European Thyroid Journal最新文献

The therapeutic landscape of Graves' hyperthyroidism has been rapidly evolving in the past few years. There has been a shift worldwide toward antithyroid drugs as the preferred first-line therapy with significant interest in thyroid function preservation, even if it requires more than 2 years of antithyroid drug treatment. This approach, long term antithyroid drug therapy, has gained traction as a therapeutic option after it has been shown to be safe and associated with significantly higher rates of remission than the traditional 18-month course of medical treatment. In parallel, we see, after 80 years of antithyroid drugs as the only medical therapy available for Graves' disease, a strong interest in new drug development that follows more closely the pathophysiology of the disease. These approaches span the spectrum of targeting antigen presentation, B cell activation, TSHR antibody cycle and TSHR signaling. Separately, advances in wearable devices and artificial intelligence models present new opportunities for more timely diagnosis, monitoring, and treatment of patients with Graves' disease. Finally, new therapies will pose novel challenges in the management of patients that will necessitate adjustments to our clinical practices and development of guidelines suited for these new therapeutic options.

Objective: This study examined the relationship between levothyroxine dosage and free thyroxine levels in hypothyroid patients. The aim was to ascertain whether elevated free thyroxine in treated patients suggests overmedication or is essential for maintaining appropriate free triiodothyronine levels, guiding improved monitoring practices during therapy.

Methods: A retrospective analysis was conducted on 3,020 free thyroxine measurements from 1,409 patients between July 2021 and March 2024. Patients with thyrotropin receptor antibodies or treated with antithyroid drugs such as thiamazole, propylthiouracil, and potassium iodide were excluded. Measurements were performed using the Elecsys FT4 III immunoassay, and statistical comparisons were made between levothyroxine-treated and untreated groups.

Results: Levothyroxine-treated patients showed significantly higher median free thyroxine levels (17.9 pmol/L, interquartile range (IQR): 15.6-20.1) than untreated patients (16.2 pmol/L, IQR: 14.5-17.9, P < 0.0001). In addition, the free triiodothyronine/free thyroxine ratio was significantly lower in levothyroxine-treated patients (0.24, IQR: 0.20-0.29) than in untreated patients (0.28, IQR: 0.25-0.32, P < 0.0001). Free thyroxine levels increased with levothyroxine dosage, whereas the free triiodothyronine/free thyroxine ratio decreased. Although thyroid-stimulating hormone levels did not differ significantly between the groups, higher levothyroxine doses were associated with mild suppression.

Conclusion: The findings emphasize the importance of higher free thyroxine levels for maintaining adequate free triiodothyronine in levothyroxine-treated patients, underscoring the need to monitor free thyroxine, free triiodothyronine, and their ratio during therapy to optimize treatment outcomes. In addition, clinicians should recognize that higher levothyroxine doses may elevate free thyroxine levels beyond the reference range.

Congenital hypothyroidism (CH) is a lifelong condition, diagnosed shortly after birth through newborn screening in one-third of countries worldwide. When diagnosed and treated early in nonsyndromic CH, most patients exhibit similar fertility, metabolic and cardiovascular health, bone health, and quality of life compared to unaffected individuals. Special precautions are required for adult female patients with CH during pregnancy to ensure optimal management and to prevent serious maternal and fetal complications. In this review, we summarize the current knowledge on comorbidities and the long-term management of adults with CH, with a particular focus on pregnancy.

Background: Thyroid nodule (TN) is a common entity, and TNs assessed by Thyroid Imaging and Reporting Data Systems (TIRADSs) as low-risk lesions (TIRADS 3) can significantly impact the rate of unnecessary biopsy (UN-FNAC). This study reviewed a consecutive series of patients undergoing surgery to analyze TNs assessed as TIRADS 3.

Methods: Thyroid surgeries performed from January 2019 to August 2024 were reviewed. Patients with preoperative thyroid ultrasound were selected, and TNs were classified according to American College of Radiology (ACR), European Thyroid Association (EU), and Korean (K) TIRADS. Cases assessed as TIRADS 3 were finally included. Histology was the reference standard to calculate the rate of UN-FNAC.

Results: The study series included 284 TNs assessed as TIRADS 3. The risk of malignancy was 8.7% in ACR-, 10.7% in EU-, and 10.1% in K-TIRADS, higher than expected. The frequency of TNs with indication for biopsy according to K-TIRADS (66.7%) was significantly (P = 0.003) higher than ACR-TIRADS (46.7%), with an intermediate value of EU-TIRADS (56.5%). The percentage of cancers with indication for biopsy according to ACR-, EU-, and K-TIRADS was 25%, 50%, and 50%, respectively. The overall rate of UN-FNAC was 95.3% in ACR-TIRADS, 90.3% in EU-TIRADS, and 92.4% in K-TIRADS.

Conclusion: How to save on UN-FNACs in low-risk TNs is challenging. Although ACR-TIRADS can be effective in reducing the total number of biopsies, the rate of UN-FNAC remains significant. Alternative strategies should be developed.

Objective: Hypothyroidism in pregnant women has been linked to deviations in birth weight, but associations are not consistent and the role of confounding factors, including maternal body mass index (BMI), is not clear. This study aimed to evaluate the association between maternal hypothyroidism, birth weight of the child, and placental weight.

Methods: This was a retrospective register-based study of singleton live births in Denmark from 2004 to 2015 (n = 694,734). Small for gestational age (SGA) (<10th percentile), large for gestational age (LGA) (>90th percentile), and placental weight Z-scores were defined according to gestational week at birth and sex of the child. Associations were evaluated using logistic and linear regression, adjusting for potential confounders, which included maternal BMI.

Results: Altogether, 9.8 and 9.9% of pregnant women with no diagnosis of hypothyroidism gave birth to SGA and LGA children. The frequency of SGA was higher among children whose mothers were newly diagnosed with hypothyroidism in pregnancy (12.4%; adjusted odds ratio (aOR) = 1.16 (95% confidence interval (CI): 1.00-1.34)), but not LGA (9.3%; aOR = 1.03 (95% CI: 0.87-1.21)). Children born to mothers with treated hypothyroidism in pregnancy did not have higher frequencies of SGA (aOR = 0.94 (95% CI: 0.86-1.03)) or LGA (aOR = 1.06 (95% CI: 0.98-1.14)). No association between maternal hypothyroidism and placental weight Z-score was found (adjusted beta coefficient: 0.004 (95% CI: -0.016; 0.024)).

Conclusions: The findings from a large Danish cohort point toward an association between hypothyroidism in pregnancy and lower birth weight of the child, whereas no association with placental weight was found.

As new precision oncology therapies become available in the thyroid cancer (TC) treatment landscape, appropriate and timely biomarker testing is crucial for treatment selection and requires a multidisciplinary approach. Recently published European guidelines on advanced/metastatic TC management include a special focus on biomarker testing. However, to date, there remains a need for comprehensive European guidance for standardized molecular testing strategies in TC that encompass a broad set of targetable or potentially targetable alterations, timing of testing, and patients to be tested. This expert opinion article outlines consensus testing algorithms for differentiated TC, medullary TC, and anaplastic TC from a team of endocrinologists, oncologists, molecular biologists, and pathologists to provide standardized recommendations for physicians involved in treating patients with advanced TC. In the differentiated TC algorithm, patients recommended for comprehensive testing by DNA and RNA next-generation sequencing (NGS) include those whose disease has progressed on or is resistant to radioactive iodine treatment. The medullary TC algorithm recommends RET germline testing for all patients at diagnosis. For patients exhibiting high-risk clinical or pathological features and those whose disease progresses, somatic RET testing with NGS should be discussed and conducted before considering systemic treatment. As anaplastic TC is a highly aggressive disease, molecular reflex testing for BRAF mutations is recommended for all patients at diagnosis, followed by DNA and RNA NGS for those who test BRAF negative. The article also provides consensus recommendations on the use of tumor tissue for testing and on centralization of molecular testing involving multidisciplinary tumor boards.

Traditionally, thyroid-stimulating hormone receptor (TSHR) has been utilized primarily to increase the efficacy of radioactive iodine therapy by promoting iodine uptake. However, the rise of personalized medicine has prompted reassessment of the potential of TSHR as a therapeutic target. Recent studies have indicated that TSHR plays a critical role in the progression of thyroid cancer and may serve as a key target for the treatment of residual or metastatic thyroid cancers, particularly radioiodine-refractory differentiated thyroid cancer (RAIR-DTC). This review focuses on the biological characteristics of TSHR and its potential as a therapeutic target, emphasizing that optimizing TSHR-targeted drugs and integrating them with existing treatment strategies could offer new therapeutic avenues for patients with RAIR-DTC.

Thyroid cancer (TC), particularly aggressive forms such as poorly differentiated thyroid carcinoma and anaplastic thyroid carcinoma, presents considerable clinical challenges due to limited treatment options and suboptimal outcomes. Organoid models, derived from patient samples or pluripotent stem cells (PSCs), offer a robust framework for elucidating the biology of these malignancies. Recent advancements in patient-derived tumor organoid (PDTO) methodologies have facilitated more accurate representations of TCs, encompassing the heterogeneity of the disease and mechanisms of therapeutic resistance. PSC-derived models have further enabled the investigation of fundamental driving mechanisms behind thyroid carcinogenesis. This review highlights the progress made in the development of TC organoids, focusing on their utility in studying aggressive subtypes. We discuss innovative techniques for creating PDTOs and their applications in replicating essential features of the tumor microenvironment (TME), analyzing tumor progression, conducting drug screenings, and developing personalized therapeutic strategies tailored to individual patients. While PDTOs have become the predominant model for TC research, PSC-derived organoids provide insights into early carcinogenic events and mutation-specific processes that are often inaccessible in established tumors. Through these advancements, we emphasize the critical role of organoid models in bridging the divide between fundamental research and clinical application, offering a promising avenue for uncovering novel insights into TC biology and enhancing therapeutic strategies.

Objective: Serum thyroglobulin measurements are used in the long-term management of patients with differentiated thyroid cancer following thyroidectomy and radioiodine therapy. The use of predictive biomarkers, such as post-operative stimulated thyroglobulin levels and absorbed dose, may help to identify patients at risk of disease recurrence or an unsuccessful initial treatment.

Methods: Differentiated thyroid cancer patients treated with 1.1 or 3.7 GBq of radioiodine using recombinant human thyrotropin stimulation or thyroid hormone withdrawal were recruited into observational clinical studies in France, Germany and the UK with aligned study endpoints (MEDIRAD). The maximum absorbed dose to the thyroid remnant was determined and compared to post-operative stimulated thyroglobulin with respect to its ability to predict ablation success. Radioiodine therapy success was defined as unstimulated or stimulated thyroglobulin level of <0.2 or <1.0 ng/mL 9-12 months post-radioiodine.

Results: Ninety-four patients had follow-up data and negative antithyroglobulin antibody tests. Seventy-eight patients (83%) were deemed excellent biochemical responders. Post-operative thyroglobulin and maximum absorbed dose predicted ablation success with receiver operating characteristic area under the curves of 0.83 ± 0.05 (P < 0.001) and 0.64 ± 0.08 (P = 0.12). A dose-response relationship between maximum absorbed dose and ablation success was found for patients with a post-operative stimulated thyroglobulin of ≥1 ng/mL.

Conclusions: Predictions of ablation success using post-operative stimulated thyroglobulin or the absorbed dose to the thyroid remnant could inform personalisation of management of differentiated thyroid cancer and identify patients where further treatments or more intensive follow-up are required. Patients with a post-operative stimulated Tg of <1 ng/mL likely do not benefit from radioiodine.

Objective: To establish thyroid ultrasound volume norms appropriate for studies of diffuse goiter in a cohort of children and adolescents from an iodine-deficient population exposed to 131I by the Chernobyl fallout.

Methods: A cohort of 11,970 Belarusians aged ≤18 years at the time of the 1986 Chernobyl accident with individual thyroid radiation dose estimates was screened 10-18 years later. From these, a low-dose subset of 2,392 with no thyroid diseases was selected to construct age- and sex-specific normative values for thyroid ultrasound volume, compared to Belarusian Ministry of Health (MOH) norms and existing WHO and European standards.

Results: Cohort-specific values were generally lower than MOH norms and WHO standards for 11-17-year-olds. For those aged ≥18 years, internal norms were 30% higher in males and 15-30% lower in females than MOH norms, and exceeded European values for both sexes. Thyroid volume norms were about 40% higher in males and 30% higher in females as a function of BSA compared to European values. Thyroid volume continued to increase in both sexes, and by age 30-34 years, cohort-specific norms were 6% higher in males and 26% higher in females than European values. Urinary iodine concentration did not significantly explain variance in thyroid volume beyond sex, age, and BSA.

Conclusions: In this iodine-deficient cohort of young Belarusians exposed to 131I by Chernobyl fallout, thyroid ultrasound volumes differed substantially from MOH norms and established WHO standards, prompting a revision of diffuse goiter definition using cohort-specific normative values.