European Thyroid Journal最新文献

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.

Primary congenital hypothyroidism (CH) is the most common neonatal endocrine disorder, and may be etiologically subdivided into thyroid dysgenesis, referring to abnormal thyroid development, and dyshormonogenesis, where a defective thyroid hormone biosynthesis pathway results in inadequate hormone production despite a structurally intact gland. Delayed treatment of neonatal hypothyroidism may result in irreversible neurodevelopmental impairment; therefore, where available, CH screening programs facilitate prompt diagnosis. However, the molecular basis for CH remains unclear in most of the cases. This review summarizes current understanding of the genetic etiologies underlying primary CH and associated phenotypes. Classical genetic causes are discussed in the context of their role in normal thyroid physiology. Genes recently reported to play a role in the pathogenesis of CH are discussed, and novel genomic mechanisms in CH are described.

Metastatic differentiated thyroid cancer (DTC) is responsible for most thyroid cancer-related deaths, with an even worse prognosis for patients with radioactive iodine (RAI)-refractory DTC (RAIR-DTC). While multikinase inhibitors (MKIs) and tyrosine kinase inhibitors (TKIs) offer effective treatments for RAIR-DTC, most patients remain noncurative and eventually experience disease progression. In addition, long-term use of these medications is hindered by adverse events, drug resistance and high cost. Recently, the use of MKIs and TKIs has reignited interest in enhancing RAI incorporation. This approach aims to restore the effectiveness of RAI therapy in patients with RAIR-DTC by using agents that increase RAI uptake, potentially overcoming current treatment challenges. This review covers the molecular mechanisms behind RAI resistance, the definition of RAIR-DTC and the efforts to enhance RAI incorporation through various agents, including those currently undergoing clinical trials.

Background: This study aimed to investigate the changes in histological types and causes of death associated with thyroid carcinoma (TC) before and after the introduction of systemic drug therapy.

Methods: The records of 503 deceased patients treated for TC and with death from TC between January 2005 and June 2024 were reviewed in this retrospective cohort study. Multivariate logistic regression was applied to assess whether the number of patients with anaplastic TC (ATC) at diagnosis and the number of local-related deaths changed before and after the introduction of lenvatinib (i.e. 2005-2014 vs 2015-2024).

Results: Of the 503 patients, 157 (31%) had ATC, 253 (50%) had papillary TC (PTC), 67 (13%) had follicular TC (FTC), 17 (3%) had poorly differentiated TC, and nine (2%) had medullary TC. Respiratory insufficiency was the most common fatal condition, occurring in 192 cases (38%), followed by local-related death in 98 cases (19%) and brain-related conditions in 22 cases (4%). We found no difference in the frequency of patients with ATC at diagnosis (32 vs 30%; P-value = 0.772) and the frequency of local-related deaths (19 vs 20%; P-value = 0.736) between 2005-2014 and 2015-2024. These findings were supported by multivariate logistic regression models that adjusted for other covariates (adjusted P-value = 0.436 and 0.353, respectively).

Conclusions: ATC, including anaplastic transformation from PTC and FTC, still accounts for approximately 40% of thyroid cancer deaths after the introduction of systemic drug therapy. Respiratory insufficiency is the most common immediate cause of death.

Introduction: Current guidelines emphasize active surveillance (AS) over immediate surgery for low-risk papillary thyroid microcarcinomas (PTMCs). Alternative minimally invasive treatments, such as thermal ablation, are being explored. If thyroidectomy is performed, lobectomy is preferred and radioactive iodine (RAI) remnant ablation is not routinely recommended for low-risk PTMC patients.

Aim: This study aimed to assess the approach of Greek endocrinologists toward AS and the management of low-risk PTMCs.

Methods: A web-based survey was conducted among members of the Hellenic Endocrine Society (HES). Two clinical scenarios involving a 60-year-old woman with low-risk PTMC were analyzed. Surveyed endocrinologists were asked whether they would recommend AS, thermal ablation, lobectomy or total thyroidectomy as primary treatment; and if total thyroidectomy was performed in this case, whether they would recommend RAI ablation.

Results: A total of 201 endocrinologists (25% of HES members) participated. As primary treatment for low-risk PTMC, 46.8% recommended total thyroidectomy, 31.3% chose AS, 20.9% opted for lobectomy and 1.0% selected thermal ablation. If total thyroidectomy was performed, 95% considered RAI ablation unlikely and only 5% would use RAI. Demographic characteristics, including age, sex, experience and geographic location, did not significantly influence these choices. The primary reason cited by endocrinologists for noncompliance is skepticism about implementing the guidelines, likely stemming from resource limitations and educational gaps.

Conclusion: One-third of Greek endocrinologists prefer AS for managing low-risk PTMCs. More time and effort may be needed to further shift their clinical approach. Insights from our web survey aim to reduce overtreatment in low-risk PTMC management.

A growing body of evidence has established that thyroid hormone (triiodothyronine, T3) is a key factor in the differentiation and survival of the light-sensing photoreceptors in the retina. These functions include a critical role in generating the cone photoreceptor diversity that is required for color vision. Here, we review some of these functions of T3 and the critical mechanisms that regulate the T3 signal in the mammalian retina. The provision of T3, the active form of thyroid hormone, is determined by developmentally rising levels of T3 and its precursor T4 (thyroxine) in the circulation and by intrinsic control within the retina itself by deiodinase enzymes that deplete or amplify the available level of T3. Dynamic profiles of inactivating (DIO3) and activating (DIO2) deiodinases suggest that the T3 signal is progressively calibrated throughout early development, maturation and later functional maintenance of the retina. However, the benefits of T3 come at a cost: photoreceptors are susceptible to impairment and cell death when T3 signaling becomes imbalanced. These findings have implications regarding the influence of T3 in retinal diseases.