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  • Author: Enrico Papini x
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Laszlo Hegedüs Department of Endocrinology and Metabolism, Odense University Hospital, Odense, Denmark

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

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

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Enrico Papini Division of Endocrinology, Regina Apostolorum Hospital, Albano Laziale, Italy

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Objective: Image-guided interventional ultrasound (US) techniques represent diagnostic and therapeutic tools for non-surgical management of thyroid nodular disease. We sought to investigate the attitude of European Thyroid Association (ETA) members towards the use of minimally invasive techniques (MIT) in diagnosis/therapy of symptomatic nodular goitre. Methods: ETA members were invited to participate in an online survey investigating the use of MIT in benign and malignant thyroid nodular disease. Of 865 invited members, 221 (25.5%) completed the survey. The respondents were from 40 countries; 139 (74.7%) were from European countries. Results: Respondents personally performed thyroid US (91.6%), Fine needle aspiration (FNA; 75.3%), ethanol ablation (EA; 22.1%), core needle biopsy (CNB; 11%) and thermal treatments (4.8%). When skills and/or technology were unavailable, only 13.4% referred patients “often” or “always” to other centres with specific expertise in this field. Surgery was the preferred first option in patients with recurrent cysts, 4.0 cm benign nodules, local (radioiodine-avid or non-avid) lymph node metastases, or papillary cancers <1.0 cm. For autonomously functioning nodules radioactive iodine treatment was the preferred choice, followed by surgery. Thermal ablation (TA) was the preferred option only for a 4 cm benign nodule in old patients with comorbidities. Conclusions: US, US-guided FNA and surgery were available to nearly all respondents, while MIT was not. CNB and EA were employed only by about 1/3 of the respondents and TA procedures were available and personally performed only by a minority. For most thyroid lesions, surgery was the preferred option versus thermal therapies. The ETA needs to develop guidelines and establish teaching to overcome geographic inequality and promote the use of MIT as a valid therapy option in appropriate cases.

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

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Hervé Monpeyssen Thyroid Unit, American Hospital, Paris, France

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Andrea Frasoldati Department of Endocrinology and Metabolism, Arcispedale Santa Maria Nuova IRCCS-ASL, Reggio Emilia, Italy

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

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Standard therapeutic approaches for benign thyroid lesions that warrant intervention are surgery for cold and either surgery or radioiodine for autonomously functioning thyroid nodules (AFTN). Image-guided thermal ablation (TA) procedures are increasingly proposed as therapy options for selected clinical conditions. Due to mounting scientific evidence and widening availability, ETA considered it appropriate to develop guidelines for the use of TA in adult patients. TA procedures are well tolerated, but a dedicated training of the operators is required and information on possible complications needs to be shared with the patients. The following factors should be considered when weighing between observation, surgery, and TA for benign thyroid nodules. In solid non-hyperfunctioning nodules, TA induces a decrease in thyroid nodule volume, paralleled by improvement in symptoms. Nodule re-growth is possible over time and may necessitate repeat treatment, or surgery, in a dialogue with the patient. In AFTN, radioactive iodine is the first-line treatment, but TA may be considered in young patients with small AFTN due to higher probability of restoring normal thyroid function and avoidance of irradiation. In cystic nodules, ethanol ablation (EA) is the most effective and least expensive treatment. TA may be considered for cystic lesions that relapse after EA or have a significant residual solid component following drainage and EA. TA should be restricted to benign lesions that cause symptoms or cosmetic concern. Presently, laser and radiofrequency ablation are the most thoroughly assessed techniques, with similar satisfactory clinical results. Microwaves and high-intensity focused ultrasound therapy options remain to be fully evaluated.

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

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

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Roberto Attanasio Endocrine Unit, IRCCS Istituto Galeazzi, Milan, Italy

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

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Kristian H. Winther Department of Endocrinology and Metabolism, Odense University Hospital, Odense, Denmark

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Objective: Selenium (Se) supplementation has been suggested in the treatment of Graves’ disease (GD). We sought to investigate Se prescription patterns for GD across European countries. Methods: Members of the European Thyroid Association were invited to participate in an online survey investigating the use of Se in GD either without or with orbitopathy (GO). Of 872 invited members, 244 (28%) completed the survey. After exclusion of basic scientists and non-European members, 197 responses were retrieved out of clinical trials (nearly half of clinician members), of whom 61 do not use Se. Thus, 136 respondents remained for further analyses. Results: Among the 136 analyzed respondents, most (64.7%) were not aware of the Se status in their populations, did not assess Se levels (78.7%), nor considered iodine status (74.3%). In GD without GO, 38.2% recommend Se supplementation (“sometimes” [27.2%], “frequently” [5.9%] or “always” [5.1%]). When GO occurs, 94.1% recommend Se supplementation (“sometimes” [39%], “frequently” [30.1%] or “always” [25%]). Of these, 60.1% recommend Se as an alternative to watchful waiting in patients with mild ocular involvement and 44.9% as an adjuvant to the established treatment modalities in patients with moderate to severe ocular involvement. Conclusions: In Graves’ hyperthyroidism without GO, 38.2% of ETA (European Thyroid Association) members recommend Se supplementation. Conversely, Se is recommended by the majority of respondents in GO, both in patients with mild and moderate to severe ocular involvement. This clinical practice is partially in disagreement with current European treatment guidelines that recommend Se as a 6-month treatment in mild GO only.

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Kristian Hillert Winther Department of Endocrinology and Metabolism, Odense University Hospital, Odense, Denmark

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

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

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

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

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Objective: To investigate clinical practice regarding the use of selenium supplementation in patients with Hashimoto’s thyroiditis (HT) among members of the European Thyroid Association (ETA). Methods: ETA members were invited to participate in an online survey investigating the use of selenium supplementation across the spectrum of benign thyroid diseases. Of 872 invited members, 242 (28%) completed the survey. After exclusion of basic scientists and non-European members, survey data from 212 respondents were eligible for further analyses. Responses from 65 (31%) individuals who did not at all recommend selenium, or only considered its use in the setting of a clinical trial, were not included in the final analysis of survey data from 147 respondents. ­ Results: While only a minority of respondents (29 of 147, 20%) stated that the available evidence warrants the use of Se in patients with HT, a statistically significant majority (95 of 147; 65%, p < 0.001) used Se occasionally or routinely. Se was predominantly recommended for patients with HT not receiving LT4 (102 of 147; 69%) to reduce circulating thyroid autoantibody levels. Very few respondents routinely recommended Se to pregnant patients with HT. Conclusions: A minority of responding ETA members stated that the available evidence warrants the use of Se in HT, but a majority recommended it to some extent, especially to patients not yet receiving LT4. This is questionable, and selenium is not recommended to patients with HT according to current ETA guidelines. Ongoing and future trials may lead to the reversal of current medical practice.

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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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Roberto Negro Division of Endocrinology, ‘V. Fazzi' Hospital, Lecce

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Roberto Attanasio Endocrinology Service, Galeazzi Institute IRCCS, Milan

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Franco Grimaldi Endocrinology and Metabolic Disease Unit, Azienda Ospedaliero-Universitaria ‘S. Maria della Misericordia', Udine

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Claudio Marcocci Department of Clinical and Experimental Medicine, University of Pisa, Pisa

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Rinaldo Guglielmi Department of Endocrinology, Regina Apostolorum Hospital, Albano Laziale, Italy

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Enrico Papini Department of Endocrinology, Regina Apostolorum Hospital, Albano Laziale, Italy

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Background: Selenium (Se) is a trace element that plays key roles in thyroid physiology. Se deficiency is associated with increased risk of thyroid disease. Some evidence suggests that Se supplementation may be beneficial in autoimmune thyroid disease (either hypo- or hyperthyroidism). Objectives: We sought to examine the use of Se in daily clinical practice among Italian endocrinologists. Methods: Members of the Associazione Medici Endocrinologi (AME) were invited to participate in a web-based survey investigating the use of Se in different clinical conditions. Results: A total of 815 individuals (43.2% of AME members) participated in the survey, 778 of whom completed all of the sections. Among these respondents, 85.2% considered using Se for thyroid disease (58.1% rarely/occasionally and 27.1% often/always), and 79.4% prescribed Se for chronic autoimmune thyroiditis (AIT) (39.1% sometimes and 40.3% often/always). About two thirds of the respondents considered Se use in cases of subclinical autoimmune hypothyroidism, and about 40% had suggested Se use for patients with AIT who were planning pregnancy or already pregnant. About one fourth of the respondents had used Se for mild Graves' orbitopathy. Regarding the suggested daily dosage of Se, 60% of the respondents answered 100-200 µg, 20-30% recommended <100 µg, and 10-20% recommended >200 µg. Conclusions: Se use is widely considered in daily clinical practice. Moreover, Se supplementation is often used or suggested for purposes extending beyond those supported by evidence-based medicine. Ongoing studies will better clarify how Se treatment can be properly utilized in thyroid disease management.

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Roberto Negro Division of Endocrinology, “V. Fazzi” Hospital, Lecce

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Roberto Attanasio Endocrinology Service, Galeazzi Institute IRCCS, Milan

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Franco Grimaldi Endocrinology and Metabolic Disease Unit, Azienda Ospedaliero-Universitaria “S. Maria della Misericordia,” Udine

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Andrea Frasoldati Division of Endocrinology, IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia

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Rinaldo Guglielmi Department of Endocrinology, Regina Apostolorum Hospital, Albano Laziale, Italy

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Enrico Papini Department of Endocrinology, Regina Apostolorum Hospital, Albano Laziale, Italy

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Background: While thyroid nodules are frequent in endocrine clinical practice, patients are often asymptomatic and euthyroid, and death is rare in cases of malignancy. Objectives: To evaluate the perception of current international guidelines regarding thyroid nodule management among Italian endocrinologists, and to compare daily clinical practice with suggested recommendations. Methods: Italian Association of Clinical Endocrinologists (AME) members were invited to participate in a Web-based survey. Results: A total of 566 physicians responded. About 50% had read the full text of the guidelines. Over half appreciated the suggested ultrasound (US) risk categories. Fine-needle aspiration (FNA) was obtained more frequently than recommended. Follow-up of a cytologically benign nodule was largely performed according to the guidelines. Molecular testing would be most commonly requested when cytology reports showed atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) (TIR3A for Italian System). Iodine and/or levothyroxine were largely prescribed for cytologically benign asymptomatic nodules. Laser/radiofrequency ablation and percutaneous ethanol injection were commonly considered as alternatives to surgery (46.2 and 71.4%, respectively). Conclusions: Efforts are needed to make the guidelines more user-friendly and to encourage the use of codified risk categories in thyroid US reports. FNA indications remain a matter of debate as FNA is obtained in clinical practice more often than is recommended. Current US follow-up modalities for a benign nodule are correct, but probably could be performed less frequently without any harm. Molecular testing, if accessible, would be helpful in guiding clinicians' strategies in cases of AUS/FLUS-TIR3A cytologic results. Nonsurgical procedures are favorably embraced.

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Roberto Negro Division of Endocrinology, ‘V. Fazzi' Hospital, Lecce

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Roberto Attanasio Endocrinology Service, Galeazzi Institute IRCCS, Milan

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Franco Grimaldi Endocrinology and Metabolic Disease Unit, Azienda Ospedaliero-Universitaria ‘S. Maria della Misericordia', Udine

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Rinaldo Guglielmi Department of Endocrinology, Regina Apostolorum Hospital, Albano Laziale, Italy

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Enrico Papini Department of Endocrinology, Regina Apostolorum Hospital, Albano Laziale, Italy

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Background: Patients suffering from Graves' disease (GD) are quite frequent in endocrine clinical practice. In particular, overt hyperthyroidism may be complicated by serious adverse events and requires careful treatment, but its management has changed over the years in both the USA and European Union (EU). Objectives: To evaluate the current diagnosis and management of patient's with GD in Italy, and compare results with those obtained in previous similar surveys in the USA and EU. Methods: Members of the Italian Association of Clinical Endocrinologists (AME) were asked to participate in a Web-based survey on management of GD. Results: In total, 947 responses were obtained. The preferred diagnostic modality in Italy is TSH receptor antibody determination in conjunction with ultrasound, while radioactive iodine uptake/scan is preferred in the USA. Methimazole (MMI) 20-30 mg/day with a β-blocker is the initial treatment of choice in Italy and the EU, whereas the USA opts more frequently for radioactive therapy. If Graves' orbitopathy occurs, orbit CT/MRI scans are more often obtained in Italy and the EU than in the USA. In case of planned pregnancy in 6-12 months, surgery is more frequently suggested in Italy than in the EU and USA. Propylthiouracil is generally preferred to MMI in the first trimester. Conclusions: Italian endocrinologists have shown significantly different patterns in diagnosis and management of GD compared to both the USA and EU.

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

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Roberto Attanasio Endocrinology Service, Galeazzi Institute IRCCS, Milan, Italy

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Enrico Papini Department of Endocrinology, Regina Apostolorum Hospital, Albano Laziale, Italy

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Rinaldo Guglielmi Department of Endocrinology, Regina Apostolorum Hospital, Albano Laziale, Italy

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Franco Grimaldi Endocrinology and Metabolic Disease Unit, Azienda Ospedaliero-Universitaria “S. Maria della Misericordia”, Udine, Italy

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Vincenzo Toscano Endocrinology, Department of Clinical and Molecular Medicine, Sant’Andrea Hospital, Sapienza University of Rome, Roma, Italy

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Dan Alexandru  Niculescu Department of Endocrinology, Carol Davila University of Medicine of Pharmacy, Bucharest, Romania

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Diana Loreta  Paun Department of Endocrinology, Carol Davila University of Medicine of Pharmacy, Bucharest, Romania

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Catalina Poiana Department of Endocrinology, Carol Davila University of Medicine of Pharmacy, Bucharest, Romania

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Objectives: Pregnancy induces changes in thyroid function, and thyroid dysfunction during gestation is associated with adverse outcomes. We examined the management of subclinical hypothyroidism and chronic autoimmune thyroiditis in pregnancy among Italian and Romanian endocrinologists. Methods: Members of the Associazione Medici Endocrinologi (AME) and Romanian Society of Endocrinology (RSE) were invited to participate in a web-based survey investigating the topic. Results: A total of 902 individuals participated in the survey, 759 of whom completed all sections. Among the respondents, 85.1% were aware of the 2017 American Thyroid Association guidelines about thyroid disease and pregnancy, and 82.9% declared that thyroid-stimulating hormone (TSH) screening at the beginning of pregnancy should be warranted. In a patient negative for peroxidase antibodies, 53.6% considered 2.5 mIU/L and 26.2% considered 4.0 mIU/L as the upper normal limit of TSH, and 50% would treat a patient with TSH 3.5 mIU/L with levothyroxine. About 20% did not suggest iodine supplementation. Isolated hypothyroxinemia detected in the first trimester would be treated by 40.8%. In patients undergoing ovarian stimulation, a TSH < 2.5 mIU/L would be targeted by 70%. Conclusions: Respondents globally appeared well informed about the management of thyroid autoimmunity and subclinical hypothyroidism in pregnancy. A more aggressive attitude in implementing iodine supplementation would be desirable. Most endocrinologists were convinced about an evident association between mild thyroid impairment and adverse outcomes in pregnancy, thus using a TSH value of 2.5 mIU/L as the threshold for diagnosing hypothyroidism and starting levothyroxine in pregnant women.

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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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