Thyroid Tissue Research Articles

8106 An Uncommon Cause Of Hyperparathyroidism: A Case Report

Abstract Disclosure: A. Calderon: None. M.C. Aguilera: None. A. Kansara: None. Introduction: Parathyroid adenomas are the most common cause of primary hyperparathyroidism. Imaging techniques to locate parathyroid adenomas and hyperplasia include U/S (Sensitivity: 72%-89%), Sestamibi Tc-99 (Sensitivity of 68-95%), and 4D CT scan (Sensitivity of 80%). Combined imaging modalities increase sensitivity to 95%. We describe a case of symptomatic primary hyperparathyroidism with rapid development of hypercalcemia, and conflicting imaging findings. The final diagnosis was made after surgery and pathology review. Case presentation: A 76-year-old man with a history of hypertension, Parkinson’s disease, and prostate cancer was admitted due to a calcium level of 13 mg/dL (8.0 - 10.2 mg/dl) on routine blood tests. He had complained of progressive fatigue and constipation, attributed to Parkinson’s Disease. Five months prior his calcium was 9.7 mg/dL. Hydrochlorothiazide was discontinued due to hypotension after two months. Blood tests in the hospital showed a corrected calcium of 12.5 mg/dL, phosphorus of 1.7 (2.4 - 4.5 mg/dl), PTH of 195 (15 - 65 pg/ml), with normal vitamin D and undetectable PTHrP. A U/S of the neck showed a 0.4 x 0.5 cm cystic mass in the right-inferior pole of the thyroid. A 4D CT scan of the neck showed a non-enhancing 0.9 x 7 x 1 mm mass in the same location, and a 7 x 4.7 x 4.8 mm mildly enhancing mass in the left lower pole of the thyroid. A parathyroid nuclear scan did not identify a parathyroid adenoma. He underwent minimally invasive parathyroidectomy and was found to have a 3.2 cm enlarged and cystic right inferior parathyroid gland weighing 792 mg. Frozen section showed hypercellular parathyroid with cystic and fibrotic changes. The PTH level dropped 59% after removal of the right cystic mass. The left inferior mass identified on CT scan was identified as normal thyroid tissue. Conclusions: Parathyroid cysts are uncommon neck masses and represent less than 5% of causes of all neck masses. They can be divided into functional and non-functional. Large retrospective studies have shown that about 5% of patients manifest as classic hyperparathyroidism, whereas the most common presentation was neck mass (40%). Identification of parathyroid cysts through imaging can be challenging. In our case, the patient presented with symptomatic and rapidly progressive primary hyperparathyroidism, and imaging findings that were discordant among ultrasound, 4DCT scan and Sestamibi Tc-99 scan. The final surgical and pathology reports identified a large parathyroid cyst. This case emphasizes the variable clinical and imaging behavior of parathyroid cysts, imposing a puzzling medical challenge. Presentation: 6/3/2024

5039 Chronic Painful Hashimoto's Thyroiditis

Abstract Disclosure: S. Ahmed: None. M. Vahidi Rad: None. S.A. Westphal: None. M.D. Whitaker: None. Introduction: Painful Hashimoto thyroiditis is a rare variant of Hashimoto thyroiditis that mostly affects women. Most cases are empirically treated as subacute thyroiditis with corticosteroids, levothyroxine, or nonsteroidal anti-inflammatory drugs. However, no medical treatment may provide sustained pain resolution, so optimal treatment remains unclear. We describe the case of a 40-year-old female with longstanding throbbing anterior neck discomfort that failed medical therapy and her symptoms completely resolved with total thyroidectomy. Case Report: A 40-year-old lady with anterior neck pain centered over the thyroid for more than 16 years, shortly after she delivered her last child. The pain is described as intense, it tends to wax and wane but there is a constant throbbing with occasional radiation to the angle of the jaw. Over the years the pain has gradually worsened and during its flares, the thyroid itself is very tender to the point where she experiences difficulty in swallowing and hoarseness of voice. Complicating the issue is her underlying diagnosis of fibromyalgia, as she tends to experience discomfort in many other areas of her body. However, the neck pain appears to be of a different character. No symptoms of hyper or hypothyroidism. The anterior neck pain has been difficult to alleviate, she has used chronic opioids for it which seems to have helped to some extent, in the past she was on prednisone for 1 month however this made no difference to it. On examination, the thyroid is tender and somewhat firm without lymphadenopathy. Thyroid levels have been consistently normal and the most recent of which was a TSH: 1.48, FT4: 1.4, FT3: 3.5 with negative TPO and thyroid stimulating antibodies. ESR and CRP were unremarkable. Thyroid ultrasound showed mildly heterogeneous parenchyma with no solid nodules or lymphadenopathy. Interestingly she had an elevated thyroid uptake in her scan dated April 1st 2022, 4 hour and 24-hour uptakes were abnormal at 23% and 49% respectively which can be seen with Hashimoto's. She underwent total thyroidectomy and her surgical pathology showed benign thyroid tissue with multiple foci of chronic lymphocytic thyroiditis and hyperplastic nodules. Her pain completely resolved after total thyroidectomy. Discussion: Painful Hashimoto thyroiditis is a rare diagnosis and optimal treatment remains unclear. The painful variant of Hashimoto's thyroiditis should be considered in the differential diagnosis of pain and tenderness of the thyroid which can be managed successfully by surgical treatment. Thyroidectomy not only can lead to alleviation of symptoms but also provides the definitive diagnosis. The risks of surgical intervention must be taken into consideration, especially because painful Hashimoto thyroiditis can be associated with a small fibrous gland; hence, the importance of access to highly skilled, experienced surgeons cannot be overemphasized. Presentation: 6/1/2024

7272 Antineoplastic Effect of Cabozantinib in Primary and Continuous Human Anaplastic Thyroid Cancer Cells

Abstract Disclosure: G. Elia: None. S. Ferrari: None. F. Ragusa: None. V. Mazzi: None. A. Patrizio: None. E. Balestri: None. C. Botrini: None. L. Rugani: None. E. Barozzi: None. C. La Motta: None. P. Fallahi: None. A. Antonelli: None. Anaplastic thyroid cancer (ATC) is a highly aggressive cancer with a low median survival of about 6-10 months. The standard treatment include surgery, external hyperfractionated radiation therapy, and chemotherapy. However, these therapies are not effective and new therapeutical approaches are needed. Tyrosine kinase inhibitors (TKI) are a class of drugs able to inhibit different pathways that results inappropriately activated in cancer cells.To date no studies evaluated the effect of cabozantinib in primary human ATC cells, and in ATC continuous cell line in vitro. We aimed to test the efficacy of cabozantinib a multiTKI acting against VEGFR 1,2, c-MET, and RET (recently approved for aggressive differentiated thyroid cancer) in primary human ATC cells, and in ATC continuous cell line (8305C, CAL-62) in vitro. Therefore, for primary ATC cells we collected surgical thyroidal tissues from five patients with ATC, from thyroid biopsy at the moment of first surgical operation, and we tested the effect of cabozantinib. Cabozantinib showed its efficacy in inhibiting cell proliferation, and also in increasing apoptosis (p < 0.05) both in primary and in continuous ATC cells. In conclusion, cabozantinib demonstrated a good antineoplastic activity in human ATC cells in vitro. These results open the way for a possible clinical use of cabozantinib in patients with ATC, and are important for a personalized therapeutic approach to be tailored to each patient avoiding the administration of ineffective drugs. Presentation: 6/1/2024

8426 Recurrence of Papillary Thyroid Carcinoma Despite Undetectable Levels of Thyroglobulin Measured by Both Immunoassay and LCMS

Abstract Disclosure: M.G. Hamilton: None. G. Patel: None. S. Teja Sathi: None. K. Win: None. P. Lekprasert: None. Serum thyroglobulin (Tg) levels are affected by the presence of anti-thyroglobulin antibodies (anti-Tg Abs) during surveillance of differentiated thyroid cancer (DTC). About 20% of patients have positive anti-Tg Abs post-thyroidectomy and laboratory investigations for DTC surveillance may lead to false negative results. Liquid chromatography-tandem mass spectrometry (LCMS) is superior to immunoassay in measuring Tg levels in patients with the presence of anti-Tg Abs. Mass spectrometry is the only currently available method that could eliminate the interference of anti-Tg Abs in the quantification of Tg but is not readily available. We present the case of a patient who had a recurrence of DTC despite persistently undetectable Tg levels using both immunoassay and LCMS methods. The patient is a 49-year-old female with a history of papillary thyroid cancer who underwent total thyroidectomy followed by adjuvant radio-ablation. She presented to our endocrinology office for routine follow up for her DTC. She reported subjective unknown weight loss over four months. Her physical exam was unremarkable with no palpable neck swelling or mass. Vital signs were within normal limits. She continued to have undetectable levels of Tg as measured by immunoassay, stable levels of anti-Tg Abs ranging from 19 IU/mL to 33 IU/mL, and negative findings on her thyroid ultrasound for the first four years post-op. When she presented to the office five years post-thyroidectomy her anti-Tg Ab level had increased to 114 IU/mL and subsequently to 137 IU/mL a few months later despite undetectable Tg levels on both immunoassay and LCMS. A thyroid ultrasound was completed due to rising anti-Tg Abs levels which showed a suspicious one cm mass at the right thyroid bed and suspicious bilateral cervical lymph nodes. Repeated FNA biopsy of the bilateral cervical lymph nodes confirmed follicular epithelium with nuclear inclusions and grooves, compatible with recurrent papillary thyroid carcinoma. This patient had a recurrence of her DTC despite undetectable Tg levels on both immunoassay and LCMS. Tg is an important aspect of surveillance post-treatment for all patients with DTC because its presence is a surrogate for the presence of thyroid tissue and therefore the recurrence of thyroid malignancy. Clinicians must have a high index of suspicion when monitoring a patient with a history of DTC and the presence of anti-Tg Abs because it interferes with the accurate measurement of Tg levels. A study conducted by Azmat et al. demonstrated that measuring Tg levels via LCMS has been found to eliminate the confounding effect of anti-Tg Abs with a sensitivity and specificity of 44.4% and 94.1% respectively. However, our case illustrates that even LCMS is not always reliable in such situations, and increasing levels of anti-Tg Abs should be an individual risk factor for suspecting recurrence of DTC. Presentation: 6/3/2024

7962 Transformation of Poorly Differentiated Papillary Thyroid Carcinoma to Anaplastic Thyroid Carcinoma, an Atypical Course!

Abstract Disclosure: T. Altaweel: None. S. Makadsi: None. M. Hussein: None. J. Samantray: None. Introduction: Anaplastic thyroid cancers are undifferentiated, rare and aggressive. The transformation of papillary thyroid cancer to anaplastic thyroid cancer is documented in literature, however, rare. In this report, we present a case of Anaplastic thyroid carcinoma likely arising from a co-existing poorly differentiated Papillary carcinoma. Case Presentation: A 74-year-old male with past medical history of tobacco smoking who presented with the onset of voice hoarseness for 6 months. He has also noticed a left neck mass that is in the mid supraclavicular region. A Neck CT neck was performed at the time of presentation and was significant for a 4.6x3.4x5.9 cm left thyroid mass with displacement of the trachea. FNA biopsy showed papillary carcinoma with focal features of Tall Cell Variant. Poorly differentiated components with fragments of stroma and muscle were seen and suggested invasion. These findings raised the possibility of anaplastic thyroid carcinoma in the setting of papillary carcinoma and poorly differentiated carcinoma. BRAF V600E pathogenic variant mutation along with TERT mutation were found. Patient underwent direct laryngoscopy, bronchoscopy with biopsies, and tracheostomy with surgical pathology confirming papillary thyroid cancer with muscles invasion. Combination dabrafenib and trametinib were started. No surgical resection of thyroid tissue was planned. A follow up CT showed a significant decrease in the low-density soft tissue involving the medial thyroid gland bilaterally, consistent with interim positive response to therapy. Three months later, CT neck showed near complete resolution of low-density soft tissue involving the medial thyroid and parathyroid glands and subglottic trachea consistent with further interim positive response to therapy. Six months post initiation of therapy, CT Neck showed focal low density in the mid and inferior right thyroid gland which may represent residual and/or recurrent thyroid carcinoma. That density was further demonstrated on a repeat CT neck as a 1.8 cm hypodense nodule in the inferior right thyroid gland and concerning for recurrent thyroid tumor with possible infiltration of the trachea. Conclusion: ATC prognosis is affected by many factors such as metastasis, age, treatment strategies, socioeconomic status and the presence of BRAF V600E and TERT mutations. Diagnosis can be challenging. Our patient presented months after his symptoms started and this is an atypical course of Anaplastic Thyroid Carcinoma as it usually progresses aggressively and rapidly. Given the pathology reports and the more slow presentation of this patient’s carcinoma, it can be suggested that this is a case of papillary carcinoma with a later transformation to ATC. In these cases, surgical resection Presentation: 6/2/2024

8578 Papillary Thyroid Carcinoma in Autonomous Nodule with Low Risk Characteristics in Adolescent

Abstract Disclosure: A. Aponte Velez: None. M.M. Mangual Garcia: None. Thyroid nodules in children are uncommon but are known to carry a greater risk of malignancy than adult thyroid nodules. Additionally, differentiated thyroid cancer (DTC) in children is more commonly found with extrathyroidal extension and metastases which makes the approach and treatment similar but with important differences. The incidence of DTC in children is increasing, making a personalized evaluation of thyroid nodules in pediatric patients even more valuable. Guidelines recommend evaluation of nodules based on sonographic characteristics rather than size of nodule. However, not having worrisome sonographic characteristics may not be as reassuring as in adult patients. A 13 year old female patient presented with a palpable non tender right sided solid thyroid mass. She had no family history of thyroid cancer or history of irradiation. Thyroid function tests were remarkable for TSH:0.017 and positive thyroid stimulating immunoglobulin. Thyroid Ultrasound findings described heterogenous parenchyma with multiple discrete lesions on right thyroid lobe with a dominant solid isoechoic nodule at upper lobe measuring 2.1 x 3.5 x 1.9cm and a smaller nodule in lower lobe. Thyroid scan demonstrated a large functional hot nodule occupying most of right thyroid lobe with suppression of rest of thyroid parenchyma. Ultrasound guided FNA was performed of this lesion and results were negative for malignancy. Patient underwent total thyroidectomy with pathology report revealing right thyroid nodule encapsulated classical variant of papillary thyroid carcinoma. No lymph node metastases were identified. Non neoplastic thyroid parenchyma revealed chronic lymphocytic thyroiditis. Patient underwent radioiodine therapy with Whole Body Scan post radioiodine therapy demonstrating focal increased radionuclide localization at in region of neck consistent with functional thyroid tissue. There was no evidence of metastatic disease. In children, risk of malignancy is underestimated in ultrasonography and cytology. In this patient, papillary thyroid carcinoma was identified despite being stratified as having low risk of malignancy based on ultrasonography characteristics, hyperfunctioning nodule in scintigraphy study along with negative FNA results. Hyperfunctional nodules are usually reassuring for low risk of malignancy but rarely DTC can be found as in our patient. Guidelines agree that FNA is not recommended in functional nodules as surgical resection is the main therapy in children. However, surgery may be deferred if subclinical hyperthyroidism and low risk sonographic characteristics are present such as in our patient. If surgery had been deferred, based on low risk of malignancy, the risk of progression of disease would have been higher. Prognosis of DTC in children is good but the recurrence rate along with morbidity at such a young age may improve with more studies of DTC in children. Presentation: 6/2/2024

7708 Navigating Thyroid Cancer With Differences in Thyroglobulin Assessment Techniques

Abstract Disclosure: M.S. Shah: None. S. Humayon: None. N.A. Mungo: None. This case report delves into the diagnostic journey of a patient with papillary thyroid carcinoma, emphasizing the importance of precise thyroglobulin measurement methods. The case highlights the differences between immunoassay and mass spectrometry in monitoring disease progression and treatment response.A 42-year-old female with a family history of thyroid-related issues, was found to have a thyroid nodule on physical exam. She underwent fine-needle aspiration (FNA) revealing papillary thyroid carcinoma, Bethesda category VI. Lymphatic invasion was present necessitating total thyroidectomy and lymph node dissection. Left level 3 and 4 lymph node excision showing 2 of 15 positive for metastatic papillary thyroid carcinoma without extranodal extension. Left superficial jugular lymph node excision showing 1 of 3 lymph node being positive for metastatic thyroid carcinoma without extranodal extension. RAI therapy and post-ablative scan showed focal moderate increased activity adjacent to the left hyoid bone. CT scan of the neck later showed stable appearance of the thyroidectomy bed with no new suspicious soft tissue mass. A small crescentic focus of enhancing soft tissue medial to the left common carotid artery is favored to represent residual thyroid tissue. Multiple small enhancing lymph node in the left neck at level llB and junction of levels ll and lll. Several of these are new or increased in size from prior examination and somewhat acidly enhanced. Although these are within normal limits by size criteria, recurrent diseases cannot be excluded. She underwent another surgical neck dissection with no cancer found. Given the negative findings, a shift from checking thyroglobulin (TG) from immunoassay to mass spectrometry was ideal.Patient was found to have persistent thyroglobulin elevation with Immunoassay, thyroglobulin level (60.5 ng/mL, n<35 ng/ml), without the presence of TG antibodies, whereas liquid chromatography-tandem mass spectrometry (LC-MS/MS) showing (<0.5 ng/mL), highlighting the methodological divergence. To date she has no imaging concerns and repeat testing from different labs similarly demonstrated undetectably Tg by LC-MS/MS and varying levels when tested by Immunoassay. Her levels by Immunoassay have trended down to her most recent level of (38 ng/ml).This case emphasizes the critical role of accurate thyroglobulin assessment in thyroid carcinoma follow-up. Immunoassay and mass spectrometry present divergent results, with LC-MS/MS proving more reliable in monitoring disease progression but more expensive and time consuming. Clinicians should consider the implications of methodological choices on patient management, particularly in cases of persistent elevation despite treatment. The potential discrepancies between these methods should be emphasized considering the impact on treatment decisions. Presentation: 6/1/2024

Effect of methimazole treatment on Th1, Th17, and Th22 lymphocytes in pediatric Graves' disease patients.

Graves' disease is the leading cause of autoimmune hyperthyroidism. Thyroid hormones are an essential element of the endocrine system, playing a pivotal role in the body's development, especially important in children with intensified growth. Disturbance within thyroid tissue certainly affected the whole body. Nowadays, numerous research studies indicate different factors contributing to the onset of the disease; however, the exact pathomechanism of Graves' disease is still not fully understood, especially in the context of immune-related processes. Th1, Th17, and Th22 effector lymphocytes were found to be crucial participants in the disease outcome, as well as in autoimmune diseases. Here, our study aimed at assessing selected effector T lymphocytes, Th1, Th17, and Th22, in newly diagnosed pediatric Graves' disease patients, together with their association with thyroid-related parameters and the potential outcome of disease management. We indicated significant increases in the frequencies and absolute numbers of selected effector lymphocytes in Graves' disease patients. In addition, their mutual ratios, as well as Th1/Th17, Th/Th22, and Th17/Th22, seem to be significant in those diseases. Notably, low Th17/Th22 ratio values were distinguished as potential prognostic factors for normalizing TSH levels in response to methimazole treatment. To sum up, our research determines the crucial contribution of Th1, Th17, and Th22 cells in the pathogenesis of Graves' disease. Moreover, the mentioned subset of T cells is highly likely to play a substantial role in the potential prediction of therapy outcomes.

Overexpression of NR1D1 portends disease recurrence in thyroid cancer.

Dysregulation of circadian rhythms has been linked to cancer susceptibility. Thyroid cancer cells demonstrate altered circadian oscillations in endogenous clock transcripts. Our previous research identified NR1D1, a component of the circadian clock, as one of the recurrence-associated genes in papillary thyroid cancer. The objective of this study was to investigate the expression pattern of NR1D1 in thyroid cancer and explore its prognostic and translational implications. We assessed NR1D1 expression using immunohistochemical analysis and examined its correlation with clinicopathological parameters. In vitro and in vivo experiments were performed to elucidate the oncogenic roles of NR1D1 and potential mechanisms. Nuclear NR1D1 expression was present in thyroid follicular epithelial-derived cancers, whereas normal thyroid tissue and benign nodular goiter showed no detectable NR1D1 immunoreactivity. Patients with high expression of NR1D1 had more advanced disease stages, extrathyroidal extension, lymphovascular invasion, and shorter recurrence-free survival compared to those with low levels of NR1D1. Through gain- and loss-of-function studies, we demonstrated that NR1D1 modulation affected the growth of organoids, resistance to anoikis, and the invasive and migratory capacity of thyroid cancer cells. The invasion-promoting effect of NR1D1 was regulated by the β-catenin/ZEB1 axis. Moreover, the overexpression of NR1D1 accelerated xenograft growth and lung metastasis in vivo. NR1D1 is overexpressed in malignant thyroid tumors and has prognostic significance. Our findings suggest therapeutic potential in targeting NR1D1 for thyroid cancer.

Intratracheal Ectopic Thyroid Tissue Mimicking a Subglottic Mass in a Patient With Thyroid Follicular Carcinoma on SPECT/CT.

Intratracheal ectopic thyroid tissue is an extremely rare condition with limited cases reported in the literature. It can be asymptomatic or present with symptoms such as dysphagia, bleeding, dysphonia, dyspnea, and a sensation of a foreign body in the throat, depending on its localization. Due to its various clinical presentations, it poses a diagnostic dilemma. Herein, we aimed to present the contribution of thyroid scintigraphy and SPECT/CT to the diagnosis and management of a case with follicular carcinoma in the orthotopic thyroid gland as well as an ectopic intratracheal thyroid causing cough and airway obstruction mimicking a subglottic mass.

Histone 3 and 4 acetylation patterns in nodular goiter and well-differentiated thyroid tumors compared with normal thyroid tissue

Histone 3 and 4 acetylation patterns in nodular goiter and well-differentiated thyroid tumors compared with normal thyroid tissue

Mesenchymal stem cells alleviate autoimmune thyroiditis by modulating macrophage phenotypes and through influencing the STING pathway

BackgroundHashimoto's thyroiditis is a chronic autoimmune inflammatory disease with a high prevalence and currently lacks effective treatment options. Previous preclinical and clinical trials have established mesenchymal stem cells (MSCs) as a promising therapeutic approach; however, there is limited research on MSC treatment for Hashimoto's thyroiditis, and the underlying molecular mechanisms remain unclear. MethodsMSCs isolated from 4 to 6-week-old Lewis rats were employed for thyroiditis treatment. The efficacy of MSCs was assessed through histological and serological parameters. Molecular mechanisms of MSC therapy for Hashimoto's thyroiditis were explored by examining macrophage presence within thyroid tissue and relevant pathways. ResultsIn this study, we observed elevated oxidative stress and endoplasmic reticulum stress within the thyroid tissue of Hashimoto's thyroiditis patients, and MSC therapy effectively mitigated this process. Furthermore, we found that the therapeutic potential of MSCs in the EAT model depended on the STING pathway. MSCs reduced endoplasmic reticulum stress and inflammasome levels within the thyroid tissue by modulating the STING pathway. Additionally, MSCs inhibited the expression of IRE1α in thyroid tissue macrophages, thereby reducing the polarization of M1-type macrophages ConclusionsThe STING pathway appears to be a crucial mechanism by which MSCs modulate macrophage polarization in thyroid tissue, offering a potential treatment for thyroiditis.

Rare Pathology: Choristoma of the Palatine Tonsil in Otorhinolaryngology.

Choristomas are aggregates of microscopically normal tissues in aberrant locations. They can be cartilage, bone, glial tissue, salivary gland, and thyroid tissue. Cartilaginous choristomas of the oral cavity are rare and occur most commonly on the tongue and less often in sites such as the soft palate and gingiva. We report two cases of cartilaginous choristoma in young females presenting with recurrent tonsillitis. Histopathological examination showed the presence of mature island of hyaline cartilage surrounded by lymphoid hyperplasia. Level of Evidence: Level 4.

Zirconium- 89 Labeled Antibody K1-70 for PET Imaging of Thyroid-stimulating Hormone Receptor Expression in Thyroid Cancer.

Thyroid-stimulating hormone receptor (TSHR) is a G-protein coupled receptor that is highly expressed on benign and malignant thyroid tissues. TSHR binding and activation has long been a component of thyroid cancer molecular imaging and radiotherapy, by promoting expression of the sodium-iodide symporter (NIS) and incorporation of I-131 into thyroid hormones. Here, we report the radiosynthesis and preclinical evaluation of a Zirconium-89 (89Zr) labeled TSHR antibody to serve as a positron emission tomography (PET) diagnostic correlate for therapeutic agents targeting TSHR without reliance on NIS. TSHR human monoclonal antibody K1-70 was conjugated to chelator desferrioxamine-p-benzyl-isothiocyanate, followed by labeling with Zr-89, yielding the radiotracer 89Zr-DFO-TSHR-Ab. The in vitro cellar uptake and binding affinity of 89Zr-DFO-TSHR-Ab were analyzed in three new TSHR stable overexpressing tumor cell lines and their corresponding wild types (WT) with low or no TSHR expression. 89Zr-DFO-TSHR-Ab PET/CT imaging of TSHR expression was evaluated in tumor mouse models bearing one TSHR-positive tumor and other negative control with or without the coinjection of antibody K1-70, and then verified by radiotracer biodistribution study and tumor immunohistochemistry (IHC). The conjugate DFO-TSHR-Ab was labeled with Zr-89 at 37°C for 60min and purified by PD-10 column in radiochemical yields of 68.8 ± 9.9%, radiochemical purities of 98.7 ± 0.8%, and specific activities of 19.1 ± 2.7mCi/mg (n = 5). In vitro cell studies showed 89Zr-DFO-TSHR-Ab had significantly high uptake on TSHR expressing tumor cells with nanomolar affinity and high potency. Preclinical PET/CT imaging revealed that 89Zr-DFO-TSHR-Ab selectively detected TSHR expressing thyroid tumors and displayed improved in vivo performance with the coinjection of unlabeled TSHR antibody K1-70 leading to higher uptake in TSHR expressing tumors than parental WT tumors and physiologic tissues; this observation was confirmed by the biodistribution and immunostaining analyses. We synthesized 89Zr-labeled antibody K1-70 as a new radiopharmaceutical for PET imaging of TSHR. 89Zr-DFO-TSHR-Ab has high radioactive uptake and retention in TSHR expressing tumors and cleared quickly from most background tissues in mouse models. Our study demonstrated that 89Zr-DFO-TSHR-Ab has the potential for PET imaging of TSHR-positive thyroid cancer and monitoring TSHR-targeted therapy.

TGFBR3 inhibits progression of papillary thyroid cancer by inhibiting PI3K/AKT pathway and EMT.

Transforming growth factor beta receptor III (TGFBR3) has been shown to play a tumor suppressive role in a variety of cancers. However, its role in papillary thyroid cancer (PTC) remains unknown. TGFBR3 expression levels in PTC were analyzed utilizing TCGA and GEO database. Edu, wounding healing and Transwell assays were used to evaluate cell proliferation, migration and invasion. Transcriptome sequencing, qRT-PCR and Western blotting were used to detect the underlying mechanism of TGFBR3 in PTC progression. This study demonstrated that TGFBR3 expression was significantly down-regulated in PTC compared to normal thyroid tissues. Low expression of TGFBR3 was associated with poor prognosis of patients with PTC. Furthermore, TGFBR3 expression positively correlated with thyroid differentiation score. In investigating the biological impact of TGFBR3 over-expression in PTC cell lines, we found that the proliferation, migration and invasion of PTC cells were significantly inhibited in response to TGFBR3 overexpression. Moreover, we also demonstrated that overexpression of TGFBR3 inhibited PI3K/AKT pathway and epithelial mesenchymal transformation processes. Lastly, TGFBR3 expression was found to be involved in tumor immune infiltration, highlighting its potential influence on immune dynamics within the tumor microenvironment in PTC. TGFBR3 plays a tumor suppressive role in PTC progression by inhibiting PI3K/AKT pathway and EMT.

Tight Junctions and Cancer: Targeting Claudin-1 and Claudin-4 in Thyroid Pathologies.

Purpose: Claudins are tight junction proteins partaking in epithelial-mesenchymal transition and cancer progression. In this study, we investigated the expression patterns of claudin-1 and claudin-4 in thyroid pathologies, discussed their links with the pathogenesis of thyroid cancers, and reviewed the therapeutic potential of targeting claudins in cancers. Methods: The research group 162 cores of thyroid samples from patients (70 female and 11 male) diagnosed with thyroid adenoma, goiter, papillary, medullary, and anaplastic thyroid cancers. All samples were stained for the expression of claudin-1 and claudin-4, and the analysis of IHC was performed. Results: Goiter samples showed negative claudin-1 and mostly positive expression of claudin-4. Papillary thyroid cancer and thyroid adenoma showed positive expression of claudin-1, while claudin-4 was positive in papillary thyroid cancers, goiters, and adenomas. In The Cancer Genome Atlas cohort, claudin-1 and claudin-4 were overexpressed in papillary thyroid cancer compared to normal thyroid tissues. Patients with high claudin-1 expression had significantly lower 5-year overall survival than patients with low claudin-1 levels (86.75% vs. 98.65, respectively). In multivariate analysis, high claudin-1 expression (HR 7.91, CI 95% 1.79-35, p = 0.006) and advanced clinical stage remained statistically significant prognostic factors of poor prognosis in papillary thyroid cancer. Conclusions: The pattern of claudin-1 staining was pathology-specific and changed between cancers of different histology. This phenomenon may be associated with the different pathogenesis of thyroid cancers and early metastasis. The loss of claudin-1 and claudin-4 characterized more aggressive cancers. Several studies have shown the benefits of targeting claudins in cancers, but their implementation into clinical practice requires further trials.

Comparative Analysis of Metastatic Thyroid Carcinoma versus Ectopic Thyroid Carcinoma in Lateral Neck Masses without Identifiable Primary Thyroid Carcinoma

Background/Objectives: Thyroid carcinoma, presenting as a lateral neck mass without an identifiable primary tumor within the thyroid, poses a diagnostic challenge. This comparative analysis aimed to explore the differences between metastatic thyroid carcinoma and ectopic thyroid carcinoma, as both present with a lateral neck mass without evidence of primary thyroid carcinoma. Methods: Searches were conducted for studies on thyroid carcinoma in the lateral neck without evidence of primary thyroid carcinoma. A total of 39 patients were identified from 32 reported studies. Results: Metastatic and ectopic thyroid carcinomas were found in 11 and 28 patients, respectively. Metastatic thyroid carcinoma is characterized by evidence of spontaneous primary tumor regression within the thyroid and commonly associated with multiple lymph node metastases in central and lateral neck compartments. Ectopic thyroid carcinoma is more commonly diagnosed in younger patients and is frequently identified in branchial cleft cysts. The coexistence of normal thyroid tissue adjacent to the ectopic thyroid carcinoma was confirmed, and patients with ectopic thyroid carcinoma exhibited significantly higher rates of second-stage thyroidectomy or neck dissection. When complete surgical excision was considered adequate, excision alone was chosen for patients with ectopic thyroid carcinoma. Conclusions: Identifying these differences is valuable for the differential diagnosis and development of treatment strategies for metastatic and ectopic thyroid carcinomas in lateral neck masses without evidence of primary thyroid tumor.

Track recurrence after remote-access thyroid surgeries: A systematic review.

Remote-access thyroidectomies have gained popularity, but track recurrence, which is the implantation of thyroid tissue or lesions along the surgical access route, has been reported in case studies. This systematic review aims to review cases of track recurrence following remote-access thyroidectomies. A comprehensive literature search was conducted using PubMed, the Web of Science, the Cochrane Library, and Google Scholar to identify case reports on track recurrence after endoscopic or robotic thyroidectomy up to June 2024. Data included patient demographics, details of the initial surgery and diagnosis, methods and timing of recurrence detection, and management strategies. The search yielded 1578 articles, of which 17 case reports comprising 18 patients were included. The patients (16 females and two males) had a mean age of 34.6±14.9years. The mean size of initial tumors was 3.9±1.2cm, with diagnoses of eight cancers and 10 benign lesions. The initial surgeries included 12 endoscopic and six robotic procedures. Track recurrence was most often detected by palpable nodules followed by routine imaging and elevated serum Tg levels. The interval between initial surgery and recurrence ranged from 3months to 8years. Management varied from surgical resection and radioactive iodine therapy to close observation. There were no further recurrences in all but one case postoperatively. Track recurrence after remote-access thyroidectomy is rare but significant. Proper surgical techniques, careful handling of thyroid tissue, and rigorous postoperative monitoring are essential to minimize this risk. Awareness and prompt management of track recurrence may lead to favorable outcomes.

Влияние послеоперационного гипотиреоза на гормональную регуляцию сперматогенеза и функциональное состояние семенников у экспериментальных животных

Abstract: the aim of the study was to determine the effect of postoperative hypothyroidism on spermatogenesis in experimental dogs. Materials and Methods: experimental studies were performed on 20 mongrel male dogs. The study was randomized, 3 groups were identified. The first group was a control group, 4 dogs served as controls. Hemithyroidectomy was performed in the second group, subtotal thyroidectomy was performed in the third group. The operations were performed under general anesthesia. The testes, thyroid gland and blood were the objects of the study. In the postoperative period, biochemical and histological analyses of the removed thyroid gland tissue and testicles of the examined dogs were performed. The determination of hormones in the blood before and after surgery was carried out using a chemiluminescent analyzer Roche Codas E601 (Switzerland). Results: in the course of the study, in the postoperative period, experimental dogs had a decrease in testosterone in serum by 15% on day 5-8, and from 15% to 30.1% on day 20; in dogs after subtotal thyroidectomy, this indicator was 41.1% on day 20 (p < 0.005). Changes in FSH and prolactin in the blood were different in all groups. The FSH index had a significant increase on day 5-8, and a decrease on day 20, and the prolactin index on the contrary: a decrease on day 5-8 and an increase on day 20. The hormonal activity of the thyroid gland was reduced, especially after subtotal thyroidectomy. Morphological studies have shown a marked decrease in the activity of the spermatogenic layer and interstitial edema of the testes on 5-8 days in both groups. On the 30th day, in both groups after surgery, there was a noticeable decrease in both the spermatogenic layer and the interstitial cells of the testes. Conclusion: the results of experimental studies have shown that as a result of hemithyroidectomy and subtotal thyroidectomy, there is a noticeable change in the regulation of spermatogenesis and structural and functional changes in the testes of experimental animals, especially in the iodine-deficient region. Keywords: postoperative hypothyroidism, spermatogenesis, semens, hormones, hemitireoidectomy.

Lipoma: An Unusual Iodine-131 Uptake on Whole-Body Scanning: A Case Report

Whole-body radioiodine scintigraphy plays a major role in detecting metastases or recurrence of differentiated thyroid cancers. However, radioactive iodine uptake is not specific to thyroid tissue, and many physiological and pathological variants can bind radioactive iodine, resulting in false positives that can compromise the correct interpretation of results. We report the case of a 73-year-old patient with papillary thyroid carcinoma who underwent surgery 2 years ago, and whose whole-body scan, performed in the face of rising thyroglobulin levels, revealed abnormal fixation on the thigh, and further investigations suggested a lipoma. Our aim in reporting this case is to contribute to the knowledge of new false positives linked to iodine-131 fixation, in order to avoid unusual diagnostic errors that can lead to the unnecessary administration of therapeutic doses of iodine-131 or to aberrant surgical interventions.