Radioiodine Therapy Research Articles

Prognosis and ablation success in thyroid cancer: overcoming the challenges of incomplete clinical profiles.

Differentiated thyroid carcinoma (DTC) is managed by surgery followed by radioiodine (RAI) therapy in most intermediate and high-risk patients. Most nonmetastatic patients have excellent treatment responses and have long-term disease-free status. A lack of comprehensive medical services in resource-limited nation leads to attrition of critical clinical prognostication information. This study aimed to identify readily available clinical, biochemical, and histopathological parameters to predict remnant ablation success and long-term outcomes. The study included DTC patients who underwent RAI after surgery. Ablation success was determined by thyroglobulin (Tg) and whole-body radioiodine scan. Patients were followed for at least 5 years to assess biochemical incomplete response (BIR) and structural recurrence. The study included 383 patients (a mean age of 37.8 ± 12.9 years). Successful ablation was noted in 251 (65.5%). High preablative stimulated serum Tg (presTg), papillary variants, and central and lateral compartment lymph nodal metastases were associated with ablation failure. PresTg (P < 0.001) was the most significant predictor. After a 102.9 ± 34.5 months follow-up, 280 (73.1%) patients were disease-free. BIR and structural recurrence were noted in 103 and 32 patients. PresTg (8.1 ± 27.7 vs. 92.3 ± 99.9 ng/ml), ATg (112.9 ± 389.8 vs. 43.2 ± 89.8 IU/ml), papillary variant, central [109 (66.1%) vs. 56 (33.9%)], and lateral compartment [65 (63.7%) vs. 37 (36.3%) lymph nodal metastases were associated (P < 0.05) with BIR. PresTg >10.5 has a sensitivity and specificity of 86.6 and 86.0% for predicting BIR. Patients with successful remnant ablation and a presTg level <10.5 ng/ml had a low risk of long-term disease recurrence (less than 5%). This ambispective study found that successful ablation and long-term disease-free survival were achievable in a significant proportion of DTC patients. BIR (26.9%) and structural recurrence (8.4%) were not uncommon. PresTg levels emerged as a crucial predictor of ablation success and subsequent outcomes. In resource-limited regions, presTg levels and ablation failure can aid in optimizing treatment strategies and improving patient care.

Trends in the use of thyroid diagnostics and treatments between 2008 and 2019 in Germany

Following implementation of a national prevention program against iodine deficiency-related disorders in 1993 in Germany, the prevalence of thyroid disorders declined, but aggregated drug dispensation data suggested a recent increase in thyroid hormone use. We aimed to systematically investigate trends in the use of thyroid diagnostic and treatment measures between 2008 and 2019 in Germany. Using the GePaRD database (claims data from ~ 20% of the German population), we determined the annual age-specific and age-standardized prevalence of the use of thyroid diagnostics (thyroid-stimulating hormone (TSH) measurement, thyroid ultrasound, scintiscan, biopsy) and treatment (medication, surgery, radioiodine therapy) from 2008 to 2019 stratified by sex. Between 2008 and 2019, the age-standardized prevalence of TSH measurement increased by 44% in males (from 165 to 238 per 1,000 persons) and by 31% in females (from 134 to 176 per 1,000). The prevalence of thyroid ultrasound use showed no clear time trend, while there was a decrease in the prevalence of scintiscan use (males/females: decrease by 42/43%) and biopsy (males/females: decrease by 42/34%). The prevalence of levothyroxine use increased by ~ 31% both in males (from 36 to 47 per 1,000) and females (from 134 to 175 per 1,000), while the prevalence of thionamide use, iodine use, thyroidectomy, and radioiodine therapy decreased. Our study suggests a continued decline in the prevalence of clinically significant thyroid disorders between 2008 and 2019. The substantial increase in the prevalence of TSH measurement and levothyroxine use during this time period might indicate overuse of diagnostics and overtreatment, warranting further investigation.

The Prognostic Impact of Radioiodine Therapy in Patients with Papillary Thyroid Cancer.

Radioiodine (RAI) therapy after surgery, is an important component for the treatment of patients with papillary thyroid cancer (PTC), the most common thyroid cancer. In this study we sought to evaluate the cancer-specific survival (CSS) impact of RAI in specific thyroid cancer subgroups. The Surveillance, Epidemiology, and End Results (SEER) database were used to identify patients with PTC who underwent surgery between 2000 and 2019. Patients not treated with RAI were compared to those treated with RAI using propensity score matching (PSM) on the basis of identical inclusion criteria. A total of 106 333 patients were identified from the SEER database. RAI therapy was associated with improved CSS in the matched cohort (HR: 0.83; 95% CI: 0.72-0.96, p=0.01) but not in the unmatched data set (HR: 1.46; 95% CI: 1.30-1.64, p<0.001) among all PTC patients regardless of disease stage. Detailed analyses, however, showed that only patients with high-risk disease (pT3N1, pT4N1) experienced the greatest benefit in CSS. In the lower disease stages, no significant differences were recognized in the group of PTC patients with or without RAI therapy. One exception: in the group of PTC patients in stage pT1bN0, a significant difference was seen towards RAI. This is, however, most likely due to the large number of patients investigated. In summary, RAI therapy should not be used in low-risk PTC patients and might be used to some extent in intermediate-risk PTC patients. The histological suptype of the tumor needs to be considered in this context.

Molecular theranostics: principles, challenges and controversies.

Theranostics is a new term for long-established principles in nuclear medicine. The generalisability of the term means there is a very broad use of the term across the medical literature, not all of which is consistent with the intent in nuclear medicine. The term molecular theranostics better reflects the philosophy and application in nuclear medicine. Even with a clearer definition, there are a number of challenges or controversies whose debate provides a richer understanding of the principles and applications of molecular theranostics. Radioiodine imaging and therapy of hyperthyroidism and thyroid cancer provide the historical context for theranostics. The prototype molecular theranostic is the 68Ga/177Lu DOTATATE pair that targets somatostatin receptor subtype 2 in neuroendocrine tumors. The potential value of precision medicine of radiation dosimetry in molecular theranostics needs a balanced discussion with limitations of reactive dosimetry and the opportunities for predictive or pre-treatment dosimetry. Despite challenges and limitations, molecular theranostics is a powerful tool in the precision medicine landscape. Molecular theranostics is a vehicle for improved outcomes in cancer patients with a future-facing portfolio of opportunities.

Systemic Immune-Inflammation Index and Systemic Inflammation Response Index Predict the Response to Radioiodine Therapy for Differentiated Thyroid Cancer.

This research sought to evaluate the clinical value of systemic immune-inflammation index and systemic inflammation response index in predicting the response to radioactive iodine (RAI) therapy in individuals diagnosed with differentiated thyroid cancer. This retrospective study included 406 patients with differentiated thyroid cancer who received initial RAI therapy and follow-up from December 2019 to December 2023. Patients were divided into two groups based on imaging and serum indicators to evaluate the response to radioactive iodine treatment: the ER group (excellent response) and the non-ER group (suboptimal response). Systemic immune-inflammation index and systemic inflammation response index were calculated based on peripheral blood cell counts before treatment. Multivariable logistic regression analysis was used to assess the independent associations of these indices with the therapeutic response to radioiodine treatment. Receiver operating characteristic (ROC) curves were graphed and the area under the curve (AUC) was calculated to evaluate their predictive ability. Compared to the ER group, patients in the non-ER group had significantly elevated systemic immune-inflammation index and systemic inflammation response index levels (p < 0.001). After adjusting for confounding factors, there was a significant association between these indices and the response to radioactive iodine treatment in patients with differentiated thyroid cancer. The optimal cutoff values for predicting the response to RAI treatment were 668.91 for systemic immune-inflammation index (AUC=0.692, sensitivity 58.2%, specificity 73.1%, 95% CI: 0.639-0.745, p < 0.001) and 0.47 for systemic inflammation response index (AUC=0.664, sensitivity 85.6%, specificity 42.7%, 95% CI: 0.612-0.717, p < 0.001). Systemic immune-inflammation index and systemic inflammation response index could be valuable for predicting the response to RAI treatment in individuals diagnosed with differentiated thyroid cancer. Further research is needed to explore their practical utility, and these novel inflammation markers could serve as adjunct tools in clinical practice.

Recurrence patterns in differentiated thyroid cancer (DTC) following adjuvant radioiodine therapy.

With an increasing incidence of differentiated thyroid cancer (DTC) diagnosis, questions emerge about the optimal duration of follow-up for detecting recurrent disease and its outcomes. The objective of this retrospective research was to assess the clinical course of differentiated thyroid cancer after radioiodine adjuvant treatment in patients monitored over an extended period. Special attention was paid to the analysis of the time from treatment to recurrence. We also assessed patient outcomes after recurrence. A total of 650 patients with DTC after total/near-total thyroidectomy and adjuvant radioiodine post-recombinant human thyrotropin (post-rhTSH) stimulation were evaluated. All patients were followed up with neck ultrasound, serum thyroid-stimulating hormone (TSH), thyroglobulin (Tg), and antithyroglobulin antibody (anti-Tg) measurements at intervals of 6 to 18 months. Only structural recurrences were considered. They were defined as locoregional recurrence confirmed by biopsy or distant metastases [confirmed by computed tomography (CT) or magnetic resonance imaging (MRI), or abnormal foci on radioiodine scintigraphy or 18F-gluorodeoxyglucose positron emission tomography [18 F] FDG-PET scan], regardless of thyroglobulin (Tg) or anti-Tg levels. The median follow-up was 12 years (5-15.5). Structural recurrence was observed in 47 out of 650 patients (7%). All but 3 locoregional recurrences were suitable for surgery. The median time to structural recurrence was 16 months, with only 9 (1.4%) patients presenting with recurrence after more than 60 months. At the time of the database closure, 601 patients (92%) had an excellent response, including 20 out of 47 (42%) patients with structural recurrence. Eighty-one out of 650 patients had died (12.5%) before the database closure. The median age at the last follow-up of the patients who died was 72 years (range 20-88). A second recurrence was diagnosed in 10 out of 650 patients (1.5%), corresponding to 21% (10 out of 47) of patients who had already experienced a recurrence. The median time from radioiodine (RAI) therapy to the second structural recurrence was 108 months. Structural recurrences in DTC are uncommon, with most patients showing a favourable response to treatment. Improved understanding of recurrence timing may define the duration of patient surveillance at reference centres that can be safely discontinued after 5 years in low- and intermediate-risk groups, as indicated in our study.

Progressive Unilateral Proptosis and [18F]FDG-Avid Lesions Connoting Aggressive Disease in Radioiodine-Refractory Differentiated Thyroid Carcinoma

AbstractRadioiodine-refractory differentiated thyroid carcinoma (RAIR-DTC) have poor prognosis as compared with radioiodine concentrating thyroid carcinoma. We present a case of follicular thyroid carcinoma presenting as a disseminated disease initially, underwent thyroid surgery and radioiodine (RAI) therapy. Following RAI, the patient developed a sudden-onset unilateral proptosis, finally diagnosed as orbital metastasis. [18F]-Fluorodeoxyglucose (FDG)-positron emission tomography-computed tomography identified FDG-avid metastatic lesions more numerous than the RAI-avid lesions. The patient was treated with local and systemic targeted therapy, but despite these treatments, he developed progressive disease indicating aggressive nature of the disease consistent with [18F]FDG-avid RAIR-DTC.

Comparison of Thyroid Size-Specific Radioiodine Dose and New Modified Dose Calculation in the Treatment of Graves' Disease.

Previous studies of fixed-dose radioiodine therapy (RIT) for Graves' disease (GD) have utilized a variety of techniques and reported differing success rates. This study sought to compare the efficacy of RIT using two fixed-dose protocols and to estimate the optimal radioiodine (RAI) activity for the treatment of GD. This retrospective trial enrolled 658 patients with GD who received RIT between January 2014 and December 2021. Participants were divided into two groups: protocol 1, which utilized a thyroid size-specific RAI dose, and protocol 2, which employed a modified dose calculation approach. The primary outcome assessed was the presence of euthyroidism or hypothyroidism at the 6-month follow-up. The success rates of RIT were compared between the two protocols. The RIT success rate was marginally lower for protocol 2 than for protocol 1 (63.6% vs. 67.2%); however, the risk of treatment failure did not differ considerably between the groups (relative risk, 1.1089; 95% confidence interval, 0.8937 to 1.3758; P=0.3477). The median RAI activity associated with protocol 2 was lower than that for protocol 1 (10.7 mCi vs. 15.0 mCi, P=0.0079), and the frequency of hypothyroidism was significantly lower in the protocol 2 group (39.0% vs. 48.9%, P=0.0117). The success rate of the modified dose calculation protocol was comparable to that of the thyroid size-specific RAI dose protocol. The former approach reduced RAI activity and the incidence of hypothyroidism following RIT without compromising the success rate.

Consideration of Early Dynamic Risk Stratification to Guide Discharge from Oncologic Follow-Up in Patients with Differentiated Thyroid Cancer.

Background: The current dogma is a life-long follow-up for patients treated for follicular-derived differentiated thyroid cancers (DTC). Our primary objective was to determine the time to recurrence in a series of DTC patients with an excellent response to therapy 6 months after total thyroidectomy and radioiodine therapy. The secondary objectives were to determine the time to suspicion of recurrence and to identify factors associated with recurrence. Methods: This retrospective cohort study included patients treated for DTC between 2008 and 2012 and in remission 6 months after total thyroidectomy and radioiodine treatment. The criteria for remission were negative imaging and suppressed thyroglobulin (Tg) <0.2 ng/mL or rh-TSH-(recombinant human TSH) stimulated Tg <1 ng/mL according to the 2015 ATA (American Thyroid Association) guidelines. Recurrence was defined by cytologically and/or histologically proven cervical lymph node metastasis or the administration of a second radioiodine treatment. Results: Among 721 patients treated for DTC, 158 were excluded because of persistent disease at 6 months, 71 because of missing follow-up data, and 492 were included. The mean and median follow-up time were 7.0 and 7.9 years (interquartile range IQR [2.1-11.3]). Recurrence occurred for 7 patients (1.4%), 1 initially classified as high recurrence risk, 3 as intermediate, and 3 as low risk according to the 2015 ATA guidelines. All relapses occurred within 10 years after initial management (4 within the first 5 years). For patients with recurrence, rise in Tg and/or suspicious lymph nodes were detected in six out of seven cases in the first 8 years and for the last case 10 years after initial surgery. Conclusion: Low and intermediate recurrence risk DTC patients with excellent response 6 months after total thyroidectomy and radioiodine and in remission 10 years later have an extremely low recurrence risk. Follow-up might be undertaken by primary care providers from this time point. These discharge recommendations should be confirmed by further prospective studies.

Descriptive Analysis of Common Fusion Mutations in Papillary Thyroid Carcinoma in Hungary

Thyroid cancer is the most common type of endocrine malignancy. Papillary thyroid carcinoma (PTC) is its predominant subtype, which is responsible for the vast majority of cases. It is true that PTC is a malignant tumor with a very good prognosis due to effective primary therapeutic approaches such as thyroidectomy and radioiodine (RAI) therapy. However, we are often required to indicate second-line treatments to eradicate the tumor properly. In these scenarios, molecular therapies are promising alternatives, especially if specifically targetable mutations are present. Many of these targetable gene alterations originate from gene fusions, which can be found using molecular diagnostics like next-generation sequencing (NGS). Nonetheless, molecular profiling is far from being a routine procedure in the initial phase of PTC diagnostics. As a result, the mutation status, except for BRAF V600E mutation, is not included in risk classification algorithms either. This study aims to provide a comprehensive analysis of fusion mutations in PTC and their associations with clinicopathological variables in order to underscore certain clinical settings when molecular diagnostics should be considered earlier, and to demonstrate yet unknown molecular–clinicopathological connections. We conducted a retrospective fusion mutation screening in formalin-fixed paraffin-embedded (FFPE) PTC tissue samples of 100 patients. After quality evaluation by an expert pathologist, RNA isolation was performed, and then NGS was applied to detect 23 relevant gene fusions in the tumor samples. Clinicopathological data were collected from medical and histological records. To obtain the most associations from the multivariate dataset, we used the d-correlation method for our principal component analysis (PCA). Further statistical analyses, including Chi-square tests and logistic regressions, were performed to identify additional significant correlations within certain subsets of the data. Fusion mutations were identified in 27% of the PTC samples, involving nine distinct genes: RET, NTRK3, CCDC6, ETV6, MET, ALK, NCOA4, EML4, and SQSTM1. RET and CCDC6 fusions were associated with type of thyroidectomy, RAI therapy, smaller tumor size, and history of Hashimoto’s disease. NCOA4 fusion correlated with sex, multifocality, microcarcinoma character, history of goiter, and obstructive pulmonary disease. EML4 fusion was also linked with surgical procedure type and smaller tumor size, as well as the history of hypothyroidism. SQSTM1 fusion was associated with multifocality and a medical history of thyroid/parathyroid adenoma. NTRK3 and ETV6 fusions showed significant associations with Hashimoto’s disease, and ETV6, also with endometriosis. Moreover, fusion mutations were linked to younger age at the time of diagnosis, particularly the fusion of ETV6. The frequent occurrence of fusion mutations and their associations with certain clinicopathological metrics highlight the importance of integrating molecular profiling into routine PTC management. Early detection of fusion mutations can inform surgical decisions and therapeutic strategies, potentially improving clinical outcomes.

Assessing radioiodine therapy long-term outcomes in differentiated thyroid cancer using nomograms.

This study explored the role of radioiodine therapy (RAI) in low-risk thyroid cancer patients and examined the disease-specific survival (DSS) rates in a large cohort of differentiated thyroid cancer patients (DTC). We obtained patient data from SEER database. Patients who underwent total thyroidectomy were included and categorized into three groups based on histology: classical papillary thyroid carcinoma (C-PTC), follicular type variant carcinoma (FV-PTC), and follicular thyroid cancer (FTC). Patients with distant metastasis, tumor size ≥ 200mm, chemotherapy, or any type of radiation other than RAI were also excluded. A nomogram was developed and tested for discrimination and calibration. In total, 96,532 thyroid cancer cases were examined, including 59,460 C-PTC, 31,583 FV-PTC, and 5,489 FTC cases. Age > 65years and male sex were correlated with lower survival rates across the subtypes. In addition, extrathyroidal extension had a worse survival effect in patients with FTC. DSS rates were compared between patients who received RAI and those who did not, with a 3% difference in C-PTC (94% vs. 91%, p < 0.001), 2% in FV-PTC (92% vs. 90%, p < 0.001), and 1% in FTC (89% vs. 88%, p = 0.084) at 15years. The nomograms for long-term DSS showed high discriminatory abilities with C-indices of 0.815, 0.805, and 0.781 for C-PTC, FV-PTC, and FTC, respectively. The developed nomogram can be used in the treatment plan for patients with DTC. Our study emphasizes the prognostic factors for DTC and highlights the need for personalized treatment plans based on individual risk profiles.

Radioiodine treatment in female survivors of pediatric differentiated thyroid carcinoma does not affect future pregnancy rates.

Patients with pediatric differentiated thyroid carcinoma (DTC) treated with radioiodine (RAI) therapy may experience long-term side effects, such as gonadal dysfunction. Therefore, it is crucial to understand the impact of this therapy on ovarian reserve and future pregnancy rates. Retrospective analysis of 64 female DTC survivors of childbearing age to assess the risk of infertility due to RAI performed before the age of 19 years. Thirty-two out of the 64 DTC survivors had a history of at least one pregnancy during follow-up. No significant differences were observed between the cumulative RAI activity, treatment regimens (multiple versus single RAI treatment), age at first treatment, or presence of lymph node or distant metastases. Notably, the group without a history of pregnancy had a younger age at the time of diagnosis and larger tumors. Age at first pregnancy was slightly higher than that in the general population, but no increase in negative maternal or fetal outcomes was observed. The results of this study show little observational evidence suggesting important adverse effects of RAI on fertility or pregnancy outcomes among female survivors of childhood DTC. Still, studies including larger populations are warranted.

7847 Radiomic Ultrasound Checkup of Thyroid Nodules Before Radiodiodine Therapy

Abstract Disclosure: A.A. Trukhin: Grant Recipient; Self; Russian Science Foundation (project N 22-15-00135). A.V. Manaev: Grant Recipient; Self; Russian Science Foundation (project N 22-15-00135). S.M. Zakharova: Grant Recipient; Self; Russian Science Foundation (project N 22-15-00135). M.S. Sheremeta: None. E.A. Troshina: Grant Recipient; Self; Russian Science Foundation (project N 22-15-00135). Background: Over 83 years radioiodine therapy (RIT) of autonomous thyroid nodules still have uncovered pages, according to its complexity and thyroid nodules variety. There are two main criteria to allow RIT – no malignancy and presence of iodine uptake, the last one could be checked by Tc-99m-pertachnetate or I-123, I-131 iodine scintigraphy. Case with thyroid nodules first undergo ultrasound (US) TI-RADS classification, then fine needle aspiration stratification according to the Bethesda system. Publications applied such algorithm shows 75-85% accuracy in malignancy determination, that in 15-25% can lead to improper RIT application. Aim: Method development for thyroid nodules ultrasound checkup before I-131 administration and I-131 24h uptake prognosis. Methods: Study includes 150 nodules (65 benign, 60 malignant, 25 autonomous benign thyroid nodules). Both US longitudinal and transversal thyroid nodule projections were obtained via GE Voluson E8 (36% benign cases / 27% malignant cases) and GE Logiq E (64% benign cases / 73% malignant cases) in cinematic loop regime. Autonomous thyroid nodules underwent I-131 pharmacokinetics examination with 24h uptake determination and RIT. Statistical textural features were obtained through spatial adjacency matrix. Results: Analysis of 16 statistical textural features shows weak correlation between 11 statistical textural features E (Energy), S (Entropy), LU (Local homogeneity), MP (Maximum probability), TR (Matrix trace), CORR (Correlation), IMC (information measure of correlation), DV (Difference variance), DE (Difference entropy), SE (Sum entropy), SA (Average value of the sum). ROC-analysis using 11 statistical textural features shows the best model for benign/malignance determination with AUC = 0.83, Se = 74%, Sp = 73%, PPV = 75%, NPV = 72%, Acc = 74%. I-131 pharmacokinetics examination shows strong correlation SA to I-131 24h uptake. Conclusions: The performed study demonstrates the possibility of using textural statistical features of ultrasound images as instrument for thyroid nodules ultrasound checkup before I-131 administration, for extra FNA prescription and prognosis the I-131 24h important in exact therapeutic I-131 activity calculation. 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

12243 The Case of a Metastatic Papillary Thyroid Cancer Presenting as an Unresectable Pelvic Mass

Abstract Disclosure: M. Tucktuck: None. Y. El Soufi: None. O.G. Adeniran: None. A.A. Gliwa: None. Background: Papillary thyroid cancer (PTC) represents around 85% of all thyroid cancers, of which 2-10% of patients will present with metastasis distant to the neck. The frequency of bone metastasis in PTC occurs in only 1-4% of patients. Studies have shown that distant and multi-organ metastasis is associated with higher mortality rates. Clinical case: A 69-year-old woman with diabetes mellitus, cerebrovascular accident, and right lower extremity deep venous thrombosis, presented with right foot and hip pain for 1 week after a mechanical fall. She had a 50 pound weight loss over a year without personal or family history of thyroid cancer or disease or radiation exposure. A soft and nontender mass in the right lower abdomen was noted during a physical exam. Imaging revealed a large heterogeneous lesion (16.3 x 13.3 x 15.5 cm) in the right bony pelvis with internal necrosis, destructing the right iliac bone, and extending into the right sacrum, acetabulum, and musculature, with mass effect on the surrounding vasculature, and enlarged lymph nodes suspicious for metastasis. Thyroid imaging showed a hypervascular hyperechoic 1.3 cm nodule within the right thyroid gland and a large 2 cm left thyroid nodule with scattered microcalcifications. Thyroid function tests were within normal limits. The patient underwent an initial ultrasound guided biopsy of the pelvic mass with indiscriminate results, and later a laparoscopic excisional biopsy of the pelvic mass showed neoplastic papillary proliferation with typical nuclear features, without necrosis or associated ovarian tissue. The immuno-histopathological profile was positive for PAX-8, TTF-1, thyroglobulin, and CK7, and the Ki-67 proliferation index was ∼20-30%. The patient was diagnosed with papillary thyroid cancer with metastasis to the pelvic bone, and was classified as stage IV, cT1bN0M1. As the pelvic mass was inoperable, the patient completed total thyroidectomy and was started on hormone replacement therapy. Subsequent thyroid pathology report was negative for papillary carcinoma. Further review of imaging did not show ectopic thyroid tissue in the neck or an ovarian pathology. Before the patient’s next visit to evaluate for struma ovarii, she passed away. Conclusion: Thyroid cancer is usually treated through thyroidectomy or lobectomy, with radioiodine (RAI) therapy as an effective treatment for differentiated cancers. Our patient, who presented with extremity pain revealing a distant metastasis, completed thyroidectomy with plans to undergo RAI therapy. Our case highlighted the importance of recognizing musculoskeletal presentations as an initial and possibly only finding of a distant metastasis. It also emphasized the utility of multidisciplinary collaboration in detecting and recognizing PTC as a primary thyroid cancer, as early management can reduce mortality and lead to more favorable outcomes. Presentation: 6/2/2024

7771 Surveillance Role in Differentiated Thyroid Cancer Through Ultrasensitive Thyroglobulin IRMA with High Negative Prediction Value

Abstract Disclosure: J. Jang: None. H. Kim: None. S. Ha: None. K. Jung: None. G. Jung: None. S. Cho: None. D. Park: None. G. Cheon: None. Y. Park: None. TSH-stimulated serum thyroglobulin (s-Tg) is a well-established marker for monitoring differentiated thyroid cancer (DTC) following remnant ablation therapy. The 2nd-generation immunoradiometric assay for Tg (ultrasensitive Tg, uTg) was developed to detect Tg with higher sensitivity compared with the 1st generation (conventional Tg, cTg). This study aimed to compare efficacy of both methods, cTg and uTg, to determine whether unstimulated Tg (us-Tg) could predict s-Tg levels. Paired serum samples were collected from 274 DTC patients before (us-Tg) and after (s-Tg) TSH stimulation for 1st radioiodine therapy after surgery (1st Tg) or both 1st therapy and 2nd therapy/diagnostic test (1st and 2nd Tg, respectively). Both cTg (Dynotest Tg-plus, BRAHMS Gmbh, Germany, LOD 0.1 ng/mL and functional sensitivity (FS) 0.2 ng/mL) and uTg (RIAKEY, Shinjin Medics, South Korea; LOD 0.01 ng/mL and FS 0.06 ng/mL) were measured. For analysis, samples with inadequate TSH stimulation (&amp;lt;30 μIU/mL) or with anti-thyroglobulin antibody levels &amp;gt; 60 U/mL were excluded. Ultimately, the included samples consisted of 296 for us-Tg and 352 for s-Tg.. Among these, paired samples for us-Tg and s-Tg were available in 260 cases (189 for 1st Tg and 71 for 2nd Tg). Comparing all Tg values, cTg and uTg levels had a correlation (Intraclass correlation coefficient r=0.752, P &amp;lt; 0.001), with no significant difference between us-Tg (r=0.803, P &amp;lt; 0.001) and s-Tg (r= 0.752, P &amp;lt; 0.001). The optimal cut-off level for predicting s-cTg at 1 ng/mL was 0.12 ng/mL in uTg or 0.16 ng/mL in cTg tests using AUC-ROC curve analysis. Considering the FS for cTg, diagnostic performance was assessed with a cut-off level of 0.2 ng/mL for cTg and 0.16 ng/mL for uTg. For s-cTg positivity as ≥ 1 ng/mL, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of uTg were 72.1%, 59.8%. 52.0%, and 78.0%, respectively, while for cTg, they were 33.3%, 95.3%, 78.4%, and 73.9%, respectively. Similar trends were observed for s-cTg ≥ 2 ng/mL (69.0%, 71.4%, 35.0%, and 91.2% for uTg, respectively; 49.0%, 93.8%, 64.9%, and 88.7% for cTg, respectively). In essence, uTg demonstrated higher sensitivity than cTg, while having lower specificity and PPV, with a similar NPV. Of the 71 patients with paired 2nd Tg levels, 7 (9.8%) had biochemical disease (BCD) by s-cTg (1 ng/mL), whereas only 1 (1.4%) showed BCD using us-cTg ≥ 0.2 ng/mL. Conversely, 40 (56.0%) were classified as BCD using us-uTg ≥ 0.16 ng/mL. During the 6.48 years of follow-up, 4 patients developed structural recurrence; all had positive us-Tg levels with uTg tests, while only 1 patient demonstrated positivity with cTg tests. Although, the ultrasensitive Tg is sensitive in predicting positive stimulated Tg and recurrence, the specificity is very low resulting high frequency of BCD cases without clinical significance. Therefore, the clinical utility of uTg appears to be limited. Presentation: 6/2/2024

7179 Efficacy of radioactive iodine for the treatment of thyrotoxicosis in a prospective cohort in Aotearoa/New Zealand

Abstract Disclosure: J. Tamatea: None. S. Nottingham: None. V. Boyle: None. M.S. Elston: None. Background – The outcome following treatment of thyrotoxicosis with a single fixed-dose radioiodine (RAI) can be difficult to predict and has been shown to have a lower success rate in Māori vs. non-Māori (1).Aim – the aim of this prospective study was to compare RAI treatment outcomes between Māori and non-Māori, identify factors that are associated with RAI treatment failure in thyrotoxicosis and whether these factors affect the difference in ethnicity outcomes seen.Method – all patients over the age of 16 years referred to Waikato Hospital (Hamilton, New Zealand) for the treatment of thyrotoxicosis with RAI between March 2013 and February 2015 were invited to participate in this study. Demographic information was collected with a questionnaire prior to treatment. Aetiology and severity of thyrotoxicosis at time of diagnosis was retrospectively collected. Laboratory investigations, ultrasound thyroid volume and thyroid pertechnetate uptake were carried out prior to RAI treatment. Participants were followed up for12 months after RAI to assess outcome to treatment. Univariate analysis of variables were carried out for the full cohort and for Graves’ Disease (GD) cohort. Logistic regression analysis was carried out including ethnicity and additional variables of age, gender, diagnosis, thyroid volume, smoking status, and BMI.Results – a total of 162 participants were included: 71 identified as Māori and 91 as non-Māori. At 12 months follow up, 146 participants (90.1%) had a successful treatment outcome follow a single dose of RAI. Successful outcome was achieved in 85.9% of Māori vs 93.4% of non-Māori (p = .113), however when only looking at the GD cohort, Māori were less likely to have successful outcome than non-Māori (68.75% vs 89.4% p = .022). Following regression analysis ethnicity was no longer a variable associated with treatment failure. When controlling for other variables, factors found to increase the risk of failing RAI were diagnosis of TMNG/STA (OR 0.03; 95%CI 0.002-0.035), larger thyroid volumes (OR 1.04; 95%CI 1.01 - 1.07 per mL of thyroid volume) and smoking (OR 6.71; 95%CI 1.2 - 37.4 for current smokers).Conclusion - RAI is an effective definitive treatment option for thyrotoxicosis. Factors found to be associated with treatment outcome are aetiology of thyrotoxicosis, thyroid volume, and smoking status. These factors likely explain the ethnicity difference in treatment outcome following RAI in Māori vs non-Māori.References – 1. Tamatea JAU, Conaglen JV, Elston MS. Response to Radioiodine Therapy for Thyrotoxicosis: Disparate Outcomes for an Indigenous Population. International Journal of Endocrinology. 2016;2016:7863867. Presentation: 6/2/2024

Health-related quality of life and radioiodine therapy in thyroid cancer patients: a before-and-after study.

Thyroid cancers are on the rise, but the associated vital prognosis and long-term survival rates are very good. Therefore, treated patients' quality of life and psychological well-being are important considerations. The treatment usually involves surgery and radioactive iodine (radioiodine) ablation. This study aims to investigate potential effects of radioiodine ablation therapy on health-related quality of life, anxiety and depression symptoms, and nutritional status at 6 months post-therapy. This study included 136 patients diagnosed with thyroid cancer. Absorbed doses to the salivary glands were estimated from dosimeters worn by patients. Patient health-related quality of life, psychological status and nutritional status were assessed before and 6 months after therapy using standardized questionnaires (including SF-36, Hospital Anxiety and Depression (HAD) scale). Statistical analyses included random-effects logistic and linear regressions adjusted for potential confounders. While no significant association was found between radioiodine exposure and anxiety or depression symptoms, or nutritional status, a significant increase in the SF-36 role physical sub- score was observed in relation with the salivary gland dose (β= 6.54, 95%CI 2.71;10.36 for a 1-Gy increase). The findings suggest an improved physical health-related quality of life, namely reduced pain and functional impairment, 6 months after radioiodine therapy in thyroid cancer patients. No significant association was found between radioiodine exposure and mental health-related quality of life, anxiety or depression scores nor nutritional status. This study does not provide any evidence that radioiodine therapy has a potentially adverse effect on patient health-related quality of life.

Hyperthyroidism in thyroid carcinoma originating in struma ovarii.

Thyroid carcinoma originating in Struma Ovarii (SO) is a rare thyroid ectopic cancer that accounts for 0.01% of all ovarian malignancies and is associated with hyperthyroidism in less than 15% of cases. In a 44-year-old patient with pelvic pain, the CT scan revealed a solid-cystic formation in the ovarium. A left oophorectomy was performed and showed a borderline serous tumor and papillary thyroid carcinoma ('thyroid carcinoma originating in Struma Ovarii') measuring 10 cm. Thyroid function was assessed, and hyperthyroidism was diagnosed. Surgical complementation and a pelvic re-approach were performed. The histological findings showed a papillary thyroid carcinoma in the uterine serosa and the right adnexa. Thyroid function was re-evaluated, and despite normal thyroid function, the TRAb test remained positive. The patient underwent total thyroidectomy and radioiodine therapy (RIT), after which the TRAb test became negative. During 3 years of follow-up, no evidence of tumor was observed. In our case of thyroid carcinoma originating in SO, hyperthyroidism was treated with ovarian surgery, total thyroidectomy, and RIT. It is worth noting that thyroid function was normalized after ovarian surgery, but the TRAb test only became negative after total thyroidectomy. We hope to draw attention to the importance of evaluating thyroid function in patients with SO and treating high-risk SO patients with RIT after total thyroidectomy to achieve disease remission. Struma ovarii can cause hyperthyroidism. Thyroid carcinoma can originate in Struma Ovarii. Differentiated thyroid carcinoma and hyperthyroidism originating in Struma Ovarii are rare conditions.

Increased cardiovascular morbidity and reduced life expectancy in a large Italian cohort of patients with resistance to thyroid hormone β (RTHβ).

Decreased survival and higher cardiovascular morbidity have been recently reported in a UK cohort of 61 RTHβ patients, but there is no evidence from other countries. Retrospective cohort study from an historical group of 284 Italian RTHβ patients, diagnosed between 1984 and 2023. We collected data on diagnosis of 284 cases and longitudinal data of 249 RTHβ who carried heterozygous pathogenic variants in the THRB gene. We studied how thyroid function and recognized risk factors for cardiovascular disease, such as hypertension and diabetes, affected overall mortality and major cardiovascular events. The cumulative prevalence of sinus/supraventricular tachycardia and atrial fibrillation was 40% and 18%, respectively. FT4 values 57% higher than the upper limit of normal were associated with premature cardiovascular manifestations. Major cardiovascular events (MACEs) occurred in RTHβ patients at a median age (IQR) of 59.4 years (50.4-66.4) and early mortality resulted in a mean of 11 years of life lost. While at univariable analysis hypertension, dyslipidemia, high fasting glucose/diabetes were also associated with MACEs, at multivariable analysis only age at diagnosis, increased fT4 levels, and male gender remained significantly associated with MACEs and age at diagnosis and higher fT4 levels with mortality. Previous thyroidectomy or radioiodine therapy had no statistically significant effect in the prevention of major cardiovascular events or all-cause mortality. These data should raise the general awareness on the cardiovascular risk and prompt a proactive cardiovascular monitoring in RTHβ, especially in men and those with fT4 levels above 30 pmol/L.