Thyroid Research最新文献

Background: The discovery of driver oncogenes for thyroid carcinomas and the identification of genomically targeted therapies to inhibit those oncogenes have altered the treatment algorithm in thyroid cancer (TC), while germline testing for RET mutations has become indicated for patients with a family history of RET gene mutations or hereditary medullary TC (MTC). In the context of an increasing number of selective RET inhibitors approved for use, this paper aims to describe challenges and barriers affecting providers' ability to deliver optimal care for patients with RET-altered TC across the patient healthcare journey.

Methods: A mixed-method educational and behavioral needs assessment was conducted in Germany (GER), Japan (JPN), the United Kingdom (UK), and the United States (US) prior to RET-selective inhibitor approval. Participants included medical oncologists (MO), endocrinologists (EN) and clinical pathologists (CP) caring for patients affected with TC. Data collection tools were implemented in three languages (English, German, Japanese). Qualitative data were coded and thematically analyzed in NVivo. Quantitative data were analyzed via frequency and crosstabulations in SPSS. The findings presented here were part of a broader study that also investigated lung cancer challenges and included pulmonologists.

Results: A total of 44 interviews and 378 surveys were completed. Suboptimal knowledge and skills were self-identified among providers, affecting (1) assessment of genetic risk factors (56%, 159/285 of MOs and ENs), (2) selection of appropriate genetic biomarkers (59%, 53/90 of CPs), (3) treatment plan initiation (65%, 173/275 of MOs and ENs), (4) management of side effects associated with multitargeted tyrosine kinase inhibitors (78%, 116/149 of MOs and ENs), and (5) transfer of patients into palliative care services (58%, 160/274 of MOs and ENs). Interviews underscored the presence of systemic barriers affecting the use of RET molecular tests and selective inhibitors, in addition to suboptimal knowledge and skills necessary to manage the safety and efficacy of targeted therapies.

Conclusion: This study describes concrete educational needs for providers involved in the care of patients with RET-altered thyroid carcinomas. Findings can be used to inform the design of evidence-based education and performance improvement interventions in the field and support integration into practice of newly approved RET-selective inhibitors.

Purpose: Lacrimal gland enlargement can be a feature of thyroid eye disease (TED). Unilateral or asymmetric lacrimal gland enlargement is poorly described and may impede diagnosis. We present the histological and clinical findings of four patients with asymmetric lacrimal gland enlargement.

Methods: A retrospective case note review was performed for patients over two tertiary orbital clinics (Royal Adelaide Hospital, South Australia and the Sussex Eye Hospital, Brighton, United Kingdom) presenting with an asymmetrical lacrimal gland enlargement with a background of TED that underwent biopsy to exclude alternate diagnoses. Baseline data was collected for each patient and histopathological images and reports were reviewed.

Results: All four patients were hyperthyroid at time of lacrimal gland biopsy. Biopsy demonstrated nonspecific, lymphoid aggregates, typically of B cell type, with no diagnostic findings to support lymphocyte clonality or IgG4-related disease. One biopsy specimen demonstrated evidence of some fibrosis.

Conclusion: Asymmetrical lacrimal gland enlargement can occur as part of the TED spectrum but may require biopsy to exclude alternate pathology. Histology demonstrates a non-specific lymphocytic infiltrate.

Background: Papillary thyroid carcinoma (PTC) and follicular thyroid carcinoma (FTC) are common differentiated thyroid cancers, but the detection of a collision tumor is an extremely rare event.

Case presentation: The patient was a 69-year-old Japanese female with multiple cervical lymph node swellings and a thyroid tumor. Preoperative fine needle aspiration cytology of the enlarged lymph node revealed a cytological diagnosis of papillary thyroid carcinoma (PTC). A total thyroidectomy, right cervical dissection and paratracheal dissection were performed. Histopathological and immunohistochemical analyses of resected specimens revealed a collision tumor of PTC and FTC. Multiple metastases of papillary carcinoma were found in the dissected lymph nodes. In the PTC lesion, IHC for BRAF (V600E) was positive but negative for the FTC lesion. Genetic analyses further revealed a TERT promoter C228T mutation in PTC and a NRAS codon 61 mutation in FTC. The patient died of recurrent cancer 8 months after surgery.

Conclusions: A case of a collision tumor of PTC and FTC is very rare, and even fewer cases have been subjected to genetic scrutiny. The present case was successfully diagnosed by pathological examination using immunohistochemical and genetic analyses. The TERT promoter mutation in the PTC lesion was consistent with the aggressive behavior of the cancer.

Purpose: The aim of this study was to evaluate macular blood flow in patients with thyroid-associated orbitopathy (TAO) as compared to healthy subjects. The inflammatory nature of the disease, as well as the vascular congestion caused by the increase in the volume of orbital soft tissue and extraocular muscles, rationalize the assessment of retinal blood flow changes in these patients.

Methods: This is a cross-sectional study with the convenience sampling method. Macular flow density was assessed using optical coherence tomography angiography (OCTA) and compared between patients with TAO and healthy individuals. We also compared macular flow density in two subgroups of patients based on clinical activity score (CAS).

Results: Eighty-five cases, including 30 healthy individuals and 55 patients with TAO, participated. The foveal avascular zone (FAZ) area was significantly larger in the patient group than in the control. Patients with active TAO with CAS 3 or more had significantly larger FAZ areas than those with CAS less than 3 (p = 0.04).

Conclusion: We showed that the FAZ area is larger in active TAO patients and can be considered a possible candidate feature for monitoring disease activity and thyroid-associated vasculopathy.

The thyroid gland's neurovascular relationship is commonly portrayed as the recurrent laryngeal nerve (RLN) coursing posteriorly to the thyroid gland. We report a rare case with the RLN running anteriorly to a thyroid tumor. A 56-year-old Japanese woman underwent a thyroidectomy for a benign thyroid tumor. Preoperatively, computed tomography confirmed that part of the tumor had extended into the mediastinum and was descending posteriorly up to the brachiocephalic artery. Intraoperatively, when the sternothyroid muscle was incised to expose the thyroid gland, a cord (nerve)-like structure was observed directly anterior to the thyroid tumor. Although the course of this cord-like structure was clearly different from the "traditional" course of the right RLN, the possibility that the structure was the RLN could not be excluded. The structure was traced back in order to preserve it; we saw that it entered the larynx at the lower margin of the cricothyroid muscle and approximately at the level of the cricothyroid junction through the back of the normal thyroid tissue. With intraoperative neuromonitoring, the structure was identified as the RLN. As a result, the course of the RLN run anterior to the tumor but then posterior to the 'normal thyroid' i.e. into it normal anatomical position. Had we assumed that the RLN was behind the thyroid tumor, we would have damaged the RLN. It would not be possible to diagnose this abnormal running course of the RLN reliably before surgery, but extra care should be taken in similar cases, that is, when a large thyroid tumor is descending posteriorly up to the brachiocephalic artery on the right side.

Background: In the last decade, the combination of the widespread use of streptavidin-biotin technology and biotin-containing supplements (BCS) in the daily clinical practice, have led to numerous reports of erroneous hormone immunoassay results. However, there are no studies assessing the clinical and biochemical significance of that phenomenon, when treating patients with hypothyroidism. Therefore, a prospective study was designed to investigate the potential alterations in the measurement of thyroid hormone concentrations and clinical consequences in patients with hypothyroidism using low -dose BCS containing less than 300 μg/day.

Methods: Fifty-seven patients on thyroxine supplementation, as a result of hypothyroidism and concurrent use of BCS at a dose <300μg/day for 10 to 60 days were prospectively evaluated. Namely, TSH and free T4 (FT4) concentration measurements were performed, during BC supplementation and 10 days post BCS discontinuation and compared to 31 age-matched patients with supplemented hypothyroidism and without BCS.

Results: A statistically significant increase in TSH and decline in FT4 concentrations was observed after BCS discontinuation. However, on clinical grounds, these modifications were minor and led to medication dose adjustment in only 2/57 patients (3.51%) in whom TSH was notably decreased after supplement discontinuation.

Conclusion: Our study suggests that changes in thyroid hormones profiling, due to supplements containing low dose biotin, are of minimal clinical relevance and in most cases don't occult the need to adjust the thyroxine replacement dose in patients with hypothyroidism. Larger, well-designed trials are required to further evaluate this phenomenon.

Background: Thyroid hormones are of fundamental importance for brain function. While low triiodothyronine levels during acute ischemic stroke (AIS) are associated with worse clinical outcomes, dynamics of thyroid function after AIS remains unknown. Thus, we longitudinally evaluated thyroid hormones after stroke and related them to stroke severity.

Methods: We prospectively traced thyroid stimulating hormone (TSH), free triiodothyronine (fT3), and free thyroxin (fT4) levels from the hyper-acute (within 24 h) to acute (3-5 days) and chronic (3-6 months) stages of ischemic stroke using a mixed regression model. Then, we analyzed whether stroke severity at presentation, expressed by National Institute of Health Stroke Scale (NIHSS), is associated with change in thyroid function.

Results: Forty-five patients were evaluated in hyper-acute and acute stages, while 29 were followed through chronic stage. TSH levels decreased from hyper-acute (2.91 ± 0.65 μIU/mL) to acute (2.86 ± 0.46 μIU/mL) and chronic stages of stroke (1.93 ± 0.35 μIU/m, p = 0.95). fT3 levels decreased from hyper-acute (2.79 ± 0.09 pg/ml) to acute (2.37 ± 0.07 pg/ml) stages, but recovered in chronic stage (2.78 ± 0.10 pg/ml, p < 0.01). fT4 levels decreased from hyper-acute (1.64 ± 0.14 ng/dl) to acute (1.13 ± 0.03 ng/dl) stages, and increased in the chronic stage (1.16 ± 0.08 ng/dl, p = 0.02). One-unit increase in presenting NIHSS was associated with 0.04-unit decrease of fT3 from hyper-acute to the acute stage (p < 0.01).

Conclusion: There is a transient decrease of thyroid hormones after ischemic stroke, possibly driven by stroke severity. Larger studies are needed to validate these findings. Correction of thyroid function in acute stroke may be investigated to improve stroke outcomes.

Background: Thyroid cancer (TC) patients are understudied but appear to be at risk for poor physical and psychosocial outcomes. Knowledge of the course and determinants of these deteriorated outcomes is lacking. Furthermore, little is known about mediating biological mechanisms.

Objectives: The WaTCh-study aims to; 1. Examine the course of physical and psychosocial outcomes. 2. Examine the association of demographic, environmental, clinical, physiological, and personality characteristics to those outcomes. In other words, who is at risk? 3. Reveal the association of mediating biological mechanisms (inflammation, kynurenine pathway) with poor physical and psychological outcomes. In other words, why is a person at risk?

Design and methods: Newly diagnosed TC patients from 13 Dutch hospitals will be invited. Data collection will take place before treatment, and at 6, 12 and 24 months after diagnosis. Sociodemographic and clinical information is available from the Netherlands Cancer Registry. Patients fill-out validated questionnaires at each time-point to assess quality of life, TC-specific symptoms, physical activity, anxiety, depression, health care use, and employment. Patients are asked to donate blood three times to assess inflammation and kynurenine pathway. Optionally, at each occasion, patients can use a weighing scale with bioelectrical impedance analysis (BIA) system to assess body composition; can register food intake using an online food diary; and can wear an activity tracker to assess physical activity and sleep duration/quality. Representative Dutch normative data on the studied physical and psychosocial outcomes is already available.

Impact: WaTCh will reveal the course of physical and psychosocial outcomes among TC patients over time and answers the question who is at risk for poor outcomes, and why. This knowledge can be used to provide personalized information, to improve screening, to develop and provide tailored treatment strategies and supportive care, to optimize outcomes, and ultimately increase the number of TC survivors that live in good health.

Introduction: Papillary thyroid carcinoma (PTC) is the most common malignant lesion of the thyroid characterized by unique histological features like nuclear grooving, nuclear clearing, and intra-nuclear inclusions. However, nuclear grooves are observed even in benign thyroid lesions (BTL) like nodular goiter (NG), Hashimoto's thyroiditis (HT), and follicular adenoma (FA) resulting in diagnostic dilemma of the presence of PTC in such BTL. RET/PTC gene translocation is one of the most common oncogenic rearrangements seen in PTC, known to be associated with nuclear grooving. Among different types of RET/PTC translocations, RET/PTC1 and RET/PTC3 gene translocations are the most common types. These translocations have also been identified in many BTL like hyperplastic nodules and HT. Our study aimed to determine the frequency of nuclear grooving in BTL and evaluate their association with RET/PTC1 and RET/PTC3 gene translocation.

Methods: Formalin-fixed, paraffin-embedded (FFPE) tissue blocks of NG, HT, and FA were included in the study. The hematoxylin and eosin (H&E) stained sections were evaluated for the presence of nuclear grooving/high power field (hpf) and a scoring of 0 to 3 was used for the number of grooves. Sections of 10 μ thickness were cut and the cells containing the nuclear grooves were picked using Laser-Capture microdissection. About 20 to 50 such cells were microdissected in each of the cases followed by RNA extraction, cDNA conversion, realtime-polymerase chain reaction (RQ-PCR) for RET/PTC1 and RET/PTC3 gene translocation, and the findings were analyzed for statistical significance.

Results: Out of 87 BTL included in the study, 67 (77.0%) were NG, 12 (13.7%) were HT, and 8 (9.2%) were FA. Thirty-two cases (36.8%) had nuclear grooving with 18 out of 67 NG, 6 out of 12 HT, and all 8 cases of FA showing a varying number of nuclear grooves. A significant association between the number of nuclear grooves with RET/PTC gene translocation (p-value of 0.001) was obtained. A significant association of HT with RET/PTC gene translocation (p-value of 0.038) was observed. RET/PTC1 and RET/PTC3 translocation were seen in 5 out of 87 cases, with HT showing positivity in 2 and FA in 1 case for RET/PTC1 and HT in 1 and FA in 2 cases for RET/PTC3 gene translocation with 1 case of FA being positive for both RET/PTC1 and RET/PTC3 gene translocation.

Conclusions: The frequency of nuclear grooving among BTLs in our study was 36.8%. Our study shows, that when BTLs, show nuclear grooves, with an increase in the nuclear size, oval and elongated shape, favors the possibility of an underlying genetic aberration like RET/PTC gene translocation, which in turn supports the reporting pathologist to suggest a close follow up of the patients on seeing such nuclear features on cytology or histopathology sample, particularly in HT.