Normal Thyroid Research Articles

Real Practice Assessment of Persistent Symptoms After Initiation of Levothyroxine

ObjectiveLevothyroxine (LT4) is the standard treatment for hypothyroidism. However, certain patients experience persistent symptoms even after achieving euthyroid status with LT4 therapy. We aimed to determine the frequency of persistent or new symptoms in patients with hypothyroidism after initiating LT4. MethodsThis retrospective study included patients with hypothyroidism who started on LT4 between January 2017 and December 2019 at Mayo Clinic in Rochester, Minnesota, USA. Five hundred patient charts were randomly selected for review. Patients with at least 1 documented follow-up encounter after LT4 initiation were evaluated for ≤3 follow-up visits regarding their biochemical status and symptoms. ResultsWe included 356 patients, a majority of whom were female (66.6%), white (92.3%), and obese (71.9%), with an average age of 59.5 years. At the baseline visit, approximately one-half of the patients (177/356, 47.7%) reported hypothyroid symptoms, with fatigue being the most common symptom. During the follow-up periods, we observed that 17.8% (28/157), 17.9% (19/106), and 19.3% (11/57) of patients had normal thyroid stimulating hormone (TSH) values but persistent symptoms, while 12.3% (19/156), 19.9% (16/107), and 8.9% (5/56) had normal TSH values but new symptoms. Overall, during each respective follow-up period, 26.7% (42/157), 27.3% (29/106), and 28% (16/57) of patients experienced persistent or new symptoms alongside normal TSH values, with fatigue being the most constant symptom. ConclusionOur findings indicate that approximately 1 in every 4 patients with hypothyroidism receiving LT4 therapy and achieving normal TSH levels experience persistent or new hypothyroid symptoms. The cause of these symptoms remains unclear, emphasizing the need for a better understanding of their underlying causes and the development of effective management strategies.

TRPC5 expression promotes the proliferation and invasion of papillary thyroid carcinoma through the HIF-1α/Twist pathway

ObjectiveThis study aimed to investigate the effect of TRPC5 on PTC (papillary thyroid carcinoma) proliferation and invasion. MethodsImmunofluorescence and western blot were used to evaluate the expression of TRPC5 in paraffin sections and clinical tissues. Overexpression and silencing of TRPC5 to generate the cells for in vitro experiments. Wound-healing assay, transwell invasion assay, MTT assay, and in vivo tumorigenicity assay were used to determine cell proliferation and cell migration in vitro and in vivo. Real-time PCR was used to test the expression of TRPC5. Western blot was used to test the expression of downstream factors: E-cadherin, Vimentin, MMP-9, MMP-2, TRPC5, ZEB, Snail, and Twist. ResultsThe level of TRPC5 protein expression was higher in PTC than in adjacent normal thyroid tissue. TPC-1 cells overexpressing TRPC5 were more proliferative, had longer migration distances, and increased the number of invading cells. TPC-1 cells silenced with TRPC5 had a weaker proliferation capacity, shorter migration distances, and a reduced number of invading cells. Overexpression and silencing of TRPC5 modulated E-cadherin, Vimentin, MMP-9, MMP-2, TRPC5, and Twist, but did not affect ZEB and Snail. The results of tumor formation experiments in nude mice showed that inhibition of TRPC5 expression suppressed the volume and weight of transplanted tumors. ConclusionTRPC5 induced papillary thyroid cancer metastasis and progression via up-regulated HIF-1α signaling in vivo and in vitro. High TRPC5 expression is a biomarker for lymph node metastasis at its early stages.

Sistrunk technique as a surgical approach in thyroglossal duct cyst of His or Bockdalek

Thyroglossal duct cyst is one of the most common lesions in the midline of the neck and is found in around 7% of the population. It occurs equally in both genders and is detected in the first five years in 25 to 35%, between six to 10 years in 40 to 50% and in adolescence between 75 and 90% of cases and in some cases it preserves tissue. functional thyroid and in 0.17 to 1% it is the absolute ectopic thyroid. The diagnosis is fundamentally clinical, although an ultrasound may be useful. A thyroid scintigraphy is recommended not for a positive diagnosis of a thyroglossal duct cyst, but to demonstrate the existence of a normal thyroid gland and rule out the rare thyroid ectopias, whose inadvertent removal would cause permanent hypothyroidism. Diagnostic errors are the most frequent cause of inadequate surgical technique, which produces a high recurrence rate. Since its introduction in 1920, sistrunk surgery is the ideal treatment with the best results, with recurrence limits of 0.5 to 3%, this technique considerably reduces the risk of cyst recurrence to <3%, and one of the key points for the success of the surgery is the need to resect the medial third of the hyoid bone by approximately 1.5 cm. We present the case of a female patient who underwent resection of a thyroglossal cyst with the sistrunk technique to confirm the effectiveness of the technique in reducing the percentage of recurrences.

Loss of CDH16 expression is a strong independent predictor for lymph node metastasis in Middle Eastern papillary thyroid cancer

Papillary Thyroid Cancer (PTC) is the most common type of thyroid cancer. The membrane-associated glycoprotein cadherin-16 (CDH16) plays a significant role in the embryonal development of thyroid follicles and cell adhesion. Previous studies have indicated a substantial downregulation of CDH16 in PTC. However, its role in Middle Eastern PTC has not been elucidated. We analyzed a tissue microarray comprising 1606 PTC and 240 normal thyroid tissues using immunohistochemistry to assess CDH16 expression and determine its clinico-pathological associations. We also conducted BRAF and TERT mutations analyses through Sanger sequencing. Disease-free survival (DFS) was assessed using Kaplan–Meier curves. CDH16 immunostaining was seen in 100% of normal thyroid tissues but only in 9.4% of PTC tissues (p < 0.0001). The loss of CDH16 expression was associated with aggressive PTC characteristics including bilaterality, multifocality, extrathyroidal extension, tall cell variant, lymph node metastasis (LNM) and distant metastasis. Additionally a correlation between loss of CDH16 expression and BRAF and TERT mutations was identified. Intriguingly, upon conducting multivariate logistic regression analysis, CDH16 was determined to be an independent predictor for LNM (Odds ratio = 2.46; 95% confidence interval = 1.60–3.79; p < 0.0001). Furthermore, CDH16 loss was associated with a shorter DFS (p = 0.0015). However, when we further subdivided CDH16 negative patients based on the co-existence of TERT and/or BRAF mutations, we found that patients with both CDH16 negative expression and TERT mutation exhibited the shortest DFS (p < 0.0001). In conclusion, our results suggest that CDH16 protein expression could serve as a valuable diagnostic tool for PTC. Furthermore, these findings demonstrate that the loss of CDH16 expression is an independent predictor of LNM and may contribute to the aggressiveness of PTC. Therefore, downregulation of CDH16 in PTC might be a potential target for designing novel therapeutic strategies to treat PTC.

RARγ promotes the invasion and metastasis of thyroid carcinoma by activating the JAK1-STAT3-CD24/MMPs axis

The nuclear receptor superfamily RAR is generally considered to play a crucial role in the development of tumors by regulating the transcription of target genes. Nevertheless, whether RARγ performs tumor-promoting or tumor-suppressing functions and its specific mechanism in thyroid carcinoma (TC) remain unknown. Here, our study demonstrated that RARγ was abnormally overexpressed in TC tissues compared with normal thyroid tissues. Moreover, RARγ expression was remarkably correlated with cell phenotypes such as cell proliferation, migration and invasion. Mechanistically, RARγ knockdown effectively decreased the phosphorylation levels of JAK1 and STAT3, leading to decreased expression of the membrane protein CD24. In a coculture system, TC cells with high levels of CD24 in the membrane were more likely to escape phagocytosis by macrophages via the combination of CD24 with the inhibitory receptor Siglec-10 in the membrane of macrophages. In contrast, the ability of macrophages to engulf TC cells was notably elevated through exogenous addition of CD24 antibody. Collectively, our study revealed a previously undiscovered molecular mechanism of RARγ in promoting the development of TC, shedding light on RARγ as a promising therapeutic target for TC.

Neoplasms in Struma Ovarii: A Review.

Struma ovarii is a well-known ovarian teratoma made up of benign thyroid tissue. These lesions demonstrate variable, normal architecture and normal thyroid immunohistochemical staining with positivity for TTF1, PAX8, and thyroglobulin. Though most are benign, some of these lesions can also present with a malignant component. Within this article, we review the most common diagnostic malignancies including papillary thyroid carcinoma, strumal carcinoid, highly differentiated follicular thyroid carcinoma, and other thyroid carcinomas. We additionally review the use of TTF1 staining to assist in differentiating these lesions from surrounding gynecologic epithelium, which is imperative in making such diagnoses. In highlighting these entities, we hope to provide practicing pathologists with an effective and concise review of these lesions to assist in more challenging cases of struma ovarii.

CHARACTERISTICS OF THYROID ANATOMY IMAGES ON SONOGRAPHY IN PATIENTS VISITING THE CAN THO UNIVERSITY OF MEDICINE AND PHARMACY HOSPITAL IN 2022

Background: Currently, there are no studies providing data on normal thyroid anatomy images on ultrasound to document thyroid imaging for doctors in the country in general and in the Mekong River Delta in particular. Therefore, it is necessary to determine the size of a normal adult human thyroid gland by ultrasound and contribute to providing reference data for the training of clinicians, especially determining the dose of drugs to treat some thyroid diseases related to the size of the gland. Objectives: To determine the thyroid anatomical imaging features in people without thyroid disease on ultrasound. Materials and method: A cross-sectional descriptive study was conducted on 172 patients who visited the Can Tho University of Medicine and Pharmacy Hospital from May 2021 to October 2022. Subjects are selected by the convenient sampling method met the selection and exclusion criteria. Results: The average size of the right lobe (height x width x thickness) was 45.59 x 16.67 x 14.03mm and the left lobe was 43.04 x 16.08 x 12.08mm. The mean thyroid isthmus thickness was 2.62 mm. The mean thyroid volume of the right and left lobes in the study subjects was 5.24ml and 4.31ml, respectively. Conclusions: In general, the size of the right lobe of the thyroid gland is larger than that of the left lobe (p&lt;0.001), and the thickness of the right lobe of the thyroid gland is larger in men than in women (p=0.04). No statistically significant differences were found between thyroid size and factors such as age, sex, ethnicity, and BMI.

PRMT1 accelerates cell proliferation, migration, and tumor growth by upregulating ZEB1/H4R3me2as in thyroid carcinoma.

Thyroid carcinoma (TC) represents the most prevalent malignancy of the endocrine system. Protein arginine methyltransferase 1 (PRMT1) is a critical member of the protein arginine methyltransferase family in mammals and is involved in multiple biological processes. This study aimed to investigate the function of PRMT1 in TC. In the present study, human TC cell lines (8505C, CAL62, and BCPAP) and a normal human thyroid cell line Nthy‑ori 3‑1 were employed. Small interfering RNA targeting PRMT1 was used to knock down PRMT1 expression in 8505C cells, and PRMT1 overexpression plasmids were transfected into BCPAP cells. Cell viability was assessed using a CCK‑8 and colony formation assays. Apoptosis was measured using flow cytometry and TUNEL assays. Cell migration was assessed using wound healing and Transwell assays. Reverse transcription‑quantitative PCR was used to determine the mRNA expression levels of PRMT1. Western blotting was used to detect the protein expression levels of PRMT1, E‑cadherin, vimentin, H4R3me2as, and zinc‑finger E homeobox‑binding 1 (ZEB1). Notably, PRMT1 expression was elevated in TC (P<0.01). PRMT1 knockdown inhibited TC cell proliferation and migration and concurrently enhanced migration. Furthermore, PRMT1 knockdown suppressed tumor growth and metastasis in a mouse model of TC. PRMT1 downregulation increased E‑cadherin expression and decreased the expression of vimentin, H4R3me2as, and ZEB1 in the TC cells and the mouse model of TC. Conversely, PRMT1 overexpression had the opposite effect on TC malignant characteristics (P<0.05). These findings suggest that PRMT1 knockdown inhibited TC malignancy by downregulating H4R3me2as/ZEB1, thereby highlighting novel therapeutic targets and diagnostic markers for the management of TC.

PREGNANCY OUTCOME IN WOMEN WITH GRAVES’ DISEASE

Background and Aims: Pregnancy complicated with poorly controlled thyrotoxicosis is associated with an increased risk of adverse pregnancy outcomes, and maternal complications. To study the clinical characteristics, feto-maternal outcomes in women with Graves’ disease (GD) during pregnancy. Methods: This was observational study on 98 patients with GD during pregnancy at the tertiary care hospital. GD was documented by Thyrotropin receptor antibody (TRAb). Patients were subjected to complete clinical work up and thyroid profile. The diagnosis of TAO was based on the criteria of Bartley and Gorman. 100 pregnant women with normal thyroid function were taken as control. Birth outcomes recorded were: route of delivery (vaginal or cesarean section), neonatal birth weight, spontaneous abortion, stillbirth, and small for gestational age (SGA). Maternal outcomes accessed were: gestational hypertension, gestational diabetes (GDM), preeclampsia, gestational age at delivery, preterm delivery, antepartum hemorrhage, and postpartum hemorrhage. Results: The mean age of the patients was 30.8±7.6 years as compared to 32.9±6.8 years in controls. Compared with the controls; the pregnant women with GD had significantly higher rates of small for gestational age (SGA) (23.5% vs. 12.0%; p: 0.034), preterm birth (22.4% vs. 12.0%; p: 0.049), preeclampsia (15.3% vs. 5.0%; p: 0.016) and cesarean section (82.7% vs.70.0%; p: 0.036). Maternal and neonatal outcomes in pregnant women with GD with controlled and uncontrolled thyrotoxicosis were not significantly different except for birth weight. Conclusion: GD was significantly associated with an increased risk of adverse pregnancy outcomes.

Serum Levels of Thyroid Hormones in Infertile and Fertile Women Attending a Tertiary Care Hospital in North-Central Nigeria: A Comparative Reproductive Medicine Study

Thyroid hormones have profound effects on reproduction. Normal thyroid function is necessary to maintain reproductive physiology, but its functional abnormalities may cause infertility manifesting as menstrual cycle irregularities. Aim of this research was to determine the serum levels of thyroid hormones in infertile and fertile women attending a tertiary care hospital in North-Central Nigeria. This comparative, reproductive medicine, cross-sectional study was carried out among one hundred and six (106) women attending the Gynecology Clinic of the Department of Obstetrics and Gynecology and the Family Planning Clinic of a tertiary care hospital in North-Central Nigeria. Women with a history suggestive of either primary or secondary infertility and the control women with no history of infertility were evenly grouped. Venous blood samples were collected and analyzed using Enzyme-Linked Immunosorbent Assay (ELISA) technique to determine fT3, fT4 and TSH levels. Data obtained were entered and analyzed using Statistical Package for Social Sciences (SPSS) version 23, and the level of statistical significance was set at p&lt;0.05 and at a confidence interval of 95% for all inferential statistics. Majority (90.6%) of the 106 participants were euthyroid. However, most of the thyroid disorders (80%) were noticed in the infertile women, as 15.1% of them had one form of thyroid disorder. The mean TSH, fT3 and fT4 levels were higher in the infertile patients than in the control group, but the values were still within normal reference range. Mean values of TSH, fT3 and fT4 for the patients and controls were 1.35±1.65 versus 0.85±1.08 mIU/mL, 2.79±1.51 versus 2.19±1.15 pg/mL, and 1.15±0.33 versus 0.99 ± 0.29 ng/dL respectively. Median for TSH, fT3 and fT4 in the patients and controls were as follows: 0.80 (0.40–1.55) versus 0.60 (0.40-0.85) mIU/mL, 2.40 (1.45-4.20) versus 1.70 (1.35-2.95) pg/mL, and 1.10 (1.00-1.30) versus 1.00 (0.90- 1.10) ng/dL respectively. The differences in the median between the patients and controls were statistically significant for fT3 and fT4 with p-values of 0.031 and 0.002 respectively. Subclinical hypothyroidism was the most prevalent (7.5%) thyroid disorder identified in the infertile women. Serum levels of thyroid hormones and prevalence of thyroid disorders were significantly higher in the infertile patients compared to the fertile women, although the overall prevalence of thyroid disorders was quite low.

In-silico studies of Brassica oleracea active compounds and their role in thyroid peroxidase activity

Cabbage, a leafy vegetable that is widely consumed across the globe, holds a significant place within the Brassica family. For almost a century, its potential anti-thyroid effects have captured attention. The presence of compounds such as thiocyanate and goitrin in cabbage has been extensively investigated for their ability to impede sodium-iodide symporter and thyroid peroxidase (TPO) activities. The present study is focused on uncovering the active constituents in cabbage that could interact with TPO, while also examining their stability under cooking temperatures. Employing molecular docking and molecular dynamic simulation techniques, we quantified the binding strength of phytochemicals present in cabbage with the target. Out of the 60 compounds identified in cabbage leaves, only 18 exhibited docking scores surpassing those of the commercially available anti-thyroid drug, methimazole. These chosen compounds were studied for binding free energy and pharmacokinetic properties. A specific compound, gamma-Terpinene, classified as a monoterpene, emerged as noteworthy due to its alignment with all criteria and the highest observed binding free energy compared to others. Furthermore, we explored the stability of gamma-Terpinene at 373.15K (cooking temperature) and observed its susceptibility to degradation. This might contribute to the relatively diminished anti-thyroid effects of cabbage when consumed in cooked form. Consequently, our findings suggest that the consumption of cooked cabbage could be more conducive to maintaining normal thyroid function, as opposed to its raw counterpart. Communicated by Ramaswamy H. Sarma

Expression of the Calcium-Sensing Receptor on Normal and Abnormal Parathyroid and Thyroid Tissue

IntroductionCurrent imaging techniques have several limitations in detecting parathyroid glands. We have investigated the calcium-sensing receptor (CaSR) as a potential target for specifically labeling parathyroid glands for radiologic detection. For accurate imaging it is vital that a large differential expression exists between the target tissue and adjacent structures. We sought to investigate the relative abundance of the CaSR in normal and abnormal parathyroid tissue, as well as normal and abnormal thyroid. MethodsExisting clinical specimens were selected that represented a wide variety of pathologically and clinically confirmed malignant and benign thyroid and parathyroid specimens. Sections were stained for the CaSR using immunohistochemistry and scored for intensity and abundance of expression. (H score = intensity scored from 0 to 3 multiplied by the % of cells at each intensity. Range 0-300). ResultsAll parathyroid specimens expressed the CaSR to a high degree. Normal parathyroid had the highest H score (271, s.d. 25.4). Abnormal parathyroid specimens were slightly lower but still much higher than normal thyroid (H score 38.3, s.d. 23.3). Medullary thyroid cancer also expressed the CaSR significantly higher than normal thyroid (H score 182, s.d. 69.1, P < 0.001) but below parathyroid levels. Hürthle cell carcinoma expressed the CaSR to a lesser degree but higher than normal thyroid (H score 101, s.d. 46.4, P = 0.0037). ConclusionsThe CaSR is differentially expressed on parathyroid tissue making it a feasible target for parathyroid imaging. False positives might be anticipated with medullary and Hürthle cell cancers.

Differentiated thyroid cancer: a focus on post-operative thyroid hormone replacement and thyrotropin suppression therapy.

This review focuses on post-operative thyroid hormone replacement and thyrotropin suppression therapy in patients with differentiated thyroid cancer. A clinical review. Differentiated thyroid cancers (DTC), including papillary and follicular thyroid cancers, have an excellent prognosis and their management leverages a unique set of clinical tools arising from homology to the normal thyroid follicular cell. Surgery is the cornerstone of initial management, and post-operative care often requires thyroid hormone replacement therapy, which may be approached with the intent of physiologic normalization or used pharmacologically to suppress TSH as part of a DTC treatment. Management of DTC and approaches to TSH suppression are tailored to an individual's risk of DTC recurrence and are adjusted to a patient's clinical status and comorbidities over time with the goal of mitigating risk and maximizing benefit.

Substance P and Neurokinin-1 Receptor System in Thyroid Cancer: Potential Targets for New Molecular Therapies.

In recent years, numerous approaches have been developed to comprehend the molecular alterations underlying thyroid cancer (TC) oncogenesis and explore novel therapeutic strategies for TC. It is now well established that the neurokinin-1 receptor (NK-1R) is overexpressed in cancer cells and that NK-1R is essential for the viability of cancer cells. The binding of substance P (SP) to NK-1R in neoplastic cells plays a pivotal role in cancer progression by promoting neoplastic cell growth, protecting tumor cells from apoptosis, triggering invasion and metastasis through the enhanced migration of cancer cells, and stimulating endothelial cell proliferation for tumor angiogenesis. Remarkably, all types of human TC (papillary, follicular, medullary, anaplastic), as well as metastatic lesions, exhibit the overexpression of SP and NK-1R compared to the normal thyroid gland. TC cells synthesize and release SP, which exerts its multiple functions through autocrine, paracrine, intracrine, and neuroendocrine processes, including the regulation of tumor burden. Consequently, the secretion of SP from TC results in increased SP levels in plasma, which are significantly higher in TC patients compared to controls. Additionally, NK-1R antagonists have demonstrated a dose-dependent antitumor action. They impair cancer cell proliferation on one side and induce apoptosis of tumor cells on the other side. Furthermore, it has been demonstrated that NK-1R antagonists inhibit neoplastic cell migration, thereby impairing both invasiveness and metastatic abilities, as well as angiogenesis. Given the consistent overexpression of NK-1R in all types of TC, targeting this receptor represents a promising therapeutic approach for TC. Therefore, NK-1R antagonists, such as the drug aprepitant, may represent novel drugs for TC treatment.

EVALUATION OF THYROID PROFILE AND ITS PROGNOSTIC VALUE IN PATIENTS OF ACUTE CORONARY SYNDROME

Objective: The objective of the study is to study the association of thyroid dysfunction with acute coronary syndrome (ACS), its complications and duration of hospital stay. Methods: This prospective comparative study was done on 100 patients divided equally into ACS patients with control (normal thyroid function) and ACS patients with thyroid dysfunction admitted in a tertiary care center, Udaipur, Rajasthan with ACS during the period of February 2021–July 2022. We studied the prevalence, prognostic factor of thyroid hormone in these patients. Results: The mean ejection fraction of the control group was 51.16±11.72%, of hypothyroid group was 49.00±13.55% and of hyperthyroid group was 51.12±13.78%. 29 cases of cardiac failures, 38 cases of arrhythmias, and 32 cases of major adverse cardiac events were observed. 56% of patients required thrombolysis, out of which 67.86% were from the subclinical hypothyroid group. The mean hospital stay in control group was 4.53±1.55, in hypothyroid group was 5.27±1.84 and in hyperthyroid group was 7.00±1.92.18% mortality. Conclusion: Patients with acute myocardial infarction, initially develop alteration in thyroid hormone levels, which is possibly a compensatory mechanism to reduce the metabolic demand of the heart, by reducing myocardium contraction and cardiac output but may cause cardiac failure and higher rates of cardiovascular complications like arrhythmias and death in some of the patients. Thyroid dysfunctions in patients with ACS may also need a longer duration of intensive care and close monitoring during follow-up.

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

OR32-05 Proteogenomics-based Development For Thyroid Cancer Molecular Classifier

Abstract Disclosure: Y. Kim: None. I. Wang: None. J. Jung: None. S. Cheon: None. S. Cho: None. D. Han: None. Y. Park: None. BackgroundCurrent leading-edgemolecular tests of thyroid nodule/cancer were based on DNA mutation/fusionprofile, and/or the expression profiles of mRNA and miRNA. They discriminated normalthyroid nodule from thyroid cancer with high performances. However, they could notsuggest any protein markers for the discrimination, and evaluate the risk ofcancer progression. Here, we deployed proteogenomics to discriminate normalthyroid from thyroid cancer, as well as capture the risk of cancer progression. MethodmRNAsequencing data of 86 normal thyroid (NT), 125 papillary thyroid cancer (PTC), 64follicular thyroid cancer (FTC) were obtained from our previous studies. Ofthese, 62 PTC samples harbored BRAFV600E, and 24 FTC samplesharbored H/N/K RAS mutations, referred to as PTC-B and FTC-R, respectively. Freshfrozen tissues from 4 NT, 3 PTC-B, and 5 FTC-R were preparedfor tandem mass tag labeling, and followed by LC-MS/MS analysis. Differentiallyexpressed genes and differentially expressed proteins were determined betweenNT and PTC-B, as well as between NT and FTC-R, which were 86 genes and referredto as NPF (NT-PTC-FTC) genes. NPF genes were tested for their discriminativepower in our development cohort, and validated in TCGA-THPA, and new globalproteomics data including 72 FTC, and 76 PTC. Protein markerswith high discriminative performances validated with tissuemicroarray, which included formalin-fixed paraffin-embedded samples of 22 NT, 196PTC, and 76 FTC. NPF scores were calculated, and analyzed for the progressionof thyroid cancer in our development cohort and TCGA-THPA. ResultK-meansclustering using NPF genes identified 4 clusters; BRAF-like, RAS-like, Immune-rich,and NT-like subtypes. Samples with lymphoid thyroiditis were mainly involved inimmune-rich subtypes. We developed thyroid molecular classifier with NPF usingdecision tree model. The accuracy of this model to predict thyroid cancersubtypes was 0.92 in our development cohort. We validated our model with TCGA-THPAwhich predicted 97% of tumors with BRAFV600E and 84% of tumors with H/K/N RASmutation, and new global proteomics data which predicted 77.8% of FTC and 64.4%of PTC. MarkerA, MarkerB, and MarkerCshowed best discriminative performances in our classifier. In thevalidation by immunohistochemistry, MarkerAhigh- MarkerBlow-MarkerChigh indicated 70.6% of NT, MarkerAlow- MarkerBhigh-MarkerClow indicated 97.2% of PTC, and MarkerBlow-MarkerClow indicated 58.2% of FTC. Both in PTCand FTC, high NPF score was associated with intermediate to high risk based on ATArisk stratification in our development cohort and TCGA-THPA, and poorprogression-free survival in TCGA-THPA. ConclusionWedeveloped thyroid cancer molecular classifier which reflected molecularsubtypes of thyroid cancer, and their risk of progression using proteogenomics. Presentation: Sunday, June 18, 2023

SAT533 The Case of an Ectopic Thyroid Twin

Abstract Disclosure: A. Abu Limon: None. S.A. Aldasouqi: Consulting Fee; Self; Abbott Laboratories. P. Kachhadia: None. S. Khan: None. Introduction: Ectopic thyroid tissue is a rare but known developmental abnormality during the descent of the thyroid tissue from the floor of the foregut to its final location Infront of the trachea. The most frequent ectopic locations are the base of the tongue and anywhere along the course of the thyroglossal duct. It is very rare to have an ectopic thyroid tissue located in the mediastinum. It’s even more rare when the patient still has an almost normal thyroid gland in its usual location in the neck, and both are sizable and functional. Case Presentation: We are reporting the case of a 38-Year-old African American Female, who was involved in a car accident with non-critical injuries to her neck and chest area. She underwent a contrasted CT scan of her neck and chest that showed an anterior mediastinal mass towards the right at the level of the great vessels and arch, right paratracheal location overall measuring 6.0 x 4.6 x 4.5 cm. She was seen by Cardiothoracic surgery group and underwent Mediastinoscopy that confirmed a large firm to hard mass just inferior to the innominate artery was firmly adherent to the trachea as well as surrounding structures. Multiple biopsies showed thyroid tissue with focal mild chronic inflammation, benign. No atypia or malignancy is noted. Then, she was referred to our clinic for further evaluation. When interviewed, the patient denies any compressive symptoms (Shortness of breath, palpitations, chest pain or dysphagia). The patient has no personal or family history of thyroid disorders, including no thyroid cancer history. She has no Goiter on exam and no Pemberton sign is elicited. Laboratory work up was unremarkable including normal thyroid functions. Neck Ultrasound confirmed presence of a thyroid gland in its expected location, with Right Lobe Measurement: 5.04 x 1.70 x 1.47 cm Vol: 6.02 ml and Left Lobe Measurement: 3.94 x 1.25 x 1.21 cm Vol: 2.87 ml. We were keen to explore this matter further and ordered a thyroid uptake scan with 0.97 uCi iodine-123, that showed a 24-hour normal uptake of 27.4% at the thyroid bed and a separate substernal and RT paratracheal location uptake. Discussion: This patient has supplementary ectopic thyroid tissue in her mediastinum along with a normal thyroid gland in her neck. From the literature review and search, This is a very rare occurrence. The discussion with the patient is about the specific concern of the malignant potential of this ectopic thyroid and if surgical intervention is needed. The probability of cancer on ectopic thyroid tissue is less than 1% and when it occurs papillary carcinoma is the most common histology. Our patient has benign biopsy results and no signs nor symptoms related to this ectopic thyroid gland. The final decision is to not undergo surgery, but rather, a follow up with CT scan in 6 months. Presentation Date: Saturday, June 17, 2023

FRI257 Adrenal Insufficiency Secundary Due Immune Checkpoint Inhibitors Therapy

Abstract Disclosure: S.R. Rivera: None. J. Valencia: None. E. Figueroa: None. J. Calisto: None. Background: Immune checkpoint inhibitors (ICIs) are new anticancer immunotherapies that can trigger a variety of immune related adverse events (irAEs) in different organs, including the endocrine system. Adrenal insufficiency is uncommon with a nonspecific clinical presentation that must be recognized in time due to its potential mortality. Clinical Case: 41 year old man diagnosed with papillary renal cell carcinoma. He underwent surgery, performing a ​​right radical nephrectomy plus bilateral lymphadenectomy. He started chemotherapy in March 2022 with ICIs, Nivolumab and Ipilimumab. Three months later he presents with myalgias, fatigue and 6 kilogram weight loss. Physical exam: in regular conditions, vital signs with blood pressure 70/40 mmHg, heart rate 84 bpm, with no signs of hyperpigmentation or dehydration. No evidence of clinical hyperthyroidism. Lab results: low ACTH levels: 6.4 pg/ml (9 - 69 pg/ml), low cortisol: 0.06 µg/dl ( 6.02-18.4 µg/dl), low TSH: 0.1 µU/ml ( 0.4- 4.2 µU/ml) and normal free T4: 1.01 ng/dl ( 0.93-1.7 ng/dl). Antibody tests were negative: anti thyroglobulin, anti TPO and TRAB. Normal thyroglobulin levels. Sellar MRI was requested: normal, metastasis were ruled out. Thyroid ultrasound: normal thyroid gland. Exclusion of exogenous use of corticosteroids and levothyroxine was done. Case was interpreted as an adrenal insufficiency due to hypophysitis with associated thyrotoxicosis. Treatment with hydrocortisone was started, while thyroid function progression was observed. In the following lab control, elevation of TSH was noted. Two months later, we documented elevation of TSH levels: 5 µU/ml and decline of free T4 levels: 0.58 ng/dl, starting levothyroxine supplementation. Patient had a favorable clinical evolution. Conclusion: Adrenal insufficiency due to hypophysitis is uncommon and is mostly linked to Ipilimumab use. In those cases pituitary gland MRI is often normal most of the time. Thyroid involvement, which is frequently seen with Nivolumab therapy, varies from thyrotoxicosis, hyperthyroidism and hypothyroidism. Usually produces chronic damage and needs permanent treatment. The potentially lethal nature of these events makes it essential for oncologists and endocrinologists to be aware of these manifestations in order to achieve early treatment. Presentation: Friday, June 16, 2023

SAT450 High Diagnostic Yield Of NGS Analysis In Congenital Hypothyroidism With Thyorid Dyshormongenesis

Abstract Disclosure: E. Joo: None. S. Kim: None. J. Lee: None. Introduction: Congenital hypothyroidism is the most common neonatal metabolic disorder and detected at a rate of 1 in 3000 to 4000 live births. 10-15 % of congenital hypothyroidism is caused by thyroid dyshormonogenesis. And Its clinical manifestations are individually different. Thus, to evaluate exact causes and predict clinical course for congenital thyroid dyshormonogenesis and establish precise strategies for treatment, we conduct Next-Generation Sequencing (NGS) to patients who diagnosed congenital hypothyroidism with normal thyroid gland and analysis the results. Methods: We conducted NGS to 31 patients patients who were diagnosed congenital hypothyroidism with normal contour of thyroid gland in ultrasonography from Jan. 2018 to April. 2022 in a single university hospital. We also analyzed their thyroid function test results, dose of levothyroxine and clinical manifestations. Result: Among the 31 patients, 25patients were detected from NGS. 4patients have oligogenic mutations. 7 DUOX2 variants were detected in 7 patients (22.6%), 3 DUOXA2 variants were detected in 4 patients (12.9%), 4 TSHR variants were detected in 7 patients (22.6%) 5 TG variants were detected in 4 patients (12.9%), 2 GLIS3 variants in 2 patients (6.5%), 1 TPO variants in 1 patient, 1 THRB variants in 1 patient, 1 NKX2-1 variants in 1 patient, 1 TRH variants in 1 patient, 1 SLC5A5 variants in 1 patient. The patients with GLIS3 stop levothyroxine at 3years old and have remission. The patients with DUOX2 variants and DUOXA2 variants showed low remission rate. DUOXA2 variants has high association with goiter. None of the patients with TSHR c.1349G&amp;gt;A mutation to stop medicine. But patients with other mutation of TSHR stop levothyroxine at 3 years old and have remission. None of the patients with TG variants showed remission. The patients with GLIS3 have remission at 3 years old. Conclusions: We cautiously recommend that using the NGS to strategize treatment plan for CH based on the clinical manifestations and genetic analysis of the family members of the index patients. Presentation: Saturday, June 17, 2023