European Thyroid Journal最新文献

Objective: The prevalence of Thyroid-Cancer (TC) has increased worldwide and an association with metabolic and cardio-vascular disorders has been reported. Moreover, an increasing percentage of patients are currently diagnosed incidentally through non-thyroid related imaging for other clinical conditions. Our aim was to assess the prevalence of Thyroid-Related (TD) versus Incidental (ID) pre-surgery reasons leading to TC diagnosis and to compare the two groups in terms of clinical characteristics, size and severity of TC at presentation and rate of non-thyroid cancers and cardiovascular/metabolic comorbidities.

Design: we performed a retrospective cohort study in three high-volume hospital-based centers for thyroid diseases (Pavia, Latina and Messina) in Italy.

Patients: Consecutive patients with TC Measurements: data on pre-surgery reasons leading to TC diagnosis, age, sex, BMI, presence of cardio-metabolic comorbidities and non-thyroid cancer.

Results: among the 327 enrolled subjects the diagnosis of TC was prompted by thyroid-related reasons in 262 (80.1%, TD group) and incidental in 65 (19.9%, ID group). The ID group patients were more frequently males, significantly older and with a higher BMI than the TD group ones, they had a higher rate of non-thyroidal cancers and cardiovascular/metabolic comorbidities. No significant differences could be observed in terms of TC histotype, cancer size, extra-thyroidal extension, lymph-node metastases, AJCC Staging or ATA Risk stratification.

Conclusions: biological features of TC are similar in the TD and ID groups, but patients in the two groups display significant differences regarding their clinical features.

Background Selection between open thyroidectomy (OT) and minimally invasive (endoscopic/robotic) thyroidectomy (MT) for patients with thyroid cancer has been a subject of considerable debate. Comprehensive analysis of the short-term outcomes of endoscopic thyroidectomy (ET), robotic thyroidectomy (RT) and OT for thyroid cancer using a large-scale dataset is important. Methods This cohort study evaluated the outcomes of patients receiving ET, RT vs OT for thyroid cancer from January 1, 2003, to December 31, 2022. Propensity score matching was performed among patients treated with ET, RT or OT to balance covariates distribution. This study involved single-institutional patients (aged 18-70) who had undergone ET, RT or OT for thyroid cancer. Results The study included 11066 thyroid cancer patients (OT group: mean [SD] age, 42.45 [10.84] years; ET group: mean [SD] age, 36.75 [9.32] years; RT group: mean [SD] age, 40.27 [10.42] years). After PSM for demographic and clinical characteristics, 908 matched pairs of patients (ET vs. OT) and 1480 matched pairs (RT vs. OT) were included for further analysis. Complication analysis revealed that RT was associated with a lower rate of transient hypoparathyroidism (339 [22.9%] vs. 687 [46.4%]; p <0.001), a lower rate of permanent hypoparathyroidism (4 [0.3%] vs. 16 [1.1%]; p =0.012) and a lower rate of transient recurrent laryngeal nerve injury (63 [4.3%] vs. 89 [6.0%]; p =0.037). Conclusion This cohort study analyzed the short-term outcomes between ET, RT and OT in a large sample of patients with thyroid cancer over a period of two decades. PSM provided a comparable cohort, and the results suggested the advantage of RT, which reduced Clavien‒Dindo grade Ⅰ complications in the surgical treatment of thyroid cancer.

In recent years, germline mutations in the microRNA (miRNA) processor genes DICER1 and DGCR8 have been coupled to the development of thyroid follicular nodular disease (TFND), thereby casting new light on the etiology of this enigmatic, benign condition in non-iodine-deficient regions. Moreover, DICER1 and DGCR8 mutations have also been reported in rare subsets of follicular cell-derived thyroid carcinomas. Specifically, truncating germline or missense somatic DICER1 mutations have been reported in small subsets of pediatric and adolescent follicular thyroid carcinoma (FTC) and poorly differentiated thyroid carcinoma (PDTC). Similarly, a recurrent somatic mutation of the DGCR8 gene has been observed in highly aggressive FTCs and in some indolent cases of encapsulated follicular variant of papillary thyroid carcinoma. The reason why identical mutations in the same miRNA processor gene can lead to such a myriad of thyroid conditions, ranging from benign TFND to FTCs and PDTCs, remains unclear. This review highlights key features of miRNA regulator gene mutations in thyroid disease and explores their potential roles as drivers or progression events in tumor development.

Background: Thyroid hormones and sympathetic stimulation are needed for activating Brown adipose tissue (BAT) during cold exposure. Studies of human cold exposure have demonstrated both increased production and raised clearance of triiodothyronine (T3). Greenlandic hunters provide a unique model for evaluating metabolic effects of cold exposure.

Aim: We aimed to explore the dynamics of thyroid hormones when blocking sympathetic activity in Greenlandic hunters during winter to inspire knowledge on mechanisms of BAT activation.

Methods: We conducted a 7-day field study of Greenlandic hunters (n=7) in East Greenland in February. The sympathetic system was blocked using a non-selective beta blocker for seven consecutive days. A group of non-hunter Greenlanders (n = 8) from the same settlement were included for parallel sampling. All participants were healthy men. Blood samples were drawn daily for measurement of TSH, thyroid hormone levels, and thyroglobulin.

Results: Hunters had higher serum thyroglobulin, TSH, and high fT3/fT4 ratio compared to controls. Blocking the sympathetic activity was followed by changes in serum thyroglobulin and fT3 with an initial decrease and subsequent restoration of levels, while TSH and fT4 showed a gradual increase over the course of the study. The fT3/fT4 ratio showed a continuous and marked decrease.

Conclusion: We hypothesise that when blocking the sympathetic system, TSH increases to uphold the production of T3 needed for maintaining BAT activity. Additionally, alterations of fT3/fT4-ratio support a hypothesis of adrenergic stimulation promoting T3 over T4 secretion from the thyroid via the adrenergic nerve terminals in the thyroid.

Background: Thyroglobulin (Tg) is a biomarker of iodine status. Newborn Tg is a more sensitive marker than neonatal TSH in detecting variations in iodine intake. This study aims to validate an enzyme-linked immunosorbent assay (ELISA) for Tg determination on dried blood spots (DBS) in newborns. This study also sets out to assess the stability of Tg and the influence of newborns' hematocrit on Tg determination.

Methods: A commercially available ELISA Tg assay was adapted for use on DBS. DBS-Tg in cord blood was measured in 209 newborns delivered from healthy euthyroid pregnant women. Sensitivity, linearity, repeatability, and intermediate fidelity were determined using the appropriate standards and quality control materials.

Results: The limit of detection of the DBS-Tg assay was 2.4 µg/L, and the limit of quantification was 5.8 µg/L. Repeatability and intermediate fidelity were 7.7-8.3% and 11.0-11.2%, respectively. The median cord plasma Tg and DBS-Tg values in newborns were not significantly different, 30.2 (21.3-44.4) µg/L and 31.6 (19.3-48.7) µg/L (P = 0.48) with the ELISA, respectively, and 76.5 (40.0-101.5) µg/L with the Elecsys assay with an R = 0.88. DBS-Tg concentrations decrease with increasing hematocrit values (P < 0.05). DBS-Tg values were stable at a concentration of 25 µg/L for 12 months at -20ºC and 4ºC.

Conclusion: This DBS-Tg assay demonstrated good analytical performance over a wide range of Tg concentrations, suggesting it is well suited to detecting variations in Tg concentrations. Studies comparing populations with different prevalence of anemia should consider the effect of hematocrit on DBS-Tg determination. The availability of a DBS-Tg assay for newborns makes it possible to integrate iodine status monitoring with newborn screening for inherited metabolic diseases.

Patients with an inactive thyroid hormone (TH) transporter MCT8 (Allan-Herndon-Dudley Syndrome, AHDS) display severe neurological impairments and motor disabilities, indicating an indispensable function of MCT8 in facilitating TH access to the human brain. Consequently, the CNS of AHDS patients appears to be in a TH deficient state, which greatly compromises proper neural development and function. Another hallmark of this disease is that patients exhibit elevated serum T3 levels, leading to a hyperthyroid situation in peripheral tissues. Several treatment strategies have been developed and evaluated in preclinical mouse models as well as in patients. Here, we discuss these different therapeutic approaches to overcome MCT8 deficiency and summarize the current achievements and challenges in improving brain maturation in the absence of MCT8.

Objective: Poorly differentiated thyroid carcinomas (PDTCs) are rare and aggressive head and neck malignancies with a poor prognosis. Systemic treatment for incurable PDTC consists of multi-kinase inhibitors (MKIs) based on extrapolation from the experience with radioiodine refractory differentiated thyroid cancer (DTC). Cabozantinib is an approved second-line MKI therapy for DTC, but there are limited data regarding the safety and efficacy of cabozantinib for PDTC.

Methods: We conducted a single-institution, retrospective analysis of patients with PDTC who received cabozantinib in any line of therapy. Baseline demographics, disease characteristics, treatment history, toxicity, and clinical outcomes were abstracted from the electronic medical record. Median progression-free survival (PFS) and overall survival (OS) were primary endpoints and estimated using Kaplan-Meier methodology.

Results: Seven patients with PDTC who received cabozantinib were included. 4/7 (57%) patients had a partial response to cabozantinib, while 2/7 (29%) had stable disease (SD) as their best response. The median time on treatment for cabozantinib was 10.53 months. The median PFS from the start of cabozantinib was 12.9 months, and median OS was 14.21 months. Most adverse events to treatment (5/6) were low grade. Two (29%) patients were alive at the date of the last follow-up.

Conclusion: Cabozantinib is an effective and reasonably well-tolerated treatment option for patients with PDTC. Prospective studies are needed to further investigate the role of cabozantinib in the treatment of PDTC, alone and in combination with other agents, including checkpoint inhibitors.

Objective: Thyrotoxic periodic paralysis is a rare manifestation of thyrotoxicosis. Here, we describe the clinical and biochemical features and treatment outcomes of this disorder.

Methods: This retrospective study was conducted at a tertiary care centre in southern India. The clinical and biochemical features, treatment received, and therapeutic outcomes of all patients with thyrotoxicosis and acute flaccid paralysis without any other identifiable causes (cases for the study) were compared with an equal number of consecutively selected patients who presented with thyrotoxicosis but without features of paralysis (controls for the study) during the same period.

Results: In total, 41 cases and controls were included in this study. The proportion of males was 92.6% and 43.9% in the cases and controls, respectively. The mean age was 32.8 (±7.6) years (cases) and 39.7 (±11.3) years (controls). In the cases, 20% of patients presented without clinical thyrotoxic features. Graves' disease was the most common aetiology of thyrotoxicosis in both groups (92.6% of cases and 87.8% of controls). The prevalence of goitre was significantly higher among controls (90.2%) than among cases (53.7%). The mean serum potassium, free T4, total T4 and total T3 levels were significantly lower in the cases than in the controls. In these cases, two patients had an additional aetiology for persistent hypokalaemia, likely Gitelman's syndrome.

Conclusion: This is one of the largest series of thyrotoxic periodic paralysis cases in India. In subjects with thyrotoxicosis, serum potassium, free T4, total T4 and total T3 levels were significantly lower in those with periodic paralysis than in those without.

Objectives: When exposed to iodine contrast medium (ICM), thyroid dysfunction may develop, due to excess amounts of iodide. The incidence of contrast-induced thyroid dysfunction has been difficult to interpret, because of the observational and retrospective designs of most previous studies. With the Swedish CArdioPulmonary bioImage Study (SCAPIS), where randomly selected individuals aged 50-65 years, underwent contrast-enhanced coronary CT angiography (CCTA), we were able to prospectively assess the incidence, magnitude and clinical impact of contrast-induced thyroid dysfunction.

Methods: In 422 individuals, thyroid hormone levels were analysed before and 4-12 weeks after CCTA. Thyroid-related patient-reported outcome questionnaires (ThyPRO) at the time of pre and post-CCTA blood samplings were provided by 368 of those individuals. Thyroid peroxidase antibodies (TPOab) were analysed and an ultrasound of the thyroid gland was performed to detect any thyroid nodules.

Results: There was a small statistically significant effect on thyroid hormone levels but no cases of overt hypo- or hyperthyroidism after ICM. Subclinical hypo- or hyperthyroidism or isolated low/high levels of free thyroxine (fT4) developed in 3.5% of the population with normal hormone levels pre-CCTA but without any increased thyroid-related symptoms compared to the remaining cohort. Elevated TPOab and being born outside Sweden were risk factors for developing subclinical hypothyroidism. The presence of thyroid nodules was not associated with ICM-induced thyroid dysfunction.

Conclusion: The results of this prospective study support the notion that in iodine-sufficient countries, ICM-associated thyroid dysfunction is rare, usually mild, self-limiting and oligo/asymptomatic in subjects aged 50-65 years.

Objective: As thionamide is associated with various adverse effects, we re-evaluated the practical efficacy of potassium iodide (KI) therapy for Graves' hyperthyroidism (GD).

Methods: We administered KI (mainly 100 mg/day) to 324 untreated GD patients and added methimazole (MMI) only to those remaining thyrotoxic even at 200 mg/day. When the patient became hypothyroid, MMI, if taken was stopped, then levothyroxine (LT4) was added without reducing the KI dose. Radioactive iodine (RI) therapy or thyroidectomy was performed whenever required. We evaluated the early effects of KI at 2-4 weeks and followed patients for 2 years.

Results: At 2 weeks, serum thyroid hormone levels decreased in all 324 patients. At 4 weeks, fT4, fT3, and both fT4 and fT3 levels became normal or low in 74.7%, 50.6%, and 50.6% of patients, respectively. In a cross-sectional survey over 2 years, GD was well-controlled with KI or KI + LT4 (KI-effective) in >50% of patients at all time points. Among 288 patients followed for 2 years, 42.7% remained 'KI-effective' throughout the 2 years (KI Group), 30.9% were well-controlled with additional MMI given for 1-24 months, and 26.4% were successfully treated with ablative therapy (mainly RI). Among 'KI-effective' patients at 4 weeks, 76.5% were classified into the KI Group. No patients experienced adverse effects from KI.

Conclusion: KI therapy was useful in the treatment of GD. A sufficient dose of KI was effective in >50% of GD patients from 4 weeks to 2 years, and 42.7% (76.5% of 'KI-effective' patients at 4 weeks) remained 'KI-effective' throughout the 2 years.