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Purpose: To evaluate the possible association between Covid-19 infection and subacute thyroiditis. Patients and Methods: We reviewed the medical and imaging records of patients referred to our outpatient setting dedicated to “thyroid emergency” (“bollini verdi”) from April 2020 to October 2020 of our Department. This out-patient clinic is devoted to patients who required an evaluation for severe hypothyroidism, thyrotoxicosis and neck discomfort or pain. All patients with a newly diagnosed subacute thyroiditis were selected. A retrospective collection of the data of all patients receiving a diagnosis of subacute thyroiditis was performed taking into account the same period of time (April-October) starting from 2016.Results: During the COVID-19 outbreak in our Region, (April 2020 to October 2020), 396 patients attended the out-patient emergency clinic. Among them, 10 (2.7%) patients received a diagnosis of subacute thyroiditis. In a single patient, a 44 yr old man, Covid-19 pulmonary infection had been diagnosed seven weeks before the diagnosis of subacute thyroiditis. All of the remaining patients were and still are Covid-19 free as confirmed by phone interview. The percentage of patients who received diagnosis of subacute thyroiditis in the same period starting from 2016 was superimposable (2.9%, 2.9%, 2.6% and 3.0% in 2016, 2017, 2018 and 2019, respectively). Conclusions: Our data do not demonstrate an increase of the incidence of subacute thyroiditis in Brescia areas, a region with the highest prevalence of COVID-19 in Italy during the period of the pandemic outbreak.Trial registration: no. 4631

Purpose To evaluate the possible association between Covid-19 infection and subacute thyroiditis. Methods We reviewed the medical and imaging records of patients referred to our Department’s outpatient setting dedicated to ‘thyroid emergency’ (records with a ‘bollino verde’—green sticker, classifed as urgent) from April 2020 to October 2020. This outpatient clinic is devoted to patients requiring evaluation for severe hypothyroidism, thyrotoxicosis and neck discomfort or pain. All patients with a newly-diagnosed subacute thyroiditis were selected. The data of all patients receiving a diagnosis of subacute thyroiditis was collected retrospectively, taking into account the same period of time (April–October) and starting from 2016. Results During the COVID-19 outbreak in our region (April 2020 to October 2020) 396 patients attended the outpatient emergency clinic. Among them, 10 (2.5%) patients received a diagnosis of subacute thyroiditis. In a single patient, a 44-year-old man, a COVID-19 pulmonary infection had been diagnosed 7 weeks before the diagnosis of subacute thyroiditis. All of the remaining patients were and remain COVID-19 free as confirmed by telephone interview. The percentage of patients who received a diagnosis of subacute thyroiditis in the same period starting from 2016 was very similar (2.9%, 2.9%, 2.6% and 3.0% in 2016, 2017, 2018 and 2019, respectively). Conclusions Our data do not show an increase in the incidence of subacute thyroiditis in the Brescia area, a region with the highest prevalence of COVID-19 in Italy during the period of the pandemic outbreak.

Objective Some evidence suggests that most benign nodules exhibit no significant size increase during 5 years of follow-up, although conflicting results have emerged. The aim of the present study is to evaluate the frequency and the magnitude of growth in benign nodules during 120 months of follow-up. Design We reviewed the medical and imaging records of patients who were submitted to ultrasound-guided FNA of thyroid nodules at our hospital from January 2007 to March 2009. We selected only patients with benign nodules who underwent annual ultrasound evaluation in our Department. Results Among 966 selected patients, 289 were lost during follow-up, meaning that the total number of patients analysed was 677 (474 women and 203 men), with a mean age of 45.6 (16-71) years. In 559/677 patients (82.7%), the size of the nodule remained stable during follow-up; 42 (6.2%) patients experienced spontaneous nodule shrinkage, and 75 (11.1%) patients showed nodule growth. Patients with or without nodule growth during follow-up were superimposable at baseline for age, gender, TSH values, number of patients on levothyroxine treatment and nodule characteristics. All baseline variables in predicting nodular growth were entered to an adjusted multivariate logistic regression model. None of the parameters taken into account was associated with nodular growth. Conclusions In conclusion, the majority of benign nodules remained stable over the period of monitoring. On the basis of our experience, we recommend ultrasound examination at a distance of 2 and 5 years following cytological evaluation, then every 4-5 years from then on.

Background. Serum TSH levels in the upper-normal range were reported to be associated with increased risk of thyroid malignancy. However, measurement of TSH levels is currently not recommended for assessing the risk of malignancy in patients with newly diagnosed thyroid nodules. Objective. To evaluate a possible relationship between the serum levels of TSH and the histological outcome of patients undergoing thyroidectomy for thyroid nodules with indeterminate cytology. Materials and Methods. We collected the clinical data of all patients who had performed ultrasound-guided FNA of thyroid nodules with cytological diagnosis of indeterminate lesions (TIR3A and TIR3B) and serum TSH levels within the normal range. All patients had been submitted to thyroid surgery (hemi or thyroidectomy, as appropriate), and histological diagnosis had been performed. Results. A histological diagnosis of thyroid malignancy was rendered in 74/378 (19.6%) nodules. Patients with histologically proven thyroid malignancy were characterized by higher serum levels of TSH as compared to patients with histologically proven benign nodules (3.03 ± 1.16 vs. 2.37 ± 1.19 mIU/L, p<0.001). To further analyze the role of serum TSH in predicting thyroid cancer, patients were stratified in 4 groups according to quartiles of TSH concentrations. The prevalence of malignancy was 12.2% for the first quartile and 50.0% for the last quartile. ROC curve analysis identified that a serum TSH level of ≥2.7 mIU/L predicted thyroid malignancy with a sensitivity of 61% and a specificity of 65%. Conclusions. TSH levels in the upper-normal range are associated with an increased risk of thyroid malignancy in patients affected by thyroid nodules with indeterminate cytology at FNA. The measurement of serum TSH levels represents an easily performed additional tool for decision-making in patients with indeterminate cytological findings.

Radiofrequency (RF) treatment has played an increasing role in the management of benign thyroid nodules in recent years. The aim of this retrospective study was to evaluate the efficacy of RF treatment on volume reduction in functioning and non-functioning thyroid nodules. We reviewed the medical records of patients who had thyroid nodule RF ablation at our department between August 2017 and May 2018. Patients underwent a periodical follow-up with ultrasound examinations and thyroid function tests at 1, 3, 6 and 12 months from RF. Complications were assessed using the reporting standards of Interventional societies. 43 patients were submitted to thyroid nodule RF ablation treatment. Patients were subdivided into two groups, those with functioning (17 patients) or non-functioning nodules. At baseline (i.e. pre-RF treatment), the two groups of patients were superimposable for gender, age, BMI, nodule volume and maximum nodule diameter. The volume reduction of all 43 nodules was 69.1 ± 17.3% (range 26.0–94.5%) with no difference between functioning and non-functioning lesions (72.9 ± 18.1% vs 66.7 ± 16.7%, p = 0.254). A total energy delivered per nodule was 16.5 ± 6.8 kJ, with no difference between functioning and non-functioning lesions (14.5 ± 7.2 kJ vs. 18.2 ± 6.3 kJ, p = 0.083, respectively). No major complications were observed. Radiofrequency ablation is a clinically effective and safe outpatient treatment in patients with benign nodules. In particular, we showed that a single treatment is effective in restoring euthyroidism in patients with autonomously functioning thyroid nodules.

Intriduction: The thyroid is an organ with one of the highest selenium concentrations, containing many selenoproteins implicated in thyroid hormone metabolism. Treatment with levothyroxine has been recommended for all subclinical hypothyroid patients with TSH levels > 10 mU/L, whereas for those with TSH< 10 mU/L treatment remains controversial. Aim: A randomised controlled prospective study was performed to investigate the effects of Se treatment on patients with autoimmune thyroiditis and mild sub-clinical hypothyroidism (TSH < 10 mU/L). Material and methods: A total of 196 patients with autoimmune thyroiditis were recruited in the study. Patients were assigned to receive (case) or not receive (control) an oral selenomethionine treatment. Cases received 83 mcg selenomethionine/day orally for four months. All the patient’s charts were submitted to thyroid hormonal profile (TSH, fT4) and TPOAb evaluation upon enrolment and at the end of the study. Results: In total 192 patients completed the study. Cases and controls were superimposable for age, gender, thyroid hormonal profile, and TPOAb levels. At the end of the study, 33/192 (17.2%) participants restored euthyroidism (Responders). Responders were significantly more frequent among Cases than Controls (30/96 [31.3%] vs. 3/96 [3.1%], p < 0.0001). Conclusion: Selenium supplementation could restore euthyroidism in one third of subclinical hypothyroidism patients with autoimmune thyroiditis. (Endokrynol Pol 2016; 67 (6): 567–571)

Levothyroxine (LT4) is the recommended treatment for millions of hypothyroid patients. Current guidelines recommend that LT4 tablets be taken in a fasting state, but inability to adhere to this often leads to poor therapy compliance.A randomized, double-blind, placebo-controlled, crossover trial was conducted in previously untreated hypothyroid patients randomly assigned to receive an oral solution of LT4 either at least 30 minutes before breakfast or directly at breakfast time. Each patient completed two six-week treatment periods, with different timing of active LT4 administration: placebo before breakfast and active LT4 at breakfast, or vice versa. At the end of each period, thyrotropin (TSH), free thyroxine (fT4), and free triiodothyronine (fT3) were measured. The primary endpoint was to verify any difference in serum TSH levels whether consuming liquid LT4 at breakfast or 30 minutes prior to breakfast.A total of 77 patients (64 females; median age 45.4 ± 3.7 years) completed the study. No statistically significant differences in serum TSH, fT4, or fT3 levels were observed whether LT4 was taken at breakfast or 30 minutes before, in a fasting state. No significant effect from the sequence of regimens, breakfast composition, and/or concomitantly administered drugs was observed on the dose of LT4 administered, or on the post-treatment serum TSH values.The TICO study suggests that a liquid LT4 formulation can be ingested directly at breakfast, thus potentially improving therapeutic compliance. This observation is of considerable clinical relevance, since non-adherence to LT4 therapy requirements is more likely to cause variability in serum TSH concentrations.

Background: A significant number of patients showed sub-optimal adherence to LT4 therapy, mainly due to the fact that they had to postpone their breakfast of at least 30 minutes. The aim of this observational cross-sectional study was to assess the therapeutic compliance of patients on LT4 treatment and secondly to verify the preference of a lifetime treatment in tablets or liquid formulation. Patients and Methods: To all the participant (ambulatory care patients had to be eighteen or older, affected by hypothyroidism on LT4 substitutive treatment both in tablet or liquid solution) was administered the eight-item Morisky Medication Adherence Scale (MMAS-8). The MMAS-8 questionnaire has been supplemented with other three items in order to specifically evaluate medication preference between tablet and liquid LT4 formulation for long life treating. Results: A total of 320 patients (272 female) with median age of 47.9±15.6 yrs (range 20-78) completed the MMAS-8 questionnaire. We showed a high adherence (87% of the subjects) to therapeutic compliance both for patients on tablets than those on liquid LT4 formulation, although significant difference are emerged. Patients assuming LT4 in tablet forgot more frequently medication(s) (p

Background. Toshiba Medical System has developed a new Doppler technique [Superb Microvascular Imaging (SMI)] that has improved microvascular flow imaging. SMI depicts perinodular and intranodular thyroid microvascular flow in higher detail compared to standard colour Doppler (CD) and power Doppler (PD) imaging. Objective. Assess the nodular microvascular architecture by SMI compared to CD and PD features in a series of thyroid nodules submitted to fine needle aspiration cytology, in order to evaluate the potential of SMI in detecting thyroid cancer. Materials and Methods. From April 2016 to July 2017, 254 patients with thyroid nodules, evaluated as at high risk for malignancy in agreement with AACE/ACE/AME guidelines, were submitted to cytology. All nodules were previously submitted to ultrasound grayscale, CD, PD, and SMI evaluation. Benign and malignant nodules were stratified in accordance to the number of vessels visualised by SMI: score 1 with a maximum of two blood vessels and score 2 with three or more vessels. Results. Score 1 was found in 59.6% of benign nodules and in 17.9% of malignant nodules, whereas score 2 was found in 40.4% and in 82.1%, respectively (sensitivity 81.7%; specificity 60.5%, p<0.001). Variables significantly associated with malignancy in the univariate analysis were gender (OR, 0.18; 95% CI, 0.08-0.37; p<0.001), vascularity (OR, 1.91; 95% CI, 1.65-3.89; p<0.001), and SMI (OR, 6.72; 95% CI, 3.89-11.59; p<0.001); multivariate logistic model confirmed SMI score 2 as an independent risk factor for malignancy (OR, 6.99; 95% CI, 3.46-12.09; p<0.001). Conclusions. This prospective pilot study showed that SMI can depict intranodular flow in higher detail compared to CDI and PDI, thus improving thyroid cancer detection.

To compare TSH levels of hypothyroid patients treated with liquid LT4 at breakfast or 30 min before breakfast. Subjects, aged 18–75 years old, were eligible if they presented hypothyroidism, due to Hashimoto’s thyroiditis or after thyroidectomy for proven benign goiter. Seven hundred ninety-eight patients were recruited and enrolled in the study. Thirty-seven subjects withdrew from the trial. A total of 761 patients (mean age 46.2 ± 10.8 years) completed the study. The starting dose of LT4 was determined through clinical judgment, taking into account TSH levels, estimated residual thyroid function, age, body weight and comorbidities. All patients underwent TSH, fT4, and fT3 evaluation to verify achievement of euthyroidism with their initial fasting state assumption of LT4 after 8 weeks of therapy. If euthyroidism was not achieved, an appropriately adjusted LT4 dose was administered for 8 weeks, after which thyroid function parameters were checked again. If euthyroidism was achieved, the patients were asked to take LT4 at breakfast and hormone levels were checked again after 6 months. At the end of the study period, no significant differences in serum TSH level were observed whether LT4 was ingested at breakfast or 30 min prior in a fasting state: 2.61 ± 1.79 vs. 2.54 ± 1.86 mIU/L, respectively (p = 0.455). This study confirms in a large set of patients that a liquid LT4 formulation can be taken directly at breakfast and potentially improve therapeutic compliance.

Background. Recent guidelines from the American Thyroid Association (ATA) indicate that, in many patients affected by differentiated thyroid cancer (DTC), the serum TSH should be maintained between 0.1 and 0.5 mU/L. The purpose of this study was to evaluate the TSH variability of patients affected by DTC treated with liquid L-T4 formulation or in tablet form. Patients and Methods. Patients were eligible if (a) they were submitted to a total thyroidectomy and 131I remnant ablation for DTC in our institution and (b) they were classified low-risk patients according to ATA guidelines 2009. Patients were randomized (1 : 1) to receive treatment of hypothyroidism with liquid L-T4 or tablet form. The first check-up evaluation was made from 8 to 12 months after 131I remnant ablation. TSH values were established again after further 12 months. Results. A significant increase in TSH values (median) was observed in patients taking tablets [TSH (min–max): 0.28 (0.1–0.45) versus 0.34 (0.01–0.78) mIU/L, p=0.041] as compared to those taking liquid formulation [TSH (min–max): 0.28 (0.1–0.47) versus 0.30 (0.1–0.55) mIU/L, p=0.345]. Conclusions. The use of L-T4 liquid formulation, as compared to that of tablets, resulted in a significantly higher number of DTC patients maintaining TSH values in range for the ATA risk score, reducing TSH variability over the time.

Background High resolution ultrasonography features have also been described as having a useful supporting role in the diagnosis of subacute granulomatous thyroiditis (ST), and images are generally characterized by heterogeneous hypoechoic areas of the affected tissue with lack of flow on color Doppler US. Purpose To determine the sonographic features of subacute granulomatous thyroiditis. Material and Methods We reviewed the medical records of patients referred at the Endocrine and Metabolic Unit of our Institution between January 2010 and December 2011. Results A total of 7520 patients were evaluated in our department between January 2010 and December 2011. Among them, 22 (0.3%) patients had a diagnosis of ST (19 women and 3 men, 45.4 ± 9.7 year; range, 33–62 years). Ultrasound examination showed bilateral ST in 64% of patients. Thyroid volume was 13.2 ± 7.7 mL, without difference if ST was unilateral (13.2 ± 7.1 mL) or bilateral (13.9 ± 8.3 mL). On grayscale US, heterogeneous diffusely or focally marked hypoechoic areas, like “lava flow”, were found in all the lesions. Conclusion Our data confirm the high sensitivity of US in the diagnosis of ST: diffuse hypoechoic and confluent areas with the characteristic features like “lava flow”.

To evaluate the need and the magnitude of levothyroxine (LT4) increase in hypothyroid pregnant women on liquid compared to tablet formulations.Patients were recruited by searching our "thyroid patients" database. The selection criteria were as follows: a) pregnant women on treatment for hypothyroidism (both liquid and tablet LT4) who gave birth at our hospital between February 2012 and January 2014; b) thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels obtained at least 3 months before missed menstrual cycle, with a TSH value less than 2.5 mIU/L and c) TSH and FT4 obtained within 12 weeks of pregnancy, and each month subsequently.During pregnancy, 8/31 (25.5%) of the women had to increase the dosage of LT4. Of these, 7/17 (41.2%) were on LT4 replacement therapy with tablets, and 1/14 (7.1%) with liquid formulation (p = 0.038). Daily LT4 was significantly increased in the liquid group only (52.9 ± 19.5 versus 67.5 ± 19.2 mcg/day (p = 0.013). A logistic regression analysis showed that the treatment with LT4 tablets was the only predictor of LT4 increase (OR: 0.44; 95% CI: 0.04-0.83; p = 0.031).Pregnant women on optimal replacement therapy before pregnancy require an increase of LT4 dosage more often when on a tablet than liquid formulation.

ObjectiveTaking levothyroxine (l-T4) with coffee or with water followed by coffee intake within a few minutes results in poor TSH response in many patients. T4is available in tablet form worldwide, but novel formulations in soft gel capsule or liquid form are now available.DesignWe fortuitously identified a euthyroid patient who wrongly consumed liquidl-T4with coffee at breakfast; after changing the time of consumption to 30 min before breakfast, no change in TSH, free T4(fT4), and free tri-iodothyronine (fT3) concentrations was observed. Once the first patient was identified, additional stable euthyroid patients who consumed liquidl-T4with coffee were identified.MethodsPatients were recruited by searching our ‘thyroid patients’ database. All the patients on liquidl-T4treatment were contacted by phone to ask them whether they tookl-T4at breakfast. We identified 54 patients who were submitted to TSH, fT4, and fT3evaluation, with the indication that the same dosage ofl-T4be consumed 30 min before breakfast. We determined their TSH, fT4, and fT3concentrations after 3 and 6 months again.ResultsNo significant difference in thyroid hormone concentrations was observed in patients when they consumedl-T4at breakfast or when they consumed it 30 min before breakfast for 3 and 6 months (TSH: 2.5±1.1 vs 2.5±1.1 and 2.4±1.1 mIU/l respectively, fT4: 12.4±2.4 vs 12.5±2.4 and 12.3±2.1 pg/ml respectively, and fT3: 3.4±0.6 vs 3.4±0.6 and 3.3±0.5 pg/ml respectively).ConclusionOral liquidl-T4formulations could diminish the problem ofl-T4malabsorption caused by coffee when using traditional tablet formulations.

Although fine-needle aspiration (FNA) cytology of thyroid nodules is invasive, it is simple, reliable, safe, and well-accepted by patients. Local pain and minor haematomas are the most common complications, and serious ones are rare. We report the complications associated with ultrasound-guided FNA of 7449 thyroid nodules in a series of 6323 patients (5121 women and 1202 men) treated between January 2007 and March 2016 at our institution. We reviewed their medical and imaging records, and recorded the number and type of complications, time of detection, time to recovery, management, and permanent consequences. Ten patients (0.15%) had complications, which included a focal carotid intramural haematoma that spread along the carotid wall for 7cm in a young patient, and one case of tumour seeding. No complications caused permanent problems. This series shows that ultrasound-guided FNA of thyroid lesions is safe and has few complications. However, physicians should always consider the risks and benefits for each patient before the procedure.

The thyroid is an organ with one of the highest selenium concentrations, containing many selenoproteins implicated in thyroid hormone metabolism. Treatment with levothyroxine has been recommended for all subclinical hypothyroid patients with TSH levels10 mU/L, whereas for those with TSH10 mU/L treatment remains controversial.A randomised controlled prospective study was performed to investigate the effects of Se treatment on patients with autoimmune thyroiditis and mild sub-clinical hypothyroidism (TSH10 mU/L).A total of 196 patients with autoimmune thyroiditis were recruited in the study. Patients were assigned to receive (case) or not receive (control) an oral selenomethionine treatment. Cases received 83 mcg selenomethionine/day orally for four months. All the patient's charts were submitted to thyroid hormonal profile (TSH, fT4) and TPOAb evaluation upon enrolment and at the end of the study.In total 192 patients completed the study. Cases and controls were superimposable for age, gender, thyroid hormonal profile, and TPOAb levels. At the end of the study, 33/192 (17.2%) participants restored euthyroidism (Responders). Responders were significantly more frequent among Cases than Controls (30/96 [31.3%] vs. 3/96 [3.1%], p0.0001).Selenium supplementation could restore euthyroidism in one third of subclinical hypothyroidism patients with autoimmune thyroiditis. (Endokrynol Pol 2016; 67 (6): 567-571).

Background. Recently, it has been shown that liquid L-T4 formulation can be ingested with breakfast. This study looked to extend these findings by investigating whether a soft gel capsule formulation of L-T4 could also be ingested at breakfast time.Methods. 60 patients (18–65 yrs), previously submitted to thyroidectomy for proven benign goitre in stable euthyroidism receiving liquid L-T4 therapy ingested with breakfast, were enrolled. TSH, fT4, and fT3 levels were assessed in all the patients who were switched from liquid L-T4 to a soft gel capsule formulation at the same dosage of L-T4. After 6 months, TSH, fT4, and fT3 levels were determined again.Results. There were no differences in TSH levels, but fT3 and fT4 levels during treatment with the soft gel capsule were significantly lower than those at enrolment with the liquid L-T4 formulation (TSH median (min–max): 1.9 (0.5–4.0) versus 2.2 (0.5–4.5) mIU/L, fT3: 2.5 (2.4–3.1) versus 2.7 (2.4–3.3) pg/mL,p<0.05, and fT4: 9.9 (8.0–13) versus 10.6 (8.6–13.8) pg/mL,p<0.0001).Conclusion. Both liquid and soft gel formulations of L-T4 can be taken with breakfast. However, liquid L-T4 would be the preferred formulation for patients in whom even small changes in fT4 and fT3 levels are to be avoided.

Objective: To evaluate whether a preliminary aspiration (ASP) of the cystic component and/or using spinal needles in complex thyroid nodules (CTN) could improve the adequacy of cytological sampling. Methods: Between January 2004 and December 2006, 386 consecutive patients with CTN were enrolled in this prospective investigation. Ultrasound (US) fine needle aspiration cytology (FNAC) of the solid component of the nodule (one nodule per patient) was performed using two different 25 gauge needles, with (Yale Spinal, YS) or without (Neolus, NS) a stylet, in alternate sequence on consecutive patients. In addition, a subgroup of patients presenting larger cystic component (∼50%) was submitted to total aspiration of the cystic component (ASP+) or not submitted (ASP−) before US-FNAC, in alternate sequence within each needle type group. All the samplings were performed by a single endocrinologist. Results: Adequate specimens were observed in 163 (84.5%) and 183 (94.8%) nodules investigated by NS and YS respectively. Sampling with the stylet needle was associated with an overall significant reduction of non-diagnostic specimens (15.5% vs 5.2% by NS and YS respectively, P < 0.001). The favourable result obtained with YS was independent from preliminary aspiration of the cystic component (ASP+: 14.8% vs 5.7% by NS and YS; ASP−: 16.2% vs 4.8%, not significant). A logistic regression analysis, taking into account nodule size and presence of intranodal vascularity at eco-colour evaluation of the solid component, confirmed that needle type was the only significant predictor of successful sampling (odds ratio 3.6 (95% confidence interval 1.7–7.6), P < 0.001). Conclusions: Our data show that adopting stylet needles to perform FNAC in CTN may significantly improve the percentage of adequate sampling. On the other hand, preliminary aspiration of CTN with large cystic component does not add any advantage.

Parathyroid cysts are rare but clinically significant lesions. They can be functional, mistaken for a thyroid cyst, and/or managed nonoperatively on occasion.We identified seven patients (1 male, 6 females) with the diagnosis of parathyroid cyst from 1998 to 2003.Altogether, 33% of the patients had functional cysts. Sestamibi scans were performed in three of the seven patients, including two with functional cysts; none showed focal uptake. In toto, six of the seven cysts (86%) were found in an inferior parathyroid gland. All of the cysts had crystal-clear aspirate. C-terminal parathormone (PTH) levels were obtained from the aspirate from five of the seven (71%) patients. The mean level was 269,736 pg/ml (1970-1,268,074 pg/ml). Surgery was performed in three of the seven (43%) patients. All patients who underwent surgery improved postoperatively based on symptoms and serum levels of calcium and PTH. The four patients (57%) who were treated nonoperatively were subjected to aspiration alone; three (75%) of those patients required multiple aspirations.Most parathyroid cysts are nonfunctional and are rarely symptomatic. They are usually located in an inferior gland. If aspirated, most of the cysts reaccumulate fluid. Operative management is usually straightforward and alleviates symptoms and any biochemical abnormalities caused by the cyst.

The aim of the present prospective study was to evaluate the predictive value of elastography in benign thyroid nodules of patients affected by Hashimoto’s thyroiditis (HT). From January 2011 to January 2012, 242 nodules in patients affected by HT were submitted to fine needle aspiration cytology (FNAC). All of the patients underwent sonography and elastography performed before FNAC. 230 (95%) nodules were benign, 8 papillary cancers, and 4 follicular lesions. Score 1 was found in 79.1% of benign lesions (sensitivity 79.1%; specificity 66.7%; PPV 97.8%; NPV 14.3%; accuracy 78.5%;p<0.05). In order to evaluate the outcome of thyroid ultrasound echogenicity in relation to elastography features of nodule(s), all the patients with benign nodules were stratified according to their hypoechoic pattern of thyroid (mild-moderate and severe). Following stratification score 1 was found in 84.2% of benign nodules (sensitivity 75.0%; specificity 88.9%; PPV 27.3%; NPV 98.4%; accuracy 88.2%;p<0.0001) of patients with a mild-moderate ultrasound thyroid hypoechogenicity, whereas it was found in 60% of benign nodules(p=0.715)of patients with a marked thyroid hypoechogenicity. Elastography appears to have limited value in detecting thyroid cancer in patients affected by Hashimoto’s thyroiditis with severe hypoechoic thyroid tissue.

Background Thyroglobulin measurement in the washout of the needle used in fine-needle aspiration cytology (FNAC) has been proposed for the early detection of lymph node metastasis both in patients with or without serum thyroglobulin antibodies; however, up to now, there have been no reports that recombinant human thyrotropin (rhTSH) stimulation modifies thyroglobulin measurement in lymph node aspirates. Methods We described, after rhTSH stimulation, the switching from undetectable to detectable levels of thyroglobulin in fine-needle aspiration fluid from a suspected metastatic lymph node in 2 patients. Results We hypothesized that thyroglobulin levels in the lymph node increased after rhTSH stimulation. The excess thyroglobulin saturates all thyroglobulin antibody binding sites and becomes detectable, explaining why it was undetectable when TSH was suppressed. Conclusion On the basis of our experience, we suggest submitting to thyroglobulin measurement in the washout of the needle used in FNAC all patients with detectable serum thyroglobulin antibody after rhTSH stimulation. © 2011 Wiley Periodicals, Inc. Head Neck, 2013

Purpose Recent evidences suggest that, despite the large use of levothyroxine (L-T4), up to 40% of patients are over-treated developing sub-clinical hyperthyroidism. We compared TSH, fT4 and fT3 serum levels of elderly patients in treatment with liquid and tablet L-T4 formulations over a period of time of five years. Subjects Patients were recruited by searching the database of those treated and followed at the Thyroid Unit of the University of Brescia. Results Two hundred and ninety-nine patients (251 females, 48 males) were treated with L-T4 in tablet form (group T) and 118 subjects (107 female, 11 male) with liquid LT4 (group L). The two groups were super-imposable by age, median L-T4 dosage, TSH, fT4 and fT3 values. A slightly but not significantly higher BMI value was observed among patients of group L over those of group T (26.9 ± 2.9 vs. 26.4 ± 2.1 kg/cm 2 , respectively). During five years of LT-4 treatment, sub-clinical or over-hypothyroidism was found in 13 (4.3%) and 3 (2.5%) patients of group T and group L ( P = 0.335), whereas, subclinical or clinical hyperthyroidism was significantly more frequent among patients of group T than those of group L [69 (23%) vs. 5 (4.2%) patients, ( P = 0.0001)]. Logistic regression analysis showed that only the Tablets were associated with the risk of developing subclinical or hyperthyroidism [OR 2·354 (1·136–4·827), P = 0.021]. Conclusions We show a greater stability in the thyroid profile of hypothyroid elderly patients in treatment with liquid thyroxine as opposed to those being treated by tablet formulation over five years of follow-up.

The majority of clinicians suggest that enteral feedings should be held 1-2 h prior to and after L-T4 administration despite lack of data for continuous enteral nutrition.The aim of this study was to: (1) compare the thyroid hormonal profile in patients submitted to L-T4 treatment in tablets or liquid formulation with an enteral feeding tube; (2) evaluate the nursing compliance with the two different formulations.20 euthyroid patients submitted to total laryngectomy and thyroidectomy consecutively started L-T4 treatment in tablets (Group T) or in liquid formulation (Group L) with enteral feeding tube the day after surgery. Tablets were crushed before administration and enteral feeding was stopped for 30 min before and after L-T4 treatment, whereas liquid formulation was placed into the nasoenteric tube immediately. A questionnaire about the preparation and administration of thyroxine replacement therapy was given to the nurses.No difference of TSH, fT4 and fT3 before and after L-T4 treatment was observed among patients of Group L. A slightly serum TSH increase was observed in Group T, but not reaching statistical significance (2.50 ± 1.18 vs 2.94 ± 1.22 mUI/L), whereas no difference in fT4 and fT3 levels was found. Preparation and administration of liquid L-T4 was considered excellent by 12/13 nurses, whereas tablet formulation was considered poor by 10/13.Our data showed that liquid L-T4 formulation can be administered directly through feeding tube with no need for an empty stomach, with a significant improvement in therapy preparation and administration by nurses.

OBJECTIVES The aim of this study was to evaluate the predictive value of sonography and sonographic elastography in thyroid nodules with nondiagnostic cytologic findings. METHODS The study included 101 patients (74 female, mean age ± SD, 55 ± 11 years [range, 27-70 years]; and 27 male, mean age, 62 ± 9 years [range, 42-72 years]) who had at least 1 nodule with nondiagnostic cytologic findings at two different fine-needle aspiration cytologic evaluations and with an indication for hemi or total thyroidectomy for clinical suspicion of malignancy, nodule size, or the occurrence of a coexisting nodule with cytologic findings suspicious for malignancy. All of the patients underwent sonography and elastography 2 months after the second fine-needle aspiration and before surgery. The elastogram was matched with an elasticity color scale and classified as follows: score 1, nodules with high elasticity (soft); score 2, nodules with indeterminate elasticity; and score 3, nodules with low elasticity (hard). RESULTS A total of 135 nodules (93.7%) were hyperplastic; 15 (9.4%) were papillary carcinomas; and 9 (6.3%) were follicular adenomas. The association of scores 2 and 3 identified 12 of 15 thyroid cancers (sensitivity, 80.0%; specificity, 93.7%; positive predictive value, 57.1%; negative predictive value, 97.8%; and accuracy, 92.4%), whereas the association of conventional sonographic features plus scores 2 and 3 identified all of the cancers (specificity, 70.8%; positive predictive value, 26.3%; negative predictive value, 100%; and accuracy, 73.6%). CONCLUSIONS Our data suggest that elastography could be a promising tool in the management of nodules that are nondiagnostic at cytologic evaluation, reducing unnecessary surgery.

Objective: A relevant biological role of circulating endothelial progenitor cells (EPC) was recently demonstrated. EPC are generated in the bone marrow, and interact with damaged endothelium, restoring the integrity of the monolayer. Therefore, aim of the present study was to evaluate EPC in the blood of patients with untreated Graves’ hyperthyroidism (GD), in whom an increased oxidative stress was observed. Design and methods: Twenty-three patients with untreated active GD and 18 matched normal controls (NC) were included in the study. Circulating EPC were isolated from peripheral blood. Mononuclear cells were cultured with endothelial basal medium supplemented with EGM SingleQuots, and were identified by positive double staining after 7 days in culture. Circulating levels of C reactive protein, total antioxidant power, interleukin (IL)-6, IL-18, monocyte chemoattractant protein-1, tumor necrosis facotr-α, soluble vascular cell adhesion molecule (VCAM) and intracellular adhesion molecule were evaluated by enzyme-linked immunosorbent assay kit. EPC number was also evaluated in a subgroup of GD patients after restoration of euthyroidism. Results: Systolic blood pressure resulted increased in GD patients compared with control subjects whereas diastolic blood pressure was not significantly different. Patients with GD showed an increase in circulating levels of IL-18 and VCAM-1 and a reduction of total antioxidant power (p

Riedel’s thyroiditis (RT) is a rare form of infiltrative and inflammatory disease of the thyroid, first described by Bernard Riedel in 1896. The concurrent presence of RT and other thyroid diseases has been reported, but, the association of RT with Hashimoto’s thyroiditis and acute thyroiditis has not yet been reported. We present a case of concurrent Riedel’s, Hashimoto’s and acute thyroiditis that occurred in a 45-year-old patient.

OBJECTIVE To assess the interplay between metformin treatment and thyroid function in type 2 diabetic patients. RESEARCH DESIGN AND METHODS The acute and long-term effects of metformin on thyroid axis hormones were assessed in diabetic patients with primary hypothyroidism who were either untreated or treated with levothyroxine (L-T4), as well as in diabetic patients with normal thyroid function. RESULTS No acute changes were found in 11 patients with treated hypothyroidism. After 1 year of metformin administration, a significant thyrotropin (TSH) decrease (P < 0.001) was observed in diabetic subjects with hypothyroidism who were either treated (n = 29; from 2.37 ± 1.17 to 1.41 ± 1.21 mIU/l) or untreated (n = 18; 4.5 ± 0.37 vs. 2.93 ± 1.48) with L-T4, but not in 54 euthyroid subjects. No significant change in free T4 (FT4) was observed in any group. CONCLUSIONS Metformin administration influences TSH without change of FT4 in patients with type 2 diabetes and concomitant hypothyroidism. The need for reevaluation of thyroid function in these patients within 6–12 months after starting metformin is indicated.

Objectives: Ultrasound-guided fine needle aspiration cytology (US-FNAC) represents the most effective test available to distinguish between benign and malignant thyroid nodules. The major limit is the rate of inadequate specimens which generates a much higher cost. The aim of the present study was to evaluate whether the adoption of stylet needles may result in a significant improvement of diagnostic performance in a large, unselected series of nodules. Methods: 1468 nodules were submitted to US-FNAC by two different 25-gauge needles: a traditional hollow needle (Ns) or a stylet needle (Ys). Cytological specimens were evaluated in blind conditions by the same cytopathologist. Results: Ys was associated to a significant reduction of non-diagnostic specimens (2.8% vs 9.1% by Ns, respectively, P < 0.001). Logistic regression analysis taking into account sex, age, needle type, nodule size, multiplicity and structure predictor of successful sampling [odds ratio 3.6 (95.0% CN 2.0-6.4), P < 0.001]. The cost analysis comparing the adoption of the two types of needle evidenced that the cost per adequate specimen was consistently less for Ys than for Ns (euro 78.87 vs euro 90.76). Conclusion: Our data showed that the adoption of a stylet needle significantly improves diagnostic performance, reducing by about 14% the expenditure per diagnostic procedure. Therefore, we suggest that stylet needles should be widely adopted to perform US-FNAC of thyroid procedures.

Surgery is the treatment of choice for symptomatic primary hyperparathyroidism; unlikely few patients do not meet established surgical criteria or have comorbid conditions that prohibit surgery. In these subjects, medical therapy alone offers little hope for a sustained long normocalcemic period. However percutaneous ethanol injection (PEI) may represent an alternative therapeutic procedure. It is currently in use for the treatment of secondary or tertiary hyperparathyroidism, however, few studies or case reports suggest it for the treatment of primary hyperparathyroidism. Moreover, little information is available about the long-term follow-up, where incomplete necrosis or the spreading of ethanol in the surrounding tissues is often reported. We believe that many of the side effects could be correlated to procedure itself. Taking these experiences into account, we have reasoned that in order to limit these side effects, we had to modify the standard PEI procedure. We reported this preliminary experience describing our modified PEI procedure.

Ultrasound fine needle aspiration cytology (US-FNAC) represents the most effective test available to distinguish between benign and malignant thyroid nodules, with an accuracy approaching 95%. The major limit of this procedure it is the rate of inadequate specimens which is reported to be from 10% to 31%. Also because cost considerations have always been important and have recently become even more relevant for clinical guidelines in many countries, it is desirable to limit the number of inadequate samples. Recently, we have shown that the use of stylet needles greatly reduces inadequate cytological specimens in thyroid nodules with an intranodular vascular pattern. With the aim to improve our previous results, we have extended our procedure to all thyroid solid nodules. Between February 2004 and March 2006, 312 consecutive patients with thyroid nodule without intranodular vascular pattern at color-Doppler evaluation were enrolled in this prospective study. US-FNAC was performed by two different 25 gauge needles (Neolus [Ns] and Yale Spinal [YS]), and the two procedures were performed in alternate sequence on consecutive patients. Adequate specimens were observed in 145 (92.9%) and 153 (98%) nodules respectively investigated by Ns and in YS (p0.005). The total cost to obtain a cytological diagnosis by Ns was of euro 12210.2 (156+12 repeated US-FNAC), whereas it was of euro 12449.7 by YS (156+3 repeated US-FNAC). Our data suggest that spinal needles are associated with a low proportion of inadequate FNAC, without increase of total direct cost, considering also the number of FNAC repetitions needed; therefore, their routine use could be taken into account.

In most trials, at least 30-60% of patients with Graves' disease treated with antithyroid drugs relapse within 2 years after therapy withdrawal. At present, there are no prognostic parameters available early in treatment to indicate patients likely to achieve long-term remission. Because thyrotropin receptor autoantibodies (TRAb) are specific for Graves' disease, we evaluated the ability of their levels and of their rate of change to predict long-term prognosis. In our study 216 consecutive patients with newly diagnosed Graves' disease started a therapy with methimazole. Patients were treated until they achieved euthyroidism and TRAb were measured at 6-month intervals throughout a follow up of 120 months. Our study demonstrated that at the onset of hyperthyroidism patients' age, sex, fT4 levels and goiter size had no prognostic value in predicting long-term prognosis (respectively p = 0.79; p = 0.98; p = 0.83; p = 0.89). On the contrary, at the time of diagnosis TRAb titer was a good predictor of the final outcome (p

Summary Background Little information is available concerning the possible antiproliferative effects of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) on the thyroid gland. We have hypothesized that the antiproliferative effects of statins observed in thyroid cell lines in vitro may have a clinical counterpart that could be detected by investigating the prevalence and size of thyroid nodules in patients on long-term treatment with statins. Methods We retrospectively evaluated 135 dyslipidaemic patients receiving statin therapy continuously for at least 5 years, and 137 controls. All the subjects were submitted to ultrasound investigation of the thyroid gland, to establish prevalence, number and volume of thyroid nodules. Results Subjects treated with statins showed markedly lower prevalence of thyroid nodules (36·3%vs. 67·9%, P

Background Papillary thyroid carcinoma (PTC) represents 70%–75% of well-differentiated thyroid cancers. Although most reports have shown that papillary thyroid microcarcinomas (PMC) follow an indolent course, a few series have demonstrated that a significant number of them are associated with extrathyroidal extension and nodal or distant metastases. Methods Four hundred eighty-four patients with papillary thyroid cancer (102, PMC; 382, PTC) were enrolled in this study. The median follow-up was 102 months. Results No difference between PTC and PMC patients was observed for age, gender, multifocality, extrathyroidal extension, and lymph nodes metastasis. The prevalence of nodal involvement developing during the follow-up period was significantly higher in PMC than PTC (58.8% vs. 38.5%, P = 0.002). An unfavorable clinical course occurred in 96 subjects (21.8%). Logistic analysis showed that the strongest association with the worst prognosis was found for age and TNM stage III (P

Background: Thyroid nodules are a common medical problem, but whether fine-needle aspiration cytology (FNAC) is mandated for smaller non-palpable nodules, is controversial. Aim: To evaluate whether ultrasonographic features of thyroid nodules are associated with histological malignancy, and to identify useful criteria for clinical decision-making. Design: Prospective observational study. Methods: From January 1991 to September 2004, 5198 patients were referred to our hospital for ultrasound evaluation of thyroid nodules. Overall, 7455 nodules (diameters from 6 to 100 mm) were examined; 2865 (38.4%) were

To test the prognostic significant of clinicopathologic factors in patients affected by well-differentiated thyroid carcinoma (WDTC).A retrospective review of patients treated for WDTC (thyroidectomy and a radioactive iodine (1131) thyroid ablation) at our Institute with a minimum of 10 years of follow-up was carried out. The unfavourable prognosis at the end of the follow-up was defined as persistence/recurrence of WDTC or death due to the cancer.234 patients (162 female, 72 male), mean age of 47.6 +/- 166 years, were included in this study (mean follow-up 158.4 +/- 34.8 months): 78 (33.4%) subjects had persistence/recurrence of neoplasia while 5 (2.1%) died for cancer. The multivariate regression showed that prognostic factors were old age, size of cancer, detectable thyroglonulin levels six months after metabolic ablation, and DeGroot staging system.Our mortality rate is lower (2.1%) than reported in literature (10%): this could be explained by the different pathological classification and treatment. The mortality rate appears higher in patients treated with emitiroidectomy and TSH suppressive therapy than in those with total thyroidectomy and I131 ablation. Even if we have chosen an "aggressive" therapy and our mortality rate is lower, one third of patients have persistence/recurrence of cancer: it seems that tumour recurrence rate better reflects clinical problems related to cancer.WDTC has with a good disease-specific survival but a significant recurrence rate. The most important predictors are the old age and the size of lesion. We suggest a radical surgery followed by radiometabolic ablation in all patients with WDTC.

Ectopic thyroid tissue with thyroid gland in its normal location is an extremely rare phenomenon. We present a case of a 38-year-old woman who was referred to our hospital with symptoms of hypothyroidism. Thyroid hormone measurement revealed clinical hypothyroidism with elevated anti-thyroid antibodies, neck ultrasonography showed a small tissue with the characteristic of Hashimoto thyroiditis, while the scintigraphy demonstrated only a lingual thyroid. Treatment consisted in L-thyroxina replacement to the euthyroid state. We reviewed the literature with respect to the embryological background and the clinical management of such cases.

Objective: To evaluate if a nodule with shape taller than wide (anteroposterior/transverse diameter ratio, A/T≥ 1) is a good predictor of malignancy independent of the size. Methods: We retrospectively examined the cytological and histological results of 7455 nodules (5198 patients) referred for ultrasound-guided-fine needle aspiration cytology (US-FNAC) in our hospital from January 1991 to September 2004. Results: A suitable FNAC was obtained from 6135 nodules (4495 patients); 34.6% were less than 1 cm in diameter (small nodules, SN). A diagnosis of carcinoma was histologically confirmed in 284/349 suspicious lesions after FNAC. The size of carcinoma nodules was not significantly associated with the occurrence of extracapsular growth (large nodules (LN): 10.5%, SN: 4.9%, NS) and lymph node metastasis (LN: 23.6%, SN: 25.0%, NS). Malignant lesions showed microcalcifications more frequently than benign nodules (72.2 vs 28.7%; P < 0.001; (odds ratio, OR(confidence intervals, CI) = 9.9(7.2–13.4)). Similarly, A/T≥ 1 (76 vs 40%; P < 0.001; OR(CI) = 8.6(5.5–13.1)), blurred margins (52.8 vs 18.8%; P < 0.001; OR(CI) = 7.7(5.6–10.2)), solid hypo-echoic appearance (80.6 vs 52.4%; P < 0.001; OR(CI) = 3.2(2.2–4.3)) and intranodular vascular pattern (type 2) (61.6 vs 49.7%; P < 0.001; OR(CI) = 1.7(1.3–2.3)) were significantly more frequent in malignant than in benign nodules. Conclusions: Our data show that no single parameter, including nodule size, satisfactorily identifies a subset of patients to be electively investigated by FNAC. We concluded that A/T≥ 1 with at least two of US features (microcalcification, blurred margins, hypo-echoic pattern) is today the best compromise between missing cancers and cost–benefit.

Background As a consequence of the increasing application of ultrasound (US) technology, the detection of asymptomatic nonpalpable thyroid nodules has generally increased. The aim of our study was to assess if the anteroposterior and transverse diameter ratio of nonpalpable thyroid nodules (A/T) > or = 1 could be a sonographic criterion for recommending fine-needle aspiration cytology (FNAC). Methods From January 2002 to January 2004, 828 consecutive solid nonpalpable thyroid nodules were evaluated by ultrasonography, colour-Doppler and FNAC in our department. Cases were selected from 2217 patients, referred to our thyroid unit for US-guided FNAC from the greater Brescia area, an endemic zone for goitre. Entry criteria included the presence at US of a solid thyroid nodule that was nonpalpable at physical examination, euthyroid condition and no previous diagnosis of thyroid malignancy. All patients with suspicious or malignant cytology underwent surgery. Results One hundred and twenty-seven nodules with inadequate cytology were excluded from the study. Thyroid malignancy was observed in 67 (9.6%) nodules. At US, cancers presented a solid hypoechoic appearance in 79.1% of cases, blurred margins in 47.8%, microcalcification in 73.1%, intranodular vascular pattern in 56.7% and A/T > or = 1 in 83.6%. A hypoechoic appearance (OR 4.3), blurred margins (OR 2.6), microcalcification (OR 6.1), intranodular vascular pattern (OR 10.2) and A/T > or = 1 (OR 22.4) were independent risk factors of malignancy. Conclusions A/T > or = 1 in conjunction with at least one other sonographic risk factor is able to detect the majority of carcinoma and, moreover, it limits the FNAC procedures to only 15.9% of all the nodules.