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Open access

Benjamin Chevalier, Oriane Karleskind, Arnaud Jannin, Olivier Farchi, Catherine Vermaut, Alexandre Escande, Clio Baillet, Stéphanie Espiard, Marie-Christine Vantyghem, Bruno Carnaille, Emmanuelle Leteurtre, and Christine Do Cao

Introduction

Anaplastic thyroid carcinoma (ATC) is the most aggressive form of thyroid cancer with a bleak prognosis. Favorable outcomes are rare but help decipher molecular pathophysiology, investigate prognosis factors, and discover new therapeutic targets.

Case presentation

Two patients were diagnosed with locally advanced nonresectable ATC, one with metastatic extension. Each patient received chemotherapy and radiotherapy, allowing thyroid surgical resection. In both cases, the pathological examination was consistent with complete response with no viable tumor cells. After follow-ups of 48 and 70 months, both patients remain disease-free. Molecular explorations on thyroid biopsies revealed microsatellite instability (MSI) and alterations on mismatch repair–gene complex, also PTEN and ATM variants in both cases. Both also presented with non-classical immune infiltrate composed of equal parts T CD4+ lymphocytes and macrophages.

Conclusion

We report two cases of patients cured from advanced ATC and for the first time provide genetic and immunological explorations in this setting. It seems with these two cases that MSI-ATCs may indicate a better prognosis. Our study hypothesizes different responsible mechanisms including increased sensitivity to chemoradiotherapy and/or immune tumor infiltrate modulation.

Open access

Inês Damásio, Joana Simões-Pereira, Sara Donato, Mariana Horta, Branca Maria Cavaco, Miguel Rito, Pedro Gomes, and Valeriano Leite

Background

Anaplastic thyroid carcinoma (ATC) is one of the most aggressive solid tumors. ATC is frequently diagnosed at advanced stages with unresectable disease and palliative care is often indicated. Recently, several patient-tailored therapies for ATC are emerging due to advances in molecular profiling of these tumors. Entrectinib is a potent oral selective inhibitor of neutrotrophic tropomyosin receptor kinase (NTRK), ROS1, and anaplastic lymphoma kinase fusions. The experience regarding ATC and other thyroid carcinomas, particularly in the neoadjuvant setting, is minimal.

Case report

We present a case of a 51-year-old female patient presenting with a bulky mass of the left thyroid lobe measuring 100 × 108 × 80 mm that was considered surgically unresectable. While waiting for next-generation sequence (NGS) profiling, lenvatinib was initiated. There was an initial clinical and imagiologic response; however, progression occurred after 12 weeks, and at this time NGS identified an ETV6-NTRK3 fusion and entrectinib was started. After 12 weeks, tumor diameters reduced to a minimum of 68×60×49 mm, and the patient underwent total thyroidectomy plus central lymphadenectomy. Histological diagnosis confirmed an ATC (pT4a R2 N1a). Adjuvant radiotherapy (RT) (60 Grays) with weekly paclitaxel (45 mg/m2) was then administered followed by maintenance entrectinib 600 mg daily. Fluorodeoxyglucose positron emission tomography performed 3 months after completion of RT showed only non-specific uptake in the posterior wall of the hypopharynx and larynx, suggestive of inflammation.

Conclusion

We report the first case of an ATC with a dramatic response to neoadjuvant therapy with entrectinib, which enabled surgical resection of an ab initio unresectable tumor.

Open access

Eduardo Crespo Vallejo, Antonio Hermosin, Manuel Gargallo, Álvaro Villalba, Eduardo Daguer, José Flores, Javier Periañez, Joaquim Amorín, and Ernesto Santos

Objective

This study aimed to evaluate the safety and long-term efficacy using the multiple overlapping ablation technique with a novel non-cooled microwave system in benign symptomatic thyroid nodules.

Methods

This prospective cohort single-center study collected complication data from the start of the procedure to 30 days postoperatively and evaluated the safety and effectiveness with a follow-up of 24 months. Ultrasound examinations were performed to determine the volume shrinkage during follow-up. Thyroid function cosmetic and symptoms scores and satisfaction degree were evaluated.

Results

A total of 30 symptomatic benign thyroid nodules were treated by microwave ablation using a power between 15 and 30 W depending on the size of the nodule to be treated. The volume reduction rates in months 1, 3, 6, 9, 12, and 24 after ablation were 32, 59, 67, 69, 73, and 81%, respectively. The mean symptom score and mean cosmetic score before treatment were 4 and 3, respectively, while after treatment they dropped to 3 and 1, respectively. Thyroid function indicators fluctuated in the normal range and those with hyperthyroidism recovered to normal parameters. One case of temporary laryngeal paralysis occurred postoperatively and fully recovered in less than 3 months.

Conclusions

The novel microwave ablation system presented herein can help achieve good clinical success rate in benign thyroid nodules with a satisfying safety profile. The microwave ablation performed with the multiple overlapping ablation technique could be a good alternative to surgery and radiofrequency ablation in the management of benign thyroid nodules.

Open access

Simona Censi, Jacopo Manso, Teresa Benvenuti, Ilaria Piva, Maurizio Iacobone, Alberto Mondin, Francesca Torresan, Daniela Basso, Gino Crivellari, Stefania Zovato, and Caterina Mian

Objective

Calcitonin (Ct) represents the most important biochemical marker of medullary thyroid cancer (MTC), but has certain limits. We analyzed the performance of procalcitonin (ProCt) in follow-up MTC patients.

Methods

In this monocentric and retrospective study, we consecutively obtained ProCt and Ct values from all MTC patients that we visited during the period from April 2021 to May 2022. Patients were defined as having structural evidence of disease (29/90, 32.2%) irrespective of Ct values or, in its absence, as not evident disease (NED) if Ct was ≤10 ng/L (47/90, 52.2%), or minimal residual disease if Ct was >10 ng/L (14/90, 15.6%).

Results

Ct and ProCt values were highly correlated (r = 0.883, P < 0.01). Median ProCt values differed between NED, minimal residual disease, and structural disease, being 0.04 ng/mL, 0.26 ng/mL, and 1.98 ng/mL, respectively (P < 0.01). ProCt was undetectable (<0.04 ng/mL) in 40/47 (85.1%) of NED patients, in 3/14 (21.4%) patients with minimal residual disease and in none of the patients with a structural disease (P < 0.01). Among the 11 patients with detectable but ≤10 ng/L Ct and undetectable ProCt values, none had a structural disease. The most accurate cut-off of ProCt to distinguish between the presence or absence of a structural disease was >0.12 ng/mL (P < 0.01, area under the curve: 0.963), with the following sensitivity, specificity, positive predictive value, and negative predictive value (NPV): 100%, 83.61%, 74.4%, and 100.0%.

Conclusions

ProCt and Ct have a high correlation in MTC follow-up. ProCt may be useful as an adjunct to Ct, especially for its NPV concerning the structural disease.

Open access

Tomohiro Kikuchi, Shouhei Hanaoka, Takahiro Nakao, Yukihiro Nomura, Takeharu Yoshikawa, Ashraful Alam, Harushi Mori, and Naoto Hayashi

Objective

This study aimed to determine a standardized cut-off value for abnormal 18F-fluorodeoxyglucose (FDG) accumulation in the thyroid gland.

Methods

Herein, 7013 FDG–PET/CT scans were included. An automatic thyroid segmentation method using two U-nets (2D- and 3D-U-net) was constructed; mean FDG standardized uptake value (SUV), CT value, and volume of the thyroid gland were obtained from each participant. The values were categorized by thyroid function into three groups based on serum thyroid-stimulating hormone levels. Thyroid function and mean SUV with increments of 1 were analyzed, and risk for thyroid dysfunction was calculated. Thyroid dysfunction detection ability was examined using a machine learning method (LightGBM, Microsoft) with age, sex, height, weight, CT value, volume, and mean SUV as explanatory variables.

Results

Mean SUV was significantly higher in females with hypothyroidism. Almost 98.9% of participants in the normal group had mean SUV < 2 and 93.8% participants with mean SUV < 2 had normal thyroid function. The hypothyroidism group had more cases with mean SUV ≥ 2. The relative risk of having abnormal thyroid function was 4.6 with mean SUV ≥ 2. The sensitivity and specificity for detecting thyroid dysfunction using LightGBM (Microsoft) were 14.5 and 99%, respectively.

Conclusions

Mean SUV ≥ 2 was strongly associated with abnormal thyroid function in this large cohort, indicating that mean SUV with FDG–PET/CT can be used as a criterion for thyroid evaluation. Preliminarily, this study shows the potential utility of detecting thyroid dysfunction based on imaging findings.

Open access

Tamas Solymosi, Laszlo Hegedűs, Steen J. Bonnema, Andrea Frasoldati, Laszlo Jambor, Zsolt Karanyi, Gabor L. Kovacs, Enrico Papini, Karoly Rucz, Gilles Russ, and Endre V. Nagy

OBJECTIVE: Thyroid nodule ultrasound characteristics are used as indication for FNA, usually as the basis for Thyroid Imaging Reporting and Data System (TIRADS) score calculation. Few studies on inter-observer variation are available, all of which are based on analysis of preselected still ultrasound images and often lack surgical confirmation.

METHODS: After the blinded online evaluation of video-recordings of the ultrasound examinations of 47 consecutive malignant and 76 consecutive benign thyroid lesions, 7 experts from 7 thyroid centers answered 17 TIRADS-related questions. Surgical histology was the reference standard. Inter-observer variations of each ultrasound characteristic were compared using Gwet's AC1 inter-rater coefficients; higher values mean better concordance, the maximum being 1.0.

RESULTS: On a scale from 0.0 to 1.0, the Gwet's AC1 values were 0.34, 0.53, 0.72, 0.79 for the four most important features in decision making, i.e. irregular margins, microcalcifications, echogenicity and extrathyroidal extension, respectively. The concordance in the discrimination between mildly/moderately and very hypoechogenic nodules was 0.17. The smaller the nodule size the better the agreement in echogenicity, and the larger the nodule size the better the agreement on the presence of microcalcifications. Extrathyroidal extension, was correctly identified in just 45.8% of the cases.

CONCLUSIONS: Examination of video recordings, closely simulating the real-world situation, revealed substantial inter-observer variation in the interpretation of each of the four most important ultrasound characteristics. In view of the importance for management of thyroid nodules, unambiguous and widely accepted definitions of each nodule characteristic are warranted, although it remains to be investigated whether this diminishes observer-variation.

Open access

Ilaria Muller, Anita Daturi, Matteo Varallo, Tiziana E Re, Davide Dazzi, Sara Maioli, Erica Crivicich, Francesco Di Marco, Virgilio Longari, Beatrice Dazzi, Massimo Castellani, Giovanna Mantovani, Maura Arosio, and Mario Salvi

Objective: We have previously observed thyroid dysfunction, i.e. atypical thyroiditis (painless thyrotoxicosis associated to non-thyroidal illness syndrome), in patients with severe-acute-respiratory-syndrome-coronavirus-2 disease (Covid-19). This study aimed to analyse the evolution of thyroid dysfunction over time.

Methods: 183 consecutive patients hospitalised for severe Covid-19 without known thyroid history were studied at hospital admission (baseline). Survivors were offered 12-month longitudinal follow-up including assessment of thyroid function, autoantibodies and ultrasound scan (US). Patients showing US focal hypoechoic areas suggestive of thyroiditis (focal-hypoechogenicity) also underwent thyroid 99mTc or 123I uptake scan.

Results: At baseline, after excluding from TSH analysis 63 out of 183 (34%) Covid-19 patients commenced on steroids before hospitalisation, 12 (10%) showed atypical thyroiditis. Follow-up of 75 patients showed normalisation of thyroid function and inflammatory markers, and no increased prevalence of detectable thyroid autoantibodies. Baseline US (available in 65 patients) showed focal-hypoechogenicity in 28% patients, of whom 82% had reduced thyroid 99mTc/123I uptake. The presence of focal-hypoechogenicity was associated with baseline low TSH (p=0.034), high FT4 (p=0.018) and high IL-6 (p=0.016). Focal-hypoechogenicity persisted after 6 and 12 months in 87% and 50% patients, respectively, but reduced in size. After 9 months thyroid 99mTc/123I uptake partially recovered from baseline (+28%), but was still reduced in 67% patients.

Conclusions: Severe Covid-19 induces mild transient thyroid dysfunction correlating with disease severity. Focal-hypoechogenicity, associated with baseline high FT4, IL-6 and low TSH, does not seem to be related to thyroid autoimmunity and may persist after one year although decreasing in size. Long-term consequences seem unlikely.

Open access

Liliana Ribeiro Santos, Inês Vasconcelos Bessa, Adriana Gaspar da Rocha, Celestino Neves, Cláudia Freitas, and Paula Soares

Objective: Previous trials show that selenium could be a very useful tool in control and treatment of autoimmune thyroid diseases. In this cross-sectional study, through a survey, we aim to evaluate Portuguese endocrinologists' perception and pattern of prescription of selenium supplements in these diseases and verify its agreement with current guidelines.

Methods: The endocrinologists registered in the Portuguese Medical Association were sent an email with a web-based questionnaire, regarding their knowledge and use of selenium supplements in thyroid autoimmune pathology.

Results: A total of 105 physicians (33% of the total) submitted the survey. The selenium serum concentration in the general population was unknown to 80% of respondents. Over a third of respondents have never prescribed selenium in Autoimmune Thyroid Disease. However, 89% are not afraid of recommending it, and 61% indicate Graves’ Orbitopathy as the pathology they would supplement. In Hashimoto’s Thyroiditis, 36% of respondents use selenium occasionally or frequently, and this percentage rises to 60% in Graves’ Disease. Conclusions: Although recommendations only encompass mild Graves’ Orbitopathy, selenium is prescribed across the spectrum of autoimmune thyroid diseases, probably due to recent studies that consistently show improvement of biochemical hallmarks in these patients. Further investigation is required on the impact of selenium supplements on primarily clinical outcomes and to identify disorders and/or patients who will benefit the most. Also, there is still insufficient knowledge on this field in the medical community, and evidence-based practice should continue to be promoted by endocrinology societies.

Open access

Frédéric Flamant and Juan Ren

Thyroid hormones are known to trigger metamorphosis in amphibian. This review discusses the hypothesis according to which they act in a similar manner to synchronize the post-natal development of mice, using brain, brown adipose tissue and heart as examples.

Open access

Chantal A Lebbink, Thera P Links, Agnieszka Czarniecka, Renuka P Dias, Rossella Elisei, Louise Izatt, Heiko Krude, Kerstin Lorenz, Markus Luster, Kate Newbold, Arnoldo Piccardo, Manuel Sobrinho-Simões, Toru Takano, A S Paul van Trotsenburg, Frederik A Verburg, and Hanneke M van Santen

At present, no European recommendations for the management of pediatric thyroid nodules and differentiated thyroid carcinoma (DTC) exist. Differences in clinical, molecular, and pathological characteristics between pediatric and adult DTC emphasize the need for specific recommendations for the pediatric population. An expert panel was instituted by the executive committee of the European Thyroid Association including an international community of experts from a variety of disciplines including pediatric and adult endocrinology, pathology, endocrine surgery, nuclear medicine, clinical genetics, and oncology. The 2015 American Thyroid Association Pediatric Guideline was used as framework for the present guideline. Areas of discordance were identified, and clinical questions were formulated. The expert panel members discussed the evidence and formulated recommendations based on the latest evidence and expert opinion. Children with a thyroid nodule or DTC require expert care in an experienced center. The present guideline provides guidance for healthcare professionals to make well-considered decisions together with patients and parents regarding diagnosis, treatment, and follow-up of pediatric thyroid nodules and DTC.