Background: Hypothyroidism is a common endocrine disease associated with increased oxidative stress, increased cardiovascular (CV) risk, CV events and endothelial dysfunction. Endothelial progenitor cells (EPCs) are a well-known marker of CV risk. Objective: The aim of this work was to ascertain whether hypothyroidism is associated with lower EPC counts and if treatment with levothyroxine (LT4) or selenium (Se) improves EPC counts compared to placebo. Methods: Hypothyroid patients (n = 100) were randomly divided into five groups to receive placebo (group A), LT4 (group B) or Se at doses of 83 µg (group C), 166 µg (group D) or 249 µg (group E) for 3 months. Each group comprised 20 patients: 10 with ‘mild' hypothyroidism and 10 with ‘severe' hypothyroidism. A healthy control group (group F) with 20 euthyroid subjects was also recruited. Subjects had to be free of CV disease, diabetes and drugs that interfere with EPCs. Anthropometric measurements (height, weight, BMI), blood pressure, fasting lipids and EPC analyses were performed at baseline and after 3 months. Results: EPC counts were significantly lower in hypothyroid patients compared to controls. EPCs increased after 3 months of treatment with LT4, but not with Se at any dosage. CD133+ and CD34+ EPC counts were negatively correlated with thyroid-stimulating hormone (TSH; r² = 0.523, p < 0.01 and r² = 0.517, p < 0.01, respectively) and positively correlated with FT4 (r² = 0.394, p < 0.01 and r² = 0.369, p < 0.01, respectively). TSH and FT4 were the only predictors of EPC counts. Conclusions: Hypothyroidism is associated with low EPC counts. Treatment with LT4, but not Se, can improve EPC counts.

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.

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.

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.

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).

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.

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.

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.