European Thyroid Journal最新文献

Objective: Ultrasound-guided percutaneous ethanol injection therapy (US-PEIT) is used in patients with recurrent symptomatic thyroid cysts as a credible alternative to surgery. Young patients commonly do not wish to undergo surgery and prefer ethanol ablation, if available. The effect of this approach on quality of life is an essential factor in deciding on the treatment options, especially in the young with a long life expectancy and no comorbidity.

Methods: We performed US-PEIT in a cohort of young patients, 15-30 years, from 2015 to 2020. The patients' general quality of life (QoL), self-reported compression symptoms and neck appearance were evaluated.

Results: The cohort comprised 59 patients with 63 cysts, more women than men, with a mean age of 23.8 years. About 1.5 mL of injected alcohol were needed to reach a 90.7% mean cyst volume reduction ratio in 12 months. The method did not fail in any of the patients; a single US-PEIT session was undertaken in 46% of them. The procedure significantly improved each of the patients' symptoms with a significant total score difference (P < 0.001). The total symptom score correlated with the initial cyst volume (P = 0.002; r = 0.395). The mean QoL score by SF-36 6 months after the last US-PEIT was significantly different for physical component summary 56.5 (P < 0.001) but not different for mental component summary 47.7 (P = 0.125), compared to age-corresponding norms.

Conclusions: US-PEIT is a safe and effective method for the young, leading to improvements in cosmetic and subjective complaints, and should also be considered as first-line treatment in the young.

Background: Most thyroid cancers of follicular origin have a favorable outcome. Only a small percentage of patients will develop metastatic disease, some of which will become radioiodine refractory (RAI-R). Important challenges to ensure the best therapeutic outcomes include proper, timely, and appropriate diagnosis; decisions on local, systemic treatments; management of side effects of therapies; and a good relationship between the specialist, patients, and caregivers.

Methods: With the aim of providing suggestions that can be useful in everyday practice, a multidisciplinary group of experts organized the following document, based on their shared clinical experience with patients with RAI-R differentiated thyroid cancer (DTC) undergoing treatment with lenvatinib. The main areas covered are patient selection, initiation of therapy, follow-up, and management of adverse events.

Conclusions: It is essential to provide guidance for the management of RAI-R DTC patients with systemic therapies, and especially lenvatinib, since compliance and adherence to treatment are fundamental to achieve the best outcomes. While the therapeutic landscape in RAI-R DTC is evolving, with new targeted therapies, immunotherapy, etc., lenvatinib is expected to remain a first-line treatment and mainstay of therapy for several years in the vast majority of patients and settings. The guidance herein covers baseline work-up and initiation of systemic therapy, relevance of symptoms, multidisciplinary assessment, and patient education. Practical information based on expert experience is also given for the starting dose of lenvatinib, follow-up and monitoring, as well as the management of adverse events and discontinuation and reinitiating of therapy. The importance of patient engagement is also stressed.

Objective: The aim of this multicentre study was to investigate the progression of patient-reported outcomes after thyroid surgery, with emphasis on voice and swallowing difficulties.

Methods: An online platform was used to collect replies to standardised questionnaires (voice handicap index, VHI; voice-related quality of life, VrQoL; EAT-10) preoperatively and at 2-6 weeks and 3-6-12 months after surgery.

Results: A total of 236 patients were recruited from five centres that contributed with median of 11 cases (range 2-186 cases). Average symptoms scores showed voice changes lasting up to 3 months: VHI increased from 41 ± 15 (preop) to 48 ± 21 (6 weeks) and returned to 41 ± 15 at 6 months. Similarly, VrQoL increased from 12 ± 4 to 15 ± 6 and returned to 12 ± 4 (6 months). Severe voice changes (VHI > 60) were reported in 12% of patients preop, 22% at 2 weeks, 18% at 6 weeks, 13% at 3 months and 7% at 12 months. Only five patients with normal preoperative voice had persistent severe voice changes after 6-12 months. Those with severe voice changes at 2 weeks (median VHI 70.5, IQR 65-81) had significant improvement by 6 months (median VHI 54, IQR 39-65) (P < 0.001). Swallowing assessment showed a median preop score of 0 (IQR 0-3) increasing to a median of 2 (IQR 0-8) at 2 weeks and normal values afterwards.

Conclusion: The ThyVoice online platform allows the assessment of patient-reported outcome measures in thyroid surgery. Voice morbidity appears to be more frequent than commonly reported, and this risk should the quoted during informed consent. Swallowing difficulties are mild but significant in the first 2 weeks.

Background: Successful radioiodine treatment of differentiated thyroid cancer requires iodine avidity: that is, the concentration and retention of iodine in cancer tissue. Several parameters have previously been linked with lower iodine avidity. However, a comprehensive analysis of which factors best predict iodine avidity status, and the magnitude of their impact, is lacking.

Methods: Quantitative measurements of iodine avidity in surgical specimens (primary tumour and lymph node metastases) of 28 patients were compared to immunohistochemical expression of the thyroid-stimulating hormone receptor, thyroid peroxidase (TPO), pendrin, sodium-iodide symporter (NIS) and mutational status of BRAF and the TERT promoter. Regression analysis was used to identify independent predictors of poor iodine avidity.

Results: Mutations in BRAF and the TERT promoter were significantly associated with lower iodine avidity for lymph node metastases (18-fold and 10-fold, respectively). Membranous NIS localisation was found only in two cases but was significantly associated with high iodine avidity. TPO expression was significantly correlated with iodine avidity (r = 0.44). The multivariable modelling showed that tumour tissue localisation (primary tumour or lymph node metastasis), histological subtype, TPO and NIS expression and TERT promoter mutation were each independent predictors of iodine avidity that could explain 68% of the observed variation of iodine avidity.

Conclusions: A model based on histological subtype, TPO and NIS expression and TERT promoter mutation, all evaluated on initial surgical material, can predict iodine avidity in thyroid cancer tissue ahead of treatment. This could inform early adaptation with respect to expected treatment effect.

Thyroid hormone (TH) is indispensable for brain development in utero and during the first 2-3 years of life, and the negative effects of TH deficiency on brain development are irreversible. Detection of TH deficiency early in life by neonatal screening allows early treatment, thereby preventing brain damage. Inborn shortage of TH, also named congenital hypothyroidism (CH), can be the result of defective thyroid gland development or TH synthesis (primary or thyroidal CH (CH-T)). Primary CH is characterized by low blood TH and elevated thyroid-stimulating hormone (TSH) concentrations. Less frequently, CH is due to insufficient stimulation of the thyroid gland because of disturbed hypothalamic or pituitary function (central CH). Central CH is characterized by low TH concentrations, while TSH is normal, low or slightly elevated. Most newborn screening (NBS) programs for CH are primarily TSH based and thereby do not detect central CH. Only a few NBS programs worldwide aim to detect both forms of CH by different strategies. In the Netherlands, we have a unique T4-TSH-thyroxine-binding globulin (TBG) NBS algorithm for CH, which enables the detection of primary and central CH. Although the necessity of central CH detection by NBS is still under debate, it has been shown that most central CH patients have moderate-to-severe hypothyroidism instead of mild and that early detection of central CH by NBS probably improves its clinical outcome and clinical care for central CH patients with multiple pituitary hormone deficiency. We are therefore convinced that detection of central CH by NBS is of utmost importance.

Background: Hypothyroidism is clinically characterized by a decrease in levels of the circulating thyroid hormones namely thyroxine and triiodothyronine. The main treatment for hypothyroidism is thyroid hormone replacement using levothyroxine to normalize serum thyroid hormone levels.

Objectives: In this study, we explored the metabolic changes in the plasma of patients with hypothyroidism after reaching a euthyroid state with levothyroxine treatment.

Methods: Plasma samples from 18 patients diagnosed as overt hypothyroidism were collected before and after levothyroxine treatment upon reaching a euthyroid state and were analyzed by high-resolution mass spectrometry-based metabolomics. Multivariate and univariate analyses evaluated data to highlight potential metabolic biomarkers.

Results: Liquid chromatography-mass spectrometry-based metabolomics revealed a significant decrease in the levels of ceramide, phosphatidylcholine, triglycerides, acylcarnitine, and peptides after levothyroxine treatment; this could indicate a change in the fatty acid transportation system and an enhanced β-oxidation, compared with a hypothyroid state. At the same time, the decrease in the peptides suggested a shift in protein synthesis. In addition, there was a considerable rise in glycocholic acid following therapy, suggesting the involvement of thyroid hormones in stimulating bile acid production and secretion.

Conclusions: A metabolomic analysis of patients with hypothyroidism revealed significant changes in several metabolites and lipids after treatment. This study showed the value of the metabolomics technique in providing a complementary understanding of the pathophysiology of hypothyroidism and as a crucial tool for examining the molecular impact of levothyroxine treatment on hypothyroidism. It was an important tool for investigating the therapeutic effects of levothyroxine on hypothyroidism at the molecular level.

Objective: A decrease in the use of radioactive iodine (RAI) treatment for thyroid cancer has been described in the last decade in the US following subsequent updates of the American Thyroid Association guidelines. By contrast, population-based data from European countries are lacking. The study aims to assess the frequency and long-term trends in the use of RAI in Italy.

Methods: From the Italian national hospital discharge database, the proportion of RAI treatment after total thyroidectomy with thyroid cancer diagnosis has been assessed by sex and age class during 2001-2018.

Results: Throughout the whole study period, RAI was performed after 58% of 149,419 total thyroidectomies. The use of RAI was higher for men and younger patients; it peaked in 2007 (64% in women and 68% in men) and declined thereafter (2018: 46% in women and 53% in men), with a similar pattern observed across all ages and areas.

Conclusion: National data show that in Italy trends in RAI treatment paraleled those observed in the US. Further monitoring of the use of RAI is warranted in Italy, as elsewhere, to assess the impact of international guidelines on real-life clinical management of thyroid cancer.

Objective: Mental fatigue, depression, anxiety, and cognitive complaints are common in Graves' disease (GD). Our aims were to assess the relationship between these variables in patients with GD during both hyperthyroidism and a long stable euthyroidism.

Methods: A prospective longitudinal case-control study where 65 premenopausal women diagnosed with GD and 65 matched controls were assessed twice with 15 months in between. The first visit for patients was in overt hyperthyroidism and the second after treatment.

Results: During the hyperthyroid phase, mental fatigue, depression, and anxiety were significantly increased for GD patients compared to controls (all P < 0.001). Among GD patients, 89% reported mental fatigue and among controls 14%. No difference in cognitive tests was found. After 15 months, significant improvements for GD patients after treatment were found for the items of mental fatigue, depression, and anxiety (all P < 0.001), but these were unchanged in controls. GD patients reported residual mental fatigue (38%), 23% without depression, and 15% mental fatigue combined with depression. Self-reported cognitive complaints were pronounced while cognitive tests did not reveal any deficiencies.

Conclusion: Mental fatigue and emotional distress are common in the hyperthyroid phase. These improve with treatment but are still more common in GD patients after 15 months of therapy than in controls. The residual mental fatigue is shown to be a phenomenon distinct from depression in this study. This indicates the importance of assessing mental fatigue in GD patients and underlines the need for rehabilitation and healthcare support as fatigue will have consequences for work ability.

Aim: The prevalence of thyroid nodules and the risk of thyroid cancer in patients with Graves' disease is uncertain. We aimed to evaluate the prevalence of thyroid nodules and cancer in patients with Graves' disease.

Methods: Retrospective observational study of adult subjects with Graves' disease (positive autoantibodies thyrotropin receptor antibodies (TRAbs)) between 2017 and 2021 at our center was done. We evaluated the prevalence of thyroid nodules and cancer in this population and characterized the predictive factors for thyroid malignancy using linear and logistic regression models.

Results: We evaluated a total of 539 patients with Graves' disease during a median follow-up of 3.3 years (25th-75th percentiles 1.5-5.2 years). Fifty-three percent had thyroid nodules and 18 (3.3%) were diagnosed with thyroid cancer (12 papillary microcarcinomas). All tumors were classified using TNM classification as T1, and only one had lymph node metastasis; there were no recordings of distant metastasis. Sex, age, body mass index, smoking, TSH, and TRAbs levels were not significantly different between patients with and without thyroid cancer. Patients with multiple nodules on ultrasound (OR 1.61, 95%CI 1.04-2.49) and with larger nodules (OR 2.96, 95%CI 1.08-8.14, for 10 mm increase in size) had a greater risk of thyroid cancer diagnosis.

Conclusion: Patients with Graves' disease had a high prevalence of thyroid nodules and their nodules had a significant risk of thyroid cancer. The risk was higher in those with multiple and larger nodules. Most had low-grade papillary thyroid cancer. More studies are needed to clarify the clinical relevance of these findings.

Background: Hypertension (HTN) is the most frequent adverse event during treatment with lenvatinib (LEN), but data on its best management are limited.

Aim: The objective of this study was to assess incidence, features and best management of LEN-related HTN in a consecutive single tertiary-care centre cohort.

Methods: Twenty-nine patients were followed up for a mean time of 29.8 months (6-77 months).

Results: After a mean follow-up of 6.8 months, HTN was recorded in 76% of cases, as a de novo occurrence in half of them. HTN significantly correlated with LEN dose and was of grade 1, grade 2 and grade 3 in 5%, 50% and 45% of patients, respectively. The majority (77%) of patients with HTN developed proteinuria. There was no correlation between HTN and proteinuria or clinical features or best morphological response or any other adverse event (AE), with the exception of diarrhoea. Patients with or without pre-existing HTN or any other cardiovascular disease had a similar incidence of HTN during LEN, thus excluding the impact of this potential predisposing factor. After evaluation by a dedicated cardiologist, medical treatment was introduced in 21/22 patients (polytherapy in 20 of them). The most frequently used drugs were calcium channel blockers (CCBs) due to their effect on vasodilation. In case of poor control, CCBs were associated with one or more anti-hypertensive drug.

Conclusion: HTN is a frequent and early AE in patients on LEN treatment. We suggest a diagnostic and therapeutic algorithm to be applied in clinical practice to allow efficient HTN control and improve patient compliance, reducing LEN discontinuation.