bluuebunny/crossref_metadata_2025 huggingface dataset:
FRI530 Immune-Modulation By Rapamycin, Or Mycophenolic Acid, Of Th1 And Th2 Chemokines Secretion In Retro-orbital Cells Of Patients With Graves’ Ophthalmopathy
Authors: Elia Giusy , Ragusa Francesca , Rosaria Paparo Sabrina , Mazzi Valeria , Patrizio Armando , Fallahi Poupak , Antonelli Alessandro , Martina Ferrari Silvia
Published: October 2023

Disclosure: G. Elia: None. F. Ragusa: None. S. Paparo: None. V. Mazzi: None. A. Patrizio: None. P. Fallahi: None. A. Antonelli: None. S. Ferrari: None.

Objectives: Cytokines and chemokines contribute to the inflammation of Graves’ ophthalmopathy (GO). Indeed cytokines stimulate the T helper (Th)1 and Th2 chemokines release from orbital cells (fibroblasts, preadipocytes and myocytes).We aim to investigate the effects of rapamycin or mycophenolic acid on the secretion of these chemokines in GO orbital cells. Methods: We obtained primary cultures of fibroblasts, preadipocytes and myoblasts from the orbits of GO patients, and we tested increasing concentrations of rapamycin and/or mycophenolic acid evaluating the secretion of the prototype Th1 [chemokine (C-X-C motif) ligand 10 (CXCL10)] and Th2 [chemokine (C-C motif) ligand 2 (CCL2)] chemokines. Results: We observed that CXCL10 secretion in the retro-orbital cells of GO was undetectable in the supernatants, whereas interferon (IFN)-gamma induce its release in a dose-dependently manner. No effect was observed under the tumor necrosis factor (TNF)-alpha stimuli, while the combination of both cytokines had a significant synergistic effect on CXCL10 secretion. As regards the effect on the CCL2 secretion, it was released in low amounts in basal condition; TNF-alpha dose-dependently induced its release, whereas IFN-gamma alone had no effect. The combination of TNF-alpha plus IFN-gamma had a significant synergistic effect on CCL2 secretion. By adding mycophenolic acid, or rapamycin, (in a pharmacological range) at the time of IFN-gamma and TNF-alpha stimulation, we observed a dose-dependently inhibitory effect on the chemokines release in the retro-orbital cells of GO. Furthermore, the combination of mycophenolic acid with rapamycin, have a synergistic inhibitory effect on the release of chemokines. Conclusion: Our data showed an immune-modulating effect of mycophenolic acid or rapamycin on the Th1 and Th2 chemokines secretion, in GO orbital cells. These findings suggest the therapeutic role of these drugs that could obtained, at least in part, through this mechanism.

Presentation: Friday, June 16, 2023
FRI535 Quality Of Life And Symptomatology In Patients With Autoimmune Thyroiditis
Authors: Miguel Pereira Luis , Neves Celestino , Sérgio Neves João , Delgado Luís , Carvalho Davide
Published: October 2023

Disclosure: L.M. Pereira: None. C. Neves: None. J. Neves: None. L. Delgado: None. D. Carvalho: None.

Introduction: Autoimmune thyroiditis (AIT) may be associated with physical, psychological and behavioral symptoms even in patients achieving normal TSH and free T4 levels with levothyroxine treatment. Objective: Our aim was to evaluate the associations the resistance to thyroid hormone, assessed by the Parametric Thyroid Feedback Quantile-Based Index (PTFQI), and laboratorial parameters with Quality of life (QoL) in AIT. Methods: We evaluated 145 patients with AIT treated with levothyroxine followed in outpatient clinic. We assessed lipid profile, high-sensitivity C-reactive protein, B12 vitamin, folic acid, thyroid antibodies, thyroid function tests and calculated the index PTFQI of resistance to thyroid hormones. The following questionnaires were applied to participants: the Thyroid Dependent Quality of Life questionnaire (ThyDQoL), the Thyroid Symptom Rating Questionnaire (ThyTSQ), the Thyroid Treatment Satisfaction Questionnaire (ThyTSQ) and the Brief Symptom Inventory (BSI). Statistical analysis was performed with the One-way ANOVA test and Pearson’s correlation test. P values ≤ 0.05 were considered as statistically significant. Results: In this sample, the age was 54.4 ± 15.3 years, 89.7 % were female, BMI was 28.4 ± 5.2 Kg/m2, TSH was 2.69 ± 8.48 µUl/mL and FT4 was 1.15 ± 0.40 ng/dL. Patients reported a mean QoL value of -2.11 points (range from -9 to 1). In regard to the ThySRQ, 46.2 % of patients reported at least moderately memory problems, 50.4% of patients reported at least being moderately tired and 62.7 % showed some type of depressive feelings. Regarding ThyTSQ, 83.5 % demonstrated being satisfied with treatment and 82 % believe that treatment is working well. We found that PTFQI correlates positively with thyroid peroxidase antibodies (r = 0.19; p = 0.03) and negatively with triglycerides (r = -0.26; p = 0.002) and BMI (r = -0.21; p = 0.01). In relation with symptomatology, we observed negative correlations among PTFQI and constipation (r = -0.18; p = 0.02), skin problems (r = -0.27; p = 0.01), nail problems (r = -0.19; p = 0.01) and dizziness symptoms (r = -0.18; p = 0.03). Conclusions: In this study, we observed a high prevalence of memory problems, tiredness and depressive feelings in patients with AIT treated with levothyroxine. We also found that PTFQI is associated with physical and psychological symptoms. Further studies are needed to analyze the role of autoimmunity and PTFQI for the worsening of the QoL in patients with AIT.

Presentation: Friday, June 16, 2023
FRI541 The Epidemiology Of Thyroid Eye Disease In Olmsted County, Minnesota
Authors: Rachmasari Kharisa N , Thapa Prabin , Sighoko Dominique , Abdul Jabbar Layla , Stan Marius N
Published: October 2023

Disclosure: K.N. Rachmasari: None. P. Thapa: None. D. Sighoko: Employee; Self; Horizon Therapeutics. L. Abdul Jabbar: None. M.N. Stan: None.

Objective: To describe the epidemiology of Thyroid Eye Disease (TED). Methods: A population-based cohort of all Olmsted County, Minnesota, residents who had newly diagnosed TED between April 3, 2002, and December 31, 2021, was identified through the medical diagnostic index of the Rochester Epidemiology Project. Individuals aged 18 years and older were included. Incidence rates and point prevalence were calculated. Results: We identified 137 incident patients, of whom 124 (90.5%) were female (p < 0.0001). The overall incidence was 6.24 cases/100,000 person-years in Olmsted County, corresponding to 6.25 cases/100,000 person-years for the US population (age and sex adjusted incidence). Women had higher incidence (10.94 cases/ 100,000 person-years) compared to men (1.22 cases/100,000 person-years). The distribution of incidence rates by ten-year age groups demonstrated peak incidence rates in the age groups 70 to 79 years (17.94 cases/100,000 person-years for women compared with 4.04 cases for men). The majority of cases (77/137) occurred between 50-79 years of age. No clear trend was identified for the yearly incidence between 2002 and 2021. The overall estimated point prevalence per 100,000 was 65.6 (95% CI, 57.8 – 72.9). Prevalence was 117.6 (95% CI, 96.5 – 141.4) for females and 11.2 (95% CI, 5.1 – 21.2) for males (p < 0.0001). Conclusions: Incidence rates for TED remained stable and significant over the last 2 decades. Majority of disease burden is present after the age of 50 with the peak between 70-79 years, a decade later than in the previous study from our population (1). Based on reported incidence and prevalence of Graves’ disease (2), our data indicates that TED continues to affect about 20-30% of that population and appropriate resources should be devoted to furthering education, management, and research into this condition.

References:

1. Bartley GB, Fatourechi V, Kadrmas EF, et al. The incidence of Graves' ophthalmopathy in Olmsted County, Minnesota. Am J Ophthalmol 1995;120(4):511-7, doi:10.1016/s0002-9394(14)72666-2

2. Hussain YS, Hookham JC, Allahabadia A, et al. Epidemiology, management and outcomes of Graves' disease-real life data. Endocrine 2017;56(3):568-578, doi:10.1007/s12020-017-1306-5

Presentation: Friday, June 16, 2023
FRI543 Effect Of Vitamin D Replacement On Thyroid Autoimmunity And thyroid Functions In Subclinical Hypothyroid And Vitamin D Deficient Patients: A Randomized Controlled Trial
Authors: Aljohani Naji J
Published: October 2023

Disclosure: N.J. Aljohani: None.

Background: Vitamin D status has been implicated to influence several non-skeletal diseases including diabetes, cardiovascular diseases, and auto-immunity. Several observations have also associated vitamin D deficiency with thyroid disorders, but prospective data is lacking. In this randomized clinical trial, we aimed to determine whether vitamin D correction improves subclinical hypothyroid status of Arab adult patients. Subjects and Methods: A total of 84 subjects with subclinical hypothyroidism were recruited and allocated (1:1) to receive either vitamin D 50,000 IU weekly in first four months (cases) or placebo (Vitamin D 5000 IU weekly). Thyroid function and thyroid autoantibodies was repeated after 3 and 6 months with vitamin D level to see sufficient vitamin D replacement status. Results: Post-intervention, 31 cases and 37 controls completed the intervention. Cases had a significant increase in 25(OH)D levels after 3 and 6 months of intervention. In both cases, and controls, there was a significant decrease in TSH over time (p<0.05), with no significant changes in both circulating FT4 and FT3 levels. A significant decrease in TPO ab and anti-TG ab levels after 6 months (p<0.05) were observed only in cases. In conclusion, vitamin D correction modestly improves thyroid status of Arab patients with known subclinical hypothyroidism. Further investigations are needed as to whether vitamin D supplementation is more beneficial among subclinical hypothyroid patients who were deficient at baseline.

Presentation: Friday, June 16, 2023
FRI544 Serological Profile In Rheumatoid Arthritis And Its Interplay With Autoimmune Thyroid Diseases
Authors: Kolitz Tamara , Kivity Shaye , Tessler Idit , Marcus-Perlman Yonit , Izkhakov Elena , Yaish Iris , Greenman Yona
Published: October 2023

Disclosure: T. Kolitz: None. S. Kivity: None. I. Tessler: None. Y. Marcus-Perlman: None. E. Izkhakov: None. I. Yaish: None. Y. Greenman: None.

Objective: Autoimmune thyroid diseases (AITD) are the most common organ-specific autoimmune disorders, with an estimated prevalence of 5%. AITD encompass the clinical scope of Hashimoto’s thyroiditis (HT) and Graves’s disease (GD). Rheumatoid arthritis (RA) is a relatively common non-organ-specific autoimmune disease with an estimated global prevalence of 0.5-1%. Numerous studies have investigated the association of thyroid disorders and RA in various populations, but results were inconsistent. This study is aimed to assess the rate of AITD in RA patients and to further investigate these rates in subgroups of patients with seronegative RA, seropositive RA and dual-positive RA antibodies [i.e., positive anti-cyclic citrullinated peptide (CCP) and rheumatoid factor (RF)]. Methods: We used a big-data platform (MDClone Ltd., Israel) to create a cohort of RA patients with and without coexistent AITD. The cohort included 1316 patients who were treated in the Tel Aviv Sourasky Medical Center for any diagnosis between January 2008 and December 2022. Results: There were 340 men (25.8%) and 976 (74.2%) women in the cohort. The mean age at time of initial coding of RA diagnosis in our referral center was 62.5±15 years. AITD was found in 15.5% of the entire RA cohort. Hypothyroidism was the most common thyroid-associated diagnosis (in 95.8% of patients with RA and AITD). When RA patients were further sub-classified to seronegative, seropositive, and dual-positive RA, the rates of AITD were 11.8%, 17.6% and 25%, respectively (p=0.007). AITD rates in seropositive women and men were 20.6% and 8%, respectively (p<0.001). In the RA-seronegative subgroup, the rate of AITD was 15.6% in women and 2.7% in men (p<0.001). The mortality rates in RA-seronegative patients, RA-seronegative patients with AITD, RA-seropositive patients and RA-seropositive patients with AITD were 5.5%, 8.3%, 21.6% and 29.5%, respectively (p=0.05). Conclusion: Our findings suggest that the prevalence of AITD in patients with RA is associated with the specific serological profile, with highest rates in RA patients who are positive for both anti-CCP and RF. Randomized prospective studies are required to explore any cause-and-effect correlation and to delineate the impact of AITD on RA outcome and mortality rates.

Presentation: Friday, June 16, 2023
SAT462 TSI Versus TRAb In The Diagnosis Of Grave’s Disease
Authors: Ibrahim Katherine , Raju Karishma , Morkos Michael
Published: October 2023

Disclosure: K. Ibrahim: None. K. Raju: None. M. Morkos: None.

Objective: Improvement in the thyroid antibody titers can help in predicting the remission of Graves’ disease. We aimed to assess the level of elevation of the antibody titers, thyroid stimulating immunoglobulin (TSI) and thyroid receptor antibody (TRAb) in patients with Grave’s disease. Research and Design Methods: This is a retrospective cross-sectional study of patients diagnosed with Graves’ disease at an academic outpatient endocrinology clinic from August 2019 to November 2022. TSI and TRAb were measured synchronously during the initial assessment of the patients, titers were compared against the upper limit of normal to assess their level of elevation. TSI was measured using Semi-Quantitative Chemiluminescent Immunoassay and TRAb using Quantitative Electrochemiluminescent Immunoassay. SPSS® (version 28) was used for statistical analysis, descriptive statistics were utilized and paired-sample t-test was used to compare TSI And TRAb ratios. Results: We identified 41 patients who presented for initial assessment of Graves’ disease, 31 (75.6%) were female, 23 (56.1%) Caucasian, and 16 (39.0%) African American. Mean age (± standard deviation) 46.3 ± 14.2 years. Mean TSI 8.3 ± 15.9 IU/L (ref <0.55), TSI ratio of elevation above the upper limit of normal was 11.1 ± 15.3, Mean TRAb 8.9 ± 9.4 (ref ≤1.75), TRAb ratio of elevation above the upper limit of normal was 5.1 ± 5.4. The correlation coefficient for both TSI and TRAb ratios was 0.92 (p <0.001). One patient had a normal TSI but elevated TRAb level and two patients had a normal TRAb level but elevated TSI levels. Conclusion: TSI was more highly elevated above its normal range than TRAb. TSI can be a reasonable initial antibody test for patients with Graves’ disease to establish a baseline.

Presentation: Saturday, June 17, 2023
SAT464 Hyperthyroidism Does Not Negatively Impact Outcomes of Adult Hospitalizations for Pulmonary Embolism: A Nationwide Analysis
Authors: Gbenga Olafimihan Ayobami , Deenadayalan Vaishali , Ehiremen Ojemolon Pius , Litvin Rafaella , Annabel Ogar Ufeh , Krishnaraju Ellil , Sami Faria , Hilda Olojakpoke Eloho
Published: October 2023

Disclosure: A.G. Olafimihan: None. V. Deenadayalan: None. P.E. Ojemolon: None. R. Litvin: None. U.A. Ogar: None. E. Krishnaraju: None. F. Sami: None. E.H. Olojakpoke: None.

Introduction: Acute pulmonary embolism (PE) is a medical emergency associated with high mortality rates. Hyperthyroidism has been associated with an increased risk of venous thromboembolism and PE. However, there are limited studies on its impact on the outcomes of patients with PE. We aimed to assess hyperthyroidism’s effect on in-hospital PE outcomes using the National Inpatient Sample (NIS). Methods: Data were extracted from the US Nationwide Inpatient Sample (NIS) from 2016 to 2019. The NIS contains hospital discharge information estimating yearly US hospitalizations. We included hospitalizations with a principal discharge diagnostic code for PE using the ICD-10-CM code (E22.2). Hospitalizations of patients less than 18 years of age were excluded from the study. This cohort was divided based on the secondary diagnosis of hyperthyroidism.The primary outcome was inpatient mortality, and secondary outcomes were hospital length of stay (LOS), total hospital charge, odds of acute respiratory failure (ARF), acute renal failure (AKI), undergoing embolectomy, tissue plasminogen activator (tPA) use and Inferior vena cave (IVC) filter placement. Multivariate linear regression analysis was used to adjust for confounders. Statistical significance was set at a p-value < 0.05. Results: There were 745,360 hospitalizations involving PE as the reason for admission, and 20.1% had comorbidity with hyperthyroidism. Admissions for PE with comorbid hyperthyroidism had similar in-hospital mortality (adjusted OR:1.17, P=0.41), mean LOS (4.9 vs 4.3 days, P=0.11) and mean THC ($53,127 vs $48,236, P=0.43) compared to those without hyperthyroidism. The odds of developing ARF (aOR: 0.93, P=0.466) or AKI (aOR: 0.95, P=0.71) were similar. Odds of undergoing embolectomy (aOR: 1.07, p=0.83), receiving tPA (aOR=1.03, P=0.87) and placing IVC filter (aOR=0.80, P=0.19) were similar between both groups. Conclusion: Hospitalizations for pulmonary embolism with hyperthyroidism had similar inpatient mortality compared to those without hyperthyroidism. Also, mean LOS, total hospital charge, ARF and AKI complications, and odds of embolectomy, tPA administration and IVC filter placement were alike for both categories.

Presentation Date: Saturday, June 17, 2023
SAT467 Monitoring TSH Over Time May Not Be Necessary in Patients With Thyroid Nodules
Authors: Kaul Sabrina , Gupta Ankur
Published: October 2023

Disclosure: S. Kaul: None. A. Gupta: None.

Introduction: A substantial number of patients with thyroid nodules receive monitoring of blood thyroid stimulating hormone (TSH) levels after the initial diagnosis. There is not enough literature supporting long-term monitoring of blood TSH levels in these patients with thyroid nodules. The objective of this study was to evaluate the change in blood TSH level in patients with known thyroid nodules over time and to determine if repeat blood TSH testing is required in these patients. We hypothesized that monitoring of blood TSH level is not warranted in patients with thyroid nodules in the absence of a history of medical conditions or medications that are known to affect thyroid hormone levels. Methods: We studied 100 patients aged 18 to 99 years at the Dayton VA Medical Center with at least one thyroid nodule on imaging studies from January 2010 to December 2016 with normal blood TSH level at time of the diagnosis of the thyroid nodule. Subjects with abnormal thyroid hormone level, history of hot thyroid nodule, autoimmune thyroid disease (on imaging or blood work), thyroid or pituitary surgery, radioactive iodine treatment, neck irradiation, or usage of thyroxine or any other medications known to affect thyroid hormone levels were excluded. Blood TSH level at the time of diagnosis of thyroid nodule and after were retrospectively studied and analyzed for 100 subjects. Normal blood TSH level range at time of diagnosis was noted to be 0.35-5.50 uIU/mL or 0.35-4.00 uIU/mL depending on the assay method used. Normal repeat blood TSH level range was noted to be 0.35-5.50 uIU/mL, 0.35-4.00 uIU/mL, or 0.55-4.78 uIU/mL depending on the assay method used. Results: 100 subjects with normal blood TSH at the time of diagnosis of their thyroid nodule had blood TSH level monitoring for an average time period of 5.74 years. Out of the 100, six subjects (6%, 95% CI [2.52%, 12.73%]) developed an abnormal blood TSH level in a mean time period of 6.94 years. One subject’s initial blood TSH level increased from 3.38 uIU/mL to 7.76 uIU/mL after 8.52 years. This subject did not receive treatment with thyroxine. In the other five subjects, blood TSH level decreased to below normal range in a mean time period of 6.63 years and ranged from 0.25-0.52 uIU/mL. Blood TSH level remained within normal range for 94 subjects in a mean time period of 5.67 years. Conclusion: Monitoring of blood TSH level over time may not be required in most patients with thyroid nodules in the absence of symptoms, medical conditions, or medications that are known to affect thyroid hormone levels.

Presentation Date: Saturday, June 17, 2023
SAT483 Role of Cholestyramine in Refractory Amiodarone-induced Thyrotoxicosis
Authors: Zhao Huaying , Leung Joseph
Published: October 2023

Disclosure: H. Zhao: None. J. Leung: None.

Role of Cholestyramine in Refractory Amiodarone-Induced Thyrotoxicosis. Background: Amiodarone-induced thyrotoxicosis (AIT) is divided into type 1 (AIT1; treated with thioamides) and type 2 (AIT2; treated with glucocorticoids). Combined therapy is utilized in mixed or indefinite forms. When medical treatment is unsuccessful, radioiodine ablation or thyroidectomy are considered. Clinical Case: A 76-year-old gentleman, with a history of atrial fibrillation treated with amiodarone, presented with recurrent atrial fibrillation refractory to cardioversion. Investigations revealed TSH <0.01, FT4 58.1 (ref 10.0-20.0 pmol/L), FT3 16.0 (ref 3.5-6.5 pmol/L), TPO negative and TRAB negative. As thyroid ultrasound revealed absence of focal nodules or hypervascularity and technetium pertechnetate scan demonstrated no thyroid activity, AIT2 was suspected. Prednisone was initiated and amiodarone discontinued. Due to minimal response after a month, a mixed type was suggested and methimazole added. Despite intensification of the antithyroid regimen, FT4 increased to 59.5. Methimazole was discontinued for radioiodine ablation assessment. Given low thyroid uptake (<3%), ablation was deemed unlikely beneficial. After patient refused thyroidectomy, cholestyramine was initiated, resulting in significant improvement, with FT4 declining from 46.0 to 29.0 in 2 weeks. Euthyroidism was achieved after 2 months of cholestyramine treatment and medications were stopped. At 6 months post presentation, he developed amiodarone-related hypothyroidism and began levothyroxine. Conclusion: Previous reports propose that cholestyramine, an ion exchange resin, interrupts enterohepatic circulation of thyroid hormone and demonstrated the use of cholestyramine in refractory Grave’s hyperthyroidism. This is one of the first few reports demonstrating the possible role of cholestyramine in AIT refractory to first line medical therapy.

Presentation Date: Saturday, June 17, 2023
SAT491 Development of Thyroidal Nodule in Congenital Hypothyroid Girl With Thyroid Peroxidase Gene Mutation
Authors: Lee Jisu , Oh Arum , Han Heon-Seok
Published: October 2023

Disclosure: J. Lee: None. A. Oh: None. H. Han: None.

Background: Reduced thyroxine synthesis in dyshormonogenesis induces increased thyrotropin (TSH) secretion through reduced negative feedback of thyroxine. Consequently, the affected patients are born with goiter or develop postnatal goiter, when L-thyroxine (LT4) supplementation is delayed. Cases of thyroid cancer have been reported in congenital hypothyroidism (CH) due to dyshormonogenesis, usually of follicular histology. Clinical Case: A 22-year lady has been taking LT4 since 8-years, under the diagnosis of goitrous CH. Her mother recalled neck swelling at newborn period. However, normal newborn screening test prevented neonatal goiter from further investigation. Initial test at 8-year of age revealed normal thyroid function without thyroid auto-antibodies, diffuse enlarged thyroid gland with increased uptake on 99mTc scan, and diffuse thyroid enlargement with heterogeneous echogenicity on ultrasonography (US). The goiter size waxed and waned according to the drug compliance. The highest TSH level (normal 0.17-4.05 μIU/mL) was 8.68 μIU/mL even without medication for 8 months by her own judgement. At 11.5-years, US found isoechoic solid nodule of 1.8 x 1.7 x 1.6 cm with peripheral halo in the inferior aspect of right thyroid, which was demonstrated to be benign follicular lesion favoring nodular hyperplasia on fine needle aspiration biopsy. With good drug compliance, the nodule size decreased to 1.1 x 0.9 cm at 18-years, and peripheral calcification appeared around the isoechoic solid nodule previously reported without change in size at 22-years. NGS panel for CH reported compound heterozygous variants in TPO gene. One pathogenic variant from asymptomatic father is c.2757del;p.(Met921Trpfs*53), the other likely pathogenic variant from asymptomatic mother is c.1580G>T;p.(Trp527Leu). Conclusion: This case is demonstrating development of thyroid nodule even with mild increased TSH level during LT4 medication in dyshormonogenic CH caused by TPO mutation. Regular follow-up and compliance to LT4 might be important to avoid thyroid tissue stimulation and possibly nodule formation by elevated TSH.

Presentation Date: Saturday, June 17, 2023
SAT496 Tobacco Smoking May Mimic Subclinical Hyperthyroidism
Authors: Alshantti Raeda , Rafat Ummara , Alkhaurri Bashar , Barsano Charles P , Siddiqui Mahwash
Published: October 2023

Disclosure: R. Alshantti: None. U. Rafat: None. B. Alkhaurri: None. C.P. Barsano: None. M. Siddiqui: None.

Introduction: Studies have shown lower levels of TSH in smokers and a positive association of smoking with hyperthyroidism. The urinary nicotine level is reported to be negatively correlated with TSH. Moreover, smoking cessation have shown reversible effects on thyroid functions and risk of having overt hypothyroidism increased more than 6-fold in the first 2 years after cessation of smoking. Whether transient smoking cessation, prior to blood work would alter thyroid functions is unknown. We report the case of an elderly woman who had normalization of suppressed TSH after smoking abstinence prior to her blood work, suggestive of smoking-induced alteration of the TSH level. Clinical Case: A 77- year-old woman was referred to endocrinology clinic for an abnormal TSH level. She had a suppressed TSH <0.01 uIU/mL [Ref range: 0.45-5.33], with normal free T4 0.78 ng/dl [Ref range: 0.70-2.70], and free T3 3.66 pg/ml [Ref range: 2.5-3.9], consistent with subclinical hyperthyroidism. Thyroid auto-antibodies were negative. She had a long-standing history of multinodular goiter with mild tracheal deviation for which she had declined surgical management. She was an active smoker with 40 pack years smoking history. There was no preceding viral illness. She was not taking any biotin-containing supplements or medications that would interfere with thyroid hormones. The patient denied symptoms of overt hyperthyroidism. On physical examination she had a large multinodular goiter with negative Pemberton’s sign. There was no exophthalmos, lid lag, tachycardia, tremors or hyperreflexia. Her subsequent blood tests, 2 and 4 months apart, were also consistent with subclinical hyperthyroidism with TSH levels of 0.115 to 0.144 uIU/mL with normal free T4 0.72 ng/dl and total T3 136.3 to 153 ng/dl [Ref range 80-187]. Based on her age, she met the treatment threshold. However, as the patient continued to smoke 10 cigarettes daily, even on the days when thyroid labs were drawn, treatment was deferred considering the possibility of smoking-induced altered thyroid function. Blood work re-drawn after a smoking abstinence of 10-12 hours showed normalization of TSH 0.58 uIU/mL consistent with a euthyroid state. Conclusion: When evaluating patients with abnormal thyroid functions, it is important to address smoking status. Cigarette smoking may alter thyroid function tests in a pattern consistent with subclinical or overt hyperthyroidism and its effect on thyroid functions may be transient and reversible. Therefore, the possibility of smoking-induced alteration of thyroid functions should be considered in active, clinically euthyroid smokers. It may be judicious to hold treatment with thionamides in such patients and to re-evaluate thyroid functions after smoking abstinence.

Presentation Date: Saturday, June 17, 2023
SAT497 Radiofrequency Ablation of Thyroid Cancer in A Patient With Steinert’s Disease
Authors: Solis Pazmiño Andrea Paola , Carvajal Mishel Arboleda , Godoy Richard , Garcia Cristhian
Published: October 2023

Disclosure: A.P. Solis Pazmiño: None. M. Arboleda Carvajal: None. R. Godoy: None. C. Garcia: None.

Background: Radiofrequency Ablation (RFA) is a non-surgical, minimally invasive technique for benign or microcarcinoma thyroid nodule (TN); and it has emerged as an alternative option for patients deemed at high risk for surgery. Steinert’s Disease or Myotonic dystrophy type 1 (DM1) is a genetic multisystem disease that affects almost all organs and tissues, including the thyroid. In these patients the prevalence of TN is increased, regardless they are benign or malignant. Patients with DM1 commonly have post-anesthetic complications such as cardiorespiratory arrest. Clinical Case: A young man diagnosed with DM1 and no other comorbidities came to the office for a TN. The patient was asymptomatic and had normal thyroid function. Nothing relevant was found on physical examination, and no cervical lymph nodules were found. The thyroid ultrasonography (US) showed a 12x11x13 mm solid isoechoic left lobe nodule, with microcalcifications, irregular borders and the color-flow Doppler US detected increased perfusion, classifying it as a TI-RADS 5 nodule, elastography score of 2.2, and Bethesda VI. Due to DM1 high risk of surgery, the patient underwent RFA with no complications and successful recovery. Results: At the first month follow-up after RFA, the thyroid nodule was fibrosed with a size of 10x14x15 mm and with a volume of 1,11 cc. The thyroid function was normal without late complications. Conclusions: RFA is a non-invasive and effective technique for the treatment of benign and malignant TN. It is safe and very useful in cases where surgery is contraindicated or in patients with a high probability of post-surgical or post-anesthetic complications. Data on a longer follow-up are needed to confirm long-term efficacy.

Presentation Date: Saturday, June 17, 2023
SAT500 Thyroglossal Duct Cyst Cancer: Diagnosis And Management
Authors: Solis Pazmiño Andrea Paola , Rocha Carla , Figueroa Luis , Garcia Cristhian
Published: October 2023

Disclosure: A.P. Solis Pazmiño: None. C. Rocha: None. L. Figueroa: None. C. Garcia: None.

Background: Thyroglossal duct remnants form during the embryologic development of the thyroid gland. In rare cases, with an incidence of about 1%, carcinoma is present within these cysts, most commonly papillary thyroid carcinoma. Sistrunk procedure (SP) is the main treatment and optimal patient management includes multidisciplinary consultation in order to improve survival. However, there is a debate about whether SP is enough if there is a malignancy in the thyroid or if total thyroidectomy should be done on patients 45 years of age and individuals with aggressive disease [1]. TGDCC harbors an excellent prognosis and low recurrence rate. Clinical Case: We present a case of an elderly woman with a large submental mass that had been gradually enlarging for about 2 years. She had symptoms of dysphagia but denied odynophagia, hoarseness, or shortness of breath. Our patient had high blood pressure and a penicillin allergy but was otherwise healthy without a family history of carcinoma. Physical examination revealed a large submental mass (4.5x4x3.5 cm) that was hard and with smooth edges and did not move with deglutition. There was no extension into the oral cavity on bimanual palpation or palpable masses/nodules in the cervical region. There was a thyroid gland enlargement (right lobe 5x3x1.5, left lobe 4.5x2x1.2 cm). The ultrasound showed enlarged cervical lymph nodes. Fine needle aspiration (PAAF) suggested metastasis of thyroid cancer. Clinical lesson: Although Sistrunk surgery is accepted, performing a total thyroidectomy for TGDCC is controversial. Evidence suggests that it should be reserved for patients older than 45 years, like the patient described in this case. Total thyroidectomy is preferably performed based on the FNAB result (high-risk malignant) or if both thyroid lobes do not consist of healthy tissue anymore, regarding postoperative complication. Since TGDCC is a rare malignancy, a broad differential diagnosis should be considered: metastasis from an unknown primary, paraganglioma, hyalinizing trabecular tumor, and thyroglossal duct cyst, among others. The clinicopathological correlation, as well as the use of the FNA and the immunohistochemical markers, improve the diagnosis accuracy and help to decide the best treatment for the patient.

Presentation Date: Saturday, June 17, 2023
SAT506 A Unique Case of Large Pericardial Effusion In Hypothyroidism
Authors: Ahmad Malik Waseem , Arshad Bushra , Tarabichi Ula , Calimag Angela Pauline
Published: October 2023

Disclosure: M. Ahmad: None. B. Arshad: None. U. Tarabichi: None. A.P. Calimag: None.

Introduction: Hypothyroidism if left untreated can have devastating consequences both short and long term. We present you a case in which patient developed large pericardial effusion within a few months of stopping levothyroxine. Pericardial effusion is a relatively infrequent finding in hypothyroidism. This case is unique as large pericardial effusion is typically associated with severe thyroid hormone insufficiency such as myxedema, which wasn’t the case in our patient. Case: Patient is a 46-year-old female with PMHx of papillary thyroid cancer, s/p total thyroidectomy 2008, , HTN, obesity, Vit D Deficiency, iron deficiency anemia, sickle cell trait who presented to the ED with complaints of shortness of breath. Her symptoms started about a week ago and were associated with progressive dyspnea on exertion and fatigue. Patient mentioned that she stopped taking her levothyroxine 188 mcg daily and tried to treat herself with supplements. Workup was relevant for TSH 94.7 (0.350-5.0 mcU/ml), WBC 5.2 (4.2-11.0 k/mcl), Hgb 9.2 (12.0-15.5 g/dl),​ Na 141 (135-145 mmol/L), Cr 1.71 (0.51-0.95 mg/dl), ​negative Troponins,​ NT pro BNP 2590 (less then125 pg/ml)​ D Dimer 1.06. Vitals on presentation to the ED were Bp 194/135, HR 97, RR 18, T 98.4, Spo2 99% on room air.​ Chest x ray revealed new cardiomegaly, mild right sided pleural effusion. CTA chest was negative for pulmonary embolism but showed massive pericardial effusion. This was followed with transthoracic echo which demonstrated the pericardial effusion on the posterior surface of heart without tamponade. Cardiothoracic surgery was consulted but it was decided to treat the patient with IV levothyroxine rather than pericardial drainage as there was no hemodynamic compromise. Patient received 2 doses of IV levothyroxine and followed by PO levothyroxine per home dose. Shortness of breath improved by day 4 and patient was discharge in stable condition. Discussion: Complications related to hypothyroidism are preventable. There is a lot of misleading information about alternative medicine, which in turn can lead to life-threatening complications. Fortunately, pericardial effusion associated with severe hypothyroidism can rarely lead to cardiac tamponade and cardiovascular compromise. More emphasis and counselling about the importance of compliance with levothyroxine can prove vital to prevent thyroid hormone deficiency related complications.

Presentation Date: Saturday, June 17, 2023
SAT509 The Clinical Significance of Cribriform Morular Thyroid Carcinoma
Authors: Soh Gilbert , Sek Kathleen , Yang Samantha Peiling , Nga Min En , Mok Shao Feng
Published: October 2023

Disclosure: G. Soh: None. K. Sek: None. S. Yang: None. M. Nga: None. S. Mok: None.

We present two young (aged below 30) female patients who were diagnosed with the rare cribriform morular thyroid carcinoma. Both patients presented with neck swellings and underwent total thyroidectomy for the thyroid malignancies. The histological diagnosis prompted subsequent genetic evaluation. Both patients demonstrated genotypic and phenotypic evidence of familial adenomatosis polyposis (FAP) syndrome. One of the patients had a mutation which resulted in a premature translational stop signal in the adenomatous polyposis coli (APC) gene. She was eventually diagnosed with adenocarcinoma in 2 colonic polyps and underwent a curative pan-proctocolectomy. The other patient was diagnosed clinically with FAP as she had multiple (30-40) colonic polyps which were tubular adenomas. She had a variant of unknown significance in the APC gene. She declined surgery and remained on colonoscopic surveillance. Both patients’ thyroid cancers are in clinical remission. While uncommon, diagnosing cribriform-morular thyroid carcinoma is significant as 25 to 30% of patients harbour genetic mutations in the APC gene on chromosome 5q21. This is associated with FAP syndrome, an autosomal dominant genetic syndrome characterized by young-onset colonic polyposis, usually of malignant potential. Additionally, these patients may exhibit features of Gardner’s syndrome, a subset of FAP syndrome in which patients can develop extra-colonic manifestations such as osteomas of the mandible and supernumerary teeth. Histologically, cribriform morular thyroid carcinoma are well circumscribed and show a variable combination of follicular, cribriform, papillary, trabecular, solid and morular patterns. There is nuclear and cytoplasmic staining for beta catenin, as the inactivating APC mutation causes a loss of beta catenin destruction complex, impeding beta catenin degradation and increasing its nuclear translocation. This is a key event in thyroid tumorigenesis. The diagnosis of cribriform morular thyroid carcinoma should alert the clinician about the possibility of FAP with consideration for further clinical and genetic evaluation to confirm the diagnosis. References1)Cameselle-Teijeiro, J. M., Peteiro-González, D., Caneiro-Gómez, J., Sánchez-Ares, M., Abdulkader, I., Eloy, C., Melo, M., Amendoeira, I., Soares, P., & Sobrinho-Simões, M. (2018). Cribriform-morular variant of thyroid carcinoma: A neoplasm with distinctive phenotype associated with the activation of the Wnt/β-catenin pathway. Modern Pathology, 31(8), 1168–1179. https://doi.org/10.1038/s41379-018-0070-2 2)Peiling Yang, S., & Ngeow, J. (2016). Familial non-medullary thyroid cancer: Unraveling the Genetic Maze. Endocrine-Related Cancer, 23(12). https://doi.org/10.1530/erc-16-0067

Presentation Date: Saturday, June 17, 2023
SAT526 Limited Utility of Routine Neck Ultrasound Follow-up in Advanced Stage Differentiated Thyroid Cancer
Authors: Munro Vicki , Mustafa Syed , Siddiqi Ferhan S , Rajaraman Murali , Imran Syed Ali
Published: October 2023

Disclosure: V. Munro: None. S. Mustafa: None. F.S. Siddiqi: None. M. Rajaraman: None. S.A. Imran: None.

Background: Most guidelines recommend periodic cervical ultrasound (US) for ongoing surveillance of differentiated thyroid cancer (DTC). While recent studies do not support routine US surveillance in low-risk DTC, to date, no study has assessed the clinical utility of cervical US in advanced DTC. Methods: We conducted a retrospective study of our hospital DTC registry using the following criteria: a) AJCC stage III and IV, b) minimum follow-up of >4 years since total thyroidectomy +/-I-131 ablation, and c) at least one US per 3 years of follow-up. Patients with hemithyroidectomy only or positive anti-thyroglobulin antibody at the initial visit were excluded. Two years after initial treatment, patients were categorized by Dynamic Risk Stratification (DRS) as excellent, indeterminate, biochemically incomplete, or structurally incomplete response. Data obtained at each visit included: treatment response, thyroglobulin (TG) level, and US findings. Results: A total of 114 patients (85 AJCC stage III and 29 stage IV patients) met the inclusion criteria. Mean age (yrs) at diagnosis was 59, and 67% were female. Mean duration of follow-up was 8.5 years. Based on DRS, 73 patients had excellent response, 28 indeterminate, 8 biochemically incomplete, and 5 structurally incomplete. Recurrence or progression was detected in 20 patients (17.5%): 5 excellent response, 6 indeterminate, 5 biochemically incomplete, and 4 structurally incomplete. Recurrence sites included cervical region (14), distant metastases (5) and both (1). The TG rose from a mean of 4.76 ng/mL at baseline to 40.37 ng/mL at time of recurrence/progression. In those with structurally incomplete disease, US demonstrated progression in all 4 patients. However in other DRS categories, only 5/10 had definite US abnormalities. Of those without recurrence, 4 patients (4.3%) had false positive TG (mean baseline TG 0.08 rose to 11.8 ng/ml) without clinical/radiologic recurrence whereas the rate of false positive US abnormalities was 32% (37/114). The sensitivity and specificity of US vs. TG in diagnosing recurrence was 45% and 60% vs 100% and 95.7%, respectively. Conclusion: Our study suggests that routine cervical US surveillance after initial DRS does not improve the detection of recurrence in patients with excellent, indeterminate, or biochemically incomplete disease, and has a high false positive rate. Therefore, we suggest TG should be considered the mainstay of surveillance and any further imaging guided by DRS status and change in TG.

Presentation Date: Saturday, June 17, 2023
SAT538 Thyrotoxicosis in the Setting of Metastatic Poorly Differentiated Thyroid Carcinoma, a Marker of Disease Progression?
Authors: Chang Bolin L , Fernandez Mayumi A , Shikuma Lee Kelsey M
Published: October 2023

Disclosure: B.L. Chang: None. M.A. Fernandez: None. K.M. Shikuma Lee: None.

Background: Thyrotoxicosis is a rare manifestation of thyroid cancer, and poorly differentiated thyroid carcinoma (PDTC) causing thyrotoxicosis has even more rarely been reported. Here, we report a case of PDTC with thyrotoxicosis developing in a previously euthyroid individual with longstanding untreated follicular neoplasm. Clinical Case: A 79-year-old veteran presented to routine endocrine follow up with new symptoms of thyrotoxicosis. Although previously euthyroid, the evaluation revealed new findings of low serum thyrotropin (TSH) (<0.01 uIU/mL, n=0.34 – 5.60 uIU/mL), elevated free thyroxine (FT4) (2.6 ng/dL, n=0.58 – 1.64 ng/dL), and high total T3 (TT3) levels (223 ng/dL, n=76 – 181 ng/dL). Thyroid stimulating immunoglobulin antibodies (TSI) were positive (214, n<140). Patient has a nine-year history of a fine needle aspiration (FNA) of a large right-sided thyroid nodule with cytology suspicious for follicular neoplasm but declined surgical removal. Thyroid uptake and scan showed heterogeneous uptake throughout the right lobe with a relative photopenic region centrally and spots of more increased activity in areas within the right lobe. The left thyroid lobe showed uniformly low uptake. PET-CT evaluation confirmed spotty FDG-avid areas within the right thyroid mass but did not show other areas of hyperactivity. Methimazole was started with clinical and biochemical improvement. Patient underwent total thyroidectomy, and histopathologic examination showed PDTC with extensive angioinvasion involving the majority of the right thyroid lobe with the left lobe containing a mix of benign thyroid tissue and PDTC fragments. Areas of hyperintensity on the uptake scan correlated to pathological PDTC locations within the right lobe. Within three weeks of thyroidectomy, patient developed recurrent hyperthyroidism. Laboratory studies showed low TSH (0.04 uIU/mL) and elevated FT4 (2 ng/dL). In contrast to pre-operative studies, repeat TSI was below the reference range. Levothyroxine (LT4) was held in anticipation of radioactive iodine therapy, but four weeks later the TSH remained suppressed. 131I was administered which showed accumulation within small thyroid remnants and a single left level three 131I-avid lymph node without other metastases. Following 131I treatment, patient returned to a euthyroid state on standard LT4. Conclusion: Hyperthyroidism has rarely been associated with PDTC, although previous reports have linked more aggressive, multifocal, and locally invasive thyroid cancers to concurrent Graves’ disease or productive bulky metastatic disease. Even without bulky metastatic disease, clinicians should be aware that hyperproductivity may indicate development of autoimmune thyrotoxicosis within PDTC.

Presentation Date: Saturday, June 17, 2023
OR26-02 VRDN-001, A Full Antagonist Antibody To IGF-1 Receptor In Development For Thyroid Eye Disease (TED), Binds To A Distinct Epitope From Teprotumumab
Authors: Bedian Vahe , Tsai Jordan C , Newell Rachel N , Zhao Yang
Published: October 2023

Disclosure: V. Bedian: Employee; Self; Viridian Therapeutics Inc. J.C. Tsai: Employee; Self; Viridian Therapeutics Inc. R.N. Newell: Employee; Self; Viridian Therapeutics Inc. Y. Zhao: Employee; Self; Viridian Therapeutics Inc.

Introduction: VRDN-001, a full antagonist antibody to IGF-1 receptor (IGF-1R), is under development for the treatment of thyroid eye disease (TED). Clinical and preclinical evidence confirm IGF-1R antagonism reduces the inflammation and proptosis that occur in TED. As different anti-IGF-1R antibodies may have distinct characteristics, we compared the binding epitope and in vitro antagonist properties of VRDN-001 with teprotumumab. Methods: We generated a panel of IGF-1R extracellular domain point mutants of 40 potential IGF-1 interacting residues and 3 N-terminal truncations and assessed the binding pattern of the 2 antibodies to these variants by bio-layer interferometry (Octet). Antagonist characteristics were determined by dose-responses of inhibition of biotinylated IGF-1 binding to IGF-1R expressing FreeStyle™ 293-F cells by flow cytometry and inhibition of IGF-1 mediated signaling in primary human ocular choroidal fibroblasts. Results: VRDN-001 binding was affected by the same domain deletions/truncations as teprotumumab but was not affected by the same point mutations; while teprotumumab binding was reduced or abolished by 2 of the mutations, VRDN-001 binding was not affected by any of the 40-point mutations. These results are consistent with overlapping binding sites but distinct receptor interactions. In antagonism studies, at ≥50 nM, VRDN-001 nearly completely inhibited IGF-1 binding, while teprotumumab only partially inhibited IGF-1 binding through 300 nM. Similarly, VRDN-001 more completely antagonized IGF-1 mediated signaling (phosphorylation of IGF-1R and AKT) than teprotumumab. Conclusion: Despite having overlapping epitopes, VRDN-001 is distinct from teprotumumab in both its mutational signature and its more complete antagonism of IGF-1 mediated signaling. VRDN-001’s unique binding and functional antagonism characteristics may contribute to the robust pharmacodynamic responses observed in healthy volunteers and favorable efficacy signals observed in early clinical trials of TED patients.

Presentation: Saturday, June 17, 2023