bluuebunny/crossref_metadata_2025_split huggingface dataset:
ODP529 Update on the Prevalence and Pathogenesis of Central Hypothyroidism
Authors: Heshmati Hassan M , Fatourechi Vahab 
Published: November 2022

Abstract

Background
Central hypothyroidism (CH) is a rare form of hypothyroidism characterized by insufficient stimulation of a normal thyroid gland by the thyroid-stimulating hormone (TSH). It can be of pituitary origin (secondary hypothyroidism) or hypothalamic origin (tertiary hypothyroidism). The diagnosis is suspected by the finding of low serum free thyroxine associated with low, normal, or slightly elevated serum TSH, in the absence of goiter. This review presents an update on the prevalence and pathogenesis of different types of CH.

Methods
A systematic search of literature was conducted using the search terms hypothyroidism, central hypothyroidism, congenital central hypothyroidism, acquired central hypothyroidism, TSH deficiency, prevalence, and pathogenesis.

Results
The prevalence of overt hypothyroidism in the US population is at least 0.3% and the prevalence of subclinical hypothyroidism ranges from 4% to 10%. Primary hypothyroidism is more prevalent in females. The prevalence of CH ranges from 1: 13,000 to 1: 120,000. CH is observed in less than 1% of hypothyroid subjects, with no evidence of sex predominance. Itcan occur prenatally (congenital CH) or after birth (acquired CH). Congenital CH, which is a rare cause of CH (prevalence around 1: 13,000), may result from genetic/malformative causes [e. g., pituitary-specific transcription factor defects, TSH-beta subunit gene mutations, isolated TSH-releasing hormone (TRH) deficiency, TRH receptor gene mutation, immunoglobulin superfamily member 1 deficiency, De Morsier syndrome, Prader Willi syndrome]. In 60% of the cases, congenital CH is associated with other pituitary hormone deficiencies and in 40% of the cases, congenital CH is due to isolated TSH deficiency. Acquired CH, which is the most common cause of CH andusually associated with other pituitary hormone deficiencies, results from the destruction or inhibition of the pituitary and/or hypothalamus. In decreasing order of frequency, acquired CH can be secondary to invasive and/or compressive lesions (e. g., pituitary macroadenomas, craniopharyngiomas, pituitary metastases, carotid aneurysm), iatrogenic factors (e. g., surgery or irradiation, glucocorticoids, dopaminergic drugs, somatostatin analogs, immune checkpoint inhibitors), trauma (e. g., brain injury), vascular causes (e. g., pituitary apoplexy, postpartum pituitary necrosis, hemorrhage), autoimmunity (e. g., lymphocytic hypophysitis), infiltrative lesions (e. g., hemochromatosis, sarcoidosis), and infections (e. g., tuberculosis, syphilis).

Conclusion
CH is a rare cause of hypothyroidism resulting from a variety of congenital or acquired causes. Acquired CH is the most common cause of CH. In many cases, both congenital and acquired CH are associated with multiple pituitary hormone deficiencies. Isolated TSH deficiency is rare and usually of congenital origin.
Presentation: No date and time listed
ODP530 When "Taller-Than-Wide" Is Not Taller-Than-Wide
Authors: Khan Anum , Paduri Swetha , Elahi Amna , Patel Sabah , Anbari Raghda A , Veeramachaneni Ravali , Siddiqui Mahwash , Carvajal Karen , Shrestha Isha , Barsano Charles 
Published: November 2022

Abstract
The thyroid nodule ultrasonic characteristic referred to as "Taller-than-Wide" (TtW) is defined as a nodule's anterior-posterior diameter/left-right diameter ratio (i. e. AP/LR ratio) on transverse view. This characteristic is regarded as a major feature suggesting malignancy. On the Amer College of Radiology's TIRADS ("Thyroid Imaging Reporting and Data System") guidelines, TtW status usually indicates the need for an aspiration biopsy (FNA). Given this importance, and the subjective and technical limitations of ultrasonic linear measurements of nodule diameters, it would be prudent to be aware of the probabilities that an AP/LR ratio may be under-estimated or over-estimated, potentially causing a false-negative or false-positive TtW interpretation, respectively. To assess these probabilities two approaches were taken. Eight observers were trained how to carefully measure the AP and LR diameters of thyroid nodules by ultrasound. The observers measured these diameters on the same transverse image from each of 34 benign thyroid nodules without knowledge of the measurements obtained by other observers. Thus, 272 independently obtained, rank-ordered individual AP/LR ratios (34 nodules×8 observations each) were plotted on the y-axis against themean AP/LR for each nodule (34mean AP/LRs, regarded as the consensus "true" AP/LRs for the corresponding nodule). By Spearman's rank correlation method, variations in individual AP/LR ratios (i. e., the individualAP/LR ratios minus their correspondingmean AP/LR ratios) were plotted on the x-axis as a function of their rank-ordered fraction of the total population on the y-axis. By this method, the top 20% ofindividual AP/LR ratios were 0. 075 to 0.550 greater than their correspondingmean AP/LRs. The bottom 20% ofindividual AP/LR ratios were 0. 085 to 0.300 lower than their correspondingmean AP/LR ratios. To determine the clinical significance of these variations, theindividual AP/LR rations of the 34 nodules were plotted on the y-axis as a function of their correspondingmean AP/LR ratios. Of the 28 nodules whosemean AP/LR ratios were &lt;1, 31 (13.8%) of the 224 associated individual AP/LR ratios (28×8) were read as &gt;1 (False Pos TtW status). Of the 6 nodules whosemean AP/LR ratios were &gt;1, 6 (12.5%) of their 48individualAP/LR ratios (6×8) were read as &lt;1 (False Neg TtW status). In conclusion, although interpretive deviations in the AP/LR ratio are common and frequently large, their clinical consequences in terms of generating false positive and false negative attributions of Taller-than-Wide nodular status are fortunately much less frequent (13.8% and 12.5%, respectively). None of the authors have any relevant disclosures.
Presentation: No date and time listed
ODP532 Fractionated Radioactive Iodine Therapy in Management of Differentiated Thyroid Cancer
Authors: Khan Adeel Ahmad , Karuppasamy Gowri , Yousaf Zohaib , Zawahreh Amer Ibrahim , Khan Aisha Noor , Rohani Zaina Seros , Naem Emad , Zirie Mahmoud Ali Humeidan , Jaber Tania 
Published: November 2022

Abstract

Introduction
Management of differentiated thyroid cancer (DTC) requires individualized treatment plans that are tailored to the risk of disease recurrence. Radioactive iodine treatment (RIT) remains a treatment modality that is valuable in certain patients with DTC. The lack of institutional availability and travel bans imposed by the COVID-19 pandemic did not allow a subset of our patients to get intermediate or high-dose RIT. As an alternative, fractionated low-dose RITs given over a short time interval have been used. We aim to study the response to therapy in this patient population.

Materials and methods
This retrospective study was performed at a tertiary care hospital in Qatar. Between 2015-2020, patients who completed at least 2 doses of low-dose RIT within 6-12 months with at least one staging visit 3-6 months after their last treatment were included in the study.

Results
69 patients met our inclusion criteria, 30 (43.5%) of whom were males and 39 (56.5%) females. The mean age at diagnosis was 40.7 +/- 9.35 years. Classic papillary thyroid cancer was the predominant histological variant (76.6%). Based on surgical pathology, the initial risk of disease recurrence was high in 24 (34.8%) patients, intermediate in 21 (30.4%) patients, and low in 21 (30.4%) patients. 3 (4.3%) patients did not have complete data for classification. Lymphatic invasion was noted in 16 (23.2%), vascular invasion in 15 (21.7%), positive margins in 30 (43.5%) and extra-nodal invasion in 10 (14.5%) patients. Patients underwent between 2-6 fractionated RITs, with the majority having undergone 2. In the low-risk group, 9 (42.9%) patients had an excellent response to therapy at last follow-up, 3 (14.3%) had the persistent structural disease, and 9 (42.8%) patients had an indeterminate response. In the intermediate-risk group, 7 (33.4%) patients had excellent response, 2 (9.5%) had the biochemically persistent disease, 8 (38.1%) had the structurally persistent disease, and 4 (19%) had an indeterminate response. In the high-risk group, 5 (20.8%) patients had excellent response, 13 (54.2%) had a structurally persistent disease, and 6 (25%) patients had an indeterminate response to therapy.

Conclusion
A similar response to therapy has been reported in the literature in the low and high-risk recurrence groups, suggesting that additional RIT may not be beneficial. In the intermediate risk of recurrence group, there is a higher percentage of patients with structural evidence of disease compared to what is reported in the literature, suggesting that perhaps a single intermediate or high dose RIT may be more beneficial. Either way, the c urrent management of DTC should be based on dynamic risk assessment to guide the need for further therapies.
Presentation: No date and time listed
ODP574 Characteristics of Grave's Disease Among Children and Adolescents in KSA
Authors: Alradadi Rasha , Omar Noura , Alhusayni Renad , Altaleb Mawaddah , Alraddadi Reem , Abdullah Sundus , Almokhtar Amirah , Muhawish Shahad , Alamri Randa 
Published: November 2022

Abstract

Background
Graves’ disease (GD) is an autoimmune thyroid condition that causes hyperthyroidism in children and adolescents through stimulation by thyroid receptor antibodies.

Objective
The aim of this study is to determine the characteristics of Graves’ disease in children and adolescents in Medina, the Kingdom of Saudi Arabia, with comparison to those seen in other countries.

Methods
This is a retrospective chart review of children and adolescents diagnosed with Graves’ disease between January 2010 and May 2021.

Results
Fifty-eight patients aged 12. 02 ± 4.85 years were identified, of which 44 (75.9%) were females. Exophthalmos (63.8%), neck swelling (60.3%), palpitation (46.6%), and tremors (29.3%) were the most common presenting manifestations. Vitiligo and alopecia were the only autoimmune diseases seen in our patients with (1.72%) each. One (1.72%) patient was treated with radioactive iodine, 54 (93.1%) received carbimazole, and 6 (10.3%) underwent thyroidectomy.

Conclusion
In our study we found that Graves’ disease is more common in females. Neck swelling, palpitation, and tremor were the main manifestations. Compared with other countries, there was a higher frequency of exophthalmos and lower frequencies of associated autoimmune conditions. The primary treatment was antithyroid medication, whereas thyroidectomy and radioiodine were used less frequently.
Presentation: No date and time listed
ODP578 Utility of the ACR-TIRADS Score – A Survey of Primary Care Providers
Authors: Wang Yiqiao (Daniel) , He Jialin , Wang Stephen , Ji Catherine , Yu Catherine 
Published: November 2022

Abstract

Background
The American College of Radiology – Thyroid Imaging Reporting and Data System (ACR-TIRADS) score is an ultrasound-based tool used to assess the risk of malignancy in thyroid nodules. Despite evidence supporting its efficacy, the use of this score in clinical practice has not yet been reported. Since primary care providers commonly identify and manage thyroid nodules, we aimed to determine 1) current diagnostic approach to thyroid nodules and 2) perceived utility of ACR-TIRADS in Canadian primary care providers.

Methods
We conducted a cross-sectional survey study with family medicine physicians and nurse practitioners working in Canada. The 23-question survey was developed and distributed electronically on Qualtrics using convenience sampling from August 31 2021 to January 3, 2022. Sociodemographic and other quantitative questions using Likert scales were analyzed using descriptive statistics; Likert scale responses were analyzed as proportion of individuals who agreed or strongly agreed. Qualitative data from free text answers was assessed using content analysis.

Results
One hundred and four primary care providers responded to our survey. Of these, 90 (87%) completed the entire survey and were included. Fifty-six percent were female, 58% were aged &lt;40 years, and 48% were in practice for five or fewer years. In terms of management of thyroid nodules, only 47% were confident in their ability to risk-stratify. Ninety-four percent of participants risk-stratified using imaging characteristics, but only 57% of respondents reported using a risk stratification tool. Despite 64% percent of participants agreeing with being familiar with the ACR-TIRADS score, only 28% used this scoring system, and 80% of participants had a desire to learn more about it. Only 68% of physicians believed the score was present on ultrasound reports, and &lt;5% requested it on reports themselves. After being shown a diagram demonstrating the ACR-TIRADS scoring system, 93% thought that the ACR-TIRADS score was useful. Of the 31 (34%) participants who were not initially familiar with the score, 61% would use the ACR-TIRADS score more, and 77% would ask radiology to report the ACR-TIRADS score more often. In terms of qualitative data, respondents believed educational tools and increased reporting by radiologists would increase use of ACR-TIRADS.

Conclusion
In this Canadian survey study, the majority of respondents were not confident with risk stratification of thyroid nodules, and only half used a risk stratification tool. With education, almost all participants thought ACR-TIRADS was useful, and most participants would use it more often. Further interventions to educate primary care providers regarding the ACR-TIRADS score may help enhance its uptake and improve systematic management of thyroid nodules.
Presentation: No date and time listed
ODP614 Two cases of Graves Disease Associated Hypokalemic Periodic Paralysis
Authors: Reddy Bendaram Snigdha , Azmath Misbah , Luthra Pooja , Dulipsingh Latha 
Published: November 2022

Abstract

Introduction
Periodic paralysis (PP) is a rare neuromuscular disorder due to a defect in ion channels in muscle, characterized by episodes of painless muscle weakness or paralysis, which may be precipitated by heavy exercise or high-carbohydrate meals. Hypokalemic PP (HPP) is most common of the periodic paralyses, however is still very rare, with an estimated prevalence of 1 in 100,000. An acquired form of hypokalemic PP can be seen in thyrotoxicosis of any cause. We present 2 cases of HPP due to thyrotoxicosis.

Case 1
27 year old Asian male presented to the ED due to sudden onset of acute weakness/near paralysis in lower extremities, with weakness of bilateral upper extremities. He was found to be hypokalemic with a potassium of 2.0 mmol/L (3.5-5.1). At the same time, he was also found to be hyperthyroid with a suppressed TSH of 0.03 uIU/Ml (0.35-5.5) and a free T4 2.2 ng/mL (0.5-1.3), Total T3 225 ng/Dl (70-204), Free T3 5.9 pg/mL (1.5-4.1). TSI antibodies elevated at 1.39 IU/L (&lt;0.10). He was started on potassium supplements and methimazole. At a 3-month follow-up, patient reported no further episodes of weakness or paralysis.

Case 2
23 year old White male presented to ED with severe muscle weakness and was found to have hypokalemia of 2 mmol/L (3.5-5.1). On further labs, TSH was undetectable at less than 0.01 uIU/mL (0.35-4.94), Free T4 2.81 ng/dL (0.61-1.82), Total T3 of 451 ng/dL(48-178), TSI antibodies were positive at 178%(&lt;/=122%). Nuclear uptake scan confirmed Graves’ disease with radioactive iodine uptake of 58.1% at 4 hours and 70% at 24 hours with homogenous uptake in the entire gland and no evidence of hot or cold nodules. He was started on methimazole and propranolol for tachycardia and palpitations and potassium supplements. Muscle weakness resolved on treatment methimazole.

Discussion and conclusion
We present two cases of HPP likely caused by Graves’ disease. Both patients presented with hypokalemia and further workup revealed underlying thyrotoxicosis. The exact mechanism behind HPP due to thyrotoxicosis is not well understood. It is proposed that excess thyroid hormone may predispose to paralytic episodes by increasing the susceptibility to the hypokalemic action of epinephrine or insulin. This condition has been most widely reported in Asian populations, in which the incidence is approximately 2% in contrast to non-asian population with incidence of 0.1 to 0.2%, and is more common in men. Treatment of thyrotoxicosis with restoration and maintenance of euthyroid state ceases attacks. To summarize, few case series report the association of HPP with Graves’ disease. These patients usually present acutely with severe muscle weakness or paralysis. In conclusion, in diagnosis of HPP, possibility of thyrotoxicosis should be considered, especially in the absence of family history of PP.
Presentation: No date and time listed
OR09-4 Novel Murine Models of BrafV600E driven Papillary Thyroid Cancer
Authors: Casado Medrano Victoria , Franco Aime , O’Neill Alison , Scheerer Michele , Spangler Zachary , Purvis Grace 
Published: November 2022

Abstract
Thyroid cancer is the most prevalent endocrine malignancy and is estimated to have affected 52,890 individuals in the United States in the year 2020. Papillary thyroid cancer (PTC) accounts for up to 80% of all thyroid cancer diagnoses. Within PTC, BRAFV600E is the most common mutation in adults and the second most common mutation in pediatrics. While there are several validated human thyroid cancer cell lines harboring BRAF mutations, no pediatric derived cell line has been established to date, limiting generalizations in pediatric disease. Patient-derived pre-clinical models are valuable tools but are limited due to their need to be studied in vitro or in an immunocompromised host. However, in vivo mouse models recapitulate the complex interactions between tumor cells, the immune system, and components of the microenvironment, allowing more comprehensive investigation of thyroid oncogenesis and response to therapy. In this study we describe a new subcutaneous mouse model that can be used to understand differences between pediatric onset and adult onset PTC.
We have developed multiple independent, congenic murine cell lines from different stages of thyroid cancer progression. Two independent BRAFV600E-driven cell lines harboring the same genetic mutations were utilized in this study, one representing a well-differentiated tumor (WD) and one representing a poorly-differentiated tumor (PD). Despite coming from different stages of disease, both cell lines showed similar expression of the thyroid specific genes: Pax8, Ttf1, Tg, and Slc5a5, but expression of Pax8, Tg, and Slc5a5 was lower compared to WT thyrocytes. Activation of the Pi3Kinase pathway and the Akt Pathway were assessed via western blot analysis. The WD cell line had increased pERK activation compared to the PD cell line, and the PD cell line had increased pAKT compared to WD cell line.
Both cell lines were injected subcutaneously into the hind flank of Wt SJV129 mice of pediatric age (4-5 weeks) and adult age (20-22 weeks). These animals were monitored for 10 weeks post injection. While the PD cell line developed tumors at approximately the same rate and penetrance in both age groups, tumors reached end point more rapidly in the adult cohort. Adult hosts injected with the WD cell line developed tumors more rapidly than in pediatric hosts, however, tumors receded in both cohorts.
While adult and pediatric thyroid cancer share common driving mutations, there are distinct differences in disease pathogenesis between these patient populations. There are known differences in the immune system, metabolism, and other variables between pediatrics and adults. However, it is unknown what causes the difference in PTC pathogenesis between pediatric versus adult patients. We believe these new models provide a great opportunity to evaluate the role of age in PTC development and progression.
Presentation: Saturday, June 11, 2022 12:15 p.m. - 12:30 p.m.
OR09-6 Identification of MicroRNAs Critical to the Lymph Node Metastatic Process of Thyroid Cancer
Authors: Barreto Icléia S , Bezerra Mateus L , Bufalo Natassia E , Cunha Lucas L , Freitas Leandro L L , Geraldo Murilo V , Matos Alexandre H B , Rabi Larissa T , Tincani Alfio J , Tincani Priscila C , Ward Laura S , Peres Karina C 
Published: November 2022

Abstract
The identification of thyroid tumors with the potential for poor evolution is a major concern, as current management can range from simple active surveillance to aggressive therapeutic measures. MicroRNAs are small non-coding RNAs that play a key role in the regulation of gene expression and therefore in the pathogenesis and progression of different types of cancers. Here we employed several bioinformatics tools to investigate deregulated miRNAs in the lymph node metastasis (LNM) of two different types of thyroid tumors. Using thyroid cancer RNA-seq data available on Gene Expression Omnibus (GEO), we identified 14 common deregulated miRNAs in LNM of both medullary and papillary thyroid carcinomas, three of them still negatively deregulated when compared to their respective primary tumor: miR-199a-3p, miR-199a-5p, and miR-148a-5p. Public data available on TCGA confirmed the downregulation of miR-148a-5p in LNM and tumors with advanced AJCC stage. Looking at their predicted target genes, ITGA3, PVRL1 (also called NECTIN1), SNN, and FBXO28 genes were confirmed as positively deregulated in LNM papillary thyroid carcinomas when compared to normal tissues. Public data available on TCGA once again confirmed higher expression of the ITGA3 gene in LNM, larger and invasive tumors (T4a), and stage III and IV. Similar results were observed for PVRL1 (NECTIN1) and FBXO28, but not for SNN. These bioinformatic analysis findings suggest that miR-199a-3p, miR-199a-5p, and miR-148a-5p dysregulation, leading to epithelial-mesenchymal transition and cell adhesion failure, are associated with thyroid tumors’ LNM.
Presentation: Saturday, June 11, 2022 12:45 p.m. - 1:00 p.m.