Family History Of Thyroid Cancer Research Articles

Comparison of Patient Reported Outcomes between Active surveillance and Immediate Lobectomy in Patients with Low-risk Papillary Thyroid Microcarcinoma: Initial Findings from the KoMPASS cohort.

Patients diagnosed with low-risk papillary thyroid microcarcinoma (PTMC) face the decision between thyroid lobectomy and active surveillance (AS). This study aimed to investigate the factors influencing treatment decisions in low-risk PTMC and to compare the quality of life (QoL) according to the treatment plan. The multicenter prospective cohort study comparing AS and thyroid lobectomy was conducted. Clinical characteristics were compared between the AS and Lobectomy groups. QoL questionnaires were administered every 6 months in the initial year and annually thereafter. A total of 927 patients (453 in the AS group and 474 in the Lobectomy group) with low-risk PTMC were included in this study. The mean age was 47.4 ± 12.2 years, and 72.2% of the patients were women. Older age (odd ratio [OR] 1.04, 95% confidence interval [CI] 1.02 - 1.05, p <0.001), smaller tumor size (OR 0.78, 95% CI 0.69 - 0.87, p <0.001), family history of thyroid cancer (OR 1.48, 95% CI 1.03 - 2.12, p = 0.035), prior awareness of AS (OR 1.53, 95% CI 1.16 - 2.02, p = 0.003), and higher income (OR 1.79, 95% CI 1.13 - 2.83, p = 0.013) were significantly associated with a higher likelihood of choosing AS. The median follow-up was 27.3 months (23.9 - 43.9) in the AS group and 28.7 months (20.4 - 44.5) in the Lobectomy group. During the follow-up period, the AS group showed significantly better QoL scores compared to the Lobectomy group (β 0.17, 95% CI 0.02 - 0.33, p = 0.029). Although baseline QoL scores favored the AS group significantly (7.1 ± 1.2 vs. 6.7 ± 1.2, p < 0.001), no significant difference was observed after 12 months (7.2 ± 1.2 vs. 7.1 ± 1.2, p =0.592). This study demonstrated that age, tumor size, family history of thyroid cancer, awareness of AS, and income were associated with patients' treatment choices. Although the overall QoL scores were significantly higher in the AS group, the QoL became similar between the two groups after 12 months.

Oncocytic carcinoma of the thyroid: Conclusions from a 20-year patient cohort.

Oncocytic carcinoma (OCA) was recently reclassified as a distinct differentiated thyroid carcinoma (DTC). Given its rarity, OCA studies are limited. This study describes the characteristics of OCA in a 20-year cohort. Retrospective analysis of patients with OCA at a single tertiary care hospital from 2000 to 2021. Fifty-one OCA patients (22M:29F) were identified. The mean age at diagnosis was 60.3 years; 90% presented as palpable mass; 24% had a family history of thyroid cancer. None had vocal fold paresis. On ultrasound, most tumors were solid and hypoechoic. FNA (n = 14) showed Bethesda-4 lesions in 93%. All were treated surgically. Histologically, 63% demonstrated angioinvasion, 35% had lymphovascular invasion, and 15% had extrathyroidal extension. Radioactive iodine was used as adjunct therapy in 77%. OCA has distinct features that distinguish it from other DTCs, and additional focused studies will help clarify the aggressive nature, treatment options, and prognosis of the disease.

A nomogram for predicting adverse pathologic features in low-risk papillary thyroid microcarcinoma

BackgroundIdentifying risk factors for adverse pathologic features in low-risk papillary thyroid microcarcinoma (PTMC) can provide valuable insights into the necessity of surgical or non-surgical treatment. This study aims to develop a nomogram for predicting the probability of adverse pathologic features in low-risk PTMC patients.MethodsA total of 662 patients with low-risk PTMC who underwent thyroid surgery were retrospectively analyzed in Qilu Hospital of Shandong University from May 2019 to December 2021. Logistic regression analysis was used to determine the risk factors for adverse pathologic features, and a nomogram was constructed based on these factors.ResultsMost PTMC patients with these adverse pathologic features had tumor diameters greater than 0.6 cm (p < 0.05). Other factors (age, gender, family history of thyroid cancer, history of autoimmune thyroiditis, and BRAFV600E mutation) had no significant correlation with adverse pathologic features (p > 0.05 each). The nomogram was drawn to provide a quantitative and convenient tool for predicting the risk of adverse pathologic features based on age, gender, family history of thyroid cancer, autoimmune thyroiditis, tumor size, and BRAFV600E mutation in low-risk PTMC patients. The areas under curves (AUC) were 0.645 (95% CI 0.580–0.702). Additionally, decision curve analysis (DCA) and calibration curves were used to evaluate the clinical benefits of this nomogram, presenting a high net benefit.ConclusionTumor size > 0.60 cm was identified as an independent risk factor for adverse pathologic features in low-risk PTMC patients. The nomogram had a high predictive value and consistency based on these factors.

SAT571 When Two Is Too Few: Bethesda IV Pathology On Repeat Thyroid Fine Needle Aspiration

Abstract Disclosure: C.M. Godar: None. A.J. Spiro: None. M.K. Shakir: None. T.D. Hoang: None. Background: The 2015 American Thyroid Association Guidelines for Adult Patients with Thyroid Nodules provide a strong recommendation against routine ultrasound surveillance of thyroid nodules for which two benign fine needle aspiration (FNA) cytology results have been previously obtained. Strict adherence to these guidelines may hinder detection of malignancy, especially in large nodules where there is potential to miss heterogeneous pathology based on sampling technique. Clinical Case: A 36-year-old female was evaluated for surveillance of a large non-toxic multinodular goiter. Thyroid ultrasound demonstrated a dominant right thyroid nodule greater than 7 centimeters in size. The patient had undergone FNA of this nodule in 2014 and 2019 with Bethesda II (benign) cytopathology results. A chest x-ray showed tracheal deviation without evidence of narrowing. She noted a sensation of neck pressure without dysphagia or shortness of breath. She denied fatigue, heat or cold intolerance, hand tremor, or pretibial myxedema. She denied a family history of thyroid cancer or any history of neck irradiation. Due to new compressive symptoms a repeat FNA was performed. Three passes were performed with adequate samples, and the final FNA cytopathology demonstrated a Hurthle cell oncocytic-type follicular neoplasm with Bethesda IV classification. The sample was submitted for ThyGeNEXTTM and ThyraMIRv2TM molecular testing, which returned with NRAS q61R mutation of moderate-to-high risk of malignancy (65-75%). The patient was subsequently referred for total thyroidectomy with pending surgery date. Discussion: The current ATA guidelines offer a cost-effective surveillance strategy for the vast majority of patients with thyroid nodules. False negative FNA results are rare and are reported to occur in about 1% of cases1. As in this vignette, it is reasonable to perform an additional FNA after two consecutive Bethesda II results in nodules with clinically significant growth, new compressive symptoms, or if there is concern for incomplete sampling in nodules of large size. During an FNA, care should be taken to gently move the needle at various angles to capture follicular cells from different areas within a nodule. Large nodules should be sampled via multiple, separate skin entry points when feasible. Judicious use of repeat FNA along with these sampling techniques may help to prevent under-diagnosis in nodules containing multifocal areas of heterogeneous pathology. Reference: 1) Durante C, Costante G, Lucisano G, Bruno R, Meringolo D, Paciaroni A, Puxeddu E, Torlontano M, Tumino S, Attard M, Lamartina L, Nicolucci A, Filetti S. 2015. The natural history of benign thyroid nodules. JAMA 313:926-935 Presentation: Saturday, June 17, 2023

SAT545 Erythropoietic Thyroid Nodule in the Setting of Myelofibrosis

Abstract Disclosure: L.M. Vasquez: None. J.M. Bruder: None. M. Koops: None. J. Trejo: None. Background: Extramedullary hematopoiesis is frequently seen in non-osseous locations but not endocrine organs, this is a case of hematopoesis in a thyroid nodule. Clinical Case: A 79-year-old man with myelofibrosis diagnosed at age 66, CAD post CABG, atrial fibrillation on anticoagulation and HFrEF was referred to the endocrinology clinic due to enlarging left lobe thyroid nodule. He was diagnosed with a goiter at age 72 but denied compressive symptoms. He had no history of radiation to his neck or family history of thyroid cancer. On physical exam, the left thyroid lobe was visibly enlarged with slight right tracheal deviation without lymphadenopathy. TSH level was normal. Thyroid ultrasound demonstrated a 6.4 x 4.0 x 4.8 cm, complex cystic-solid, taller than wide nodule in the left lobe and a sub-centimeter cystic nodule in the right lobe. FNA showed hematopoietic elements, including maturing cells in three lineages of hematopoiesis. On repeat ultrasound 5 years later. The left nodule increased in size to 7.3 x 5.4 x 4.4 cm and highly suspicious (TR4 and TR3) by Ti-RADS criteria. Repeat FNA of the nodule showed many red blood cells with few hematopoietic cells, flow cytometry did not show any abnormal populations. No thyroid follicular cells were reported. Myelofibrosis was diagnosed by bone marrow biopsy many years prior. He had maintained a stable CBC without palpable spleen or hepatomegaly. Given this history without thyroid dysfunction or reported symptoms, surgery was not pursued. External beam radiation was a treatment option should the nodule cause symptoms. He continued to have mild anemia not requiring blood transfusions. He passed away 2 years later in hospice care after hospitalization for severe heart failure decompensation. Conclusion: Extramedullary hematopoiesis involving the thyroid is rare but has been reported(1). This type of extramedullary hematopoiesis. can be treated with surgery or low-dose radiation because of the radiosensitivity of hematopoietic tissue (2). This was a potential treatment modality if compressive symptoms arose, but they did not. This case illustrates a situation in which surgical intervention on highly suspicious nodules would not have been the optimal treatment choice. Reference: 1. Jan I., Weng M., Wang C., et al. Extramedullary hematopoiesis involving the thyroid: A rare cytologic finding in otherwise healthy patients and review of literature. Journal of the Formosan Medical Association. (2018) 117, 1108-1114. 2. Taher A, Vichinsky E, Musallam K et al., authors; Weatherall D, editor. Guidelines for the Management of Non-Transfusion Dependent Thalassaemia (NTDT) [Internet]. Nicosia (Cyprus): Thalassaemia International Federation; 2013. Chapter 11, EXTRAMEDULLARY HEMATOPOIESIS. Available from: https://www.ncbi.nlm.nih.gov/books/NBK190455/ Presentation Date: Saturday, June 17, 2023

SAT532 A Rare Case of Thyroid Carcinoma Noted in a Patient with Thyroid Nodule Showing Prior Benign Biopsy and Prior Negative Molecular Testing

Abstract Disclosure: M.M. Hillhouse: None. P. Madhavan: None. F.M. Woron: None. Background: Molecular studies have a high sensitivity for ruling out malignancy (1). This patient was diagnosed with the follicular variant of papillary thyroid carcinoma despite negative molecular testing and benign cytology in multiple prior biopsies. Clinical Case: 31 y.o. female with a past medical history of Hashimoto's disease on levothyroxine presented for follow up of thyroid nodules. She does not have a family history of thyroid cancer or personal history of neck radiation. The patient was noted to have a right thyroid nodule around 14 years of age and this was monitored during her childhood. The nodule measured 2.3 x 0.6 cm on ultrasound in 2015. The nodule measured 2.0 x 1.6 x 1.5 cm in 2017. FNA in 2017 revealed benign cytology (Bethesda II). On ultrasound in 03/2019, the nodule measured 2.2 x 1.5 x 1.8 cm. The nodule demonstrated a greater than 20% increase in all dimensions on ultrasound images in 12/2020 to 2.9 x 2.0 x 2.6 cm. A repeat ultrasound in 04/2021 demonstrated no significant change in size. Repeat FNA performed in 07/2021 demonstrated clusters of follicular cells in flat and microfollicular groups and was interpreted as atypia of undetermined significance (Bethesda III). AFIRMA testing was benign (∼4% of malignancy. The nodule increased in size to 3.5 x 2.6 x 3.1 cm on ultrasound in 07/2022. It appeared solid and hyperechoic and was classified as TI-RADS 3. A new 0.8 cm nodule on the left lobe was also identified. Repeat FNA of the right nodule in 09/2022 demonstrated macrophages, colloid and groups of follicular cells and was classified as non-diagnostic (Bethesda I). She reported difficulty breathing in the supine position and she underwent a right hemithyroidectomy and isthmusectomy in 11/2022. Pathology results were remarkable for invasive encapsulated follicular variant of papillary thyroid carcinoma with focal angioinvasion and tumor capsular invasion. The margins were negative for tumor. The parenchyma was consistent with lymphocytic thyroiditis. Ultrasound after interval right hemithyroidectomy in 12/2022 in an outside facility demonstrated an unchanged subcentimeter left thyroid nodule and multiple bilateral anterior cervical/level 6 lymph nodes suspicious for metastatic disease given the absence of hilum. Patient is currently undergoing repeat imaging and work up for the lymphadenopathy. Conclusion: This case study highlights the importance of maintaining high clinical suspicion for thyroid malignancy in cases of increasing thyroid nodule size and compressive symptoms despite negative cytological and molecular testing.

SAT574 Thyroglossal Duct Papillary Thyroid Cancer With Normal Eutopic Thyroid Gland: A Management Dilemma

Abstract Disclosure: H. Belal: None. J.T. Batch: None. G.Y. Gandhi: None. Background: The incidence of thyroglossal duct cyst carcinomas is less than 1%, the majority being papillary thyroid cancer. One-third arise de novo from the thyroglossal duct. The rest are direct metastasis of eutopic papillary thyroid cancer. Management in the setting of a normal eutopic thyroid gland is challenging. Clinical Case: A 35-year-old female presented with transient right facial paresthesia. CT angiogram revealed an incidental 2.3 cm thyroglossal duct cyst with internal ectopic thyroidal tissue and micro-calcifications. She denied any compressive symptoms, radiation exposure, or family history of thyroid cancer and was euthyroid. Ultrasound noted a normal thyroid gland and complex solid-cystic mass measuring 2.3 x 2.0 x 1.5 cm superior to the isthmus. Satisfactory fine needle aspiration of the mass revealed benign-appearing epithelial cells, macrophage, and colloid-like material. Due to new anterior neck pain, a Sistrunk Procedure (SP) was performed. Pathology revealed a 1.2 cm papillary thyroid carcinoma, conventional type (confirmed by TTF-1 and thyroglobulin stains), arising within the thyroglossal duct cyst. Surgical margins were free of cancer, and there was no lymphovascular invasion. A thyroid ultrasound seven months after the procedure revealed heterogenous thyroid tissue, no thyroid nodules, and several small benign-appearing reniform-shaped cervical lymph nodes in zones 1 and 2. The patient was offered yearly thyroid ultrasound surveillance versus prophylactic thyroidectomy. She elected to proceed with thyroidectomy due to concerns about disease recurrence. Final pathology results revealed right lobe 2 mm papillary microcarcinoma limited to the thyroid. Conclusion: Fine needle aspiration of thyroglossal duct cysts can have a high false negative rate, as in our patient. There is currently no consensus on treatment of thyroid carcinomas arising from thyroglossal duct cysts. There are four possible surgical strategies: 1) SP alone 2) SP with concurrent thyroid lobectomy or pyramidal lobe resection 3) SP with total or near total thyroidectomy in all patients and 4) SP and selective addition of total or near total thyroidectomy in high-risk patients. The role of radio-iodine ablation and levothyroxine suppression after SP is also unclear. Management recommendations are Grade C, relying on case reports, case series, and expert opinion. Whether or not to proceed with total thyroidectomy, especially in the setting of a normal thyroid gland, remains highly controversial. Some experts even argue for an early aggressive surgical approach with SP, total thyroidectomy, and level I lymph node sampling in all patients to provide accurate staging and allow for the use of thyroglobulin and whole-body scintigraphy in surveillance. Multisite comparative data on the long-term outcomes of patients who receive early aggressive versus conservative management is needed. Presentation: Saturday, June 17, 2023

Surgical management of low-risk papillary thyroid cancer in real life in Spain: a nationwide survey of endocrine neck surgeons and endocrinologists.

The extent of surgery in patients with papillary thyroid cancer (PTC) is a subject of ongoing debate. We aimed to explore the attitude of Spanish specialists (endocrinologists, surgeons, and otolaryngologists) in real life on the surgical management of low-risk PTC. We designed an anonymous, web-based survey to inquire information regarding the preferences of interviewees for hemithyroidectomy (Hem), total thyroidectomy (TT) and prophylactic central neck dissection (pCND) in one standard patient with PTC and six clinical variants. We differentiated between small (1.1-2.5 cm) and large (2.6-4.0 cm) tumors. A total of 278 valid responses were received and divided into two groups: group END (n = 135) and group SUR (n = 143, 101 general surgeons and 42 otolaryngologists). The preference for Hem was low in the standard patient and similar between both groups (40.6 vs 49.0%, NS). This preference decreased for tumors measuring 2.6-4.0 cm, multifocal, with risk location, family history of thyroid cancer, or history of irradiation, and increased in patients older than 65 years or with comorbidity. Preference for pCND ranged from 12.6-71.1% in the group END and from 22.4-65.0% in the group SUR, with few differences between the two. In multivariate analysis, being a high-volume specialist was associated with a lower preference for Hem, while having private practice was associated with a more favorable opinion of Hem. The real clinical practice of Spanish specialists is far from what is recommended by the clinical guidelines in patients with low-risk PTC, especially among high-volume professionals.

Factors for second non-diagnostic ultrasound-guided fine-needle aspiration cytology in thyroid nodules

IntroductionResults in fine-needle aspiration cytology (FNAC) of thyroid nodules may be non-diagnostic (ND). In these cases, it is recommended to repeat the FNAC. The aim of our study was to evaluate the influence of demographic, clinical and ultrasound (US) characteristics in the recurrence of an ND result in thyroid nodule FNAC. MethodsA retrospective study of ND thyroid nodule FNAC was performed for the period 2017–2020. Demographic and clinical data (age, gender, cervical radiotherapy, presence of Hashimoto's thyroiditis, and TSH value) and US characteristics (nodule size, echogenicity, composition and microcalcifications) were collected at first ND FNAC. ResultsOut of 230 nodules with first ND FNAC (83% women; mean age 60.2±14.1 years), 195 (84.8%) underwent a second FNAC: 121 benign, 63 non-diagnostic, 9 indeterminate and 2 malignant. Nine (3.9%) underwent surgery, only 1 of which showed malignant histology and 26 (11.3%) remained under US monitoring. Demographically, patients with second ND FNAC were older (63.4±14 vs. 59±14 years; P=0.032). Females had lower risk of second ND FNAC (OR, 0.4, 0.2–0.9; P=0.016); risk of second ND FNAC was higher in patients treated with anticoagulant/antiplatelet drugs (OR, 2.2, 1.1–4.7; P=0.03). Previous cervical radiotherapy, family history of thyroid cancer, Hashimoto's thyroiditis and TSH value did not influence the risk of second ND FNAC. On US, nodule echogenicity differed significantly between the ND and diagnostic FNAC, with greater risk of an ND result in hypoechogenic nodules. Microcalcification increased the risk of ND FNAC (OR 2.2, 1.1–4.5; P=0.03). Nodule composition and size did not significantly differ according to ND or diagnostic second FNAC. ConclusionMale gender, advanced age, anticoagulant/antiplatelet drug therapy, hypoechogenic nodules and microcalcified nodules are likely factors for second ND FNAC. Nodules with two ND FNACs were rarely malignant, and a more conservative approach in these cases is not unsafe.

Ultrasound screening for thyroid nodules and cancer in individuals with family history of thyroid cancer: a micro-costing approach.

Screening programs that target healthy populations are an important tool for identifying unrecognized, asymptomatic disease. However, ultrasound screening for thyroid cancer has no obvious advantage in terms of cost-effectiveness in asymptomatic adults. There is far less consensus (and data) on the indications for screening in high-risk individuals. The aim of the study was to estimate the costs of ultrasound screening for individuals with first-degree family history of thyroid cancer. We conducted a prospective cross-sectional study from January 1, 2009 through December 31, 2018 in the Thyroid Cancer Outpatient Clinic of a large teaching hospital in Rome, Italy. We estimated the costs of an ultrasound screening protocol using the micro-costing bottom-up method. For individuals without thyroid nodules, the screening examination had an estimated cost of €66.21 per screenee. For those found to have unsuspicious nodules, the estimated cost rose to €119.52 per screenee, owing to the addition of thyroid function tests. The estimated cost of screening for a subject with newly diagnosed nodules that were submitted to cytology was €259.89. The total cost of screening for the entire population of 1176 individuals was € 118,133.85. The total expenditure to confirm a single thyroid cancer diagnosis was €10,598.71. A sonographic screening implies a significant direct expenditure and is likely to detect a very large number of individuals with benign nodules (more than 45 asymptomatic individuals are diagnosed with a thyroid nodule for each newly detected cancer case), whose long-term follow-up will further increase healthcare costs.

Frequency of Thyroid Carcinoma in Multi Nodular Goiter

Objective: The objective of this study was to determine the frequency of thyroid carcinoma in patients presenting with multinodular goiter in BMCH. Study Settings: Research was conducted at Department of General Surgery, Bolan Medical Complex Hospital Quetta. Material and Methods: Eighty four patients from both the genders with age between 20-75 years presenting with multinodular goiter since 3 months and meeting inclusion criteria were included in this study after taking informed written consent. All the thyroidectomies were done by consultant general surgeon of the hospital. Post-operatively all the patients were managed as per hospital protocol. Post thyroidectomy specimen was sent for histopathology for diagnosis of thyroid malignancy as per operational definition. All the other findings of study variables such as age, gender, place of residence, BMI (weight in Kg/Height in m2), family history of malignancy, diabetes, hypertension, smoking (&gt;5 cigarettes/day for 2 years) and duration of goiter were noted in a predesigned proforma. Results: The mean age of the patients was 37.4±14.0 years. Majority (n=48, 57.1%) of the patients were aged between 25-50 years, followed by 23 (27.4%) patients aged &lt;25 years and 13 (15.5%) patients aged &gt;50 years. There were 17 (20.2%) male and 67 (79.8%) female patients with a male to female ratio of 1:4. Family history of thyroid malignancy was positive in 11 (13.1%) patients. Thyroid carcinoma was detected in 12 (14.3%) patients with multinodular goiter. When stratified, the frequency of thyroid carcinoma was significantly higher among smokers (29.2% vs. 8.3%; p-value=0.014) and those with positive family history of thyroid cancer (36.4% vs. 11.0%; p-value=0.047). However, no statistically significant difference was observed across various subgroups of patients based on age (p-value=0.978), gender (p-value=1.000), BMI (p-value=1.000), duration of goiter (p-value=0.928), place of residence (p-value=1.000), diabetes (p-value=0.928) and hypertension (p-value=0.858). Conclusion: In the present study, we observed that a substantial proportion of patients with multinodular goiter had concealed thyroid carcinoma particularly smokers and those with positive family history which warrants careful pre-operative evaluation of such patients for thyroid malignancy so that it may be identified well in time and appropriate management may be initiated to improve outcomes in future practice. Keywords: Multinodular Goiter, Thyroid Carcinoma, Positive Family History, Smoking

Incidental Thyroid Carcinomas versus Benign Thyroid Cases. A Clinico-Radiological Comparison

Abstract Introduction/Objective We aim to identify the clinico-radiological characteristics unique to incidental thyroid carcinomas (ITCs) in comparison to benign thyroid cases. Previous studies show a positive correlation between ITCs and a euthyroid state. Currently nodules greater than 4 cm (N&amp;gt;4cm) with or without a negative fine needle aspiration (FNA) are excised because of a higher risk of malignancy. Methods/Case Report A 6-year retrospective study was performed on 227 thyroidectomy specimens collected during 2017-2022. 146 patients were benign. 26 patients with a negative/absent FNA were found to have ITCs. 55 patients had malignant thyroids (MTs). Age, gender, compressive symptoms, thyroid hormone status, presence of nodules, number of nodules, N&amp;gt;4cm, suspicious radiologic findings, personal history of other malignancies, family history of thyroid cancer (FHTCA) and a family history of thyroid disease were analyzed between the benign and ITC groups. A t-test was utilized for numerical variables and a chi-square test for categorical values. For any significant correlations, a maximum likelihood estimate was used to calculate the odds ratio. Results (if a Case Study enter NA) Incidence of ITC amongst all specimen was 11.4% (26/227). 32% (26/81) of all reported MTs were ITCs. Papillary thyroid carcinomas accounted for 92.3% (24/26) of ITCs, follicular carcinomas accounted for 7% (2/26). 3/26 patients with ITC, 4/146 patients with benign thyroids and 5/55 patients with MT had a FHTCA. We found a significant correlation between FHTCA and thyroid malignancy [MT + ITC; odds ratio = 4.11 (CI = 1.198 – 14.154)]. A FHTCA was associated with more than a 4 times likelihood of having ITC compared to those without a family history (odds ratio = 4.77) (CI [1 - 22.782]). Other variables did not show any statistically significant differences between the ITC and benign groups. Conclusion Although previous studies report a correlation between ITCs and a euthyroid status and N&amp;gt;4cm, our study didn’t confirm it. However, this may be due to our smaller sample size. In our patient population, an FHTCA was associated with significantly higher incidence of ITCs which may outline a subpopulation that should be considered for more aggressive screening. No other variables were statistically significant.

ODP446 Where's the Nodule?: Atypical Presentation of an Occult Metastatic Papillary Thryoid Carcinoma

Abstract Papillary thyroid Carcinoma (PTC) with apparent distant metastasis but lacking a primary thyroid cancer on pre-operative ultrasonographic examination, is referred by some as occult PTC. In most cases, primary carcinomas are identified after careful pathologic examination of the specimen but in some rare cases the primary tumors were not detected. Hereby, we describe the rare case of a patient with metastatic PTC without initial visualization on imaging of primary tumor location along with inconsistent pathology results between fine needle aspiration (FNA) biopsy and gross specimen pathology results. A 60-year-old female with past medical history of Diabetes Mellitus type 2 and Hypothyroidism presenting for follow-up visit after being found with neck nodules on head and neck CT scan. Thyroid and neck Ultrasound (US) were performed finding three right irregularly shaped hypoechoic lymph nodes (LN's) measuring &amp;gt; 1 cm, concerning for metastatic disease, but no thyroid nodules were noted. Patient denies family history of thyroid cancer, and no head and neck radiation exposure. Physical examination did not reveal goiter or palpable nodules. Laboratory results: TSH: 2.95 and Total T4: 9.32, both within normal range. Cervical LN's FNA biopsy was performed, yielding results consistent with PTC tall cell variant. Chest CT scan showed suspicious lesions for pulmonary micrometastasis. Total thyroidectomy was performed and gross pathology findings showed an infiltrating, follicular variant PTC with multifocal tiny primary tumors of the thyroid, with lesions measuring up to 0.2 cm, dimension which explains why nodules could not be identified on imaging studies. LN's FNA biopsy results and thyroid pathology did not correlate. Thyroid gross pathology was clearly PTC with follicular variant, infiltrating a small area away from greatest dimension tumor, with cells with apparent dedifferentiation to tall cell cytologic features. Due to high risk of recurrence, radioactive iodine therapy was recommended as adjunctive therapy for metastatic disease and eradication of residual neck disease to be started with levels of TSH&amp;gt;30 mU/ml. Postopertative Thyroglobulin level (Tg) was adequate &amp;lt; 0. 01 ng/ml but unreliable based on above normal range antithyroglobulin antibody &amp;gt; 1000 IU/ml, which increases risk of recurrence. Whole body scan also done showing bilateral lung metastasis and small neck metastatic disease. Repeated postoperative thyroid US also demonstrated a suspicious cystic lymph node in right central neck for which FNA with saline washout of aspirate for Tg measurement was ordered. Metastatic thyroid carcinoma without primary tumor after extensive thyroid sampling is a rare but existent phenomenon that can be encountered in daily practice. Genotyping or immunostaining mestastatic lesions could help direct the Pathologist to the source of the metastasis. Patients with a higher risk of recurrence are monitored more aggressively as it is believed that early detection of recurrent disease offers the best opportunity for effective treatment. Presentation: No date and time listed

ODP518 Three Cases of Autoimmune Thyrotoxicosis after the BNT162b2 mRNA Covid-19 Vaccine

Abstract Background Various vaccines have been produced around the world in the battle against coronavirus disease 2019 (COVID-19) in the past year. Clinical trials and approvals of these vaccines were expedited at an unprecedented speed, with some of them approved under emergency use. Since March 2021, government coordinated vaccination program using two types of vaccines against COVID-19 were being undertaken in Hong Kong. BNT162b2 mRNA COVID-19 vaccine under the name of BioNTech was one. While it is a promising measure to control COVID-19, the new mRNA vaccine technology does cast some doubts, particularly its safety. In addition to the commonly reported injection site reactions and systemic upsets, less reported reactions after this new vaccine requires more clarifications. Here, we report 3 cases of autoimmune thyrotoxicosis all happened soon after the vaccination. Clinical Cases: Case1 A 40-year-old man with family history of thyroid cancer (mother had thyroid cancer with operation done) developed palpitations 17 days after receiving the first dose of BioNtech vaccine. Investigations confirms Graves’ thyrotoxicosis as evidenced by elevated fT4 and suppressed sTSH with positive thyroid stimulating immunoglobulin (TSI) and a diffuse vascular goiter on ultrasound (USG) thyroid. He was started on a course of anti-thyroid drug and had been advised to defer the second dose of vaccine until clinically stable. Case2 A 44-year old lady without personal/family history of thyroid disease developed progress neck swelling and palpitation with tremor 3 days after receiving the first dose of BioNtech vaccine. Investigations confirmed Graves’ thyrotoxicosis with elevated fT4 and suppressed sTSH with positive TSI, anti-TPO, and anti-ATG. USG thyroid showed diffuse vascular goiter. She was treated with a course of anti-thyroid drug and had been advised to defer the second dose of vaccine until stabilization of thyroid function. Case3 A 56-year-old man with positive family history of thyrotoxicosis (elder brother with history of thyrotoxicosis treated with radioactive iodine) developed progressive weight loss, increased appetite, insomnia, palpitation, and tremor around 7 days after the first dose of BioNtech vaccine. Patient only presented to an Endocrinologist for further workup 63 days after the first dose (42 days after second dose of BioNtech). Biochemically he had high fT4, suppressed sTSH, with positive anti-ATG, anti-TPO and TSI. USG thyroid revealed a small diffuse goiter. He was treated with a course of anti-thyroid drug with regular follow-up and monitoring. Conclusion This is the first case-series in Hong Kong demonstrating the possible triggering of Graves’ thyrotoxicosis after BioNTech vaccination. TSI and USG thyroid are invaluable tools to confirm the autoimmunity nature of the disease. Further studies are needed to clarify the prevalence, mechanisms, preventions, and treatments of this vaccine complication. Presentation: No date and time listed

ODP488 Incidental papillary thyroid cancer found after hemi-thyroidectomy in man with MUTYH-associated polyposis

Abstract MUTYH-associated polyposis (MAP) is an autosomal recessive syndrome caused by a mutation to the MUTYH gene, a base excision repair gene that repairs oxidative damage to DNA. Mutations to both allelic copies of this gene typically manifest as multiple colonic polyps, which develop by middle age. Individuals with MAP are also at higher risk for developing non-gastrointestinal (GI) cancers including those affecting the ovary, bladder, breast, endometrium, and possibly thyroid. A 66-year-old man with a history of MAP complicated by colonic polyposis requiring subtotal colectomy, an esophageal adenocarcinoma resected by esophagectomy, and a gastrointestinal stromal tumor also resected was referred to endocrinology clinic for an incidental thyroid nodule found on routine surveillance. The patient denied prior neck radiation but reported having a daughter and cousin with thyroid cancer. Ultrasound showed a left 3.3 by 2.8 by 1.6 cm thyroid nodule with multiple lobulations. Although a fine needle aspiration (FNA) of the nodule was benign, a repeat ultrasound several months later noted an increase in size to 3.5 by 3.5 by 2. 0 cm. Given the nodule's significant growth, the patient's history of MAP, and family history of thyroid cancer, the patient underwent a left hemi-thyroidectomy. Pathology revealed that the nodule was a follicular adenoma, however also identified two papillary microcarcinomas, measuring 1 and 2 mm. The patient was started on levothyroxine 50 mcg with a goal TSH below 0.5 mU/L and was monitored with ultrasounds which were unremarkable. In 2021, the national cancer institute estimated approximately 150,000 cases of colorectal cancer (CRC) with a 65% 5-year survival, compared to 44,000 cases of thyroid cancer with a 98% 5-year survival. Although the incidence of CRC in patients with MAP is high, approximately 43-63% by age 60, the risks of several associated non-GI malignancies are not as well defined. The national comprehensive cancer network (NCCN) and the American College of Gastroenterology (ACG) both published guidelines regarding appropriate screening for both GI and associated non-GI malignancies. In regards to thyroid cancer, both advise screening in patients with familiar adenomatous polyposis (FAP), another familial condition, due to the increased risk of papillary thyroid cancer (PTC) of approximately 1-2%. The evidence concerning MUTYH is not as strong, with the ACG recommending annual thyroid cancer screening, although the quality of evidence is low. Since a thyroid ultrasound is both low-cost and non-invasive and the overall survival of patients with PTC is high, we agree that patients with MAP be screened with thyroid ultrasounds. This case highlights the possibility that thyroid cancer is a manifestation of MAP, and a lower threshold to send for surgery may be warranted for those with other risk factors such as a family history or prior neck radiation. Presentation: No date and time listed

PSAT278 A Curious Case of Thyroglossal Duct Cancer

Abstract Introduction Thyroglossal duct (TGD) cyst is a common congenital anomaly. Thyroid cancer rarely occurs in TGD cysts, affecting less than 1% of cysts. Here we present a case of TGD cancer presenting as a central neck mass. Case Presentation 60 y.o female presented to her primary care physician with a neck mass without any compressive symptoms. She had no history of head/neck radiation exposure and no family history of thyroid cancer. She was noted to have a non-tender central neck mass with palpable cervical lymphadenopathy. Neck ultrasound revealed a 5.7 cm multilobulated cystic and solid mass anterior to the thyroid gland. CT scan of the neck revealed a lobulated mixed solid cystic mass at the level of the thyroid cartilage projecting anteriorly, with an abnormal right submandibular lymph node measuring 2.2×1.0 cm. She was evaluated by ENT and underwent resection of the neck mass and the hyoid bone (Sistrunk's procedure). Level 1b lymph node was also removed. Operative findings were concerning for a malignant process. This was confirmed on pathology with findings of TGD papillary thyroid cancer (PTC) and level 1b lymph node demonstrating metastatic PTC with cystic features. She was then referred to endocrine. Thyroid ultrasound revealed multiple bilateral intermediate suspicion nodules. Left inferior thyroid nodule was noted to have high suspicion sonographic features with abnormal right sided level 2 and 3 lymph nodes. She was referred for total thyroidectomy, pathology revealed multifocal PTC with lymph node involvement with extra nodal extension and metastasis to the left sternohyiod muscle, pT2, pN1b, AJCC stage 2. 6-week post-surgical labs revealed TSH of 1.69 mIU/L (ref range 0.40-4.50), thyroglobulin level of 0.8 ng/ml (ref range athyrotic &amp;lt;0.1), with undetectable thyroglobulin antibodies &amp;lt;1 IU/ml (ref range &amp;lt; or = 1 IU/mL). She underwent RAI with 104.6 mci. I-131 Metastatic survey revealed increased uptake in the thyroid bed, otherwise no increased activity elsewhere. Stimulated TSH and Thyroglobulin levels were done but not collected appropriately and therefore not mentioned here. Repeat labs 12 weeks after RAI revealed a TSH of 2.86 mIU/L, Thyroglobulin level of 0.2 ng/ml, and undetectable Thyroglobulin antibody. Conclusion There are no standardized guidelines for management of TGD cancer given the rarity of this condition. FNAB (Fine need aspiration biopsy) may be associated with high false negatives due to inadequate sampling, given the cystic nature of these lesions. In majority of these cases definitive diagnosis of cancer is made after excision of the TGD cyst. Some experts favor a conservative approach via Sistrunk's procedure and pursuing total thyroidectomy if there is high suspicion of thyroid gland involvement as well. Whereas other authors have suggested a more aggressive approach with total thyroidectomy even without evidence of concomitant involvement of the thyroid gland. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

PSAT282 A Case of Papillary Thyroid Cancer in a Thyroglossal Duct Cyst

Abstract Background Thyroglossal duct cysts (TGDC) are common congenital neck anomalies. They persist through adulthood in 7% of the general population. Associated malignancy is rare, occurring in &amp;lt;1% of cases. Over 90% of such malignancies are papillary thyroid carcinoma (PTC). Twenty to 60% of patients with TGDC malignancies are found to have concomitant cancer in the thyroid. The rarity of TGDC malignancy make its management particularly challenging, given limited long term outcome data. We describe a case of a 4cm TGDC PTC. Case A 49-year-old female with a history of autoimmune thyroid disease presented for evaluation of a goiter. She reported 6 months of painful midline neck swelling. No family history of thyroid cancer and she had no history of radiation to her head or neck. She denied swallowing, dyspnea, or hoarseness. Physical exam was notable for a mildly tender, firm 2.5 cm submental midline neck mass overlying the hyoid. TSH was normal and thyroid peroxidase antibody was &amp;gt;1000 (n: &amp;lt;5 IU/mL). Neck ultrasound showed a 3.7×2.5×1.6 cm mixed solid/cystic midline neck mass and a mildly enlarged, heterogeneous, and vascular thyroid without discrete intrathyroidal nodules. A neck CT with contrast indicated that the midline mass was heterogeneously enhancing with tiny internal cystic spaces. The differential diagnosis included an infected thyroglossal duct cyst versus malignant transformation. Fine needle aspiration of the mass was suggestive of PTC. The patient underwent the Sistrunk procedure, with excision of the thyroglossal duct cyst, the middle of the hyoid bone, and the tissue surrounding the thyroglossal tract. Final pathology was consistent with a 4 cm PTC, classical type, without lymphatic, vascular or perineural invasion. Surgical margins were negative for malignancy. Two months postoperatively, TSH remained normal, and the thyroglobulin (TG) level was 78 with negative TG antibodies. She declined a thyroidectomy. Conclusion To date, there is no consensus guideline regarding optimal management for malignancy involving TGDC. Studies suggest that surgical decision making be based on patient risk stratification. High risk factors include age older than 45 years, tumor &amp;gt;4 cm in size, extension of tumor to adjacent soft tissue, and/or the presence of nodal or distant metastases. In high-risk patients, treatment with Sistrunk procedure combined with thyroidectomy, neck dissection and radioactive iodine therapy have shown excellent results. In younger than 45 years with tumor size &amp;lt;1.5 cm, without extension beyond cyst wall and normal thyroid ultrasound Sistrunk procedure alone might be sufficient. Despite low risk factors patients should still be advised to have thyroidectomy as there could be a 20% risk of coexisting thyroid cancer. Additional longitudinal studies are needed to confirm that this approach leads to optimal long-term outcomes for patients with TGDC-associated malignancy. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

PSAT296 Graves’ Disease and Hurthle Cell Carcinoma: A Rare Presentation

Abstract Introduction Hurthle cell carcinoma is a rare thyroid malignancy, only accounting for 3-5% of all thyroid malignancies. Thyroid tumors are classified as Hurthle cell carcinomas when they contain more than 75% Hurthle cells. Hurthle cells are oncocytic cells with an acidic cytoplasm and can contain up to 5,000 mitochondria. In the thyroid, oncocytic changes are associated with conditions such as cell-mediated autoimmune thyroiditis, humoral-mediated hyperthyroidism (Graves’ disease), and hyperplastic nodules seen in multinodular goiters. Case Presentation A 64-year-old Polish female with a medical history of hypertension, hyperlipidemia, and smoking presented with fatigue, weight loss of 18kg in 6 months, palpitations, tremors, anxiety, heat intolerance, and diarrhea. Family history was pertinent for thyroid lobectomy in older sister and thyroidectomy in niece with reportedly benign pathology. She denied any family history of thyroid cancer. She resided 1,000 kilometers away from Chernobyl at the time of the nuclear accident. Diagnosis and Treatment Hyperthyroidism was attributed to Graves’ disease, and she was started on methimazole with improvement in symptoms. Fine needle aspiration of 3.4cm right thyroid nodule showed moderate to high cellularity with abundant discohesive Hurthle cells with granular cytoplasm, large nuclei with prominent nucleoli and mild nuclear atypia consistent with Hurthle cell carcinoma with a 25-40% risk of malignancy. She had a total thyroidectomy that revealed a 3cm minimally invasive Hurthle cell carcinoma with a benign lymph node. She was started on levothyroxine 100mcg. Post-surgery labs showed thyroglobulin 3 ng/mL [1.3-31.8], undetectable thyroglobulin antibody, suppressed TSH and normal calcium levels. Further course was complicated by Graves’ orbitopathy, worsened by smoking. She was started on teprotumumab and tapered dexamethasone before receiving 30 mCi radioactive iodine for remnant ablation. Discussion and Conclusion Graves’ disease is the most common cause of hyperthyroidism accounting for 60%- 80% of hyperthyroid cases. Graves’ disease has been reported to be associated with aggressive thyroid carcinomas, 88%being papillary thyroid cancers. Some studies note an increased mortality in patients with differentiated thyroid cancer associated with Graves’ disease when compared to euthyroid controls. Hurthle cell carcinoma is a rare thyroid malignancy and is uncommonly seen in conjunction with Graves’ disease. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

LBSAT291 Familial Papillary Thyroid Carcinoma

Abstract Introduction Familial papillary thyroid carcinoma is a rare entity; however, it must be considered if a strong family history of non medullary thyroid carcinoma is noted. As this cancer presents earlier and with more aggressive features with each subsequent generation, a targeted diagnostic and management approach should be utilized. Case Presentation A 26 year old female presented to the PCP after sustaining head trauma while kickboxing. During the visit, she requested for thyroid evaluation due to a strong family history of thyroid cancer in her mother, maternal aunt, maternal uncle and maternal grandfather. She reported that her mother was diagnosed with thyroid cancer at the age of 40 years; however, she was unaware of further details. She denied any personal history of cancer or exposure to radiation. An extensive review of systems was negative. TSH was within the normal range 2.65 uIU/ml (0.40 - 4. 0). Thyroid ultrasound showed a 1.1 cm nodule in the right thyroid lobe with microcalcifications suspicious for malignancy. Fine needle aspiration cytology of the nodule confirmed papillary thyroid carcinoma. A preoperative CT neck and soft tissue was negative for cervical lymphadenopathy per size criteria. She underwent a total thyroidectomy with neck dissection. Surgical pathology report showed 1.8 cm right thyroid lobe papillary carcinoma and 13 lymph nodes positive for metastatic carcinoma, the largest measuring 0.4 cm. Post-operatively, she underwent radio-active iodide therapy and was started on Levothyroxine supplementation. She was closely monitored with serial thyroid function tests, thyroglobulin levels and thyroid ultrasound examinations. Tempus XT positive for BRAF and FOXP1. Approximately one year after the surgery, serum thyroglobulin levels started to plateau. A surveillance thyroid ultrasound was concerning for left lobe thyroid tissue remnant/cancer. Thus, a radio-active iodine total body scan was planned to locate the remnant thyroid tissue followed by biopsy and excision in case of recurrent cancer. Discussion Papillary thyroid cancer runs in families and becomes more aggressive with each subsequent generation. The American Thyroid Association guidelines detail that screening with thyroid ultrasound should be considered in families with three or more family members affected by familial non medullary thyroid cancer. In addition, certain mutations such as the BRAF mutation are associated with aggressive clinicopathological characteristics and high tumor recurrence. There is limited data available on the FOXP1; however, it may also be linked to an aggressive course. Therefore, screening ultrasound should be offered in such patients and FNAC samples should be sent for genetic analysis to help formulate an appropriate treatment plan. These patients benefit from receiving early screening, more intensive management and frequent follow up. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

Prevalence of Thyroid Nodules and Thyroid Cancer in Individuals with a First-Degree Family History of Non-Medullary Thyroid Cancer: A Cross-Sectional Study Based on Sonographic Screening.

Background: The actual rates of suspicious thyroid nodules (TNs) and confirmed thyroid cancer (TC) in putatively "at-risk" selected populations (e.g., individuals with family history of TC) are still uncertain. Methods: Our aim was to explore the prevalence of TC and TN in a cross-sectional study of a consenting population of unaffected individuals (10 years of age or older) with a first-degree relative known to have non-medullary TC (NMTC). Enrolled subjects underwent ultrasonographic studies of the neck between 2009 and 2018. Nodules considered suspicious according to current guidelines were subjected to fine-needle aspiration biopsy (FNAB) for cytology. Results: The screenee population comprised 1176 individuals (median age 42 [26-56] years, 650 females, 55.3%) from 473 kindreds (346 with 1 established NMTC diagnosis at entry, 103 with 2 established NMTC diagnoses, and 24 with 3 or more established NMTC diagnoses at entry). Screening revealed TNs in 500 screenees (42.5%; confidence interval [CI] 39.7-45.4%). Ninety-seven of these (19.4%; CI 16.2-23.1%) underwent FNAB. Only 11 cases of TC were diagnosed in the whole population (0.9%; CI 0.5-1.7%). The prevalence of TC in screenees from kindreds with ≥3 cases (3/24, 12.5%) was higher than that for kindreds with one affected member (6/346, 1.7%; p = 0.01, odds ratio [OR] 7.99; CI 1.21-40.75) and for those with two affected members (2/103, 1.9%; p = 0.05, OR 7.05; CI 0.76-89.44). The prevalence of TNs was 61.8% (CI 56.6-66.8%), 75.7% (CI 66.6-83%), and 66.7% (CI 46.7-82%) in the kindreds with 1, 2, and ≥3 cases, respectively (p = 0.03). Conclusions: On the whole, ultrasound-based screening of unaffected relatives of individuals with established diagnoses of NMTC is likely to reveal a high prevalence of TN and a low prevalence of TC. However, a significantly higher prevalence of TC may be found among screenees from kindreds with at least three established NMTC diagnoses before screening, suggesting that closer surveillance may be warranted in kindreds with this level of familiality.