Small Thyroid Research Articles

Prophylactic central lymph node dissection for low-risk papillary thyroid cancer-Impact on subsequent therapy.

For small papillary thyroid cancers (PTCs) with no lateral nodal involvement, American Thyroid Association guidelines recommend performing prophylactic central lymph node dissection (pCLND) if it influences further management. Our cohort study explored to what extent performing pCLND for small PTCs can de-escalate subsequent therapy including completion thyroidectomy and adjuvant radioactive iodine (RAI) ablation. Adults with T1, T2, and cN0 PTCs were identified from 42 centers across the prospectively maintained Australian and New Zealand Thyroid Cancer Registry (ANZTCR) between 2017 and 2023. Patients were excluded if they had clinical nodal involvement or distant metastases. Subsequent therapy and complication rates were compared between patients with and without pCLND. Out of 1290 patients with T1, T2, and cN0 PTCs (78% female and median age 53years), 660 (51%) received a total thyroidectomy and 630 (49%) received a hemithyroidectomy. Prophylactic CLND was performed for 477 patients (37%) and 36% uncovered occult lymph node metastases. After adjusting for differences in age, sex, and tumor characteristics, absence of lymph node metastasis after pCLND was independently associated with fewer completion thyroidectomies (adjusted relative risk [aRR]=0.65 and p=0.008) and reduced RAI ablation (aRR 0.55 and p<0.001). Additionally, pCLND was not associated with higher risks of recurrent laryngeal nerve injury (p=0.33), temporary hypocalcemia (p=0.21), or permanent hypoparathyroidism (p=0.48). In specialized settings across Australia and New Zealand, identifying negative lymph nodes from pCLND is associated with reduced completion thyroidectomies and RAI ablation amongst low risk cN0 PTCs. There were no additional complications rates when performed by experienced thyroid surgeons.

A Risk Stratification Study of Ultrasound Images of Thyroid Nodules Based on Improved DETR

ABSTRACTThe Chinese Thyroid Imaging Reporting and Data System (C‐TIRADS) standard is based on the Chinese current medical context. However, at present, there is a lack of C‐TIRADS‐based automatic computer‐aided diagnosis system for thyroid nodule ultrasound images, and the existing algorithms for detecting and recognizing thyroid nodules are basically for the dichotomous classification of benign and malignant. We used the DETR (detection transformer) model as a baseline model and carried out model enhancements to address the shortcomings of unsatisfactory classification accuracy and difficulty in detecting small thyroid nodules in the DETR model. First, to investigate the method of acquiring multi‐scale features of thyroid nodule ultrasound images, we choose TResNet‐L as the feature extraction network and introduce multi‐scale feature information and group convolution, thereby enhancing the model's multi‐label classification accuracy. Second, a parallel decoder architecture for multi‐label thyroid nodule ultrasound image classification is designed to enhance the learning of correlation between pathological feature class labels, aiming to improve the multi‐label classification accuracy of the detection model. Third, the loss function of the detection model is improved. We propose a linear combination of Smooth L1‐Loss and CIoU Loss as the model's bounding box loss function and asymmetric loss as the model's multi‐label classification loss function, aiming to further improve the detection model's detection accuracy for small thyroid nodules. The experiment results show that the improved DETR model achieves an AP of 92.4% and 81.6% with IoU thresholds of 0.5 and 0.75, respectively.

8105 Radiation-Induced Hyperthyroidism in the Context of Palliative Radiation Therapy

Abstract Disclosure: A. Randhawa: None. G. Palaguachi: None. J.G. Karam: None. Introduction: Palliative radiotherapy, designed to alleviate focal symptoms in advanced, incurable cancer, aims to enhance quality of life with minimal treatment burden. The thyroid gland's susceptibility to neck radiation is known, primarily leading to hypothyroidism. However, hyperthyroidism is a much less frequently reported adverse effect that is poorly understood. This case report highlights an unusual instance of radiation-induced hyperthyroidism. Case Presentation:The patient is a 53 years-old woman with history of Ewing’s sarcoma of the sacrum diagnosed in August 2022, treated initially with chemotherapy (cyclophosphamide, vincristine, etoposide and ifosfamide), but diagnosed with leptomeningeal metastasis and T12/L1 mass in October 2023 when she presented with lower extremities weakness and urinary incontinence. She underwent T12-L1 laminectomy, resection of tumor and fusion, and was started on palliative intent radiation therapy for the brain and C-spine. A month later, she was admitted for altered mental status and was found to be persistently tachycardic at 140 bpm. Thyroid function testing was sent and revealed hyperthyroidism with TSH of 0.07 mIU/L (0.39-4.08), Free T4 of 1.74 ng/dl (0.58-1.64), T4 of 10.7ug/ml (4.4-9.5), T3 of 0.54 ng/ml (0.72-1.35), with undetectable Thyroid Peroxidase Antibodies and Thyroid Stimulating Immunoglobulin level. Thyroid Ultrasound showed a small and homogenous thyroid gland with no discrete nodules. Radioactive Iodine uptake and scan was not obtained because of exposure to iodized contrast during hospital stay. The patient had no available baseline thyroid function tests. She had no recent fever or viral illness. Unfortunately, her clinical condition deteriorated rapidly, and she passed away on the seventh day of admission. Conclusion: While hypothyroidism is a well-established consequence of high-dose irradiation, the mechanisms behind the rarer radiation-induced hyperthyroidism remain unclear. Speculation includes the release of autoantigens from damaged thyroid glands, triggering an immune response and potentially leading to Graves' hyperthyroidism. However, our case more likely represents a hyperthyroid phase in the triphasic sequence of destructive subacute thyroiditis, given the absence of elevated thyroid antibodies, thyroid nodules, and other causes of thyroiditis. Increasing awareness of radiation-induced hyperthyroidism, unraveling its mechanisms, and refining diagnostic strategies such as obtaining baseline and monitoring thyroid function testing are crucial, particularly in the context of palliative therapy, where striking the delicate balance between efficacy and minimizing toxicity is paramount. Presentation: 6/3/2024

6847 Poorly Differentiated Thyroid Cancer: A Rare Entity

Abstract Disclosure: S. Fatima: None. S. Ward: None. A. Champion: None. Introduction: Poorly differentiated thyroid carcinoma (PDTC) is a rare thyroid carcinoma originating from follicular epithelial cells. Regarding the degree of differentiation, PDTC ranks between differentiated thyroid cancer and anaplastic thyroid cancer. We hereby present a rare case of PDTC. Case: 29-year-old female with a history of metastatic papillary thyroid cancer (PTC) presented to the emergency department with shortness of breath. She initially noticed a left thyroid mass in 2021. CT neck in 1/2022 showed a 7 cm left thyroid mass with substernal extension, small right thyroid mass with tracheal compression, left bulky cystic nodal masses extending anterior and posterior to carotid and internal jugular vein. PET scan in 3/2022 showed left 7.6 cm thyroid mass SUV 12.1 with tracheal compression, left level II-IV adenopathy with level IV nodal masses 5.1 cm SUV 4.5. Ultrasound-guided FNA in 4/2022 showed PTC in left 8.7cm thyroid nodule; right 2.8 cm nodule showed Atypia of Undetermined Significance; Left 5.5 cm neck level III lymph node (LN) showed PTC metastasis; right 5.1 cm neck level III LN showed PTC metastasis (+ thyroglobulin and TTF-1). CT chest in 11/2022 showed additional involvement of manubrium. Repeat core needle biopsy of left thyroid mass showed left invasive thyroid carcinoma. She was started on neoadjuvant Lenvatinib in 1/2023. Follow-up CT neck in 5/2023 showed a reduction in the size of the left thyroid mass to 5.5cm x 5.8cm x 6.5cm. At this time, she had symptoms of dysphagia, orthopnea, weight loss of about 60 lbs and neck pain. In 11/2023 at time of current presentation she underwent total thyroidectomy, bilateral modified radical neck dissection and manubriectomy. Surgical pathology showed PDTC in left thyroid mass, PTC in right thyroid mass with metastatic PDTC in left proximal sternocleidomastoid, manubrium and LN involvement in neck and mediastinum. OmniSeq Insight testing showed APC and BRCA1 gene mutations, negative BRAF V600E, RET fusion, RET mutation, NTRK1/2/3 fusion and PD L1 immunohistochemistry score is &amp;lt;1%. The patient is planned to receive [1]3[1]I ablation therapy. Conclusion: PDTC accounts for 3–5% of all thyroid carcinomas. The 5, 10-, and 15-year survival rates of patients are 50–85%, 34–50%, and 0%, respectively. RAS gene alterations are found in 25–35%, BRAF mutation in 15–27%, TERT promoter mutation in 40% and mutant TP53 in 16–28% of PDTCs. TERT promoter gene and TP53 mutation usually indicate an aggressive phenotype and a dismal prognosis. Surgery, [1]3[1]I therapy, and external beam radiotherapy constitute the mainstay of traditional treatment for patients with advanced disease; however, treatment is challenging. Tyrosine kinase inhibitors i.e, sorafenib and lenvatinib, have been used in cases of progressive, recurrent, or metastatic disease not responsive to [1]3[1]I therapy. Immunotherapy may be an option in PD-L1-positive tumors. Presentation: 6/1/2024

7642 A Mixed Model of Clinical Characteristics and Ultrasound ACR-TIRADS Predicts Malignancy in Thyroid Micro Lesions

Abstract Disclosure: N. Angelopoulos: None. I. Iakovou: None. D. Goulis: None. R. Paparodis: None. S. Livadas: None. A. Boniakos: None. J.C. Jaume: None. Background: The frequency of papillary thyroid carcinoma (PTC) has increased, mainly due to the detection of small tumors incidentally found during unrelated imaging. While most of these small cancers have a non-aggressive course, some can be more biologically hostile, with potential for metastasis. Current guidelines discourage routine biopsy for nodules ≤10 mm, but the challenge is identifying higher-risk microcarcinomas. This study aims to identify ultrasound and clinical characteristics indicating malignancy in small thyroid lesions. Patients and methods: 151 patients with accidentally discovered solid nodules in thyroid ultrasound were enrolled in the study. All patients were stratified according to both ACR and EU-TIRADS systems. Two qualified endocrinologists performed ACR-TIRADS scoring and accordingly, all patients were stratified to the five ACR categories TR1-5 Strain elastography was also performed in all nodules and the elastography ratio (E2/E1) was calculated (E2 elastography of the nodule, E1 elastography of healthy thyroid gland). FNA was performed in nodules classified as EU-TIRADS 5 Results: 41 patients were classified as EU-TIRADS 5. The rest of the patients were classified as 69 EU-TIRADS 4, 40 EU-TIRADS 3, and one EU-TIRADS 2. According to FNA results, 11 patients had Bethesda II cytology (Group A), 2 Bethesda III, one Bethesda IV, 10 Bethesda V, and 17 Bethesda VI (V and VI comprised Group B). FNAs indicative of malignancy (Group B) were more frequent in patients with autoimmune thyroiditis (Chi-squared 5,833, df(1), p=0.015). In Group B, both ACR-scoring points and ACR-TIRADS categories were significantly higher than those detected in patients in Group A. Logistic regression analysis revealed a significant prognostic role of ACR-scoring points in discriminating suspicious FNA results for thyroid cancer. ROC analysis (AUC:0.993 with Youden Index:0.926, associated criterion &amp;gt;6, Sensitivity 92.59 % and Specificity 100 %). To analyze the predictive power of the clinical parameters in the presence of thyroid malignancy, age, BMI, gender, autoimmune disease, therapy, nodule diameter, and elastography ratio were examined in a “clinical model”. The overall prognostic value of the model was significant (p=0.0029, AUC:0.744) with a sensitivity of 77.78% and specificity of 72.73%, (Youden Index: 0.505, associated criterion &amp;gt;0.6). Finally, a “mixed model”, combining the clinical characteristics and the ACR scoring points, was generated for methodological reasons. The model was overall significant (p&amp;lt;0.001) with AUC:1 (95% Confidence interval: 0.907 to 1), Youden Index:1, sensitivity, and specificity 100%. Conclusion: ACR- TIRADS points &amp;gt; 6 may be a strong indicator of thyroid malignancy and the “mixed model” is an excellent predictor of thyroid malignancy, but its usefulness in everyday clinical practice may be cumbersome. Presentation: 6/1/2024

Observational cohort study on safety and efficacy of robotic thyroidectomy with super-meticulous capsular dissection versus open surgery for thyroid cancer: Postoperative dynamic risk assessment of radioactive iodine therapy.

To assess the efficacy and safety of robotic thyroidectomy (RT) with super-meticulous capsular dissection (SMCD) versus open thyroidectomy (OT) we used a dynamic risk assessment system incorporating 131I-WBS along with radioactive iodine (RAI) efficacy evaluation. Currently, the therapeutic efficacy of robotic surgery remains controversial. The 131I whole-body scan (131I-WBS) dynamic risk assessment system can detect small residual thyroid tissues and lesions, which may be used as indicators for the surgical efficacy of RT or OT thyroidectomy in differentiated thyroid cancer (DTC). This retrospective cohort study included 2,349 patients who underwent total thyroidectomy followed by RAI therapy in our department between August 2017 and June 2023. Propensity score matching was performed at a ratio of 1:3 based on surgical type and mean follow-up duration to minimize selection bias after excluding those lost to follow-up. The primary outcome was surgical completeness, assessed using a dynamic risk system incorporating 131I-WBS along with RAI efficacy evaluation. There was no significant difference in the number of metastatic lymph nodes removed between the two groups (P=0.45). The incidence rate of parathyroid gland transplantation was 395 (68.7%) in the OT group and 8 (3.8%) in the RT group (P<0.001). There were no differences in the thyroidectomy completeness based on the 3-hour iodine uptake rate and 99mTcO4- thyroid imaging between the two groups. The dynamic risk assessment with and without 131I-WBS showed significant differences (P<0.001). The postoperative and post-RAI dynamic risk scores, evaluated at the time of RAI and 6 months after RAI, did not differ significantly between the two groups (P>0.05). The rates of transient and permanent hypoparathyroidism were higher in the OT group than in the RT group (P<0.05). The local recurrence rates showed no significant difference between the groups. This study demonstrates that RT with SMCD can achieve outcomes equivalent to those of traditional open surgery when integrating the 131I-WBS dynamic evaluation system and the therapeutic effects of RAI. Additionally, robot surgery demonstrated a notable advantage in protecting parathyroid function.

The use of vacuum fine needle aspiration biopsy of small formations in the diagnosis of thyroid cancer

Introduction. Diagnosis and treatment of lesional pathology of the thyroid are important problems in Russia and worldwide. Currently, fine-needle aspiration (FNA) is the main technique of differential diagnosis of benign and malignant tumors of the thyroid. In 2023, clinical guidelines of the European Thyroid Association (ETA) on thyroid lesion treatment were published noting possible minimally invasive treatment of benign and malignant tumors of the thyroid requiring repeat cytologic verification. Despite the proven effectiveness of FNA, its informativity and specificity vary between 60 and 100 %. Additionally, this method is associated with high risk of false negative and false positive results. Therefore, there is a need to improve FNA and minimize its disadvantages.Aim. To evaluate the capabilities of vacuum FNA of small lesions using multiparameter ultrasound in diagnosis of thyroid cancer.Materials and methods. At the scientific and practical problem laboratory Diagnostic Studies and Minimally Invasive Technologies of the Smolensk State Medical University, a device for vacuum FNA was developed. Between 2023 and 2024, patients with thyroid lesions of size &lt;10 mm underwent 25 vacuum FNAs. Correlation analysis with 51 FNAs performed between 2020 and 2023 was performed.Results. A decrease in the number of nondiagnostic (category I per the Bethesda system, 2017) and undetermined (category III per the Bethesda system, 2017) results was observed. Comparison of preoperative cytologic conclusions (category V per the Bethesda system, 2017) with the results of postoperative histological examination in patients of the control group showed benign lesions in 2 (50 %) cases which correspond to false negative results. Vacuum FNA did not show this discrepancy. These results demonstrate a decrease in the probability of false negative results and effectiveness of vacuum FNA.Conclusion. Use of vacuum FNA expedites ultrasound-guided biopsy for small thyroid lesions. Due to high negative pressure (up to –0.8 bar), single-step retrieval of cytologic material is performed which leads to a decrease in the number of nondiagnostic and undetermined cytologic conclusions by 11.7 and 1.9 %, respectively.

Are we ready to bridge classification systems? A comprehensive review of different reporting systems in thyroid cytology.

The evaluation of thyroid lesions is common in the daily practice of cytology. While the majority of thyroid nodules are benign, in recent decades, there has been increased detection of small and well-differentiated thyroid cancers. Combining ultrasound evaluation with fine-needle aspiration cytology (FNAC) is extremely useful in the management of thyroid nodules. Furthermore, the adoption of specific terminology, introduced by different thyroid reporting systems, has helped effectively communicate thyroid FNAC diagnoses in a clear and understandable way. In 1996, the Papanicolaou Society thyroid cytological classification was introduced. This was followed in 2005 by the first Japanese and then in 2007 by the Bethesda System for Reporting Thyroid Cytopathology, which subsequently underwent two revisions. Other international thyroid terminology classifications include the British, Italian, Australasian and other Japanese cytology systems. This review covers similarities and differences among these cytology classification systems and highlights key points that unify these varied approaches to reporting thyroid FNAC diagnoses.

Thermoablative Treatment of Papillary Microcarcinomas of Thyroid.

Recently, locoregional treatment with ultrasound-guided radiofrequency has been proposed as a new, effective, and safe procedure for low-risk papillary thyroid microcarcinoma (PTC < 1 cm), not eligible or recruitable for surgery. Until now, the gold standard has been the surgery and then the active surveillance. The aim of the study is to present our experience of ultrasound-guidedthermoablation, a procedure performed before demolitive surgery and post-active surveillance. It is a non-invasive treatment that does not require general anesthesia, with a low risk of complications, hypothyroidism, and hypoparathyroidism. All nodules described on ultrasound showed a volumetric increase (follow-up from 12 to 36 months). The cytological examination in all cases showed TIR 4b and TIR 5 papillary microcarcinoma. All the patients were offered the possibility of radiofrequency thermoablation; they were all informed and gave their consent. 18G active tip electrode needles 7 or 10 mm (Amica Gen HS) were used with the moving shot method under local anesthesia in a day hospital setting. No severe complications were reported. Contrast-Enhanced Ultrasonography (CEUS) with SonoVue (CEUS Sonovue) was performed post-procedure and then at 1, 3, 6, and 12 months, which documented complete revascularization and progressive volumetric reduction of the treated area. Our experience has confirmed that radiofrequency ablation can effectively eliminate small papillary thyroid carcinomas with fewer complications. In our opinion, it is a valid alternative for the treatment of low-risk and indolent papillary thyroid microcarcinomas, even in the absence of surgical contraindications.

Relationship between BRAF V600E and some aggressive features in papillary thyroid carcinoma ≤1.5 cm

Objectives: Determine the association between BRAF V600E mutation in papillary thyroid microcarcinoma (PTMC), small papillary thyroid carcinoma (PTC 1-1.5 cm), with tumour-aggressive characteristics. Subjects and methods: Retrospective descriptive study of 104 patients with PTMC diagnosed by histopathology and with BRAF V600E gene mutation testing results. Study subjects were divided into 2 groups: PTMC (tumour size ≤1.0 cm) and PTC 1-1.5 cm (tumour size 1-1.5 cm) and evaluated aggressive features (macroscopic extrathyroidal invasion, lymph node metastasis, high-risk variants). Results: BRAF V600E gene mutation was detected in 72.8% of PTMC and 76.5% of PTC 1-1.5 cm. The proportion of tumours with aggressive features in PTMC with and without mutations was 66.7 and 52.63%, respectively (p=0.28). The proportion of tumours with aggressive features in PTC 1-1.5 cm with and without mutations was 80.7 and 100%, respectively (p=0.309). In the PTMC group, the rate of extrathyroidal invasion was higher in tumours with BRAF V600E mutation (p&lt;0.05). No association was found between BRAF V600E gene mutation and lymph node metastasis, high cell variation, and more than one aggressive feature in both PTMC and PTC 1-1.5 cm patient groups. Conclusions: In the PTMC group, the rate of extrathyroidal invasion was higher in patients with the BRAFV600E mutation. No association was found between BRAFV600E gene mutation and other aggressive features in patients with PTMC and PTC 1-1.5 cm.

Thyroid Cancer Incidence and Tumor Size in New Mexico American Indians, Hispanics, and Non-Hispanic Whites, 1992 to 2019.

The incidence of thyroid cancer in the United States has risen dramatically since the 1970s, driven by an increase in the diagnosis of small tumors. There is a paucity of published New Mexico (NM) specific data regarding thyroid cancer. We hypothesized that due to New Mexico's unique geographic and cultural makeup, the incidence of thyroid cancer and tumor size at diagnosis in this state would differ from that demonstrated on a national level. The New Mexico Tumor Registry (NMTR) was queried to include all NM residents diagnosed with thyroid cancer between 1992 and 2019. For 2010 to 2019, age-adjusted incidence rates were calculated via direct method using the 2000 United States population as the adjustment standard. Differences in incidence rate and tumor size by race/ethnicity and residence (metropolitan vs non-metropolitan) were assessed with rate ratios between groups. For 1992 to 2019, temporal trends in age-adjusted incidence rates for major race/ethnic groups in NM [Non-Hispanic White (NHW), Hispanic, and American Indian (AI)] were assessed by joinpoint regression using National Cancer Institute software. Our study included 3,161 patients for the time period 2010 to 2019, including NHW (1518), Hispanic (1425), and AI (218) cases. The overall incidence rates for NM AIs were lower than those for Hispanics and NHWs because of a decreased incidence of very small tumors (<1.1 cm). The incidence rates for large tumors (>5.1 cm) was equivalent among groups. In the early 2000s, Hispanics also had lower rates of small tumors when compared to NHWs but this trend disappeared over time. AIs in New Mexico have been left out of the nationwide increase in incidental diagnosis of small thyroid tumors. This same pattern was noted for Hispanics in the early 2000s but changed over time to mirror incidence rates for NHWs. These data are illustrative of the health care disparities that exist among New Mexico's population and how these disparities have changed over time.

Papillary thyroid carcinoma: ≤ 10mm does not always mean pN0. A multicentric real-world study.

The incidence of papillary thyroid carcinoma (PTC) is increasing and PTC ≤ 10mm (PTMC) accounts for most new diagnoses. PTMCs are not always low risk, as detection of lymph nodes metastasis (LNM) may occur. The purpose of the study was to analyze the clinical pattern, frequency, and independent risk factors of patients with PTMC and LNM. From January 2022 to June 2023, PTCs managed at CTO Hospital, Rome; Policlinico Vanvitelli, Naples; and Garibaldi Nesima Hospital, Catania were included. PTC management followed the same diagnostic-therapeutic procedures according to the ATA guidelines. Variables such as age, sex, maximum diameter, histologic evidence of LNM (HELNM +), Hashimoto's thyroiditis (HT), multifocality, capsule invasion, and histological subtype were considered. PTCs were divided according to HELNM and size. Two hundred ninety-eight PTCs were included. PTMCs were 136 (45.6%) and LNM occurred in 27.2% of them. In the HELNM + group, analysis of PTMC vs 'MacroPTC' (PTC > 10mm) did not show any statistical difference. Multivariate regression revealed that young age (OR 0.93; CI 95% 0.90-0.96; p < 0.01) and male sex (male OR 3.44; CI 95% 1.16-10.20; p = 0.03) were the only independent risk factors for HELNM + in PTMC. The risk of LNM in PTMC is not negligible; therefore, a careful evaluation by an expert thyroidologist is mandatory for patients with small thyroid nodule, especially in younger and male patients before excluding surgery. In the future, new tools are needed to detect early PTMC with LNM before surgery.

Decision Regret Following the Choice of Surgery or Active Surveillance for Small, Low-Risk Papillary Thyroid Cancer: A Prospective Cohort Study.

Background: It is important to understand cancer survivors' perceptions about their treatment decisions and quality of life. Methods: We performed a prospective observational cohort study of Canadian patients with small (<2 cm) low-risk papillary thyroid cancer (PTC) who were offered the choice of active surveillance (AS) or surgery (Clinicaltrials.gov NCT03271892). Participants completed a questionnaire one year after their treatment decision. The primary intention-to-treat analysis compared the mean decision regret scale total score between patients who chose AS or surgery. A secondary analysis examined one-year decision regret score according to treatment status. Secondary outcomes included quality of life, mood, fear of disease progression, and body image perception. We adjusted for age, sex, and follow-up duration in linear regression analyses. Results: The overall questionnaire response rate was 95.5% (191/200). The initial treatment choices of respondents were AS 79.1% (151/191) and surgery 20.9% (40/191). The mean age was 53 years (standard deviation [SD] 15 years) and 77% (147/191) were females. In the AS group, 7.3% (11/151) of patients crossed over to definitive treatment (two for disease progression) before the time of questionnaire completion. The mean level of decision regret did not differ significantly between patients who chose AS (mean 22.4, SD 13.9) or surgery (mean 20.9, SD 12.2) in crude (p = 0.730) or adjusted (p = 0.29) analyses. However, the adjusted level of decision regret was significantly higher in patients who initially chose AS and crossed over to surgery (beta coefficient 10.1 [confidence interval; CI 1.3-18.9], p = 0.02), compared with those remaining under AS. In secondary adjusted analyses, respondents who chose surgery reported that symptoms related to their cancer or its treatment interfered with life to a greater extent than those who chose AS (p = 0.02), but there were no significant group differences in the levels of depression, anxiety, fear of disease progression, or overall body image perception. Conclusions: In this study of patients with small, low-risk PTC, the mean level of decision regret pertaining to the initial disease management choice was relatively low after one year and it did not differ significantly for respondents who chose AS or surgery.

Laser Ablation for Benign and Malignant Thyroid Nodules - A Mini-Literature Review.

Thyroid nodules are a common disease in endocrine clinical practice. They are often benign, asymptomatic, and do not require any treatment. But, in a non-negligible proportion, they can cause local symptoms of compression or esthetic concerns. In the last two decades, the advent of laser ablation (LA) has become a valid alternative to surgery for these nodules. Moreover, LA has also been successfully used to treat small thyroid cancers and neck recurrence. This study aims to review and summarize the published literature regarding LA in the treatment of benign and malignant thyroid nodules. A comprehensive literature search on PubMed from 2000 to 2023 was carried out. The search terms included: thyroid, nodules, laser, cancer, lymph node metastasis, and autonomously functioning nodules. The most relevant investigations in the field were selected. In the last two decades, a very remarkable number of papers consistently demonstrated that LA is able to durably shrink benign nodules on average by about 50%; better results are obtained in spongiform nodules with a volume less than 15 ml; 500 J/ml of tissue should be administered. LA may be a valid option to treat autonomously functioning nodules and papillary thyroid cancers especially if they are <10 mm, and with neck recurrence in patients already submitted to surgery. LA has also been demonstrated to be cost-effective compared to surgical treatment both in benign and malignant lesions, with similar outcomes. Evidence demonstrated that LA is a valid alternative to surgery in benign and malignant thyroid lesions, but also to obtain a successful treatment, a careful selection of the lesion is mandatory.

Presentation and treatment of two cases of malignant struma ovarii

BackgroundMalignant Struma Ovarii (MSO) is a rare type of germ cell tumour which is diagnosed postoperatively on surgical pathology specimens by the presence of differentiated thyroid cancer in mature cystic teratomas in the ovaries. Treatment and follow-up procedures are not clearly established due to the paucity of MSO cases.Case 1A 44-year-old multiparous female presented with an irregular period. Ultrasound showed a left ovarian lesion mostly a dermoid cyst, however, CT showed a 3.8 × 2.7 × 4 cm complex cystic lesion with thick septation and enhancing soft tissue component. Laparoscopic left salpingo-oophorectomy was performed and histopathology showed a follicular variant of papillary thyroid carcinoma arising in a mature cystic teratoma. Peritoneal cytology was positive for malignancy. A thyroid function test was normal before surgery. Total thyroidectomy was performed followed by radioactive (RAI) iodine therapy. Later, a total laparoscopic hysterectomy and right salpingo-oophorectomy were performed. There is no evidence of recurrent disease during the 26-months follow-up.Case 2A 46-year-old single female presented with left lower abdominal pain that had persisted for 2 months. Imaging revealed an 8 × 9 × 9.5 cm left ovarian mass. Laparoscopic left salpingo-oophorectomy was performed and histopathology showed mature cystic teratoma with small papillary thyroid cancer. CT showed no evidence of metastatic disease. Later, the patient had a total thyroidectomy followed by radioactive (RAI) iodine therapy. She was started on thyroxine and later had total abdominal hysterectomy and right salpingo-oophorectomy.ConclusionMSO is a very rare tumour. Preoperative diagnosis is very difficult because of the nonspecific symptoms and the lack of specific features in imaging studies. Also, there is no consensus on the optimal treatment of women with MSO. Our two cases add to the limited number of MSO cases.

Abstract B102: Development of covalent inhibitors targeting Ras Q61 hotspot mutants

Abstract Mutations in the proto-oncogenes RAS are a key driver of various cancers, including pancreatic, colorectal, non–small cell lung cancer (NSCLC), melanoma, and thyroid cancer. Despite being considered undruggable for many years, recent efforts have led to the FDA approval of two drugs, Sotorasib and Adagrasib. They covalently target the K-Ras mutant isoform K-Ras(G12C), thereby inhibiting its oncogenic effect. However, the use of these drugs is inherently limited to cancers driven by the K-Ras(G12C) mutant, which is very common only in NSCLC. Although other covalent inhibitors targeting the K-Ras mutants K-Ras(G12S) and K-Ras(G12R) have been developed, it has so far not been possible to target the other frequently mutated amino acid Q61. Here we present our approach for the development of novel covalent inhibitors specifically targeting Q61 mutations in Ras proteins, which are prevalent in melanoma, multiple myeloma, and thyroid cancer. We demonstrate how covalent inhibitors specifically react with the mutant Q61C in both K and H-Ras proteins as proof-of-concept and show our efforts to extend this to the other Q61 mutant isoforms. We base our strategy on the modification of well-established switch-II pocket K-Ras inhibitors and explore multiple novel scaffolds specifically designed to target mutations of Q61. In addition to its occurrence in various cancers, Ras(Q61X) is also a common resistance mutation in patients treated with MAPK inhibitors. This work could further increase the number of patients potentially benefiting from Ras(Q61X) targeting drugs. Citation Format: Julius Pampel, Johannes Morstein, Qinheng Zheng, David M. Peacock, Kevan M. Shokat. Development of covalent inhibitors targeting Ras Q61 hotspot mutants [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr B102.

Sexual dimorphism in medullary thyroid cancer aggressiveness.

Thyroid cancer is the only nonreproductive cancer with striking female predominance, although men with thyroid cancer develop more aggressive disease. This study aimed to quantify sex-specific differences in medullary thyroid cancer (MTC) spread after controlling for primary thyroid tumor size. Included in this retrospective analysis were all patients with unilateral solitary MTC who underwent initial neck surgery at a tertiary referral center. A total of 565 patients, 255 men and 310 women, were identified, of whom 467 had sporadic and 98 hereditary MTC. When stratified by sex, and after correction for multiple testing, men had higher preoperative basal calcitonin levels (medians of 655 vs 181 pg/mL; P < 0.001), more frequent extrathyroid extension (25 vs 9%; P < 0.001) and node metastasis (53 vs 27%; P < 0.001) with more involved nodes (medians of 2 vs 0 nodes; P < 0.001) than women but achieved less often biochemical cure (53 vs 74%; P < 0.001). Although absent in patients with very small (≤5 mm) thyroid tumors, sex disparities were immediately apparent in patients with 5.1-40 mm (node metastasis and biochemical cure) and 10.1-40 mm (extrathyroid extension) large thyroid tumors but were lost in patients with thyroid tumors >40 mm as women caught up. Sex disparities were strongest for node metastasis with a 27-41% (overall 24.0%) point difference, followed by biochemical cure with a -15-35% (overall -20.3%) point difference and extrathyroid extension with a 17-24% (14.2% overall) point difference. These findings indicate that the male predominance in MTC aggressiveness is largely biologically driven, warranting further research.

Mechanism of multi-organ compensation under different iodine intake in pregnant rats: results from a repeated-measures study of iodine metabolism.

This study aimed to explore the differences in iodine metabolism and expression of NIS and Pendrin in pregnant rats under different iodine nutritional status. Female Wistar rats were divided into four groups: low iodine (LI), normal iodine (NI), tenfold high iodine (10HI), and fifty fold high iodine (50HI). The intervention began after one week of adaptive feeding. Iodine metabolism experiments were performed beginning on the 15th day of pregnancy. 24-h iodine intake and excretion were calculated. The concentrations of iodine in urine, fecal, thyroid, and placenta were measured by ICP-MS. PCR and Western Blot were used to detect the mRNA levels and cell membrane protein of sodium/iodide symporter (NIS) and Pendrin in the small intestine, thyroid, kidney, and placenta. Fecal iodine excretion (FIE) and urinary iodine excretion (UIE) in the 50HI group were significantly higher than those in the NI group (P < 0.05). The NIS protein and mRNA in the kidney and small intestine have an upward trend in iodine deficiency and a downward trend in iodine excess. Thyroid and placental iodine storage in the 50HI group were significantly higher than those in the NI group (P < 0.05). NIS, Pendrin protein, and mRNA in the thyroid and placenta tend to increase when iodine is deficient and decrease when there is excess. Iodine excretion and iodine stores in the placenta and thyroid gland are positively correlated with iodine intake. NIS and Pendrin are also regulated by iodine intake.

Ultrasound Imaging in Active Surveillance of Small, Low-Risk Papillary Thyroid Cancer.

The recent surge in the incidence of small papillary thyroid cancers (PTCs) has been linked to the widespread use of ultrasonography, thereby prompting concerns regarding overdiagnosis. Active surveillance (AS) has emerged as a less invasive alternative management strategy for low-risk PTCs, especially for PTCs measuring ≤1 cm in maximal diameter. Recent studies report low disease progression rates of low-risk PTCs ≤1 cm under AS. Ongoing research is currently exploring the feasibility of AS for larger PTCs (<20 mm). AS protocols include meticulous ultrasound assessment, emphasis on standardized techniques, and a multidisciplinary approach; they involve monitoring the nodules for size, growth, potential extrathyroidal extension, proximity to the trachea and recurrent laryngeal nerve, and potential cervical nodal metastases. The criteria for progression, often defined as an increase in the maximum diameter of the PTC, warrant a review of precision and ongoing examinations. Challenges exist regarding the reliability of volume measurements for defining PTC disease progression. Although ultrasonography plays a pivotal role, challenges in assessing progression and minor extrathyroidal extension underscore the importance of a multidisciplinary approach in disease management. This comprehensive overview highlights the evolving landscape of AS for PTCs, emphasizing the need for standardized protocols, meticulous assessments, and ongoing research to inform decision-making.

Graves’ disease – management of Graves’ orbitopathy and thyrotoxicosis, including new therapies

Graves' disease (GD) is the most common cause of hyperthyroidism in countries with adequate iodine supply, and its main extrathyroid manifestation is thyroid orbitopathy. For many years, thyrotoxicosis has been treated with antithyroid drugs, radioactive iodine therapy and thyroidectomy, and glucocorticoids have remained the standard treatment of thyroid eye disease (TED). Currently, there is a growing trend of using targeted therapies in the treatment of thyroid orbitopathy (TO). The significant development of immunobiology, a better understanding of the pathophysiology of the disease and a multitude of studies on new therapies give hope for better treatment results and an improvement in the quality of life of patients. The aim of the paper is to discuss the current principles of management of Graves' disease, including thyroid orbitopathy, with particular emphasis on new therapeutic methods. The potent role of K1-70TM and small molecule thyroid stimulating hormone (TSH) receptor antagonists in the treatment of hyperthyroidism is indicated. Not only do we point out the promising outcomes of combining glucocorticoids with mycophenolates, but also highlight the use of teprotumumab, rituximab, cyclosporin A, azathioprine, methotrexate, tocilizumab and sirolimus in the therapy of active moderate to severe form of orbitopathy. The protective and supportive effect of statins in the treatment of TED is noted. The limitations of the research results mentioned in the paper are remarked and the need for further randomized studies of long-term safety and efficacy in a larger group of patients is underlined.