerability index: results from the ELSA-Brasil study
Vandrize Meneghini*1, Carolina Janovsky2, William Tebar1, Itamar Santos1, José Sgarbi3, Patrícia Teixeira4, Steven Jones5, Michael Blaha5, Peter Toth5,6, Paulo Lotufo1, Isabela Bensenor1, 1Universidade de Sao Paulo, Brazil, 2Universidade Federal de São Paulo, Brazil, 3Faculdade de Medicina de Marília, Brazil, 4Universidade Federal do Rio de Janeiro, Brazil, 5Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, USA, 6CGH Medical Center, USA
Poster 0603
Thyroid Hormone Action, Metabolism and Regulation, Clinical, Poster
The relation between thyroid hormones and mental symptoms in patients hospitalized with manic and depression
Mariko Hakoshima*, Kohnodai Hospital, Japan
Thyroid hormones play a crucial role in regulating metabolism, mood, and cognitive function. This study aimed to research the association between Psychiatric symptoms and thyroid hormones in patients with manic and depression.
The patients were admitted to a psychiatric department in our hospital from April 1st 2014 to March 31st 2023 and patients under 18 years old were excluded. Psychiatric symptoms were evaluated by GAF(Global Assessment of Functioning) score.
464 patients were enrolled (123 manic /341 depression) in this study. In patients with manic, the mean age was 52 ± 17 years old and 41 were males and 82 were females. GAF Score (at the time of hospitalization) was 29 ± 15. Thyroid hormones were Free T3 3.31 ± 0.43 pg/ml, Free T4 1.08 ± 0.25 ng/ml, and TSH 1.43 ± 1.18 μIU/ml.
In patients with depression, the mean age was 62 ± 16 years old and 166 were males and 225 were females. GAF Score was 32 ± 16. Thyroid hormones were Free T3 2.76 ± 0.53 pg/ml, Free T4 1.00 ± 0.25 ng/ml, and TSH 1.56 ± 1.67μIU/ml.
With correlation analysis, in manic group, GAF score had negative correlation with Free T4 (r=−0.241, p = 0.008)and positive correlation with TSH(r=−0.242, p = 0.018). This means the higher the thyroid hormones, the psychiatric symptoms were worse. In depression group, GAF score was negatively correlated with Free T4(r=−0.210, p=＜0.001). The results were similar to that in manic group.
Thyroid hyperfunction increases adrenaline and it exacerbates psychiatric symptom. And in this study, a large proportion of the depression group were patients with hypothyroidism. As previously reported lack of T3 degrade serotonin and noradrenaline levels.
Our study clarified that patients with manic and depression had thyroid dysfunction and there is correlation between exacerbation of psychiatric symptoms and thyroid function.
Poster 0604
Thyroid Imaging, Basic, Poster
Thyroid ultrasound ordering Overkill- Thyroid ultrasound ordered by Non-Specialists under the mincroscopr
Nazia Rahman*, Ruchi Trivedi, Anthony Firek, Iqbal Munir, Almira Yang, Riverside University Health System Internal Medicine, USA
Objective: Thyroid ultrasound (TUS) is a safe, low-cost, readily available imaging tool to discern thyroid tissue composition as part of the workup for thyroid nodules/ goiter, thyroid function, and thyroid cancer.
Previous studies, including ours, demonstrate overuse of TUS by primary care providers (PCP) without clear clinical or guideline based indications, leading to inappropriate TUS that are noncontributory to the initial clinical complaint. This may lead to unnecessary interventions and stress for patients presented with TUS results and identification of thyroid lesions may even lead to anchoring or confirmational bias in PCPs.
As a continuation of our initial QI project, our study collected additional patient cases with three aims: determine the clinical rationale for TUS ordering by PCPs, determine the contribution of TUS results in addressing initial clinical problems, and determine how TUS may impact patient outcomes.
Methods: This study is an observational retrospective study collecting data from outpatient US results (n = 612) over one year from patients evaluated by PCPs in outpatient clinics. We determined patient demographics, indication given for TUS, whether a physical exam was done, TUS-based intervention, and whether that intervention had clinically positive patient outcomes.
Results: TUS-appropriate categories included, nodule follow-up, incidentalomas, palpable lesions, and thyroid cancer (n = 50%). Inappropriate categories included abnormal thyroid laboratories, neck pain, voice changes, and dysphagia. The majority of inappropriate TUS did not contribute to the initial diagnosis. PCPs continued to order inappropriate TUS (n = 25%) leading to interventions, increased costs, and potential patient stress. Specifically, we found a high proportion of TUS ordered without appropriate clinical indications by current guidelines. The data shows a significant amount of patient follow-up that was unwarranted, in many cases, resulting in non-indicated FNAs.
Discussion/Conclusion: Our follow-up study documents that PCPs are continuing to inappropriately overorder TUS to an alarming degree causing distress and potentially unnecessary follow-up studies and increased costs, most commonly in initial clinical work up in primary care settings. Solutions include medical center-wide education programs and limiting TUS ordering by appropriate diagnostic pathway requirements. We are pursuing future studies on how inappropriate imaging may promote decision bias and how this affects patient mental health.
Poster 0605
Thyroid Imaging, Clinical, Poster
Taller-than-wide sonographic feature poorly discriminates benign and malignant follicular and oncocytic thyroid neoplasms
Caitlin Bell*, Bryan Haugen, Nikita Pozdeyev, University of Colorado Anschutz Medical Campus, USA
It is challenging to separate benign neoplastic lesions such as follicular and oncocytic adenomas from follicular (FTC) and oncocytic (OTC) cancers as the latter infrequently manifests suspicious ultrasound features such as microcalcification, irregular borders, or hypoechogenicity. Taller-than-wide (TTW) shape on ultrasound transverse view is considered a strong predictor of malignancy and contributes 3 points to the ACR TI-RADS risk score. We investigated if this feature is helpful in separating benign neoplasms from difficult-to-diagnose FTC, OTC, follicular variant of papillary thyroid cancer (FV-PTC), and non-invasive follicular lesion with papillary-like features (NIFTP).
All thyroid surgical pathology reports at a single quaternary referral center from 2008 to 2023 (n = 16,291) were reviewed to identify cases of follicular and oncocytic adenomas, FTC, OTC, FV-PTC, and NIFTP. We manually reviewed each ultrasound and recorded nodule dimensions as labeled by a clinical radiologist or ultrasound technician.
480 nodules were included in our study (193 follicular adenomas, 29 FTC, 124 FV-PTC, 90 oncocytic adenomas, 20 OTC, and 24 NIFTP). 28.3% of benign nodules were TTW compared to 33.5% of malignant nodules (c2, p = 0.26). Subgroup analysis shows that 25.4% of follicular adenomas were TTW compared to 20.7% of FTC, 36.3% of FV-PTC, and 12.5% of NIFTP. 31.1% of oncocytic adenomas were TTW compared to 50% of OTC.
The accuracy of TTW when used alone to predict malignancy for difficult-to-diagnose cancers was 0.56 (95% CI 0.52–0.61; p = 0.91). TTW feature had a sensitivity of 0.34, specificity of 0.72, and PPV of 0.45.
The taller-than-wide sonographic feature is seen in a significant proportion of both benign and malignant neoplasms. When used alone, it has low accuracy and low sensitivity for difficult-to-diagnose tumors such as FTC, OTC, FV-PTC, and NIFTP. The proportion of taller-than-wide nodules was not different between benign and malignant neoplasms. We conclude that this sonographic feature is an indicator of neoplastic growth (either benign or malignant) but it is not specific to cancer. More refined risk features, such as those derived from artificial intelligence/machine learning analysis of ultrasound images, are needed to distinguish benign and malignant thyroid neoplasms.
Poster 0606
Saturday, November 2, 2024
Poster 0607
Thyroid Cancer, Basic, Poster
Exploring the BRAF V600E mutation across the bethesda categories in thyroid nodules
Anette Gastelum Quiroz1,2, Andrea Ross Orozco1,2, Marco Alvarez Arrazola3,4, Sigfrido Miracle López5, Karla Morales Hernández2,6, Alejandra Martínez Camberos6, Noemí García Magallanes*1, 1Laboratorio de Biomedicina y Biología Molecular, Universidad Politécnica de Sinaloa, Mexico, 2Universidad Autonoma de Sinaloa, Mexico, 3Universidad Politécnica de Sinaloa, Mexico, 4Alvarez & Arrazola Radiologos, Mexico, 5Centro de Investigación en Ciencias de la Salud, Universidad Anahuac Mexico Norte, Mexico, 6Lic. en Ciencias Biomédicas, Universidad Autónoma de Occidente, Mexico
Papillary thyroid carcinoma (PTC) represents up to 90% of thyroid cancers, making the distinction between malignant and benign conditions a significant clinical challenge. Fine needle aspiration biopsy (FNAB) is recommended for assessing thyroid nodules suspected of malignancy based on ultrasound findings. The Bethesda system aids in the cytological categorization of these nodules to identify malignancy. However, approximately 30% of FNAB results fall into an indeterminate category, leading to unnecessary surgeries in about 75% of these cases. The BRAF c.1799T>A (V600E) mutation, the most common mutation in PTC, is linked to the activation of the MAPK pathway, which drives carcinogenesis. This mutation is increasingly being recognized as a potential prognostic marker in PTC.
Objective: To evaluate the presence of the BRAFV600E mutation in thyroid nodules and assess its behavior across the different Bethesda system categories.
Methods. Samples of suspicious thyroid nodules detected by ultrasound were obtained via FNAB by a radiologist. The cytological diagnosis was performed by a pathologist, and the results were reported using the Bethesda System. The molecular analysis of the mutation was conducted using qPCR with allele-specific probes.
Results. A total of n = 114 thyroid tissue specimens were analyzed, with n = 47 corresponding to patients with papillary thyroid cancer, n = 49 were patients with benign thyroid neoplasms, and n = 18 with an indeterminate cytological diagnosis. According to the Bethesda classification, n = 49 were classified in category II, n = 18 in category IV, n = 8 in category V, and n = 39 in category VI. Among the cancer patients, 59.6% were carriers of the BRAF V600E mutation (TT, n = 19; TA, n = 16; AA, n = 12), while all patients with benign neoplasms and indeterminate diagnoses were non-carriers (X2 = 52.91, p < 0.001). Among the mutation carriers, n = 24 were classified as Bethesda VI (TA, n = 13; AA, n = 11) and n = 4 as Bethesda V (TA, n = 3; AA, n = 1) (X2 = 53.38, p < 0.001).
Discussion/Conclusion. The analysis of the BRAF V600E mutation in thyroid nodules reveals a clear association with the higher Bethesda system categories, particularly in samples classified as Bethesda V and VI. This mutation, present in a significant percentage of papillary thyroid cancer cases, could serve as an important molecular marker for diagnosis and clinical decision-making in patients with thyroid nodules.
Poster 0608
Thyroid Cancer, Clinical, Poster
High-Grade follicular Cell-Derived Non-Anaplastic thyroid carcinoma stratified by extent of invasion and mutation profile
Daniel Scholfield*, Bin Xu, Helena Levyn, Alana Eagan, Ashok Shaha, Jatin Shah, R Tuttle, James Fagin, Richard Wong, Snehal Patel, Ronald Ghossein, Ian Ganly,Memorial Sloan Kettering Cancer Center, USA
The 2022 World Health Organisation Classification of Thyroid Neoplasms (5th Edition) introduced the term high grade follicular cell-derived non-anaplastic thyroid carcinoma (HGFCTC) to define patients with an invasive non-anaplastic thyroid carcinoma with high grade features, including both poorly differentiated thyroid carcinoma and high grade differentiated thyroid carcinoma. Our objectives were to describe the clinicopathological characteristics, oncologic outcomes and mutation profiles of HGFCTC subgroups.
A cohort of 252 patients who had surgery for HGFCTC and its related entity encapsulated carcinoma with high grade features non-invasive between 1986–2020 were identified and categorized into 5 subgroups: A) Encapsulated non-invasive B) Encapsulated with capsular invasion only (minimally invasive) C) Encapsulated angioinvasive with focal vascular invasion (VI) D) Encapsulated angioinvasive with extensive VI and E) Infiltrative tumors. DNA from tumor and matched normal tissue specimens was available for 117/252 patients. Next Generation Sequencing was undertaken and the mutation profiles of each subgroup compared.
Patients with infiltrative tumors comprised 50% of the cohort, followed by encapsulated angioinvasive (33%) and encapsulated non-invasive/minimally invasive (18%). No patients with encapsulated non-invasive or minimally invasive disease had regional or distant metastases at presentation. Patients with infiltrative tumors were more likely to present with advanced T- N- and M-stage (p ≤0.003). 5-year disease specific survival (DSS) was poorer in patients with infiltrative disease (67.7%) compared to encapsulated angioinvasive extensive VI (88.1), focal VI (90.4%) and encapsulated non-invasive / minimally invasive (100%) (p = 0.0002). Subgroup analysis showed the infiltrative subgroup was mainly BRAFV600E driven, the encapsulated angioinvasive and minimally invasive subgroups were NRAS driven, and the encapsulated non-invasive subgroup was DICER1 driven. Patients with encapsulated non-invasive disease were managed mainly with thyroid lobectomy and did not receive RAI treatment. Of the other subgroups treated with RAI due to distant metastases at presentation, between 60 and 77% of patients demonstrated RAI uptake in at least one metastatic focus.
HGFCTC comprises different subgroups which have different clinical behaviour determined by the extent of vascular invasion and degree of infiltration. Excellent recurrence and survival outcomes occur in encapsulated non-invasive and minimally invasive subgroups compared to patients with infiltrative tumors, and each subgroup has a distinct genomic profile.
Poster 0609
Thyroid Cancer, Basic, Poster
DUAL TARGETING OF THE PI3K/AKT/mTOR and MAPK PATHWAYS IN BRAF V600E MUTANT ANAPLASTIC THYROID CANCER
FNU TEJINDER PAL*, Chandrayee Ghosh, Jiangnan Hu, Zhongyue Yang, Electron Kebebew, Stanford University, USA
Poster 0610
Thyroid Cancer, Clinical, Poster
Optimal timing for surgery in papillary thyroid cancer: Insights from a Meta-Analysis
Camilo Gonzalez-Velazquez*1,2, Andres Avalos-Bishop1, Rene Rodriguez-Gutierrez1,3, Mariana Elizondo-Alatorre1,3, Maximiliano Heredia-Martínez1,3, Dulce Manzanares-Gallegos1,3, Luis Gutiérrez-Dávila1,3, 1Universidad Autónoma de Nuevo León, Mexico, 2THANC Foundation, USA, 3KER Unit Mexico, Mexico
This study aims to evaluate the impact of the interval between diagnosis and surgical intervention on survival outcomes in patients with papillary thyroid cancer.
We conducted a systematic review of cohort studies and randomized controlled trials from databases up to May 2024, focusing on the timing of surgical intervention for differentiated thyroid cancer. The primary endpoint analyzed was overall survival.
Out of 849 screened studies, 4 observational studies with a total of 111,982 participants (follow-up range: 3.8–12.5 years) were included in the meta-analysis. Pooled hazard ratios (HRs) for surgical delay were calculated for intervals of 0–90 days, 91–180 days, and >180 days post-diagnosis. The HR for the 0–90 day interval was set as the reference (HR = 1.0). Delaying surgery to 91–180 days showed no significant impact on survival (HR = 1.17, 95% CI: 0.95–1.45). Delays beyond 180 days were associated with a significantly increased risk of mortality (HR = 1.56, 95% CI: 1.01–2.42). Specifically, for T4 stage patients, delays of 91–180 days did not significantly alter mortality risk (HR = 0.98, 95% CI: 0.72–1.33), while delays over 180 days showed a potential reduction in mortality (HR = 0.49, 95% CI: 0.24–1.00).
While surgery within 90 days of diagnosis remains the standard practice, our findings indicate that extending the surgical window up to 180 days does not compromise patient survival. Importantly, for patients with advanced T4 stage papillary thyroid cancer, delays beyond 180 days may actually reduce mortality. This suggests that in such advanced cases, the course of disease may already be largely determined, and survival is less dependent on the immediacy of surgical intervention. These results underscore the potential benefits of an individualized treatment approach, where alternative treatment modalities may offer more significant benefits than the timing of surgery itself. The lack of granular data on specific reasons for surgical delays limits our understanding of these dynamics, highlighting a need for further research to explore the implications of these findings and to refine guidelines for surgical timing, particularly in the context of advanced disease stages.
Poster 0611
Thyroid Cancer, Clinical, Poster
Comparative effectiveness of lobectomy vs. Total thyroidectomy in Intermediate-Risk Well-Differentiated thyroid carcinoma
Camilo Gonzalez-Velazquez*1,2, Mark Urken1,3, Rene Rodriguez-Gutierrez2,4, Juan Brito5, Eyal Robenshtock6, Patricia Castillo-Morales2,4, Mariano Garcia-Campa2,4, Fernanda Garcia-Garcia2,4, Daniela Gonzalez-Cruz2,4, Andres Avalos-Bishop2,4, Linda Hernandez-Soto2, 1THANC Foundation, USA, 2Universidad Autonoma de Nuevo Leòn, Mexico, 3Mount Sinai Hospiat, USA, 4KER Unit Mexico, Mexico, 5Mayo Clinic, USA, 6Rabin Medical Center, Israel
Objective:
This study evaluates the comparative effectiveness of lobectomy versus total thyroidectomy in intermediate-risk well-differentiated thyroid carcinoma, aiming to determine if lobectomy could be a viable alternative for carefully selected patients, similar to its use in low-risk thyroid cancer.
Methods:
A systematic review and meta-analysis followed a pre-registered protocol. Patients were classified as intermediate-risk per the 2015 ATA guidelines, including criteria such as microscopic invasion into perithyroidal soft tissues, aggressive histology, PTC with vascular invasion, and clinical/pathological N1. Data from MEDLINE were extracted and synthesized by KER Unit México. Primary outcomes were overall survival, disease-specific survival, and disease-free survival.
The search identified 3,275 records, reduced to 3,246 after duplicates. After screening, 2,192 records were excluded. Full-text assessment of 1,054 articles led to 1,025 exclusions due to reasons like study design, non-ATA 2015 criteria, and insufficient follow-up. Finally, 29 studies were synthesized.
Results:
Preliminary analysis suggests lobectomy offers comparable overall and disease-specific survival rates to total thyroidectomy in intermediate-risk patients, with lower surgical complications and adverse events. Meta-analysis of recurrence-free survival showed no significant difference between lobectomy and total thyroidectomy, with a combined hazard ratio of 1.00 (95% CI: 0.78 to 1.28), indicating similar effectiveness in preventing recurrence.
Discussion/Conclusion:
Lobectomy may be a feasible alternative to total thyroidectomy for intermediate-risk well-differentiated thyroid carcinoma, potentially reducing surgical morbidity without compromising survival outcomes. Further research and data synthesis are needed to confirm these findings and refine patient selection criteria, highlighting the importance of personalized surgical approaches in thyroid cancer management.
Poster 0612
Thyroid Cancer, Clinical, Poster
Fusion-Driven anaplastic thyroid cancer (ATC): characterization and clinical outcomes
Duaa Abdallah*1,2, Sarah Hamidi2, Ramona Dadu2, Naifa Busaidy2, Priyanka Iyer2, Stephen Waguespack2, Mark Zafereo2, Maria Cabanillas2, 1Baylor College of Medicine, USA, 2The University of Texas MD Anderson Cancer Center, USA
Poster 0613
Thyroid Cancer, Clinical, Poster
Oral health and salivary production in patients with differentiated thyroid carcinoma after radioiodine therapy
Jorge Terrazas1, Clarissa Marins2, Júlia Esteves1, Lígia Assumpção2, Denise Zantut-Wittmann*2, 1School of Medical Sciences, Pontifical Catholic University of Campinas, Brazil, 2Endocrinology Division, Department of Internal Medicine, School of Medical Sciences, University of Campinas, Brazil
Radioiodine therapy is often required after thyroidectomy for the treatment of cervical thyroid remnants and metastases from Differentiated Thyroid Carcinoma (DTC). Around 25% of the administered I131 activity is eliminated in saliva, which can compromise salivary glands, causing discomfort due to xerostomia and compromising oral health.
Objectives: To evaluate the characteristics related to oral health and salivary production in patients with DTC after radioiodine therapy (RIT).
Methods: Prospective, cross-sectional study, which included patients with DTC after ablative and/or adjuvant RIT followed in a tertiary service. Patients underwent assessment of oral health conditions (gingival index, plaque index, decayed, missing and filled teeth), subjective assessment of xerostomia and measurement of salivary flow. Salivary glands were assessed by cervical ultrasound at the time of clinical evaluation.
Results: 67 patients with DTC were included. Oral health was found as very good or good in 60% of patients, 84% had no dental plaque or a slight amount, and 53% had normal-looking gums. There was a negative correlation between the amount of saliva produced in 5 minutes and salivary flow with the activity of radioactive iodine administered at the ablative dose, the number of RITs received, and total activity of radioiodine administered until oral assessment. Greater parotid gland volume on ultrasound was associated with greater total saliva volume in 5 minutes. Reduction in parotid gland volume on ultrasound was associated with longer follow-up time, greater number of times receiving radioiodine therapy, longer time between RIT and patient assessment, greater 131I activity administered.
Conclusion: Good or very good oral health was observed in 60% of patients with DTC after RIT, 15% reported hyposalivation and 13%, frequent xerostomia. The reduction in the volume of the parotid gland on ultrasound was evidenced as a predictive factor for the reduction in saliva volume in these patients, while a greater number and greater total activity of radioiodine administered and heterogeneous texture of the parotid gland on ultrasound were shown to be factors associated with this condition.
Poster 0614
Thyroid Cancer, Clinical, Poster
The evaluation of nutritional status on vitamin D and the effect of supplemental therapy on bones in young DTC patients
Lu Ying*, Li Yi, Peking Union Medical College Hospital, China
Poster 0615
Thyroid Cancer, Clinical, Poster
Pre-lobectomy TSH in thyroid cancer as a predictor of post-operative thyroid hormone supplementation
Jorgelina Guerra*, María Romo Manzini, Ana Voogd, Alejandro Begueri, Pedro Valdez, Gerardo Russier, María Matsuda, María Anselmi, Silvana Posadas, Pablo Brenzoni, Javier Guerrieri, Irene Copati, Federico Piñero Fernandez Casares, Pedro Saco, María del Carmen Negueruela, Hospital Universitario Austral, Argentina
Background: Hemithyroidectomy (HT) has already become the most preferred surgical approach for patients with low-risk differentiated thyroid cancer (low-risk DTC). Our primary goal was to correlate the pre-operative (pre-op) thyroid-stimulating hormone (TSH) with the post-operative (post-op) TSH and levothyroxine (LT4) supplementation after thyroid lobectomy (TL), in order to identify those patients who may not require hormonal replacement.
Methods: We prospectively enrolled 114 patients with differentiated thyroid carcinoma (DTC) who underwent TL based on inclusion and exclusion criteria from 2015 to 2023 at a single institution. Post-op TSH was measure regularly, and patients were prescribed LT4 if the TSH was >2.0 µUI/ml at the third-month evaluation according ATA guidelines recommendation. A multiple linear regression model was conducted to determine variables associated with post-op TSH elevation following TL. To find the pre surgical TSH cut-off point, post-op TSH levels were categorized as either <2 or >= 2 and a multiple logistic regression model was carried out. Model performance and AUC were calculated, and the optimal cut-off point was selected using the Youden method.
Results: Of 79 patients, age, sex, the presence of thyroiditis and the volume of the remaining lobe were not found to be associated with elevated post-surgical TSH. Pre-op TSH was the only variable that remained significant in the ANOVA model. For every 1 μIU/ml that pre-surgical TSH increases, post-op TSH increases by 0.87 μIU/ml (95% CI 0.72–1.02 μIU/ml, p value <0.0001). Overall, the TSH AUROC was 0.816 (95% CI: 0.6247–1), and threshold was found between 1.29 and 1.73 μIU/ml and with 71 % sensitivity and 86% specificity for pre-op TSH.
Conclusion: To be compliant with the ATA guidelines, 45 patients (57 %) were prescribed with LT4. The pre-op TSH emerged as an independently significant variable for predicting post-op TSH levels greater than 2 μIU/ml following TL. Age, sex, the presence of thyroiditis and the volume of the remaining lobe were not found to be associated with elevated TSH.
Poster 0616
Thyroid Cancer, Clinical, Poster
Neck ultrasonography may not be cost effective for the long term follow up of most oncocytic thyroid cancer cases
Solangel Suarez*1,2, Emily Sanchez3,2, John Sinard2, Sachin Majumdar2, 1Griffin Hospital, USA, 2Yale School of Medicine, USA, 3Albany Medical College, USA
Objective: To assess the utility and cost effectiveness of postoperative neck ultrasound for the follow up of Oncocytic carcinoma of the thyroid.
Methods: A retrospective study of surgically treated Oncocytic thyroid cancer at our institution between 1/2014–2/2024 using pathology and electronic medical records. The study was approved by our institutional IRB. Current Procedural Terminology (CPT) codes were used for procedural charge estimates (current US dollars). Neck ultrasound 453.82 USD (CPT 76536) and lymph node aspiration 2,697.00 USD (CPT10005). Calculations performed with Excel and GraphPad Prism 9.5.1.
Results: 82 cases of Oncocytic thyroid cancer were identified between April 2014 and February 2024. Sixty five percent were female and 35% male, mean age 58.7 ± 16 years, BMI 30.4 ± 5.9 kg/m2, 73.2% White, 12.2% Black, 9.8% Hispanic, 2.4% Asian and 2.4% self-described as other. Thirty-four patients (41.5%) had lymph nodes resected and four had lymph node involvement (5% of total), and overall, 2.4% had distant metastases. Follow up data were available for 69 patients (84%) and 60 (73%) had at least one postoperative ultrasound. Median follow up was 25 months (IQR 11.5–56, range <1 to 112 months). Of 185 neck ultrasounds, 87% were benign, 23% had suspicious findings, 5% resulted in biopsy, and 1.1% (2) revealed cancer. Those with positive findings had lymph node involvement at the time of surgery. Of the other two with positive nodes at surgery one had negative neck ultrasound afterwards and the other had distant metastases followed by alternative means. Total neck ultrasound costs were $83,957, and lymph node aspiration costs were $23,736. The cost per cancer identified on neck ultrasound was $41,978 USD and $11,868 USD for cancer identified on fine needle aspiration.
Conclusion: In this study, routine postoperative neck ultrasound was only helpful in identifying lymph node metastases in those who already had N1 disease at the time of diagnosis but otherwise did not appear helpful or cost effective. Since N1 disease is typically less common in oncocytic thyroid cancer, routine neck ultrasound may only be appropriate for select patients during long term follow up.
Poster 0617
Thyroid Cancer, Clinical, Poster
Guidelines review and comparison of clinical concerns in ultrasound-guided biopsy of thyroid nodules and cervical lymph nodes
Huilin Li*1,2, Jiaojiao Ma1,3,2, Tongtong Zhou4,3,2, Shaohang Zhang1,3, Jing Zhai1,3, Bo Zhang1,3,2, 1Department of Ultrasound, China-Japan Friendship Hospital, China, 2Chinese Academy of Medical Sciences & Peking Union Medical College, China, 3National Center for Respiratory Medicine; State Key Laboratory of Respiratory Health and Multimorbidity; National Clinical Research Center for Respiratory Diseases; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences; Center of Respiratory Medicine, China-Japan Friendship Hospital, China, 4Chinese Department of Ultrasound, China-Japan Friendship Hospital, China
The incidence of thyroid cancer continues to rise globally. Ultrasound-guided biopsy of thyroid nodule and cervical lymph nodes are crucial components of clinical management. From 2016 to 2024, various associations have released and updated guidelines and consensus statements. However, controversies persist in five key areas: indications and contraindications for thyroid nodule biopsy, the choice between core needle and fine needle biopsy for thyroid, complications and management of thyroid nodule and cervical lymph node biopsy, indications for molecular testing, and the use of thyroglobulin washout in cervical lymph node biopsy. This article compares major domestic and international guidelines based on the latest literature, discussing these key issues to provide evidence-based support for the standardized management of thyroid nodules and thyroid cancer.
Poster 0618
Thyroid Cancer, Clinical, Poster
The impact of American thyroid association guidelines in diagnosis and treatment of thyroid cancer patients in China
Chi Fong Kong*1, Xiao Yi Li2, 1Chinese Academy of Medical Sciences and Peking Union Medical College, China, 2Peking Union Medical College Hospital, China
Poster 0619
Thyroid Cancer, Clinical, Poster
A review of thyroid cancers trends and insights: 10-year single center retrospective study in CEDIMAT, Dominican Republic
Enrique Capellan*1, Sebastien Strachan1, Adalberto Gonzalez2, Larissa Lembert2, Julia Rodriguez1, Sylvia Batista1, 1CEDIMAT, Dominican Republic, 2immunopath, Dominican Republic
Poster 0620
Thyroid Cancer, Clinical, Poster
Determinants of Disease-Specific mortality of thyroid cancer distant metastases
Ali Howaidi1,2, Anwar Alswailem2, Abdulrahman Hakami2, Afnan Hadadi2, Deema Alturki2, Fayha Abothenain2, Lulu Alobaid2, Najla Ewain3, Avaniyapuram Murugan2,2,2, Ali Alzahrani*2, 1King Fahad Medical City, Saudi Arabia, 2King Faisal Specialist Hospital & Research Centre, Saudi Arabia, 3King Abdulaziz Medical City, Saudi Arabia
Distant metastases (DM) are the major cause of death in patients with thyroid cancer (TC). The objective of this work was to study factors predictive of DM-associated mortality.
We searched our institution’s tumor registry for TC patients (pts) with DM during the period 2005–2020. We identified 154 pts. We excluded pts with anaplastic TC, medullary TC, and cases with short follow-up or inadequate data. The remaining 86 patients with DM were studied. These include 57 females (66.3%), and 29 males (33.7%) with a median age of 53.5 years (IQR 45–65). Pts underwent partial (4 pts) or total thyroidectomy (82 pts). Central (16 pts) and/or lateral (42 pts) lymph node dissections (LND) were done in 58 pts and were positive for LN metastases in 44 pts. I-131 ablation/therapy was administered initially to 81 pts. The tumor types include 31 classical PTC, 15 follicular variant, 5 tall cell, 5 columnar, 2 diffuse sclerosing, 1 cribriform morular and 1 Hobnail subtypes of PTC subtypes, 12 widely invasive FTC, 4 oncocytic, and 10 PDTC.
Lung metastases were the most common, isolated in 32 pts (37.2%) or with DM in other organs in 47 pts (54.6%). Skeletal metastases occurred in 50 pts (58.1%), isolated in 5 pts (5.8%), and with DM in other sites in 45 pts (52.3%). Brain metastases occurred in 8 pts (9.3%), all with DM in other organs. Multiple-site DM occurred in 49 pts (58%) The management of DM included additional surgeries surgery, RAI, external beam radiotherapy, and multi-kinase inhibitors (TKI).
Over a median follow-up of 84 months (IQR 35.5–118) for the whole cohort, 47 pts succumb to their disease (disease-specific mortality 54.7%). The median time from the initial diagnosis to death was 47 months (IQR 16–84). Factors associated with mortality were age (p = 0.001) and bone metastases (p < 0.0001). These factors remained significant in multivariate logistic regression and Cox Proportional Hazards ratio analyses [for age, p < 0.009, Hazard ratio 1.030 (95% CI 1.007–1.053) and for bone metastases, p < 0.017, HR 2.58 (95% CI 1.19–5.6)]. Sex, time of DM, and use of TKI (used in 25 pts) did not predict mortality. Similarly, BRAF V600E, TERT promoter mutations, or both did not predict mortality but this might be due to the small number of samples tested (41 pts).
DMs from DTC are associated with ∼ 55% mortality and a median survival of ∼ 4 years. Mortality is associated with age and skeletal metastases.
Poster 0621
Thyroid Cancer, Clinical, Poster
Implementing prompt care for patients with anaplastic thyroid cancer: an ongoing challenge
Ilaria Giordani*1, Valerie Cristina2, Aurélie Forget-Renaud1,3, Peter Kopp1, 1Division of Endocrinology, Diabetes and Metabolism, University Hospital of Lausanne and University of Lausanne, Switzerland, 2Department of Medical Oncology, University Hospital of Lausanne and University of Lausanne, Switzerland, 3Division of Endocrinology and Metabolism, McGill University, Montreal University Hospital Center, Canada
Objective: Anaplastic Thyroid Carcinoma (ATC) is a rare but aggressive form of thyroid cancer of follicular origin. ATC often presents with locally advanced and/or metastatic disease, and it accounts for approximately half of thyroid cancer-related deaths. The advent of novel treatment strategies for ATC harboring the BRAF V600E mutation with BRAF/MEK inhibitors, sometimes combined with immunotherapy, has led to recent improvements in outcomes. A rapid diagnosis and implementation of a structured therapy by experienced teams is essential to improve the otherwise dismal outcomes in patients with ATC.
Methods: We analyzed a cohort of patients with ATC referred to the University Hospital of Lausanne, Switzerland, between 2013 to 2023, to assess patient characteristics, time to initial diagnosis, initiation of therapy, and outcomes.
Results: 11 patients (5 males and 6 females) were included. Three patients were excluded because an anaplastic component was identified at a later time point in patients initially diagnosed with well-differentiated thyroid cancer. Mean age at diagnosis was 65.5 years (range 31.7–84.4 years). BRAF status was determined in 9/11 patients at initial diagnosis, and it was positive in 4/9 patients (44.4%). The mean time from seeking medical care to establishing the diagnosis of ATC was 29.9 days (range 3 to 69 days). The mean time from an established diagnosis to first treatment was 21 days (range 12 to 41 days). Treatment with dabrafenib/trametinib was the initial treatment of 3/4 patients with a documented BRAF V600E mutation. The fourth patient had an advanced disease and died the day following the biopsy.
The delay in establishing the diagnosis and initiating prompt therapy for patients with ATC indicate that many clinicians are still not aware of the medical urgency if ATC needs to be considered in the differential diagnosis.
Conclusions: Although the mean age of patients presenting with ATC is 65 years, it can even occur in younger patients (in this case series at age 31.7 years). There is an urgent need to better train physicians about the urgency in establishing the diagnosis, perform BRAF testing, and initiate therapy. Moreover, it is imperative to decrease the time in referring ATC patients to experienced multidisciplinary teams in tertiary centers.
Poster 0622
Thyroid Cancer, Clinical, Poster
A retrospective study of Co-existing thyroid carcinoma and sarcoma
Aditya Chauhan*, Lynn Burmeister, University of Minnesota Medical School, USA
Objective:
Literature on coexisting sarcoma and thyroid carcinoma is scarce. Our aim was to identify which subtypes of sarcoma and thyroid carcinoma were associated, which was diagnosed first, the presentation of thyroid cancer in this scenario, and differences in thyroid cancer behavior or outcomes in this cohort.
Methods:
Retrospective chart review was conducted of patients with coexisting thyroid carcinoma and sarcoma at a University tertiary referral center. Demographics, histological subtypes, treatments, and outcomes were recorded.
Results:
Twenty-three cases were identified, 57% (13/23) male and 43% (10/23) female. Mean age at diagnosis of thyroid cancer was 47 years and of sarcoma 48 years. Fourteen types of sarcoma were found with undifferentiated pleomorphic sarcoma most common in 22% (5/23). All thyroid cancers were papillary carcinoma, including multifocal in 6 (27%); 70% (16/23) classical, 26% (6/23) follicular variant, and 13% (3/23) tall cell variant. Eight patients (36%) had a third malignancy, 13.% (3/23) died, with 33% (1 of 3) deaths attributable to thyroid cancer. Sarcoma diagnosis was first in 57% (13/23) and thyroid cancer diagnosis was first in 43% (10/23). Of the 13 with sarcoma diagnosis first, 69% were male, 85% (11/13) were diagnosed with thyroid cancer within 2 years, including 61% (8/13) diagnosed within 6 months, and 80% (10/13) of the thyroid cancers were incidentally found on CT or PET scan. Thyroid cancer tumor size was 2.2 +/- 1.6 cm. Of the 10 with thyroid cancer diagnosis first, 60% were female, sarcoma diagnosis was 7.5 +/- 4.6 years after the thyroid cancer diagnosis at mean age of 56 years, and 50% had a third malignancy. Thyroid cancer tumor size was 1.7 +/- 1.7 cm.
Discussion/Conclusion:
Differentiated thyroid carcinoma and sarcoma represent two distinct groups of tumors, with the former being of epithelial origin and the latter of mesenchymal origin. We describe 23 patients with coexisting sarcoma and papillary thyroid carcinoma (PTC). Co existence could be due to common risk factors or mechanisms, the impact of one tumor diagnostic test or treatment on the other. Further research is warranted.
Poster 0623
Thyroid Cancer, Translational, Poster
DNA and RNA comprehensive genomic profiling are complementary for detection of clinically relevant fusions in papillary thyroid carcinoma
Samantha Diamond-Rossi*1, Richard Huang2, Rachel Keller-Evans2, 1Inova Schar Cancer Institute, USA, 2Foundation Medicine, Inc., USA
Poster 0624
Thyroid Cancer, Translational, Poster
scRNA validated the presence of double negative T cell as a heterogenous T cell population present in thyroid cancer microenvironment and predicted as an immunogenomic marker for thyroid cancer
Shafiya Imtiaz Rafiqi*1, Rodis Paparodis2,3, Juan Jaume2, Shahnawaz Imam1, 1University of Toledo, USA, 2Loyola University Chicago, Stritch School of Medicine/Edward Hines, Jr. VA Hospital, Hines, USA, 34Hellenic Endocrine Network, Greece
Thyroid cancer is predicted to become the fourth most common cancer in women by 2030. Approximately 600,000 fine needle aspirations (FNA) are performed annually in the US, and almost 1/5th (⁓120,000 nodules) carry features consistent with atypia of undetermined significance, are suspicious for follicular neoplasms/ thyroid malignancy. Only 15–30% of thyroid nodules with indeterminate diagnosis are diagnosed malignant, rendering the majority (∼70%) of thyroid gland removal surgeries unnecessary. Therefore, it becomes imperative to identify thyroid cancer diagnostic strategies, which could enhance our predictive capabilities and reduce the number of unnecessary thyroidectomies.
The present study is based on leveraging the use of double negative (DN) T-cells as an immunogenomic marker for the diagnosis of thyroid cancer. DN T-cells are a subset of CD3+CD4-CD8-CD56- cells having αβ/γδ TCR. Patients with DN T-cell proportion >9.14%, are at higher risk of developing thyroid cancers (1). DN T-cells need to be investigated to decipher what transcriptomic changes make them highly proliferative in the cancer microenvironment.
DN T-cells are comprised of a rare but heterogeneous T-cell subset with molecular diversity and possible individual functional subsets often overlooked in scRNA sequencing of tumor tissues. Currently there are no known transcription signatures, which readily allow to better discriminate DN T-cells. scRNA analysis of PTC dichotomizing T-cells into 2 clusters based on CD4 and CD8 expression. Okamura et al, 2024 illustrated significantly enriched DN T-cell population in the tumor infiltrates of colorectal cancers which showed similar phenotype to central memory CD8+ T-cells, it is highly likely that clustering of T-cells into CD4 and CD8 overlooked the significant presence of DN T-cells in the PTC. Two unique populations of DN T-cells within hepatocellular carcinoma, reiterating the need for strict gating and clustering of T-cells in scRNA analysis. DN T-cells were also found in malignant pleural effusions in lung cancer and seemed to be positively correlated with tumor metastasis in melanoma. To negate this clustering bias, we are the first group to aim scRNA sequencing of sorted DN T-cells from FNA of thyroid samples. DN T-cells showed lower expression of effector or activation marker genes, including GZMB, PD-1 and TNFRSF9 (CD137) as well as exhaustion markers (LAG3 and CXCL13) than CD8+ T-cells, and having a higher expression level of naïve or memory marker genes (IL7R, SELL and TCF7). DN T-cells also had a low expression of PFR1 and GZB but had a higher FasL. Most distinctly, DN T-cells express GZMK.
Poster 0625
Thyroid Cancer, Translational, Poster
Reprogramming of tumor immune microenvironment (TIM) in thyroid cancer as a new therapeutic strategy for thyroid cancer immunotherapy
Shafiya Imtiaz Rafiqi*1, Rodis Paparodis2,3, Juan Jaume3, Shahnawaz Imam4, 1University of Toledo, USA, 2Hellenic Endocrine Network, Greece, 3Loyola University, USA, 4University of Toledo, USA
Poster 0626
Thyroid Cancer, Clinical, Poster
Redifferentiation therapy (RDT) in differentiated thyroid carcinomas (DTC): Real-World data of a large cohort of patients
Helton Ramos*1,2,3, Sarah Hamidi1, Silvana Faria4, Ramona Dadu1, Mimi Hu1, Naifa Busaidy1, Steven Waguespack1, Steven Weitzman1, Steven Sherman1, Maria Cabanillas1, 1Department of Endocrine Neoplasia & Hormonal Disorders, The University of Texas MD Anderson Cancer Center, USA, 2Federal University of Bahia, Brazil, 3A.C. Camargo Cancer Center, Brazil, 4Department of Abdominal Radiology, Division of Diagnostic Imaging, MD Anderson Cancer Center, Houston, TX, United State., USA