European Thyroid Journal最新文献

Objectives: Tumor molecular genotyping plays a key role in improving the management of advanced thyroid cancers. Molecular tests are classically performed on Formalin-Fixed Paraffin-Embedded (FFPE) carcinoma tissue. However alternative molecular testing strategies are needed when FFPE tumoral tissue is unavailable. The objective of our study was to retrospectively assess the performance of targeted DNA and RNA-based Next Generation Sequencing (NGS) on the fine needle aspirate from thyroid cancer cervical recurrences to determine if this strategy is efficient in clinical practice.

Design/methods: A retrospective study of 33 patients who had had DNA and/or RNA-based NGS on ultrasound (US)-guided fine needle aspirates of cervical thyroid cancer recurrences in our Department from July 2019 to September 2022.

Results: In total, 34 DNA and 32 RNA-based NGS analyses were performed. Out of the 34 DNA-based NGS performed, 27 (79%) were conclusive allowing the identification of an oncogenic driver for 18 patients (53%). The most common mutation (n = 13) was BRAF c.1799T>A. Out of the 32 RNA-based NGS performed, 26 were interpretable (81%) and no gene fusion was found. The identification of a BRAFV600E mutation was decisive for one patient in our series, who was prescribed dabrafenib and trametinib.

Conclusions: NGS performed on fine needle aspirates of neck lymph node metastases enabled the identification of an oncogenic driver alteration in 53% of the cases in our series of advanced thyroid cancer patients and could significantly alter patient management.

Background This study aimed to examine the associations of thyroid hormone sensitivity indices, including free triiodothyronine to free thyroxine (FT3/FT4) ratio, thyroid feedback quantile-based index by FT4 (TFQIFT4), thyroid-stimulating hormone index (TSHI), and thyrotrophic thyroxine resistance index (TT4RI) with all-cause mortality in euthyroid adults. Methods The study included 6243 euthyroid adults from the National Health and Nutrition Examination Survey (NHANES) 2007-2012. FT3/FT4 ratio, TFQIFT4, TSHI, and TT4RI were calculated. The multivariable Cox proportional hazard regression, restricted cubic spline (RCS), and subgroup analysis were conducted. Results Individuals in quartile 4th (Q4) had lower all-cause mortality than those in quartile 1st (Q1) of FT3/FT4 ratio (OR 0.70, 95% CI (0.51, 0.94)). Regarding TFQIFT4, individuals in Q4 of TFQIFT4 had a 43% higher all-cause mortality than those in Q1 (OR 1.43, 95% CI (1.05, 1.96)) (P <0.05, all). Compared with participants in Q1, no associations of TSHI and TT4RI with mortality were found. TFQIFT4 was linearly and positively associated with mortality. However, the FT3/FT4 ratio showed a U-shaped association with mortality. Conclusions Increased risk for all-cause mortality was positively associated with TFQIFT4, suggesting that increased risk for all-cause mortality was associated with decreased central sensitivity to thyroid hormones. Furthermore, the FT3/FT4 ratio showed a U-shaped association with mortality, with an inflection point at 0.5. However, more cohort studies are needed to validate the conclusions.

Objective: Few studies used all nodule burdens to specify the prognosis of multinodular goiter (MNG) following radiofrequency ablation (RFA), so this study addresses this question for MNG after completely ablating dominant nodules.

Methods: The RFA indications for MNG included a total of 2-5 benign nodules with over 50% normal tissue on ultrasound, 1-3 well-defined benign dominant nodules on cytology, largest diameter ≥20 mm and/or with clinical complaints, and patient refusal or unable of surgery. A retrospective study of 185 MNG patients with completely ablated dominant nodules in a single-session RFA was conducted. The efficacy and complications were evaluated at 1, 6, 12 months and yearly thereafter. Based on retreatment risks, progressive disease (PD), stable disease (SD) and complete relief (CR) were introduced to assess all nodule load changes. PD was clarified as having new/non-target nodules newly appeared to ACR TI-RADS≥4, or new/enlarged non-target nodules ≥1 cm.

Results: The initial ablation ratios of target nodules were 100% at one month. During a mean 22.38±13.75 months (range, 12-60 months), the VRR of ablated nodules was 98.25% at 24 months without regrowth. Cosmetic and symptomatic scores decreased to 1 and 0, respectively, after 48 months. 9.7% of patients (18/185) had PD and the retreatment rate was 2.2% (4/185). The complication rate was 2.7% (5/185).

Conclusions: RFA provides cosmetic and symptomatic relief for an average of two years. RFA is an useful minimally invasive treatment modality for selected MNG patients.

Objective: Punctate echogenic foci (PEF)/microcalcifications are thought to represent psammoma bodies (PB) in histopathology. However, there are few and contradictory data on this. Different types of sonographic echogenic microfoci (EMF) are seen in papillary thyroid carcinoma (PTC), and their histopathological equivalents are not clearly known. There is also conflicting data on the interobserver agreement between the sonographers on EMF.

Methods: We prospectively collected US video records of PTC nodules with and without EMF in two large thyroid centers. All video recordings were independently interpreted by three blinded, experienced sonographers. EMF were classified as true microcalcifications (punctate echogenic foci (PEF) ≤1 mm long), linear microechogenities (>1 mm long, posterior acoustic enhancement of the back wall of a microcystic area), comet-tail artifacts/reverberations or linear microechogenities with comet-tail artifacts/reverberations, non-shadowing coarse echogenic foci (>1 mm nonlinear areas) and unclassifiable. Histopathological evaluation was performed by two blinded, qualified pathologists.

Results: A total of 114 malignant nodules were included. The average Cohen's kappa (κ) of three sonographers for the EMF presence was 0.775, indicating substantial agreement. A substantial agreement for PEF with 0.658 κ, only fair agreement for other types of EMF with 0.052 to 0.296 κ were detected. EMF were significantly associated with PB and papillae. PEF had an evident relationship with PB in multivariate analysis. There was a strong positive correlation between the amount of PEF and PB (r = 0.634, P < 0.001).

Conclusions: PEF in PTC mainly correspond to PB on histopathology. Although observation of EMF varies among sonographers, this inconsistency can be reduced by classifying EMF into subgroups and keeping the term 'PEF' only for true microcalcifications.

Objective: Active surveillance (AS) has been suggested as a management option for low-risk papillary thyroid microcarcinoma (PTMC). However, the currently proposed selection criteria for AS application do not consider various clinical factors. The purpose of this study was to analyze clinical factors related to recurrence that could be confirmed preoperatively in patients who underwent surgery for PTMC and to identify factors worth considering when deciding whether to apply AS.

Materials and methods: Data were collected from patients with PTMC who underwent surgical treatment at Chungnam National University Hospital. A retrospective cohort was established according to the presence or absence of recurrence during the follow-up period. In total, 2717 patients were enrolled, of whom 60 experienced recurrence. Various clinical factors that could be identified before surgery were analyzed.

Results: The relationship between various clinical factors that could be confirmed preoperatively and recurrence was confirmed through Cox regression analysis and Kaplan-Meier curve analysis. BRAF mutation and the tall cell variant were significantly more common in patients with recurrence. In patients aged 55 years or older, the risk of recurrence was lower than in younger patients, while the recurrence-free survival (RFS) rate was higher.

Conclusion: When choosing between surgical treatment or AS in PTMC patients, additional consideration of the patient's clinical factors, such as age and BRAF mutation status, may be required in addition to the existing criteria.

Introduction: Thyroid metastasis from clear cell renal cell carcinoma (ccRCC) is relatively rare, so ultrasound doctors lack experience with the disease, which can easily lead to misdiagnosis. We describe three cases of thyroid metastasis from ccRCC detected 12, 8, and 7 years after nephrectomy.

Case presentation: The first patient, a 78-year-old woman, was admitted to our institution for hoarseness and progressive dyspnea. Ultrasonography revealed bilateral thyroid nodules and abnormal cervical lymph nodes. Fine-needle aspiration biopsy (FNAB) and core needle biopsy (CNB) of the thyroid was nondiagnostic. The other two patients, a 54-year-old man and a 65-year-old man, were admitted to our institution for a goiter pressing on the trachea. In each case, ultrasonography revealed a partially cystic nodule of the left lobe of the thyroid gland. Histological examination of three patients after thyroidectomy showed thyroid metastasis from ccRCC.

Discussion/conclusion: For patients with a history of ccRCC, long-term follow-up and routine thyroid ultrasonography should be performed. If a new thyroid nodule is found during the examination, metastases should be highly suspected. FNAB should be performed, even if benign ultrasound features seem to be in evidence. If the diagnosis of FNAB is incorrect and inconclusive, CNB should be performed.

Objective: The physiological adaptations during a normal pregnancy affect renal and thyroid function and levels of associated biochemical markers. An association between cystatin C (CysC), creatinine, and thyroid function has been considered in nonpregnant individuals but not in pregnant women specifically.

Methods: Cohort study within the North Denmark Region Pregnancy Cohort (2011-2015) with assessment of thyroid function and autoantibodies (ADVIA Centaur XPT, Siemens Healthineers) in serum residues from the early pregnancy. Consecutive samples (n = 1112) were selected for measurement of CysC and creatinine (Atellica CH 930, Siemens Healthineers), and results were linked to information in Danish nationwide registers for (i) establishment of pregnancy-specific reference intervals for CysC and creatinine and (ii) evaluation of the prevalence of maternal hypothyroidism in early pregnancy according to levels of CysC and creatinine.

Results: The established reference intervals (2.5-97.5 percentiles) differed by week of pregnancy (week 4-8, 9-11, 12-15) and were CysC: 0.58-0.92 mg/L; 0.54-0.91 mg/L; 0.52-0.86 mg/L; creatinine: 46.9-73.0 µmol/L; 42.0-68.4 µmol/L; 38.8-66.4 µmol/L. The prevalence of maternal autoimmune hypothyroidism in early pregnancy differed by the level of CysC and creatinine (<25th percentile; 25th-75th percentile; >75th percentile) and was for CysC 1.7%, 3.8%, 7.4% and for creatinine 2.5%, 4.1%, 7.1%.

Conclusions: Reference intervals for CysC and creatinine were dynamic in early pregnancy and decreased with increasing gestational age. Furthermore, higher levels of CysC and creatinine associated with a higher prevalence of maternal autoimmune hypothyroidism. Results encourage considerations on the underlying mechanisms for the association between markers of renal and thyroid function.

Objectives: The aim was to evaluate the clinical, ultrasound (US) and, when indicated, the cytological and histological characteristics of autonomously functioning thyroid nodules (AFTN) in consecutive patients.

Methods: A prospective, single-centre study was conducted between March 2018 and September 2021. In total, 901 consecutive patients were referred for thyroid workup and of 67 AFTN were evaluated. All enrolled patients underwent 99mTcO4 - scintigraphy, additional 123I scintigraphy only in case of normal serum TSH, evaluation of thyroid function, US examination using European Thyroid Imaging and Reporting Data System (EU-TIRADS), and US-guided fine needle aspiration (FNA) cytology when indicated. All indeterminate FNA samples were subjected to DNA sequencing analysis.

Results: More than half of the evaluated patients with AFTN were euthyroid; median serum TSH was 0.41 (IQR: 0.03-0.97) mU/L. The median AFTN size measured by US was 27.0 (IQR: 21.1-35.0) mm. 28.4% of AFTN were classified as EU-TIRADS score 3 and 71.6% as EU-TIRADS score 4, indicating that the majority of AFTN had intermediate risk for malignancy according to US. Out of the 47 AFTN subjected to cytological evaluation, 24 (51%) yielded indeterminate FNA results. DNA sequencing revealed pathogenic TSHR and GNAS mutations in 60% of cases. No malignancy was detected at final histology in surgically excised AFTN (n = 12).

Conclusions: Of the 67 AFTN evaluated in this study, 50% presented with normal serum TSH, 70% displayed ultrasound features suggesting an intermediate malignancy risk and 50% of the AFTN submitted to cytology yielded indeterminate results. No malignant AFTN was detected.

Objective: Adequate iodine intake is essential for growing children, and thyroid volume (Tvol) is considered as an indicator of iodine status. We investigated Tvol and goiter using ultrasonography (US) and their association with iodine status in 228 6-year-old children living in Korea.

Methods: Iodine status was assessed using urine iodine concentration (UIC) and categorized as deficient (<100 μg/L), adequate (100-299 μg/L), mild excess (300-499 μg/L), moderate excess (500-999 μg/L), and severe excess (≥1000 μg/L). Tvol was measured using US, and a goiter on the US (goiter-US) was defined as Tvol greater than 97th percentile value by age- and body surface area (BSA)-specific international references.

Results: The median Tvol was 2.4 mL, larger than the international reference value (1.6 mL). The age- and BSA-specific goiter-US rates were 25.9% (n = 59) and 34.6% (n = 79), respectively. The prevalence of excess iodine was 73.7% (n = 168). As iodine status increased from adequate to severe excess, the goiter-US rate significantly increased (P for trend <0.05). The moderate and severe iodine excess groups showed higher risk of goiter-US (adjusted odds ratio (aOR) = 3.1 (95% CI: 1.1-9.2) and aOR = 3.1 (95% CI: 1.2-8.3), respectively; age-specific criteria) than the iodine-adequate group.

Conclusions: Excess iodine was prevalent in Korean children, and their Tvol was higher than the international reference values. Goiter rate was associated with iodine excess, which significantly increased in the moderate and severe iodine excess groups. Further studies are warranted to define optimal iodine intake in children.

Background: The optimal timing for initiating multi-kinase inhibitors (MKIs) in patients with radioactive iodine-refractory (RAI-R) differentiated thyroid cancer (DTC) remains unclear. Thus, we evaluated the real-world practice patterns and outcomes in asymptomatic patients with progressive RAI-R DTC (≥1 lesion ≥1 cm in diameter) in the United States (US) and outside the US (non-US).

Methods: In this prospective, non-interventional, open-label study, eligible patients were chosen by treating physicians to receive MKI therapy (Cohort 1) or undergo active surveillance (Cohort 2) at study entry. Cohort 2 patients were allowed to transition to MKI therapy later. The primary endpoint was time to symptomatic progression (TTSP) from study entry. Data were compared descriptively. When endpoints were inestimable, 36-month rates were calculated.

Results: Among 647 patients, 478 underwent active surveillance (Cohort 2) and 169 received MKI treatment (Cohort 1). Patients underwent surveillance at a higher rate in the US (92.6%) versus the non-US (66.9%). Half of US and non-US patients who qualified for MKI treatment had initial American Thyroid Association (ATA) low-to-intermediate-risk disease. Among Cohort 2, the 36-month TTSP rates from study entry were 65.6% and 66.5% in the US and non-US, respectively. Cohort 2 patients treated later demonstrated 36-month TTSP rates of 30.8% and 55.8% in the US and non-US, respectively.

Conclusions: Active surveillance is a viable option for asymptomatic patients with progressive RAI-R DTC. However, early intervention with MKI therapy may be more suitable for others. Further research is needed to identify patients who are optimal for active surveillance.

Registration: NCT02303444