European Thyroid Journal最新文献

Objective: Mammalian acid chitinase (AMCase; CHIA) has potential as a biomarker and drug target in the fields of medicine and pharmacology, and its role in inhibiting tumor growth and Th2 cell-mediated asthma-related inflammation has become a research hotspot. However, the role of CHIA in thyroid cancer is unclear.

Methods: Tissue microarrays and thyroid cancer cell lines were used to detect CHIA expression and determine its clinical relevance. CHIA gene expression was altered in thyroid cancer cells to examine the effects of CHIA expression on the biological behavior of thyroid cancer cells, and the related molecular mechanisms involved were explored.

Results: We first examined CHIA expression in a thyroid tissue microarray using immunohistochemistry. We found that CHIA was significantly upregulated in thyroid cancer tissues relative to paired thyroid cancer adjacent tissues. After correlation analysis, we found that upregulated CHIA expression correlated with the tumor-node-metastasis (TNM) stage of patients with thyroid cancer. Similarly, CHIA expression was significantly higher in the thyroid cancer cell lines BCPAP, TPC-1, KTC-1 and FTC133 than in the human normal thyroid epithelial cell line Nthy-ori-3-1. CHIA promotes proliferation, migration and invasion; inhibits thyroid cancer cell apoptosis; and regulates markers of proliferation and epithelial-mesenchymal transition. Mechanistically, CHIA activated the JAK2/STAT3 signaling pathway in thyroid cancer cells.

Conclusions: CHIA upregulation promoted the proliferation, migration and invasion of thyroid cancer cells through JAK2/STAT3 signaling pathway activation. Therefore, CHIA could represent a potential new oncoprotein for patients with thyroid cancer.

Objective: Maternal thyroid peroxidase antibody (TPOAb) positivity has been associated with a variety of pregnancy complications and has potential neuropsychological developmental implications for the offspring. The aim of our study was to explore the effect of maternal TPOAb levels on emotional and behavioral problems in children.

Design: The study was designed as a cohort study.

Participants: Based on the Ma'anshan birth cohort in China, 2,464 mother-infant pairs were included in this study.

Measurements: Repeated blood samples were collected from pregnant women, and TPOAb and FT4 were measured retrospectively by electrochemiluminescence immunoassay (ECLIA). The strengths and difficulties questionnaire was used to assess the emotional and behavioral problems of 4-year-old preschoolers.

Results: After adjusting for potential confounders, maternal TPOAb positivity during the third trimester of pregnancy was found to be associated with an elevated risk of conduct problems in girls, with an odds ratio (OR) of 2.190 (95% confidence interval (CI): 1.137-4.219). Conversely, maternal TPOAb positivity in the first trimester was linked to a decreased incidence of prosocial behavior in boys, with an OR of 0.451 (95% CI: 0.237-0.861).

Conclusions: Maternal TPOAb positivity during pregnancy may be associated with emotional and behavioral problems in preschool-aged children.

Introduction: Little is known about sex differences in lenvatinib treatment safety and efficacy.

Methods: Real-word retrospective Italian multicenter study enrolling patients with radioiodine-refractory differentiated thyroid cancer treated with lenvatinib.

Results: A total of 138 patients (64 females) were included, with a median follow-up of 26 months (2-72). More men performed physical activities (34% vs 17%, P = 0.024). The frequency of smoking and alcohol consumption was higher in men (58% vs 33%, P = 0.003; 45% vs 17%, P = 0.001). We did not find sex differences in lenvatinib dose reduction due to adverse events (AEs) (78% females vs 85% males). Ninety-nine percent of patients developed at least one adverse event (AE), with no sex difference in their number and the time to first AE. Severe AEs occurred in 74% of males and 66% of females (P = 0.398), with a mean dose of 18.2 mg (±5.7), and a median time to the first serious AE of 9 weeks (1-154). Stomatitis/mucositis and hematological disorders were more frequent in females (48% vs 30%, P = 0.016; 17% vs 4%, P = 0.011). Gastrointestinal disorders were higher in males (15% vs 2%, P = 0.010). Eighty-seven patients interrupted lenvatinib due to AEs (median time: 3 months (0-48), mean dose: 17 mg ±5.5). Discontinuation occurred in 21 patients, five for severe AEs. No sex differences were found in progression-free survival, overall survival or disease control rate. Liver metastases were associated with disease progression (HR: 3.73, 95% CI: 1.06-13.12, P = 0.040) or death (HR: 4.82, 95% CI: 1.75-13.25, P = 0.002) only in females.

Conclusion: Lenvatinib is effective in both sexes and exhibits a good safety profile, with a sex difference in the frequencies of some adverse events.

Objective: The optimal treatment with antithyroid drugs (ATDs) for a first episode of Graves' disease (GD) remains controversial.

Methods: Retrospective, two academic centres study of newly diagnosed GD between 1990 and 2022, treated with ATD in block-and-replace (B+R) regimen for at least 12 months and followed up for at least 1 year after ATD discontinuation or until disease relapse. Sixty patients received high-dose B+R (HD) with fixed ATD dose maintained during the study, and 60 patients received low-dose B+R (LD) with lower ATD dose adjusted during the study.

Results: Baseline characteristics were similar in both groups. The point-prevalence of euthyroidism was not different between HD and LD (38 vs 47%, P = 0.460 at 6 months, 69 vs 82%, P = 0.194 at 12 months, 70 vs 78%, P = 0.370 at 18 months, respectively). At 18 months, 27% HD vs 38% LD (P = 0.242) had thyroid eye disease. There were no differences in the number or type of ATD-related adverse events (AE) (no AE 73 vs 78%, P = 0.707). LD received mean lower ATD dose (15.3 ± 4.2 vs 30.0 ± 0.0 mg/day, P < 0.001) and lower levothyroxine dose (72.6 ± 16.7 vs 100.6 ± 24.5 μg/day, P < 0.001). After a first course of ATD, 63% of HD patients and 60% of LD patients relapsed (P = 0.707) after a median time (interquartile range) of 11.0 (18) vs 7.0 (19) months (P = 0.109).

Conclusion: We observed similar relapse rates in patients with a first episode of GD receiving up to 50% less ATD and 30% less levothyroxine dose than high-dose B+R regimen.

Anaplastic thyroid cancer is one of the rarest subtypes of thyroid cancer, accounting for only 1-2% of all thyroid cancer cases. It is also one of the most aggressive: prognosis remains dismal and the disease-specific mortality rate is close to 100%. This rarity has markedly limited the availability of prospective trial results, and no standard chemotherapeutic option for unresectable or metastatic anaplastic thyroid cancer has yet been established. Nevertheless, combination therapy with a BRAF inhibitor and MEK inhibitor has shown encouraging efficacy in patients with BRAF V600E-mutated anaplastic thyroid cancer. Other novel treatments such as immune checkpoint inhibitors have also shown promising results. Owing to these therapeutic advances, the prognosis of anaplastic thyroid cancer appears to be gradually improving. However, further development of novel treatments for this rare malignancy requires the development of substantial infrastructure for international collaborative study.

Objectives: Total thyroidectomy is the treatment of choice for medullary thyroid cancer (MTC), although the sporadic forms are usually monocentric. Aim of the present study was to evaluate i) the performance of calcitonin (Ct) levels, ultrasound scans (US) and cytology in the preoperative identification of MTC and ii) the number of total thyroidectomies that could have been avoided being the location of the MTC diagnosed preoperatively.

Materials and methods: We retrospectively analyzed 89 RET germline negative patients diagnosed with MTC in the past 30 years, treated with total thyroidectomy ± lymphadenectomy, and followed in our Tertiary Care Center. In a subgroup of 55 patients, divided in those with a mono- or bi-lateral goiter, we applied ex-post criteria for the presurgical identification of the lobe holding the MTC nodule.

Results: Only 2/89 patients (2.2%) had a bilateral MTC at histology. A strongly significant correlation was found between preoperative basal Ct levels and MTC size. According to the ex-post identification criteria, the 84.4 and 56.5% of the nodules would have been identified preoperatively as MTC in monolateral and bilateral goiters, respectively.

Conclusions: This is the first European study that aims to evaluate the feasibility of lobectomy as first-line therapy for MTC based on the evaluation of thyroid US and serum Ct levels. These tools have been shown to have a good accuracy in detecting the affected lobe and strongly support the possibility to perform a more conservative surgery to treat RET-negative patients with suspicious MTC and nodular goiter.

Background: UK guidance on the assessment and management of thyroid disease was set out in NICE guideline NG145 in 2019 and is expected to result in an increase in radioactive iodine (RAI) being offered as a first-line definitive treatment for hyperthyroidism.

Methodology: In this work we analyse longitudinal UK Biobank data to assess all-cause mortality and comorbidity risks associated with the main treatment modalities for 793 participants with hyperthyroidism, specifically antithyroid drugs (ATDs), RAI and thyroidectomy.

Results: Participants treated with RAI showed reduced all-cause mortality compared with those treated with ATD alone (time to event ratio: 1.8, 95% CI: 0.9-3.6), albeit the result did not reach statistical significance, as did those treated by thyroidectomy (time ratio: 2.0, 95% CI: 1.1-3.9). For treated patients, odds ratios were generally elevated for osteoporosis, cardiovascular events and atrial fibrillation, but again did not reach statistical significance except for those patients treated by ATDs, with an odds ratio for atrial fibrillation of 2.2 (95% CI: 1.2-4.1) versus controls.

Conclusion: Our findings were consistent with those previously reported in the literature and do not reveal any evidence from the UK Biobank to contradict the safety of RAI being offered as a first-line treatment. The data are also suggestive, however, that treatments do not fully eliminate risks of complications related to hyperthyroidism. This reinforces the need for both clear communication where there may be risks of complications such as osteoporosis as well as clinical support for patients even after definitive treatment.

Introduction: Refractory hypothyroidism often poses a clinical problem, as treatment regimens are difficult to individualise to the patient and the feasibility of its delivery is difficult to organise within a healthcare system. We present a patient who became intolerant of intramuscular (IM) levothyroxine (LT4) after 18 years of treatment; thus, subcutaneous (SC) LT4 was initiated.

Case presentation: A 13-year-old female with newly diagnosed hypothyroidism remained hypothyroid despite escalating doses of oral LT4 and LT3. Thyroxine malabsorption was further suggested by nasogastric administration of LT4, whereby high-dose thyroxine administration resulted in only a 2.8 pmol/L increase in free T4 level (normal >5.14 pmol/L). She eventually achieved long-term euthyroid status at the age of 18 with fortnightly IM LT4 alongside oral LT4 and LT3. This was maintained for 18 years. Unfortunately, scar tissue developed around injection sites, resulting in increased pain and difficulty in administration. SC LT4 was trialled with success, and she has remained euthyroid for the last 6 years with self-administration and minimal side effects.

Conclusion: Refractory hypothyroidism often presents a challenge for clinicians, both for diagnosis and management. We discuss a patient with the longest follow-up to date within the published literature for both IM and SC LT4 for patient-administered treatment of refractory hypothyroidism and review the literature on alternative formulations available.

Introduction: Insulin resistance (IR) is a phenomenon commonly observed in pregnancy. Increased insulin concentrations might impact thyroid function and structure during gestation.

Objectives: This study investigates the bidirectional relationship between IR indices and thyroid function and morphology in pregnant women.

Methods: In 1,069 gravid participants of the Polish National Programme for Elimination of Iodine Deficiency (2007-2017), blood samples were analyzed for thyroid-stimulating hormone (TSH), FT3, FT4, aTPO, fasting glucose and insulin concentrations, and the thyroid structure was assessed with ultrasound (in 1,065 subjects). Based on calculated homeostatic model assessment of insulin resistance (HOMA-IR) values, participants were stratified into two subgroups: HOMA-nl (HOMA-IR <2.5) and HOMA-h (HOMA-IR ≥2.5), comprising 894 and 175 women, respectively.

Results: Significant difference in mean TSH (1.77 ± 1.17 vs 1.96 ± 1.04; P = 0.008) and mean FT4 (12.65 ± 2.3 vs 11.47 ± 1.9; P = 0.001) concentrations between HOMA-nl and HOMA-h groups was found. The subgroups did not differ in thyroid nodularity or multinodular goiter prevalence. HOMA-IR positively correlated with TSH concentrations, BMI and thyroid volume. Serum FT3 and FT4 concentrations showed negative correlations with HOMA-IR.

Conclusions: IR seems to affect the thyroid function of gravid women by diminishing the ability to respond to increased thyroid hormone demand. Thyroid volume increase during pregnancy may be influenced by IR; however, its short-term effect on thyroid nodularity appears to be negligible.

Background: Management of benign nodular thyroid disease (BNTD) has changed dramatically over the past two decades, as reflected by international guideline recommendations.

Purpose: We sought to document the preferences regarding the management of euthyroid BNTD among thyroid-dedicated members of the Spanish Society of Endocrinology and Nutrition (SEEN) and assess the extent to which present international guideline recommendations have been incorporated into ordinary practice.

Methods: An online survey on the management of a standard case of BNTD among SEEN thyroid experts and exploration of variations in management following different clinical scenarios, in which variables such as sex, age, ultrasound characteristics, fine needle aspiration results or patient preferences change.

Results: Two hundred and eleven (9% SEEN members) participated in the survey. Most of them, 147 (69.7%), recommended periodic monitoring, 43 (20.3%) surgery and 21 (10.0%) minimally invasive procedures (MIP). No participant opted for levothyroxine or radioiodine. Management of BNTD was modified based on patient preferences, both in favour of more aggressive (surgery) and more conservative (MIP or monitoring) options.

Conclusions: The vast majority of Spanish thyroidologists followed the international guideline recommendations for BNTD management. The trend shows the positive impact of the guideline recommendations with a shift towards more conservative management, taking into account patient preference as a binding element in therapeutic decision-making.