European Thyroid Journal最新文献

Background: Observational studies in adults suggest that incidental PTC (iPTC) and non-incidental PTC (niPTC) are distinct entities. We examine the incidence of iPTC in pediatric patients undergoing thyroidectomy for benign conditions and compare clinical and histopathologic findings, and outcomes, of iPTC with those of niPTC.

Methods: A retrospective chart review was conducted at the Children's Hospital of Philadelphia between August 2010 and February 2023 to identify pediatric patients who underwent thyroidectomy and were diagnosed with pT1a PTC.

Results: iPTC was identified in 23 of 453 (5.1%) patients undergoing thyroidectomy for benign conditions. Within a cohort of 66 patients diagnosed with pT1a PTC, 23 (34.8%) were classified as iPTC and 43 (65.2%) were classified as niPTC. Compared to niPTC, iPTC had a significantly smaller median greatest dimension (iPTC: 3 mm, niPTC: 7 mm, P < 0.001), a lower rate of lymphatic invasion (iPTC: 0%, niPTC: 60.5%, P < 0.001), and AJCC N1 disease (iPTC: 0%, niPTC: 55.8%, P < 0.001). Most iPTC (22 out of 23 (95.7%)) were classified as ATA pediatric low-risk, while six out of 43 (14.0%) niPTC were categorized as intermediate/high-risk. Patients with iPTC and niPTC were followed for a median of 3.3 and 5.7 years, respectively. There was no evidence of persistent or recurrent disease in any patient with iPTC during this time frame.

Conclusions: iPTC may be found in 5.1% of pediatric patients undergoing thyroidectomy for benign conditions. Similar to adults, iPTC in pediatric patients appears to be indolent with a minimal risk for invasive features and a low risk for persistent or recurrent disease. In contrast to iPTC, niPTC exhibits the potential for invasive behavior and should be regarded as a distinct entity.

Background: Persistent Graves' disease (GD) after total thyroidectomy is sporadic and may be explained by incomplete total thyroidectomy, GD in ectopic thyroid tissue (ETT) or struma ovarii.

Methods: We present a novel case of ectopic GD in a giant paracardiac mass, including an in-depth histologic exam. We searched the PubMed database on GD in ETT.

Results: A 34-year-old woman presented with severe thyrotoxicosis, 4 months after total thyroidectomy, and 6 weeks after cessation of levothyroxine substitution. Persistently high thyrotropin receptor antibodies (TSH-R-Ab) (27 IU/L, normal: <1.5 IU/L) and thyroglobulin >5,000 μg/L (normal: <77 μg/L) suggested GD in ETT. A 99mTc-pertechnetate SPECT/CT scan showed uptake in a paracardiac mass. After surgical removal of the 13 cm paracardiac mass, euthyroidism was achieved. Histology was typically remarkable for a Graves' pattern in the ETT, as opposed to a nodular pattern in the eutopic thyroid. The additional scoping review encompasses 29 reported ETT cases, of which only 11 were in the mediastinum. Graves' eye disease was present in 11/29 subjects.

Conclusion: This is the first report showing a markedly different histology between the thyroid and the ectopic tissue. Persistent systemic severe GD post-thyroidectomy led to the detection of a giant paracardiac ectopic thyroid. GD in ETT is rare and presents a diagnostic challenge.

Objectives: In thyroid cancer with marked laryngotracheal invasion, life-threatening airway stenosis necessitates urgent procedures such as extensive curative surgery, tracheostomy, stenting, or laser bronchoscopy. These interventions are invasive and may significantly compromise quality of life. In anaplastic thyroid cancer (ATC), the delay during genetic testing turnaround time before initiating targeted therapy poses an additional therapeutic challenge. This study aimed to assess lenvatinib (LEN) as an initial and bridging treatment to rapidly alleviate airway stenosis and avoid emergency invasive interventions.

Methods: This retrospective study analyzed 14 patients with remarkable laryngotracheal invasion among 69 thyroid cancer patients treated with multikinase inhibitor(s). All 14 patients received LEN as first-line or post-paclitaxel treatment. Response was assessed by CT imaging per RECIST 1.1, with particular attention to changes in tumor size and airway diameter. Symptom improvement and adverse events, such as fistula formation, were also recorded.

Results: Of the 14 patients, 13 showed tumor reduction and airway improvement on initial CT post-LEN induction. Median response rate was 28.4%, with airway diameter improving by 15.9% on the initial CT. Airway symptoms resolved in a median of 3 days. One patient developed a tumor-tracheal fistula, managed with LEN dose adjustment. LEN was also successfully used as a bridging therapy before BRAF-targeted treatment in ATC cases.

Conclusions: Initial LEN therapy rapidly alleviates airway stenosis in advanced thyroid cancer with laryngotracheal invasion, offering a non-invasive alternative to emergency procedures under careful monitoring for fistula formation. LEN is especially valuable as a bridging therapy during the genetic testing period in ATC.

Background: Nuclear protein in testis (NUT) carcinomas are aggressive, poorly or undifferentiated cancers, generally arising from midline structures. This subtype of squamous cell carcinoma is rare and has a poor prognosis. NUT cancers are defined by NUTM1 fusions. Rearrangements of the NUTM1 gene have rarely been described in primary thyroid cancer and are mainly reported in patients ≤45 years old. NSD3::NUTM1 translocation is the most common NUTM1 fusion transcript reported in thyroid cancer. As they are very infrequent, NUTM1 fusions are not routinely sought in poorly differentiated thyroid cancer (PDTC) or anaplastic thyroid cancer (ATC).

Case presentation: We report two PDTC patients >65 years old with locally advanced disease and 18FDG-avid distant metastases. NSD3::NUTM1 translocation was evidenced in both patients by RNA sequencing using the next-generation sequencing panel of our institution.

Conclusion: We suggest including the search for NUTM1 fusions in the RNA sequencing panel for advanced and refractory thyroid cancers.

Objective: Thyrotoxic periodic paralysis (TPP) is a rare but potentially lethal complication of thyrotoxicosis. Absence of large cohorts limits the conduct of epidemiology studies. We aimed to establish a population-based registry of thyrotoxicosis and TPP in Hong Kong and evaluate their trend.

Methods: We developed algorithms to identify thyrotoxicosis and TPP cases from a representative electronic medical database in Hong Kong. Of the potential cases (thyrotoxicosis:83,184; TPP:999), we reviewed clinical notes and laboratory test records of 200 randomly selected cases. Population-based registries of thyrotoxicosis and TPP were subsequently established. Their standardized incidence rate, TPP-associated hospitalization rate, length of stay (LOS), and trends from 2002 to 2021 were evaluated.

Results: Positive predictive values for thyrotoxicosis and TPP were 0.86-0.97, respectively, enabling establishment of population-based cohorts of incident thyrotoxicosis (n = 77,856) and TPP (n = 994). Age- and sex-standardized incidence rate (per 100,000 person-years) of thyrotoxicosis increased from 41.31 in 2002 to 69.51 in 2021 (average annual percentage change: 4.77%), with a similar trend observed in both sexes. TPP patients were predominantly male (93.66%). In 2002 and 2021, the age-standardized incidence rate (per 100,000 person-years) of TPP in males was 1.43 and 1.18, respectively, while that in females was 0.11 and 0.13, without a significant trend observed. TPP-associated hospitalization rate (90.91-100%) and median LOS (2-3 days) were steady across the two decades.

Conclusion: This is the first study establishing a TPP cohort based on validated clinical data from an electronic medical database. It is important to keep monitoring the increasing incidence rate of thyrotoxicosis.

Graves' orbitopathy (GO) is characterized by orbital inflammatory infiltration, expansion of orbital tissues due to de novo adipogenesis and over-production of hydrophilic glycosaminoglycans, as well as myofibroblastic differentiation resulting in tissue fibrosis. Thyrotropin receptor antibody (TSH-R-Ab) is the major stimulus, which activates thyrotropin receptor (TSH-R)/insulin-like growth factor-1 receptor (IGF-1R) and its downstream signalling in orbital fibroblasts (OF). Clinical evaluation of TSH-R-Ab, the specific biomarker of Graves' disease (GD) and the associated orbitopathy, provides important clinical information concerning diagnosis, disease monitoring and prognosis of GO. TSH-R/IGF-1R crosstalk represents the principal mechanism of activation of OF, the key effector cells in GO. T cells and monocytes/macrophages predominate in the inflammatory infiltrates and B-T cell co-stimulation results in mutual activation. Mast cell-derived products also activate OF. In the presence of various pro-inflammatory molecules, activated OF and lymphocytes perpetuate orbital inflammation and mediate tissue remodelling. Enhanced oxidative stress drives various pathological processes in GO and many antioxidant agents have shown inhibitory effects on OF. Highly differential gene and protein expression exists between GO and normal subjects, as well as between active/severe and inactive/mild GO, providing important insights into the disease mechanisms. The lack of confirmed genetic susceptibility to GO development suggests that epigenetic mechanisms (e.g. DNA methylation and microRNAs) may play a role in regulating gene and protein expression, and hence disease phenotypes. The gut microbiome differs significantly between GO patients and healthy individuals. Modifying gut microbiota in GO animal models improves GO. Emerging evidence indicates that hypercholesterolaemia is associated with increased risk of developing GO, while statin use is a protective factor.

Objective: Iodine deficiency (ID) causes a wide range of health issues, from endemic goiter to more subtle effects resulting from reduced thyroid hormone production. The recommended daily iodine intake for adolescents and adults is 150 μg, which corresponds to a median urinary iodine concentration (UIC) of 100-299 μg/L at the population level. Individuals with anorexia nervosa typically suffer from deficiencies in micronutrients and vitamins, but there is little data on iodine status. This study assessed UIC and associated factors in a cohort of patients with anorexia nervosa.

Methods: This was a prospective monocentric exploratory observational study performed at the Centre Vaudois anorexie boulimie (abC) and the Division interdisciplinaire de santé des adolescents (DISA) of the Centre Hospitalier Universitaire Vaudois, University of Lausanne, Switzerland. The study included 39 patients with anorexia nervosa, aged ≥14 years, recruited between May and August 2022. After obtaining informed consent, anthropometric data were extracted from the electronic medical record and random spot urine samples were collected. The UIC was determined by ion-chromatography mass spectrometry.

Results: Median age (IQR) was 18 (14-62) years and median body mass index (BMI) was 17.72 (14.86-23.54) kg/m2. Median UIC was 67.7 μg/L, and 22/39 individuals had a UIC <100 μg/L. There was a positive correlation between BMI and UIC (P = 0.047).

Conclusion: The findings suggest that patients with anorexia nervosa are at risk of ID, and lower BMI predicts lower UIC. Although these data need to be corroborated in a larger cohort, clinicians caring for patients with anorexia should consider recommending an iodine-containing multivitamin.

Abstract: Apalutamide, a selective androgen receptor antagonist, is a new treatment for prostate cancer. Among the side effects observed during apalutamide treatment, an increased risk of hypothyroidism has been reported, particularly in patients previously treated with levothyroxine compared with untreated patients. Apalutamide is thought to stimulate hepatic UDP-glucuronosyltransferase activity, resulting in increased clearance and stimulation of the thyroxine enterohepatic cycle. A 65-year-old man on 150 μg/day levothyroxine treatment after total thyroidectomy for Graves' disease was euthyroid. Treatment with apalutamide (240 mg/day) was started for metastatic prostate neoplasia. After 1 month, the TSH level was 47.9 μIU/mL, and the dose of levothyroxine was gradually increased. In the presence of refractory hypothyroidism (TSH 38 μIU/mL) despite 275 μg/day of levothyroxine (3.25 μg/kg/d), a levothyroxine absorption test was performed: the basal concentration of total T4 was 5.8 μg/dL; after oral absorption of 1,000 μg of levothyroxine, total T4 concentration increased, peaking at 8.1 μg/dL after 2 h. The percentage absorption of levothyroxine was 27.1% (normal: >60%). After 14 h, total T4 concentration fell to 5.7 μg/dL before rising again to 8.5 μg/dL at 20 h. In the absence of further levothyroxine intake, the second peak of total T4 concentration may be related to stimulation of UDP-glucuronosyltransferase activity, with increased T4 solubility in the bile, released into the small intestine, and finally absorbed, with increased T4 concentration at 20 h in the patient, attesting to the stimulated T4 enterohepatic cycle during apalutamide treatment. Overall, the result of this clinical study suggests that apalutamide reduces the digestive absorption of levothyroxine, in addition to stimulating the activity of hepatic UDP-glucuronosyltransferase, explaining the higher prevalence of hypothyroidism during apalutamide treatment in patients previously treated with levothyroxine.