Search Results (28)

Radioactive iodine (RAI) therapy plays a fundamental role in the management of differentiated thyroid cancer (DTC) following appropriate surgical intervention. High levels of TSH are required in order to achieve maximum RAI uptake in residual thyroid tissue or metastatic cells. The two techniques that are most commonly used are thyroid hormone withdrawal (THW), which induces endogenous TSH elevation by creating a hypothyroid state, and exogenous stimulation with recombinant human TSH (rhTSH). This review compares both approaches over a range of DTC risk categories. Extensive evidence demonstrates that rhTSH and THW yield equivalent oncological outcomes, including remnant ablation success, recurrence-free survival, and overall survival, in low-, intermediate-, and high-risk disease. Additionally, rhTSH maintains quality of life by avoiding hypothyroid symptoms. While THW continues to be an excellent option when there is a lack of availability of rhTSH, its disadvantages, particularly the transient hypothyroid state, must be carefully weighed against the demonstrated equivalence in efficacy. In current clinical practice, rhTSH is frequently the preferred option for its convenience, safety, and patient-centered benefits; however, the selection of the optimal approach should be based on individual clinical circumstances and patients’ preferences, as well as resource considerations. Full article

Benign neoplasms and tumor-like lesions of the tongue are relatively rare entities, encompassing a heterogeneous spectrum of morphological alterations. The recent literature focusing on benign tumors and tumor-like lesions of the tongue is relatively limited, which may lead to a gap in understanding their specific imaging characteristics. Most benign tongue tumors usually appear as submucosal bulges located in the deep portion of the tongue. Both computed tomography (CT) and magnetic resonance imaging (MRI) are essential for the comprehensive diagnostic evaluation of these entities. Cross-sectional imaging plays a pivotal role in narrowing the differential diagnosis and, in selected cases, may suggest a specific histopathological entity. The benign tumors and tumor-like lesions included in this review comprise schwannoma, lipoma, angiomyolipoma, hemangioma, vascular malformations, dermoid cysts, and thyroglossal duct remnants (including cystic formations and ectopic thyroid tissue). Additionally, certain non-neoplastic conditions—such as lingual abscesses, infectious mononucleosis complicated by lingual tonsillitis, and fatty atrophy of the tongue—can mimic neoplastic processes and present as mass-like lesions; these have also been addressed in this pictorial essay. The purpose of this work is to illustrate the key CT and MRI features of the aforementioned benign lingual lesions, with the aim of improving diagnostic confidence and accuracy. Full article

Differentiated thyroid cancer treatment typically involves the surgical removal of the whole or largest part of the thyroid gland. Diagnostic procedures are useful both before and after treatment to determine the need for radioiodine ablation, re-stage the disease, monitor disease progression, or evaluate treatment efficacy. SPECT/CT imaging can be utilized to identify small, distant iodine-avid metastatic lesions and assess their uptake and volume for the above purposes as well as for performing lesion-based dosimetry when indicated. The objective of this study was to develop and validate a method for calculating small sizes of volumes in SPECT/CT imaging as well as to perform calculations utilizing I-131 and I-123 postsurgical SPECT/CT images from a neck–thyroid phantom. In this approach, the calculated volume was unaffected by radiation spillover from high-uptake voxels since it was the result from the successive application of the gray-level histogram technique to SPECT and CT 3D matrices. Beforehand, the SPECT 3D matrix was resized and aligned to the corresponding CT one. The method was validated following the clinical protocols for postsurgical thyroid imaging by using I-123 and I-131 scatter and attenuation-corrected SPECT/CT images from a neck–thyroid phantom. The phantom could accommodate two volumes of different sizes (0.5, 1, 1.5, 3, and 10 mL) and enclose anatomical tissue-equivalent main scattering structures. For the 0.5 and 10 mL volumes, the % differences between the actual and the calculated volumes were 15.2% and 1.2%, respectively. Radiation spillover was only present in SPECT images, and it was more profound at higher administered activities, in I-131 than in I-123 images, and in smaller volumes. When SPECT/low-dose-CT imaging is performed, this method is capable of accurately calculating small volumes without the need of additional modalities. Full article

Background: Differentiated thyroid carcinoma (DTC), mainly papillary (PTC), at low risk of recurrence is currently managed with active surveillance strategies or less aggressive surgeries. However, total thyroidectomy with ¹³¹I treatment is still performed both if these tumors are diagnosed before or occasionally after surgery. This real-life study aimed to evaluate the rate of biochemical, structural, and functional events in a large series of consecutive DTCs at low risk of recurrence treated by total thyroidectomy, but not with ¹³¹I, in a medium–long-term follow-up. Patients and Methods: We evaluated clinical–pathologic data of 383 consecutive patients (2006–2012) with unifocal DTC [T1a/b(s)] at low risk of recurrence, treated with total thyroidectomy but without lymph node dissection and ¹³¹I treatment after surgery. We evaluated if structural, biochemical, and functional events were detected during the follow-up. Results: Females accounted for 75.7% of our study group, and the median age was 50 years. The median tumor dimension was 0.4 cm (range 0.1–1.2). Most of the patients had a unifocal T1a tumor (98.9%), and 73.6% had a classic variant of PTC. We divided the patients according to the absence (group A—n = 276) or presence (group B—n = 107) of interfering TgAb at first control after surgery. After a median follow-up of 10 years, no structural events were detected. Sixteen out of three hundred and eighty-three (4.2%) patients developed biochemical events: 12/276 (4.3%) in group A and 4/107 (3.7%) in group B. The median time elapsed from surgery to detecting a biochemical event was 14.5 and 77.5 months in groups A and B, respectively. No patients performed additional treatments and were followed up with an active surveillance strategy. Conclusions: This study confirmed that patients with DTC at low risk of recurrence showed an excellent outcome in a medium long-term follow-up since no structural events were diagnosed. Significant variations in Tg/TgAb were detected in a few cases, all managed with an active surveillance strategy without the need for other treatments. Therefore, a relaxed follow-up with neck ultrasound and Tg/TgAb measurement is enough to early identify those very unusual cases of recurrence. Full article

Human endogenous retroviruses (HERVs) are remnants of ancient retroviral infections that, over millions of years, became integrated into the human genome. While normally inactive, environmental stimuli such as infections have contributed to the transcriptional reactivation of HERV-promoting pathological conditions, including the development of autoimmunity, neurodegenerative disease and cancer. What infections trigger HERV activation? Mycobacterium avium subspecies paratuberculosis (MAP) is a pluripotent driver of human disease. Aside from granulomatous diseases, Crohn’s disease, sarcoidosis and Blau syndrome, MAP is associated with autoimmune disease: type one diabetes (T1D), multiple sclerosis (MS), rheumatoid arthritis (RA) and autoimmune thyroiditis. MAP is also associated with Alzheimer’s disease (AD) and Parkinson’s disease (PD). Autoimmune diabetes, MS and RA are the diseases with the strongest MAP/HERV association. There are several other diseases associated with HERV activation, including diseases whose epidemiology and/or pathology would prompt speculation for a causal role of MAP. These include non-solar uveal melanoma, colon cancer, glioblastoma and amyotrophic lateral sclerosis (ALS). This article further points to MAP infection as a contributor to autoimmunity, neurodegenerative disease and cancer via the un-silencing of HERV. We examine the link between the ever-increasing number of MAP-associated diseases and the MAP/HERV intersection with these diverse medical conditions, and propose treatment opportunities based upon this association. Full article

(1) Background: After thyroid malignancy is ruled out, treatment options for multinodular goiter patients include surgery, levothyroxine suppressive therapy, and 131-I therapy. Surgery effectively reduces goiter size but carries risks of surgical and anesthetic complications. 131-I therapy is the only nonsurgical alternative, but its effectiveness diminishes with goiter size and depends on iodine sufficiency. This study aimed to assess the efficacy and safety of 0.1 mg rhTSH as an adjuvant to a fixed dose of 131-I therapy in patients with a recurrence of large multinodular goiter, several years after the initial thyroidectomy. (2) Methods: 14 patients (13 females and 1 male), aged 59.14 ± 15.44 (range, 35–78 years) received 11mciu of 131-I, 24 h after the administration of 0.1 mg rhTSH. The primary endpoint was the change in thyroid volume (by ultrasound measurements) as well as in the diameter of the predominant nodule during a follow-up period of 10 years. Secondary endpoints were the alterations in thyroid function and potential adverse effects. (3) Results: A significant decrease in the volume of initial thyroid remnants (32.16 ± 16.66 mL) was observed from the first reevaluation (at 4 months, 23.12 ± 11.59 mL) as well as at the end of the follow-up period (10 years, 12.62 ± 8.76 mL), p < 0.01. A significant reduction in the dominant nodule was also observed (from 31.71 ± 10.46 mm in the beginning to 26.67 ± 11.05 mm). (4) Conclusions: Further investigation is needed since this approach could be attractive in terms of minimizing the potential risks of reoperation in these patients. Full article

Radioiodine imaging in initial perioperative settings, after the total thyroidectomy, includes pre-treatment and post-treatment radioiodine imaging. While the benefit of post-treatment whole-body imaging (PT-WBI) is well established, the role of diagnostic whole-body imaging (dx WBI), prior to radioiodine (I-131) ablative or therapeutic doses, is controversial. Dx WBI has been abandoned in most nuclear medicine centers long ago. Planar low-dose dxWBI provides the volume of postoperative thyroid remnants, but it cannot detect occult metastatic foci in the neck. The modern integrated multimodality, i.e., SPECT/CT imaging, provides three dimensional images and accurate anatomic/metabolic data. This hybrid technology offers better spatial resolution but not better sensitivity. Dx WBI has low theranostic power because of the radioiodine indifference and low detection sensitivity for small-volume nodal disease in the neck. Since dx WBI cannot clarify the paratracheal cervical uptake, thyroid remnants may be easily misinterpreted as nodal disease, leading to a false N upstaging (from N0 stage to N1 stage) in DTC patients. Post-ablation I-131 imaging has a significant role in the initial staging of radioiodine-avid DTC and in the identification of non-radioiodine avid tumors. Additionally, SPECT/CT in the post-treatment setting provides more accurate initial TNM staging and better risk stratification of DTC patients. Post-treatment I-131 imaging is obligatory and must be performed in all DTC patients who receive radioiodine treatment. Full article

I-123 is preferential over I-131 for diagnostic SPECT imaging after a thyroidectomy to determine the presence and size of residual thyroid tissue for radioiodine ablation. Scattering degrades the quality of I-123 SPECT images, primarily due to the penetration of high-energy photons into the main photopeak. The objective of this study was to quantitatively and qualitatively investigate the impact of two widely used window-based scatter correction techniques, the dual energy window (DEW) and triple energy window (TEW) techniques, in I-123 postsurgical SPECT/CT thyroid imaging using an anthropomorphic phantom with small sizes of remnants and anatomically correct surrounding structures. For this purpose, non-scatter-corrected, DEW and TEW scatter-corrected SPECT/CT acquisitions were performed for 0.5–10 mL remnants within a phantom, with 0.5–12.6 MBq administered activities within the remnants, and without and with background-to-remnant activity ratios of 5% and 10%. The decrease in photons, the noise and non-uniformity in the background region due to scatter correction were measured, as well as the signal-to-noise ratio (SNR) and the contrast-to-noise ratio (CNR) from small remnants. The images were also visually evaluated by two experienced nuclear medicine physicians. Scatter correction decreased photons to a higher extent in larger regions than smaller regions. Larger remnants yielded higher SNR and CNR values, particularly at lower background activities. It was found from the quantitative analysis and the qualitative evaluation that TEW scatter correction performed better than DEW scatter correction, particularly at higher background activities, while no significant differences were reported at lower background activities. Scatter correction should be applied in I-123 postsurgical SPECT/CT imaging to improve the image contrast and detectability of small remnants within the background. Full article

Thyroid cancer, specifically differentiated thyroid carcinoma (DTC), is one of the most prevalent endocrine malignancies worldwide. Radioactive iodine therapy (RAIT) using I-131 has been a standard-of-care approach for DTC due to its ability to ablate remnant thyroid disease following surgery, thus reducing the risk of recurrence. It is also used for the treatment of iodine-avid metastases. RAIT dosimetry can be employed to determine the optimal treatment dose of I-131 to effectively treat cancer cells while safeguarding against undesirable radiation effects such as bone marrow toxicity or radiation pneumonitis. Conventional dosimetry protocols for RAIT, however, are complex and time-consuming, involving multiple days of imaging and blood sampling. This study explores the use of Artificial Intelligence (AI) in simplifying and optimizing RAIT. A retrospective analysis was conducted on 83 adult patients with DTC who underwent RAIT dosimetry at our institution between 1996 and 2023. The conventional MIRD-based dosimetry protocol involved imaging and blood sampling at 4, 24, 48, 72, and 96 h post-administration of a tracer activity of I-131. An AI system based on a deep-learning neural network was developed to predict the maximum permissible activity (MPA) for RAIT using only the data obtained from the initial 4, 24, and 48 h time points. The AI system predicted the MPA values with high accuracy, showing no significant difference compared to the results obtained from conventional MIRD-based analysis utilizing a paired t-test (p = 0.351, 95% CI). The developed AI system offers the potential to streamline the dosimetry process, reducing the number of imaging and blood sampling sessions while also optimizing resource allocation. Additionally, the AI approach can uncover underlying relationships in data that were previously unknown. Our findings suggest that AI-based dosimetry may be a promising method for patient-specific treatment planning in differentiated thyroid carcinoma, representing a step towards applying precision medicine for thyroid cancer. Further validation and implementation studies are warranted to assess the clinical applicability of the AI system. Full article

Medullary thyroid cancer originates from parafollicular C-cells in the thyroid. Despite successful thyroidectomy, localizing remnant cancer cells in patients with elevated calcitonin and carcinoembryonic antigen levels remains a challenge. Extranasal odorant receptors are expressed in cells from non-olfactory tissues, including C-cells. This study evaluates the odorant receptor signals from parafollicular C-cells, specifically, the presence of olfactory marker protein, and further assesses the ability of the protein in localizing and treating medullary thyroid cancer. We used immunohistochemistry, immunofluorescent staining, Western blot, RNA sequencing, and real time-PCR to analyze the expression of odorant receptors in mice thyroids, thyroid cancer cell lines, and patient specimens. We used in vivo assays to analyze acetate binding, calcitonin secretion, and cAMP pathway. We also used positron emission tomography (PET) to assess C¹¹-acetate uptake in medullary thyroid cancer patients. We investigated olfactory marker protein expression in C-cells in patients and found that it co-localizes with calcitonin in C-cells from both normal and cancer cell lines. Specifically, we found that OR51E2 and OR51E1 were expressed in thyroid cancer cell lines and human medullary thyroid cancer cells. Furthermore, we found that in the C-cells, the binding of acetate to OR51E2 activates its migration into the nucleus, subsequently resulting in calcitonin secretion via the cAMP pathway. Finally, we found that C¹¹-acetate, a positron emission tomography radiotracer analog for acetate, binds competitively to OR51E2. We confirmed C¹¹-acetate uptake in cancer cells and in human patients using PET. We demonstrated that acetate binds to OR51E2 in C-cells. Using C¹¹-acetate PET, we identified recurrence sites in post-operative medullary thyroid cancer patients. Therefore, OR51E2 may be a novel diagnostic and therapeutic target for medullary thyroid cancer. Full article

Introduction: Thyroidectomy followed by radioactive iodine therapy (RAI) is the treatment of choice for differentiated thyroid carcinoma (DTC). Serum thyroglobulin (Tg) measurement has proved to be useful for predicting persistent and/or recurrent disease during follow-up of DTC patients. In our study, we evaluated the risk of disease recurrence in patients with papillary thyroid carcinoma (PTC), who were treated with thyroidectomy and RAI, by measuring serum Tg at different time-points: at least 40 days after surgery, in euthyroidism with TSH < 1.5 and usually 30 days before RAI (Tg₋₃₀), on the day of RAI (Tg₀), and seven days after RAI (Tg₊₇). Methods: One hundred and twenty-nine patients with PTC were enrolled in this retrospective study. All patients were treated with ¹³¹I for thyroid remnant ablation. Disease relapse (nodal disease or distant disease) during at least 36 months follow-up was evaluated by serum measurements of Tg, TSH, AbTg at different time points and by imaging techniques (neck ultrasonography, ¹³¹I-whole body scan (WBS) after Thyrogen^® stimulation). Typically, patients were assessed at 3, 6, 12, 18, 24, and 36 months after RAI. We classified patients in five groups: (i) those who developed nodal disease (ND), (ii) those who developed distant disease (DD), (iii) those with biochemical indeterminate response and minimal residual thyroid tissue (R), (iv) those with no evidence of structural or biochemical disease + intermediate ATA risk (NED-I), and (v) those with no evidence of structural or biochemical disease + low ATA risk (NED-L). ROC curves for Tg were generated to find potential discriminating cutoffs of Tg values in all patients’ groups. Results: A total of 15 out of 129 patients (11.63%) developed nodal disease and 5 (3.88%) distant metastases, during the follow-up. We found that Tg₋₃₀ (with suppressed TSH) has the same sensitivity and specificity than Tg₀ (with stimulated TSH), and it is slightly better than Tg₊₇, which can be influenced by the size of the residual thyroid tissue. Conclusion: Serum Tg₋₃₀ value, measured in euthyroidism 30 days before RAI, is a reliable prognostic factor to predict future nodal or distant disease, thus allowing to plan the most appropriate therapy and follow-up. Full article

Objectives: To compare the efficacy of low and moderate ¹³¹I activities in low-risk differentiated thyroid carcinoma (DTC) patients requiring postoperative thyroid remnant ablation in a real-world clinical setting. Methods: We retrospectively reviewed the records of 299 low-risk DTC patients (pT1-T2, Nx(0) Mx) who had undergone (near)-total thyroidectomy followed by ¹³¹I therapy, using either low (1.1 GBq) or moderate (2.2 GBq) radioiodine activities. The response to initial treatments was evaluated after 8–12 months, and patient responses were classified according to the 2015 American Thyroid Association guidelines. Results: An excellent response was observed in 274/299 (91.6%) patients, specifically, in 119/139 (85.6%) and 155/160 (96.9%) patients treated with low and moderate ¹³¹I activities, respectively (p = 0.029). A biochemically indeterminate or incomplete response was observed in seventeen (22.2%) patients treated with low ¹³¹I activities and three (1.8%) patients treated with moderate ¹³¹I activities (p = 0.001). Finally, five patients showed an incomplete structural response, among which three and two received low and moderate ¹³¹I activities, respectively (p = 0.654). Conclusions: When ¹³¹I ablation is indicated, we encourage the use of moderate instead of low activities, in order to reach an excellent response in a significantly larger proportion of patients, including patients with the unexpected persistence of the disease. Full article

Post-surgical I-123 and I-131 SPECT/CT imaging can provide information on the presence and sizes of thyroid remnants and/or metastasis for an accurate re-staging of disease to apply an individualized radioiodine therapy. The purpose of this study was to develop and validate a neck–thyroid phantom with small sizes of thyroid remnants to be utilized for the optimization of post-surgical SPECT/CT imaging. 3D printing and molding techniques were used to develop the hollow human-shaped and -sized phantom which enclosed the trachea, esophagus, cervical spine, clavicle, and multiple detachable sections with different sizes of thyroid remnant in clinically relevant positions. CT images were acquired to evaluate the morphology of the phantom and the sizes of remnants. Triple-energy window scattered and attenuation corrected SPECT images were acquired for this phantom and for a modified RS-542 commercial solid neck–thyroid phantom. The response and sensitivity of the SPECT modality for different administered I-123 and I-131 activities within the equal-size remnants of both phantoms were calculated. When we compared the phantoms, using the same radiopharmaceutical and similar activities, we found that the measured sensitivities were comparable. In all cases, the I-123 counting rate was higher than the I-131 one. This phantom with capabilities to insert different small sizes of remnants and simulate different background-to-remnants activity ratios can be utilized to evaluate postsurgical thyroid SPECT/CT imaging procedures. Full article

Background: Lymph node (LN)-related risk factors have been updated to predict long-term outcomes in patients with papillary thyroid carcinoma (PTC). However, those factors’ analytic appropriateness and general applicability must be validated. This study aimed to assess LN-related risk factors, and suggest new LN-related risk categories. Methods: This multicenter observational cohort study included 1232 patients with PTC with N1 disease treated with a total thyroidectomy and neck dissection followed by radioactive iodine remnant ablation. Results: The median follow-up duration was 117 months. In the follow-up period, structural recurrence occurred in 225 patients (18.3%). Among LN-related variables, the presence of extranodal extension (p < 0.001), the maximal diameter of metastatic LN foci (p = 0.029), the number of retrieved LNs (p = 0.003), the number of metastatic LNs (p = 0.003), and the metastatic LN ratio (p < 0.001) were independent risk factors for structural recurrence. Since these factors showed a nonlinear association with the hazard ratio of recurrence-free survival (RFS) rates, we calculated their optimal cutoff values using the K-means clustering algorithm, selecting 0.2 cm and 1.1 cm for the maximal diameter of metastatic LN foci, 4 and 13 for the number of metastatic LN, and 0.28 and 0.58 for the metastatic LN ratio. The RFS curves of each subgroup classified by these newly determined cutoff values showed significant differences (p < 0.001). Each LN risk group also showed significantly different RFS rates from the others (p < 0.001). Conclusions: In PTC patients with an N1 classification, our novel LN-related risk estimates may help predict long-term outcomes and design postoperative management and follow-up strategies. After further validation studies based on independent datasets, these risk categories might be considered when redefining risk stratification or staging systems. Full article

Radioiodine remnant ablation (RRA) was previously demonstrated to be a safe and effective alternative to completion thyroidectomy for patients with differentiated thyroid cancer (DTC). However, its side effects have not been fully investigated, particularly in patients with lobectomy. We reported a young euthyroidal female who underwent RRA post lobectomy and lymph node dissection for papillary thyroid cancer, whose post-ablation ¹³¹I-whole-body scan accidentally showed diffuse radioiodine distribution on chest-mimicking pulmonary metastases. Immediately-added single-photon emission computed tomography/computed tomography (SPECT/CT), nevertheless, revealed a ¹³¹I-accumulating swollen left thyroid lobe and emerging pleural effusion, which relieved after short-term treatment with prednisone. In summary, acute pleural effusion ascribed to RRA-induced thoracic duct compression was reported for the first time. ¹³¹I-lobectomy-induced pleural effusion could be precisely diagnosed by SPECT/CT and efficiently manipulated via treating radiation thyroiditis with the short-term administration of corticosteroid. Full article