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Background Sarcoid lesions may mimic metastatic disease or recurrence in thyroid cancer (TC) patients as both diseases may affect the lungs and lymph nodes. We present the first study to systematically evaluate the clinical course of patients with (TC) after adjuvant radioactive iodine therapy (RIT) and concomitant sarcoidosis of the lung or the lymph nodes. Methods We screened 3285 patients and retrospectively identified 16 patients with TC (11 papillary thyroid cancer (PTC), 3 follicular thyroid cancer (FTC), 1 oncocytic PTC, 1 oncocytic FTC) and coexisting sarcoidosis of the lung and/or the lymph nodes treated at our institute. All patients had undergone thyroidectomy and initial adjuvant RIT. Challenges in diagnosing and the management of these patients were evaluated during long term follow-up (median 4.9 years (0.8–15.0 years)). Results Median age at first diagnosis of TC was 50.1 years (33.0–71.5 years) and of sarcoidosis 39.4 years (18.0–63.9 years). During follow-up, physicians were able to differentiate between SA and persistent or recurrent TC in 10 of 16 patients (63%). Diagnosis was complicated by initial negative thyroglobulin (Tg), positive Tg antibodies and non-specific imaging findings. Histopathology can reliably distinguish between SA and TC in patients with one suspicious lesion. Conclusion Physicians should be aware of the rare coexistence of sarcoidosis and TC. Lymphadenopathy and pulmonary lesions could be metastases, sarcoidosis or even a mix of both. Therefore, this rare patient group should receive a thorough work up including histopathological clarification and, if necessary, separately for each lesion.

Background： Postoperative preablative stimulated thyroglobulin （ps-Tg） has been evaluated in predicting prognosis and success of ablation regarding differentiated thyroid cancer （DTC）; however, its relationship with recurrence risk and radioiodine decision-making remains uncertain, especially in Chinese DTC patients. We aimed to evaluate the association between ps-Tg and recurrence risk stratification in DTC, to provide incremental values for ps-Tg in postoperative assessment and radioiodine management. Methods： Seven hundred and seven patients with DTC were included; low-risk （L; n = 90）, intermediate-risk （I; n = 283）, and high-risk （H; n = 334, 117 with distant metastasis [M 1 ]） patients were divided according to recurrence risk stratification. The M 1 group was further analyzed regarding evidence of metastasis. Cut-off values of ps-Tg were obtained using receiver operating characteristic analysis. Results： Patients with more advanced disease at initial risk stratification were more likely to have higher ps-Tg levels （I vs. L： P 〈 0.05; H vs. 1： P 〈 0.001; H vs. L： P 〈 0.001）. The corresponding cut-off value of ps-Tg for distinguishing sensitivity and specificity in each of the two groups was 2.95 ng/ml （1 vs. L： 61.5%, 63.3%）, 29.5 ng/ml （H vs, I： 41.9%, 92.6%）, 47.1 ng/ml （M1 vs. M0 in the H group： 79.5%, 88.9%） and 47.1 ng/ml （MI vs. M0 in all patients： 79.5%, 93.7%）. With the cut-offvalue at 47.1 ng/ml, ps-Tg was the only factor that could be used to identify distant metastases, and consequently if measured before radioiodine therapy would prevent 10.26% of patients with M1 from undertreatment, Conclusions： Ps-Tg, as an ongoing reassessment marker, favors differential recurrence risk grading and provides incremental values for radioiodine treatment decision-making.

Differentiated thyroid cancer (DTC) is a rare malignant disease, although its incidence has increased over the last few decades. It derives from follicular thyroid cells. Generally speaking, the prognosis is excellent. If treatment according to the current guidelines is given, cases of recurrence or persistence are rare. DTC requires special expertise by the treating physician. In recent years, new therapeutic options for these patients have become available. For this article we performed a systematic literature review with special focus on the guidelines of the American Thyroid Association, the European Association of Nuclear Medicine, and the German Society of Nuclear Medicine. For DTC, surgery and radioiodine therapy followed by levothyroxine substitution remain the established therapeutic procedures. Even metastasized tumors can be cured this way. However, in rare cases of radioiodine-refractory tumors, additional options are to be discussed. These include strict suppression of thyroid-stimulating hormone (also known as thyrotropin, TSH) and external local radiotherapy. Systemic cytostatic chemotherapy does not play a significant role. Recently, multikinase or tyrosine kinase inhibitors have been approved for the treatment of radioiodine-refractory DTC. Although a benefit for overall survival has not been shown yet, these new drugs can slow down tumor progression. However, they are frequently associated with severe side effects and should be reserved for patients with threatening symptoms only.

The aim of the present study was to retrospectively evaluate the efficacy of low (1.1 GBq) versus moderate (2.2 GBq) [sup.131]I activities in a large series (n = 299) of low-risk differentiated thyroid carcinoma (DTC) patients requiring postoperative [sup.131]I ablation. At the follow-up, according to the ATA criteria, an excellent response was observed in 96.9% of patients treated with moderate [sup.131]I activities versus 85.6% of patients treated with low [sup.131]I activities (p = 0.029). Conversely, a biochemically indeterminate or incomplete response was observed in 22.2% of patients treated with low [sup.131]I activities versus 1.8% of patients treated with moderate [sup.131]I activities (p = 0.001), and an incomplete structural response was observed in three patients treated with low [sup.131]I activities versus two patients treated with moderate [sup.131]I activities (p = 0.654). In conclusion, we encourage the use of moderate instead of low activities when [sup.131]I ablation is indicated in order to reach an excellent response in a significantly larger proportion of patients, including patients with the unexpected persistence of the disease. Objectives: To compare the efficacy of low and moderate [sup.131]I 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 [sup.131]I 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 [sup.131]I activities, respectively (p = 0.029). A biochemically indeterminate or incomplete response was observed in seventeen (22.2%) patients treated with low [sup.131]I activities and three (1.8%) patients treated with moderate [sup.131]I activities (p = 0.001). Finally, five patients showed an incomplete structural response, among which three and two received low and moderate [sup.131]I activities, respectively (p = 0.654). Conclusions: When [sup.131]I 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.

Abstract Context Over the past several decades, there have been indications of potential shifts in the diagnostic strategies, treatment, and monitoring of patients with Graves disease (GD). Objective To evaluate current practices in managing GD and compare them to previous surveys Methods We used a global online survey of endocrinologists to assess shifts in the diagnosis, monitoring, and treatment in a typical patient with GD, as well as treatment variation in 5 different clinical scenarios. Results A total of 1252 respondents from 85 countries completed the survey. Methods used to diagnose an uncomplicated GD case have changed over the past decade, reflecting increased use of thyrotropin receptor antibody (TRAb) and reciprocal decreases in nuclear medicine studies. The preferred mode of therapy for uncomplicated GD was antithyroid drugs (ATDs) by 91.5% of respondents, radioactive iodine (RAI) therapy by 7%, and thyroidectomy by 1.5%. Compared with previous surveys, the use of RAI as a first-line choice decreased in all geographic regions. The United States had the sharpest decline in the selection of initial therapy with RAI, decreasing from 69% in 1990 to 11.1% in 2023. In patients with persistent TRAb positivity after 18 months, 68.7% of respondents would continue the use of ATDs. After a relapse of GD, resumption of ATDs was selected by 59.9% of respondents. In patients with active thyroid eye disease or planning pregnancy, ATDs were the first choice (67.5% and 72.8%, respectively), and thyroidectomy emerged as the second choice (22.9% and 15.6%, respectively). Conclusion Paradigm shifts have occurred in the management of uncomplicated GD and its variants, as well as the response to persistent and recurrent hyperthyroidism.

Telomerase reverse transcriptase promoter ( TERT p) mutations are associated with non-radioiodine avidity. However, the role of these mutations in the clinical outcomes of patients with radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) remains unknown. Herein, we aim to analyze gene mutations and clinical manifestations to verify TERT p’s role in driving disease progression to RAIR-DTC and clinical outcomes. Next-generation sequencing data and clinical data were obtained from 243 patients with DTC. Of the 25 patients with TERT p mutations, 80% (20/25) had RAIR-DTC. RAIR-DTC was significantly less prevalent in patients with BRAF V600E (9/143, 6.3%) than those with both BRAF V600E and TERT p mutations (14/17, 82.4%). Patients with RAIR-DTC harboring both BRAF V600E and TERT p mutations were more likely to have > 3 distant metastatic sites (85.7%, 12/14) than those with BRAF V600E alone (33.3%, 3/9). Only one patient with both BRAF V600E and TERT p mutations had non-RAIR-DTC. The time from initial radioactive iodine therapy to RAIR-DTC diagnosis was significantly shorter in patients with TERT p mutations than in those without. Patients with BRAF V600E and TERT p mutations progressed faster to RAIR-DTC than those with BRAF V600E alone ( p  < 0.01). Our findings suggest that molecular testing for TERT p and other mutations like BRAF V600E may inform early diagnosis, prognosis, and treatment strategies before progression to RAIR-DTC.

Abstract PurposeConcern is growing about long-term side effects of differentiated thyroid cancer treatment, most notably radioactive iodine (RAI) therapy. However, published studies on the subject have had heterogeneous cohorts and conflicting results. This review seeks to provide an updated evaluation of published evidence, and to elucidate the risk of second primary malignancies (SPMs), especially secondary hematologic malignancies (SHMs), attributable to RAI therapy.MethodsAn extensive literature search was performed in Ovid MEDLINE, Ovid MEDLINE and In-Process & Other Non-Indexed Citations, Ovid MEDLINE Epub Ahead of Print, Cochrane Central Register of Controlled Trials (CENTRAL) and PubMed. Studies regarding RAI-induced SPMs or a dose–response relationship between RAI therapy and SPMs were identified, 10 of which were eligible for the analysis. We evaluated risk of bias in each study and judged quality of evidence (QOE) across all studies using the Grading of Recommendations, Assessment, Development and Evaluations approach.ResultsFor the outcome “SPM”, the relative effect (relative risk, hazard ratio, or odds ratio) of RAI vs. no RAI ranged from 1.14 to 1.84 across studies, but most results were not statistically significant. For the outcome “SHM”, reported relative effects ranged from 1.30 to 2.50, with 2/3 of the studies presenting statistically significant results. In 7/8 of the studies, increased risk for SPM was shown with increasing cumulative RAI activity. QOE was “very low” regarding SPM after RAI and regarding a dose–response relationship, and “low” for SHM after RAI.ConclusionBased on low quality evidence, an excess risk for the development of SPM cannot be excluded but is expected to be small.