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Roberto Negro Division of Endocrinology, V. Fazzi Hospital, Lecce, Italy

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Roberto Attanasio Endocrine Unit, Galeazzi Orthopedic Institute IRCCS, Milan, Italy

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Endre V. Nagy Division of Endocrinology, Department of Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

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Enrico Papini Department of Endocrinology and Metabolism, Ospedale Regina Apostolorum, Rome, Italy

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Petros Perros Department of Endocrinology, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom

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Laszlo Hegedüs Department of Endocrinology and Metabolism, Odense University Hospital, Odense, Denmark

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Background: The incidence and prevalence of hypothyroidism are increasing and the threshold for the treatment of hypothyroid as well as individuals without evident thyroid disease with thyroid hormone is declining. Objective: To investigate endocrinologists’ use of thyroid hormones in hypothyroid and euthyroid patients in Italy, a country where different formulations of levothyroxine (LT4; tablet, liquid solution and soft-gel capsule) are available on the market. Methods: Members of the Associazione Medici Endocrinologi (Italian Association of Clinical Endocrinologists) were invited to participate in a web-based survey investigating the topic. Results: A total of 797 of 2,028 (39.3%) members completed all the sections of the survey; 98.7% declared that the treatment of choice for hypothyroidism is LT4. A significant minority (37.3%) indicated that LT4 may be considered in infertile euthyroid women seeking pregnancy and harbouring positive thyroperoxidase antibodies (TPOAb) and in goitre increasing in size (18.1%). LT4 + LT3 was considered by 43.2% for LT4-replaced patients and normal TSH, if they reported persistent symptoms. High percentages of respondents chose LT4 in a liquid solution or soft-gel capsules when taken together with other drugs interfering with LT4 absorption (81.8%), in patients with a history of celiac disease, malabsorption, lactose intolerance, intolerance to common excipients (96.6%), or unexplained poor biochemical control of hypothyroidism (74.4%), or in patients not able to adhere to ingesting LT4 fasted and/or separated from food/drink (98.9%). In total, 43.6% of responders would use LT4 in a liquid solution or soft-gel capsules for hypothyroid patients with biochemical euthyroidism on LT4, who had persistent symptoms. Conclusions: The preferred treatment for hypothyroidism is LT4; LT3 + LT4 combination treatment is mainly considered in patients with persistent symptoms. A significant minority would offer LT4 to euthyroid women with positive TPOAb and infertility and to euthyroid patients with progressive simple goitre. Alternative LT4 formulations like liquid solution or soft-gel capsules are largely reserved for specific conditions (interfering drugs, actual or suspected malabsorption, inability to take LT4 in the fasting state, unexplained poor biochemical control of hypothyroidism).

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Tamas Solymosi Endocrinology and Metabolism Clinic, Bugat Hospital, Gyöngyös, Hungary

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Laszlo Hegedüs Department of Endocrinology and Metabolism, Odense University Hospital, Odense, Denmark

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Steen Joop Bonnema Department of Endocrinology and Metabolism, Odense University Hospital, Odense, Denmark

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Andrea Frasoldati Endocrinology Unit of Arcispedale S. Maria Nuova, Reggio Emilia, Italy

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Laszlo Jambor Department of Radiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

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Gabor Laszlo Kovacs 1st Department of Medicine, Flohr Ferenc Hospital, Kerepestarcsa, Hungary

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Enrico Papini Regina Apostolorum Hospital in Albano, Rome, Italy

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Karoly Rucz 1st Department of Medicine, University of Pecs, Pecs, Hungary

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Gilles Russ Unité Thyroïde et Tumeurs Endocrines – Pr Leenhardt Hôpital La Pitie Salpetriere, Sorbonne Université, Paris, France

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Zsolt Karanyi Division of Endocrinology, Department of Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

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Endre V. Nagy Division of Endocrinology, Department of Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

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Background: Thyroid nodule image reporting and data systems (TIRADS) provide the indications for fine-needle aspiration (FNA) based on a combination of nodule sonographic features and size. We compared the TIRADS-based recommendations for FNA with those based on the personal expertise of qualified US investigators in the diagnosis of thyroid malignancy. Methods: Seven highly experienced ultrasound (US) investigators from 4 countries evaluated, online, the US video recordings of 123 histologically verified thyroid nodules. Technical resources provided the operators with a diagnostic approach close to the real-world practice. Altogether, 4,305 TIRADS scores were computed. The combined diagnostic potential of TIRADS (TIRSYS) and the personal recommendations of the investigators (PERS) were compared against 3 possible goals: to recognize all malignant lesions (allCA), nonpapillary plus non-pT1 papillary cancers (nPnT1PCA), or stage II-IV cancers (st2-4CA). Results: For allCA and nPnT1PCA, TIRSYS had lower sensitivity than PERS (69.8 vs. 87.2 and 83.5 vs. 92.6%, respectively, p <0.01), while in st2-4CA the sensitivities were the same (99.1 vs. 98.6% and TIRSYS vs. PERS, respectively). TIRSYS had a higher specificity than PERS in all 3 types of cancers (p < 0.001). PERS recommended FNA in a similar proportion of lesions smaller or larger than 1 cm (76.9 vs. 82.7%; ns). Conclusions: Recommendations for FNA based on the investigators’ US expertise demonstrated a better sensitivity for thyroid cancer in the 2 best prognostic groups, while TIRADS methodology showed superior specificity over the full prognostic range of cancers. Thus, personal experience provided more accurate diagnoses of malignancy, missing a lower number of small thyroid cancers, but the TIRADS approach resulted in a similar accuracy for the diagnosis of potentially aggressive lesions while sparing a relevant number of FNAs. Until it is not clearly stated what the goal of the US evaluation is, that is to diagnose all or only clinically relevant thyroid cancers, it cannot be determined whether one diagnostic approach is superior to the other for recommending FNA.

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Karoly Rucz K Rucz, Department of Endocrinology, Siofok Hospital, Siofok, Hungary

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Laszlo Hegedus L Hegedus, Department of Endocrinology, , Odense University Hospital, Odense, Denmark

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Steen Joop Bonnema S Bonnema, Department of Endocrinology, , Odense University Hospital, Odense, Denmark

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Andrea Frasoldati A Frasoldati, Endocrinology Unit , Arcispedale S Maria Nuova, Reggio Emilia, Italy

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Laszlo Jambor L Jambor, Department of Radiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

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Gabor Laszlo Kovacs G Kovacs, 1st Department of Medicine, Flohr Ferenc Hospital, Kistarcsa, Hungary

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Enrico Papini E Papini, Regina Apostolorum Hospital in Albano, Rome, Italy

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Gilles Russ G Russ, Unité Thyroïde et Tumeurs Endocrines - Pr Leenhardt Hôpital La Pitie Salpetriere, Sorbonne Université, Paris, France

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Zsolt Karanyi Z Karanyi, Faculty of Medicine, Department of Medicine, University of Debrecen, Debrecen, 4010, Hungary

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Endre V. Nagy E Nagy, Division of Endocrinology, Department of Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

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Tamas Solymosi T Solymosi, Division of Endocrinology, Department of Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

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Objective. The ultrasound evaluation of thyroid nodules (TN) in patient selection for fine needle aspiration (FNA) requires both uniformly accepted definitions of each nodule characteristic and extensive experience of the examiner. We hypothesized that nodule echogenicity alone may provide comparable performance to the more complex approaches, in patient selection for FNA.

Patients and Methods. Seven highly experienced investigators from four countries evaluated, online, the ultrasound (US) video recordings of 123 histologically verified TN, by answering 17 nodule characteristics-related questions. The diagnostic performances of five TN image reporting and data systems (TIRADS) were compared to making decisions based alone on echogenicity of the nodule, for indicating FNA in 110 nodules ≥10 mm.

Results. In the 10 to 20 mm size range, the sensitivities and specificities of the five TIRADS systems in identifying malignant nodules was 80.5%-91.0%, and 31.4-50.9%, respectively. Had FNA been recommended in all hypoechoic nodules, disregarding other US characteristics, comparable sensitivity and specificity (87.5% and 43.4%, respectively) were obtained. Compared to nodules >20mm, a higher proportion of cancers were hypoechoic in the 10 to 20 mm size range (87.2% vs. 77.8%, p=0.05). In the 10-20 mm size range, compared to hypoechoic nodules, a significantly lower proportion of isoechoic nodules demonstrated suspicious findings (70.7% vs. 30.0%, p<0.05).

Conclusion. In contrast to >20 mm diameter nodules, the recommendation of FNA may rely on a single US feature, echogenicity, in the 10-20 mm size range. If independently confirmed in larger cohorts, this may simplify nodule evaluation in this size range.

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Annamaria Erdei Division of Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

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Annamaria Gazdag Division of Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

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Bernadett Ujhelyi Department of Ophthalmology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

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Edit B Nagy Division of Radiology and Imaging Science, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

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Ervin Berenyi Division of Radiology and Imaging Science, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

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Eszter Berta Division of Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

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Zita Steiber Department of Ophthalmology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

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Sandor Barna Division of Nuclear Medicine, Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

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Emese Mezosi First Department of Internal Medicine, University of Pecs Medical School, Pecs, Hungary

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Miklos Bodor Division of Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

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Endre V Nagy Division of Endocrinology, Department of Internal Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

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Introduction

Dysthyroid optic neuropathy (DON) is a rare, severe form of thyroid eye disease, in which decreased visual acuity is accompanied by characteristic MRI findings. The treatment of DON has always been a challenge.

Case presentation

In a patient in whom visual acuity deteriorated on the left eye, mannitol 20% 200 mL followed by furosemide 40 mg 6 h later, administered daily, were initiated on the day of admission. Visual function by ophthalmology methods, and orbital compartment volumes and water content by MRI were followed. Intravenous diuretics resulted in an immediate therapeutic response. Visual acuity improved from 20/50 to 20/25 after 2 days of treatment. MRI revealed decreasing water content of both the muscle and connective tissue compartments without any volume changes. Subsequently, corticosteroids and orbital irradiation were started. Orbital decompression surgery was not required.

Discussion/conclusion

Edematous swelling of orbital tissues is an established contributor of local pressure increase in thyroid eye disease. Diuretics reduce orbital pressure and, if confirmed by others, may be useful additions to the standard of care in sight-threatening DON.

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Tamas Solymosi Endocrinology and Metabolism Clinic, Bugat Hospital, Gyöngyös, Hungary
Division of Endocrinology, Department of Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

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Laszlo Hegedűs Department of Endocrinology, Odense University Hospital, Odense, Denmark

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Steen J Bonnema Department of Endocrinology, Odense University Hospital, Odense, Denmark

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Andrea Frasoldati Endocrinology Unit of Arcispedale S Maria Nuova, Reggio Emilia, Italy

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Laszlo Jambor Department of Radiology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

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Zsolt Karanyi Division of Endocrinology, Department of Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

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Gabor L Kovacs 1st Department of Medicine, Flohr Ferenc Hospital, Kistarcsa, Hungary

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Enrico Papini Regina Apostolorum Hospital in Albano, Rome, Italy

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Karoly Rucz 1st Department of Medicine, University of Pecs, Pecs, Hungary

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Gilles Russ Unité Thyroïde et Tumeurs Endocrines – Pr Leenhardt Hôpital La Pitie Salpetriere, Sorbonne Université, Paris, France

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Endre V Nagy Division of Endocrinology, Department of Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Hungary

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Objective

Thyroid nodule ultrasound characteristics are used as an indication for fine-needle aspiration cytology, usually as the basis for Thyroid Imaging Reporting and Data System (TIRADS) score calculation. Few studies on interobserver 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. Interobserver 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, and 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 interobserver variation in the interpretation of each of the four most important ultrasound characteristics. In view of the importance for the 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.

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