European Thyroid Journal最新文献

Background: Pediatric differentiated thyroid carcinoma (pedDTC) is rare but increasingly prevalent, requiring multidisciplinary care to ensure optimal outcomes. In 2021, the pediatric national reference program of the German Malignant Endocrine Tumor (MET) registry was established to standardize the management of pedDTC, with a particular focus on radioactive iodine (RAI) use and minimizing treatment variability.

Methods: This study evaluated the program's first 3.5 years, including 43 inquiries concerning 39 patients with confirmed or suspected pedDTC. A weekly national expert tumor board provided individualized recommendations based on multidisciplinary input and risk stratification. Data were analyzed for demographic trends, therapeutic decisions, and short-term outcomes.

Results: Among 34 patients with confirmed pedDTC, RAI use was reduced or omitted in 70.6% of cases, particularly among low-risk patients, in alignment with the American Thyroid Association 2015 guidelines. Surgical strategies were modified in 61.5% of cases to balance disease control with treatment-related morbidity. No systemic medical therapy was recommended during initial management. At a mean follow-up of 0.7 years, all patients were alive; persistent disease was observed in 15.4%.

Conclusions: The national reference program has successfully introduced a structured, individualized approach to the management of pedDTC in Germany. Ongoing data collection and longer follow-up will be essential to assess the long-term impact of this centralized, risk-adapted model.

Sodium levothyroxine (LT4) as a monotherapy represents the mainstay of treatment of hypothyroidism, and its use has increased over time. Nevertheless, it faces several potential barriers in its 'real life' utilization, and hence its clinical effectiveness may be marred. This is suggested by the frequent situation of patients failing to reach the therapeutic goals of symptom relief and serum TSH control. Thus, an expert task force was approved by the Guidelines Board of the European Thyroid Association to examine the available data and to formulate recommendations based on the available evidence and the experts' deduction. The task force provides a body of suggestions to optimize the levothyroxine treatment in monotherapy, considering the key point in the individualization of treatment. Furthermore, the nutritional, pharmacological and pathological factors, potentially leading to the increased need for levothyroxine, are discussed, with a specific focus on the use of liquid and softgel formulations of the hormone.

Background: To account for pregnancy-specific changes in thyroid physiology, international guidelines recommend the use of trimester-specific reference intervals. However, the pragmatic division in trimesters does not necessarily align with the changes in thyroid physiology. While the goal of treating gestational thyroid dysfunction is to prevent thyroid hormone-mediated adverse events, it remains unclear which method of standardizing to gestational age, if any, is most effective in identifying individuals at higher risk of adverse pregnancy events.

Methods: We included 5,675 women participating in a population-based prospective cohort with data on thyroid-stimulating hormone (TSH), free thyroxine (FT4) and thyroperoxidase antibodies (TPOAbs) during early pregnancy (median: 13.2 weeks, 95% range: 9.8-17.6). We studied the association of TSH and FT4 with pre-eclampsia, premature delivery, birth weight and offspring IQ with or without full gestational age standardization of TSH and FT4 using multivariable regression models.

Results: There was a positive association of gestational age at blood sampling with TSH (difference in mean TSH: +9.6%; P < 0.001) and a negative association with FT4 (difference in mean FT4: -20.2%; P < 0.001). Standardizing TSH to gestational age led to reclassification of 36 women as having normal TSH (9.9%) and 27 as having abnormal TSH (0.5%). For FT4, 62 women were reclassified as having normal FT4 (20.3%) and 57 as having abnormal FT4 (1.1%). Standardization of TSH and FT4 concentrations led to an attenuation of the associations with any outcome of up to 71% as compared to non-standardized TSH or FT4.

Conclusions: Full standardization of TSH and FT4 to gestational age either does not affect or weakens their associations with clinical outcomes, suggesting that accounting for gestational age offers no benefit with regard to identifying high-risk thyroid dysfunction during early pregnancy.

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.