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Objective: Thyroid nodule (TN) is usually managed according to Thyroid Imaging And Reporting Data Systems (TIRADS) with the major aim to reduce as much as possible unnecessary fine-needle aspiration cytologies (UN-FNACs). Since the assessment of autonomously functioning thyroid nodule (AFTN) according to TIRADS is heterogeneous, that virtually benign entity may increase the rate of UN-FNAC. This study retrospectively analyzed the appropriateness of TIRADS-based FNAC indication in AFTNs, also looking at the impact of TSH and nodule size. Methods: Cases diagnosed with AFTN on scintigraphy were searched. Patients who had undergone AFTN treatment, were on medications or supplementation that could affect thyroid function, or had multiple AFTNs were excluded. The AFTNs were assessed according to ACR-TIRADS. Results: Forty-eight AFTNs were included of which 37.5% had FNAC indication according to TIRADS. The FNAC indication rate in the case of TSH lower than 0.4 mIU/L was significantly higher than in other cases (P = 0.0078). The most accurate TSH cut-off and AFTN size associated with UN-FNAC were ≤ 0.41 mIU/L and > 22 mm, respectively. The multivariate analysis showed that both TSH and nodule size were independent predictors of UN-FNAC with OR of 6.65 and 6.46, respectively. According to these data, the rate of FNAC indication dropped to 4.16%. Conclusion: Inappropriate FNACs in AFTNs are primarily observed in patients with low TSH and large AFTN. Since these cases typically undergo scintigraphy, the risk of TIRADS-based UN-FNAC is clinically negligible. There is no need for integrating other imaging procedures into the TIRADS model.

Context: Ultrasound-based risk stratification systems (Thyroid Imaging Reporting and Data Systems (TIRADSs)) of thyroid nodules (TNs) have been implemented in clinical practice worldwide based on their high performance. However, it remains unexplored whether different TIRADSs perform uniformly across a range of TNs in routine practice. This issue is highly relevant today, given the ongoing international effort to establish a unified TIRADS (i.e. I-TIRADS), supported by the leading societies specializing in TNs. The study aimed to conduct a direct comparison among ACR-, EU-, and K-TIRADS in the distribution of TNs: (1) across the TIRADS categories, and (2) based on their estimated cancer risk. Methods: A search was conducted on PubMed and Embase until June 2023. Original studies that sequentially assessed TNs using TIRADSs, regardless of FNAC indication, were selected. General study characteristics and data on the distribution of TNs across TIRADSs were extracted. Results: Seven studies, reporting a total of 41,332 TNs, were included in the analysis. The prevalence of ACR-TIRADS 1–2 was significantly higher than that of EU-TIRADS 2 and K-TIRADS 2, with no significant difference observed among intermediate- and high-risk categories of TIRADSs. According to malignancy risk estimation, K-TIRADS often classified TNs as having more severe risk, ACR-TIRADS as having moderate risk, and EU-TIRADS classified TNs as having lower risk. Conclusion: ACR-, EU-, and K-TIRADS assess TNs similarly across their categories, with slight differences in low-risk classifications. Despite this, focusing on cancer risk estimation, the three TIRADSs assess TNs differently. These findings should be considered as a prerequisite for developing the I-TIRADS.

Thyroid metastases from nonthyroidal malignancies (NTMs) represent a diagnostic challenge, often displaying heterogeneous clinical manifestations. These metastases are rare but significant, accounting for approximately 2% of thyroid malignancies. Distinguishing them from primary thyroid malignancies is challenging due to the lack of specific ultrasound features, and the ultrasound-based risk stratification systems offer limited utility in such cases. Fine needle aspiration cytology is crucial for definitive diagnosis, yet it may not always provide accurate results. In this case report, we describe a unique instance of thyroid metastases originating from renal cell carcinoma, emphasizing the complexities in diagnosis and the importance of considering oncological conditions when assessing thyroid masses. Awareness of thyroid metastasis from NTMs, particularly in cases of diffuse thyroid hypoechogenicity and hypothyroidism, is essential for clinicians in their diagnostic approach.

The diagnosis of medullary thyroid carcinoma (MTC) is challenging since the accuracy of ultrasound (US) and fine-needle aspiration cytology are suboptimal. As a result, MTC has a generally poor prognosis. The aim of this study was to analyze whether perioperative data can modify the risk of relapse in these patients. The institutional database of Turin Mauriziano Hospital was searched to extract records of MTCs diagnosed between 2000 and 2021. Kaplan-Meier curves and Cox and logistic regression analyses were performed, and the hazard ratio (HR) was calculated. Seventy-three MTC patients (median age 58 yr) were found. Disease-free survival was significantly different according to staging (HR: 9.12; p = 0.037), capsular status (HR: 5.49; p = 0.02), and neck US (HR: 9.19; p = 0.04). In the logistic regression analysis, CEA level (β: –0.01; p = 0.043), histological multifocality (OR: 7.4; p = 0.034), and metastatic lymph nodes at histology (β: –0.13; p = 0.006) were significantly associated with structural recurrence. Two logistic multivariate models best explained the variance in recurrence: 1) neck US presentation plus histological multifocality (AIC: 27; r2: 0.37; x2: 12.4; p = 0.002) and 2) number of neck metastases plus capsular invasion (AIC: 26; r2: 0.40; x2: 13.7; p = 0.001). Pathological data are associated with MTC prognosis. Preoperative neck US can significantly help to predict MTC outcome.

BackgroundHypothyroidism is treated with daily levothyroxine (LT4). In recent years, soft gel caps of LT4 (LT4-C) have been commercialized, and their performance has been optimized. Since guidelines recommend dose LT4 according to the tablet preparation efficacy, the present study was undertaken to obtain data about the daily requirement, normalized per body weight, of LT4-C.MethodsPatients undergoing LT4-C after total thyroidectomy and radioiodine treatment for differentiated thyroid carcinoma were selected. There was no specific indication of suppression of TSH (i.e.,

ObjectiveCalcitonin (Ctn) measurement is crucial for the early diagnosis of medullary thyroid carcinoma (MTC). However, Ctn levels can be skewed/elevated due to other reasons, and the Ctn upper reference value remains controversial. In this field, studies have heterogeneous settings, published data are controversial, and no evidence has been achieved. The study’s aim was to evaluate all previously investigated Ctn determinants in a population with histological exclusion of MTC.MethodsThe institutional records from 2010 to 2022 were reviewed to select patients with thyroid nodules who had undergone total thyroidectomy with histological exclusion of MTC and who had tested for Ctn just before surgery. Thyroid features, demographic and anthropometric data, comorbidities, medications, and lifestyle information were collected. Univariate and multivariate analyses were performed.ResultsA total of 127 cases were included. The median age for thyroidectomy was 51 years. Median Ctn was 1.04 pg/mL (interquartile range (IQR) 1.04–2.77), with two cases having values above 10 pg/mL. In univariate analysis, Ctn was correlated with gender (p < 0.001), body weight (p = 0.016), height (p = 0.031), body surface area (p = 0.016), thyroid size (p = 0.03), thyroglobulin (p < 0.001), and chronic kidney disease (p < 0.001). After multivariate analysis, the model with the highest accuracy included gender, chronic kidney disease, and thyroid-stimulating hormone (TSH) with an adjusted R-squared of 0.4.ConclusionsThis study demonstrates, in a population histologically proven as MTC-free, that the Ctn value is mainly influenced by gender, anthropometric/thyroid features, and chronic kidney disease, with the further impact of TSH.

AbstractBackground Parathyroid adenoma (PA) is the most common cause of primary hyperparathyroidism (PHPT). One infrequent scenario (0.7%–6%) is represented by intra-thyroid PA (I-PA), an ectopic variant of the parathyroid gland included in the thyroid parenchyma. Radiofrequency (RF) of I-PA seems to be an excellent alternative to hemithyroidectomy for these patients. The present study aimed to report three cases of PHPT and I-PA treated with RF at two institutions.Materials and methods These two institutions share guidelines for thyroid RF. At both institutions, cases with surgical indication and difficult PA localization are discussed during thyroid multidisciplinary meetings involving all disciplines involved in managing these cases. RF was performed using a Viva RF System generator (STARMED). Ultrasound contrast evaluation was performed using a SonoVue (Bracco). All patients were followed-up by an expert endocrinologist.Results Three cases had indications for treating I-PA. All patients were proposed to undergo RF rather than hemithyroidectomy, and accepted this option. RF of I-PA was performed with a power of 30–50 W and delivering a total between 0.02 and 0.69 Kcal. The active treatment lasted just more than 1 min. Post-treatment follow-up revealed PTH and calcium normalization.Conclusion This study showed highly encouraging results in favor of treating I-PA with RF.

BackgroundHashimoto’s thyroiditis (HT) is the most common autoimmune disease. HT may be associated with nonthyroidal autoimmune diseases, including celiac disease (CD) or other gluten-related conditions (GRC). In the last years, interest about gluten-free diet (GFD) has increased for its supposed extraintestinal anti-inflammatory effect; thus, many patients with HT initiate GFD on their own.ObjectivesThe aim of this meta-analysis is to examine all available data in literature about the effect of a GFD on TgAb, TPOAb, TSH, FT4, and FT3 levels in patients with HT and no symptoms or histology of CD.MethodsThe study was conducted according to MOOSE (Meta-analysis Of Observational Studies in Epidemiology). The search was performed on databases PubMed and Scopus. The last search was performed on 7 February 2023. Quality assessment was performed. Meta-analyses were performed using the random-effect model. Hedges’ g was used to measure the effect size (ES). Statistical analyses were performed using StataSE 17.ResultsThe online search retrieved 409 articles, and 4 studies with a total of 87 patients were finally included for quantitative analysis. The risk of bias was generally low. The mean period of GFD was almost 6 months. The meta-analyses showed reduction in antibody levels with ES: −0.39 for TgAb (95% CI: −0.81 to +0.02; p = 0.06; I² = 46.98%) and −0.40 for TPOAb (95% CI: −0.82 to +0.03; p = 0.07; I² = 47.58%). TSH showed a reduction with ES: −0.35 (95% CI: −0.64 to −0.05; p = 0.02; I² = 0%) and FT4 showed an increase with ES: +0.35% (95% CI: 0.06 to 0.64; p = 0.02; I² = 0%). FT3 did not display variations (ES: 0.05; 95% CI: −0.38 to +0.48; p = 0.82; I² = 51%). The heterogeneity of TgAb, TPOAb, and FT3 data was solved performing sub-analyses between patients with or without GRC (TgAb p = 0.02; TPOAb p = 0.02; FT3 p = 0.04) and only for FT3, performing a sub-analysis between patients taking and not taking LT4 (p = 0.03).ConclusionThis is the first meta-analysis investigating the effect of GFD on HT. Our results seem to indicate a positive effect of the gluten deprivation on thyroid function and its inflammation, particularly in patients with HT and GRC. However, current lines of evidence are not yet sufficient to recommend this dietary approach to all patients with a diagnosis of HT.

Background: Hypothyroidism (hT) presents heterogeneous symptoms and findings. Evidence on this topic comes mainly from heterogeneous populations in terms of disease duration, residual thyroid function, and comorbidities. Therefore, it would be useful to assess systemic inflammation in a homogeneous hT population. The aim of this study was to investigate inflammation in a population that underwent standardized controlled hT. Methods: We recruited thyroidectomized patients diagnosed with thyroid cancer who were otherwise fit and healthy, showing hypothyroidism before I131 treatment using a standard protocol of LT4 withdrawal. The blood inflammatory indexes (BIIXs) (i.e., NLR, PLR, MLR, SII, SIRI, and AISI) were calculated using the blood tests collected just before I131 administration. Patients were divided according to sex, BMI, and thyroglobulin. The relationships between the BIIXs, age, and thyroid hormones were also investigated. Results: We included 143 patients. The median age of the sample was 43 years. The BIIX median values showed significant differences based on sex, BMI, and thyroglobulin levels (p < 0.05). No significant correlations were found between the BIIXs and age, TSH, FT4, and FT3. Conclusions: This study shows the BIIX median values of a population which underwent standardized hT. It suggests a role for some BIIXs in the evaluation of hypothyroidism in obese people and as hypothetical prognostic markers for thyroid cancer.

Radiofrequency (RF) ablation represents an efficient strategy to reduce the volume of thyroid nodules. In this study, a finite element model was developed with the aim of optimizing RF parameters, e.g., input power and treatment duration, in order to achieve the target volume reduction rate (VRR) for a thyroid nodule. RF ablation is modelled as a coupled electro-thermal problem wherein the electric field is applied to induce tissue heating. The electric problem is solved with the Laplace equation, the temperature distribution is estimated with the Pennes bioheat equation, and the thermal damage is evaluated using the Arrhenius equation. The optimization model is applied to RF electrode with different active tip lengths in the interval from 5 mm to 40 mm at the 5 mm step. For each case, we also explored the influence of tumour blood perfusion rate on RF ablation outcomes. The model highlights that longer active tips are more efficient as they require lesser power and shorter treatment time to reach the target VRR. Moreover, this condition is characterized by a reduced transversal ablation zone. In addition, a higher blood perfusion increases the heat dispersion, requiring a different combination of RF power and time treatment to achieve the target VRR. The model may contribute to an improvement in patient-specific RF ablation treatment.

Our institution (University Hospital “L. Vanvitelli” - Naples, Italy) is a high-volume (HV) center in Naples metropolitan area and many patients are referred there to repeat thyroid fine-needle aspiration cytology (FNAC) after initial FNAC performed in low-volume institutions (LV). The aims of the study were to 1) examine the inter-observer agreement between HV and LV institutions according to the Italian thyroid cytology system, and 2) explore how the discordant FNAC reports were distributed in the European Thyroid Imaging and Reporting Data System (EU-TIRADS) categories. All consecutive cases of repeat FNAC performed at University Hospital “L. Vanvitelli” from January 2016 to December 2021 were retrospectively reviewed. Fleiss’ kappa (κ) was used to assess the inter-observer agreement, and categorical variables were compared by chi-square testing. P < 0.05 was considered statistically significant. A total of 124 nodules from 124 adults (mean age 49 years; mean maximum diameter 19 mm) were evaluated. Initial FNAC reports at LV were: 4 (3.2%) TIR1c, 64 (51.6%) TIR2, 48 (38.7%) TIR3A, 8 (6.5%) TIR3B, 0 TIR4, 0 TIR5. The overall FNAC reports were significantly different between the LV and HV institutions. At repeated FNAC, cytological diagnosis was unchanged in 64 (51.6%) cases including TIR2 and TIR3A results. A downgraded FNAC diagnosis (i.e., TIR2 vs TIR3A, TIR2 vs TIR3B) was observed in 36 (29%) nodules. An upgraded FNAC diagnosis (i.e., TIR3B vs TIR2, TIR3B vs TIR3A, TIR4 vs TIR3A, TIR5 vs TIR2, TIR5 vs TIR3B) was recorded in 24 (19.4%) nodules. The weighted inter-observer agreement between LV and HV institutions was poor (κ=0.133). Changed FNAC results were significantly (p=0.0023) more frequent in nodules at intermediate/high-risk (i.e., EU-TIRADS 4/5) than in those at no/low risk (EU-TIRADS 2/3) [i.e., 32/48 (66.7%) and 28/76 (36.8%), respectively]. Downgraded FNAC results were significantly more frequent in EU-TIRADS 2/3 (p=0.001) while upgraded FNAC were present only in EU-TIRADS 4/5 (24/24, 100.0%). The inter-observer agreement among LV and HV thyroid services was poor. The EU-TIRADS 4 and 5 categories included all the malignant nodules with FNAC results reclassified as higher risk (i.e., TIR3B-TIR4-TIR5) by the high-volume cytology service.

After the beginning of COVID-19 vaccination campaigns, several reports of thyroid disease possibly related to the COVID-19 vaccination progressively appeared in the literature, raising the question of whether the thyroid disorder might be a SARS-CoV-2 vaccine complication. The aim of this study was to analyze the data about COVID-19 vaccination and thyroid disease, evaluate the size and quality of related literature, assess the type of these events, and investigate their timing of onset with respect the vaccination. Pubmed/MEDLINE and Cochrane were systematically reviewed until February 2022 to retrieve the largest number of original papers, case reports, and case series articles reporting thyroid disease after SARS-CoV-2 vaccination. Forty-six articles were included with a total of 99 patients aged from 26 to 73 years were described, of whom 74.75% female. Regarding the vaccination received, 49.49% of patients received Comirnaty (Pfizer/BioNTech), 14.14% CoronaVac (Sinovac), 12.12% Vaxzevria (Oxford/Astrazeneca), 11.11% Spikevax (Moderna), 3.03% Ad26.COV2.S (Janssen, Johnson & Johnson), one patient Covaxin (Bharat Biotech) and one patient Convidecia (Cansino). In 7 cases the thyroid disorder developed after the third dose with a combination of different vaccines. Regarding the type of thyroid disorder, 59 were subacute thyroiditis (SAT), 29 Graves’ disease (GD), 2 co-occurrence of SAT and GD, 6 painless thyroiditis (PT), and single cases of thyroid eye disease and hypothyroidism associated with mixedema. The timeline between vaccination and thyroid disorder ranged between 0.5 to 60 days, with an average of 10.96 days. Considering the limited follow-up time, a complete remission was reported in most of SAT and PT cases while a persistence was observed in GD. In conclusion, both size and quality of published data about thyroid inconveniences after COVID-19 vaccination are limited; thyroid disorders may occur within 2 months after COVID-19 vaccination; among all thyroid diseases after COVID-19 vaccination, GD and SAT seem to be more frequent.

Abstract Background Data on SARS-CoV-2 load in lower respiratory tract (LRT) are scarce. Our objectives were to describe the viral shedding and the viral load in LRT and to determine their association with mortality in critically ill COVID-19 patients. Methods We conducted a binational study merging prospectively collected data from two COVID-19 reference centers in France and Switzerland. First, we described the viral shedding duration (i.e., time to negativity) in LRT samples. Second, we analyzed viral load in LRT samples. Third, we assessed the association between viral presence in LRT and mortality using mixed-effect logistic models for clustered data adjusting for the time between symptoms’ onset and date of sampling. Results From March to May 2020, 267 LRT samples were performed in 90 patients from both centers. The median time to negativity was 29 (IQR 23; 34) days. Prolonged viral shedding was not associated with age, gender, cardiac comorbidities, diabetes, immunosuppression, corticosteroids use, or antiviral therapy. The LRT viral load tended to be higher in non-survivors. This difference was statistically significant after adjusting for the time interval between onset of symptoms and date of sampling (OR 3.78, 95% CI 1.13–12.64, p = 0.03). Conclusions The viral shedding in LRT lasted almost 30 days in median in critically ill patients, and the viral load in the LRT was associated with the 6-week mortality.

Abstract Background Cardiovascular outcome trials of sodium-glucose co-transporter-2 inhibitors (SGLT2i CVOTs) found the agents to be associated with clinical benefits in terms of cardiovascular and renal outcomes. We performed a meta-analysis to assess and compare the overall prevalence of eligibility for the enrollment criteria of CANVAS, DECLARE-TIMI 58, EMPA-REG OUTCOME, and VERTIS-CV among unselected patients with type 2 diabetes. Methods This meta-analysis was registered in PROSPERO (CRD42020172032). PubMed, CENTRAL, Scopus and Web of Science were researched in March 2020. Studies evaluating the prevalence of eligibility for each SGLT2i CVOT were selected. Endpoints were estimated using a random-effects model. Results Five studies, evaluating 1,703,519 patients with type 2 diabetes, were included. Overall, the prevalence of eligible patients according to the enrollment criteria of CANVAS, DECLARE-TIMI 58, EMPA-REG OUTCOME, and VERTIS-CV was 36.4%, 49.5%, 17.0% and 19.0%, respectively. In head-to-head comparisons, DECLARE-TIMI 58 was associated with the highest odds of eligibility (1.74 versus CANVAS, 5.15 versus EMPA-REG OUTCOME and 4.81 versus VERTIS-CV), followed by CANVAS and EMPA-REG OUTCOME/VERTIS-CV. A high heterogeneity was found for all the outcomes. Conclusions The present review showed that a considerable number of patients counseled in clinical practice could have been eligible for SGLT2i CVOTs. Particularly, dapagliflozin was shown to be the SGLT2i with the largest generalizability of findings from its CVOT according to the odds ratio of eligibility for the enrollment criteria among unselected patients with type 2 diabetes. Further country- or region-specific studies are needed to confirm the applicability of our results.

BackgroundThyroid nodules are frequent in adult population and thyroid cancer incidence has increased dramatically over the past three decades. The aim of this systematic review and meta-analysis was to evaluate the US-Elastosonography (USE) diagnostic performance in assessing the thyroid nodules malignancy risk.MethodsPubMed and Embase databases were searched from January 2011 to July 2021. We extracted data from selected studies and calculated the overall diagnostic accuracy of qualitative USE, semi-quantitative USE and quantitative USE. Summary receiver operating characteristic (ROC) curve was elaborated to show the results. All statistical tests were performed using Metadisc and Medcal software package.ResultsFinally 72 studies with 13,505 patients and 14,015 thyroid nodules (33% malignant) undergoing elastography were included. The pooled sensitivity, specificity and AUC were 84%, 81%, and 0.89 respectively for qualitative USE; 83%, 80%, and 0.93 for semi-quantitative USE and 78%, 81% and 0.87, for quantitative USE. The qualitative and semiquantitative USE present very similar diagnostic accuracy values and both better than the quantitative USE.ConclusionsUSE is a useful imaging tool for thyroid nodule characterization. In accordance with recent guidelines and meta-analyses, the USE could be used daily in thyroid nodule malignancy risk stratification.Systematic Review RegistrationPROSPERO: CRD42021279257.

Subacute thyroiditis (SAT) is a thyroid disease of viral or post-viral origin. Whether SAT represents a complication of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still unclear. Our aim was to systematically review the literature to 1) explore the size of the literature about SAT in COVID-19 and 2) evaluate the clinical characteristics of SAT. PubMed/MEDLINE, Embase, and Scopus were searched until April 20, 2021. Original papers, case reports, and case series reporting SAT in COVID-19 patients were included. Authors and their country, journal, year of publication, COVID-19 and SAT clinical presentation, thyroid function, therapy, and follow-up data were extracted. Nineteen papers (17 case reports and 2 case series) were included, describing 27 patients, 74.1% females, aged 18 to 69 years. COVID-19 was diagnosed by nasopharyngeal swab in 66.7% cases and required hospitalization in 11.1%. In 83.3% cases, SAT occurred after COVID-19. Neck pain was present in 92.6% cases and fever in 74.1%. Median TSH, fT3, and fT4 were 0.01 mU/l, 10.79 pmol/l, and 27.2 pmol/l, respectively. C-reactive-protein and erythrocyte sedimentation rate were elevated in 96% of cases. Typical ultrasonographic characteristics of SAT were observed in 83.3% of cases. Steroids were the most frequent SAT therapy. Complete remission of SAT was recorded in most cases. In conclusion, the size and quality of published data of SAT in COVID-19 patients are poor, with only case reports and case series being available. SAT clinical presentation in COVID-19 patients seems to be similar to what is generally expected.

BackgroundPostoperative routine radioiodine (RAI) treatment is currently debated for patients with low-risk differentiated thyroid carcinoma (DTC) patients. If performed, a low 131I activity (i.e., 1 to 2 GBq) is recommended with the aim to ablate thyroid remnant and facilitate subsequent follow-up by thyroglobulin measurement. The purpose of this study was to evaluate the relationship between postsurgical technetium-99m (99mTc)-pertechnetate scintigraphy and the rate of successful remnant ablation after low activity radioiodine ablation in patients with DTC.MethodsEnrolled were 193 patients with low risk DTC who underwent total thyroidectomy and RAI ablation with a fixed 1.1 GBq activity of 131I. 99mTc-pertechnetate scans were done and thyrotropin stimulated thyroglobulin (sTg) levels measured just before ablation. Ablation effectiveness was assessed 6 to 12 months later by sTg measurement, neck ultrasound and diagnostic whole body scan.ResultsA negative 99mTc-perthecnetate scans was the best predictor of successful ablation (P

Purpose. To search for a clinical potential link between subacute thyroiditis (SAT) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a series of patients diagnosed with SAT during the COVID-19 pandemic, by retrospective evaluation of (1) clinical symptoms and (2) contact tracing. Methods. SAT patients diagnosed from March to December 2020 were enrolled. The presence of typical clinical presentation of SARS-CoV-2, diagnostic tests for SARS-CoV-2, and contact with other individuals proven to be positive for SARS-CoV-2 were searched. Results. Ten SAT cases were included. Fever was recorded in four patients. Cough, dyspnea, and headache were rarely reported. No patient had diagnosis of pneumonia. Two patients had moderate to severe fatigue after SAT. One patient experienced loss of smell and taste and had persistent fatigue over the following five months. No patient had positive SARS-CoV-2 diagnostic tests. At contact-tracing evaluation, only one patient had a contact with people who were diagnosed with SARS-CoV-2. Conclusions. Patients diagnosed with SAT during COVID-19 pandemic rarely experienced SARS-CoV-2-related symptomatology. The contact tracing did not show close contact with SARS-CoV-2 individuals in 9/10 cases.

Despite the large number of patients worldwide being on proton pump inhibitors (PPIs) for acid-related gastrointestinal disorders, uncertainty remains over their long-term safety. Particularly, the potential side effects of these drugs on bone health have been evaluated in the last years. The purpose of our narrative review is to gather and discuss results of clinical studies focusing on the interactions between PPIs and fracture risk. Data generated mainly from nested case-control studies and meta-analysis suggest that long-term/high-dose PPIs users are characterized by an increased risk of fragility fractures, mainly hip fractures. However, in these studies, the PPIs-induced bone impairment is often not adjusted for different confounding variables that could potentially affect bone health, and exposure to PPIs was reported using medical prescriptions without adherence evaluation. The mechanisms of the PPI-related bone damage are still unclear, but impaired micronutrients absorption, hypergastrinemia, and increased secretion of histamine may play a role. Clinicians should pay attention when prescribing PPIs to subjects with a preexistent high risk of fractures and consider antiosteoporotic drugs to manage this additive effect on the bone. However, further studies are needed to clarify PPIs action on the bone.

Background: Thyroid nodules are an extremely common occurrence, as their prevalence in the general population is estimated to range between 50 and 70%. Some of these nodules are autonomously functioning such that they can cause hyperthyroidism over time. In this case, surgery and radioiodine represent the standard of care. Nevertheless, patients might have contraindications or be unwilling to undergo these treatments. Minimally-invasive ultrasound-guided techniques, such as laser and radiofrequency ablation (RFA), have been recently introduced into clinical practice as an alternative treatment for symptomatic benign thyroid nodules. Due to their efficacy and tolerability, these techniques have become increasingly available and their usage has been extended also to autonomously functioning thyroid nodules (AFTN).Methods: In this narrative review, we will describe the studies reporting the therapeutic effects of RFA on AFTN, the studies reporting how RFA compares to the other treatment modalities, as well as the current indications for the use of RFA in patients with AFTN. For this purpose, a comprehensive literature search was independently conducted by three investigators on PubMed, EMBASE, and the Cochrane Library from inception up to February 2020 to identify published articles concerning the effects of RFA on AFTN.Results and Conclusions: Current consensus statements and guidelines support the notion that RFA should be regarded as a first-line therapy for non-functioning benign thyroid nodules, while it remains a valid second-line option for AFTN treatment in case of contraindications or patient unwillingness to undergo surgery or radioiodine.

Background and Objectives: The aim of the study was to evaluate the predictive value of the ultrasound criterion “non-marked hypoechogenicity” for malignancy and to determine whether classification of these nodules as TIRADS 3 could improve the overall accuracy of consequently adjusted M-TIRADS score. Materials and Methods: A total of 767 patients with 795 thyroid nodules were subject to ultrasonography examination and ultrasound-guided fine needle aspiration biopsy. Nodules were classified by Kwak TIRADS and modified (M-TIRADS) categories 4A, 4B, and 5 according to number of suspicious US features (marked hypoechogenicity, microlobulated or irregular margins, microcalcifications, taller-than-wide shape, metastatic lymph nodes). Non-marked hypoechoic nodules were classified as TIRADS 3. Results: Thyroid nodules were classified as TIRADS 2, 3, 4A, 4B, and 5 in 14.5, 57.5, 14.2, 8.1, and 5.7%, respectively. Only histopathologic results (125 nodules underwent surgery) and highly specific cytology results (Bethesda II, VI) were accepted as a standard of reference, forming a sub-cohort of 562/795 nodules (70.7%). Malignancy was found in 7.7%. Overall, M-TIRADS showed sensitivity/specificity of 93.02/81.31%, and for PPV/NPV, these were 29.2/99.29%, respectively (OR—18.62). Irregular margins showed the highest sensitivity and specificity (75.68/93.74%, respectively). In TIRADS 3 category, 37.2% nodules were isoechoic, 6.6% hyperechoic, and 52.2% hypoechoic (there was no difference of malignancy risk in hypoechoic nodules between M-TIRADS and Kwak systems—0.9 vs. 0.8, respectively). Accuracy of M-TIRADS classification in this cohort was 78.26% vs. 48.11% for Kwak. Conclusions: The non-marked hypoechoic nodule pattern correlated with low risk of malignancy; classification of these nodules as TIRADS 3 significantly improved the predictive value and overall accuracy of the proposed M-TIRADS scoring with malignancy risk increase in TIRADS 4 categories by 20%; and no significant alteration of malignancy risk in TIRADS 3 could contribute to reducing overdiagnosis, obviating the need for FNA.

BackgroundCalcitonin measurement is pivotal in the management of medullary thyroid carcinoma (MTC), but several pitfalls can affect its reliability. Other potential markers have been proposed, and procalcitonin (ProCT) has been reported as promising. The present study was undertaken to summarize the published data and provide more robust estimates on the reliability of ProCT as marker in the management of patients with MTC.MethodsThe systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The sources comprised studies published through May 2018. Original articles that reported series of MTC patients undergone ProCT during postoperative follow-up were searched. A random-effects model was used for statistical pooling of the data. The I2 index was used to quantify the consistency among the studies. The Egger test evaluated the possible presence of significant publication bias. Quality assessment of the studies was performed according to Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2).ResultsAccording to inclusion and exclusion criteria five papers, reporting 296 MTC patients undergone ProCT evaluation, were finally selected. The number of MTC with recurrence was 140. The pooled sensitivity of ProCT in detecting recurrence was 96% (95% confidence interval [CI], 92% to 99%), with neither heterogeneity (I2=0%) nor publication bias (Egger test, 3.16; P=0.99). The pooled specificity was 96% (95% CI, 87% to 100%) with mild heterogeneity (I2=66.6%), while Egger test was not calculable.ConclusionThe present meta-analysis provides evidence that ProCT is reliable to manage MTC patients during their postoperative follow-up.

Purpose This study was undertaken to summarize the published data and to provide more robust estimates regarding the issue of core needle biopsy (CNB) for discriminating thyroid nodules with indeterminate fine-needle aspiration (FNA) results. Methods The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The sources comprised studies published through November 2017. Original articles that investigated CNB in indeterminate thyroid lesions were searched. A random-effects model was used for statistical pooling of the data. The I2 index was used to quantify the heterogeneity among the studies. The Egger test was carried out to evaluate the possible presence of significant publication bias. Quality assessment of the studies was performed according to QUADAS-2. Results A total of 205 articles were retrieved, seven were initially selected, and the data of five papers were ultimately pooled in a meta-analysis. The overall cancer rate was 34%. The rate of cancers correctly diagnosed by CNB was 83% (95% confidence interval [CI], 76 to 89), with neither heterogeneity (I2=25%) nor publication bias (Egger test, P=0.918). The rate of benign nodules correctly assessed by CNB was 84% (95% CI, 65 to 97), with significant heterogeneity (I2=93.4%) and publication bias (Egger test, P=0.016). Conclusion Evidence was found that CNB can correctly diagnose the majority of nodules previously read as indeterminate on FNA.

Objective. Hypothyroid patients are treated by sodium levothyroxine (LT4). Tablet is the mostly used LT4 formulation, and the fasting regimen is required for the absorption of active principle. Also, gastrointestinal diseases and drugs may impair the LT4 bioavailability when tablet is used. Nonsolid LT4 formulations (i.e., liquid solution (LS) and soft gel (SG) capsule) were manufactured to overcome the limitations of LT4 tablet. This study was conceived to evaluate the performance of nonsolid LT4 formulations in a real-life scenario. Methods. Two institutions participated in the study that was conducted in two phases (i.e., enrollment and re-evaluation). Adults with autoimmune or postsurgical hypothyroidism and on LT4 from a few months were selected. A nonparametric statistical analysis for paired or unpaired data was performed. Results. 121 consecutive cases were included. At the enrollment phase, a 52% of patients took the therapy at least 30 min before breakfast with no difference between tablet and SG/LS users. TSH was 1.65 mIU/L (0.86–2.70) in patients on LT4 tablet and 1.70 mIU/L (1.10–2.17) in those on SG/LS (p=0.66). At the re-evaluation phase, among the patients using correct LT4 assumption, the TSH value was stable in the tablet group (p=0.22) and significantly reduced in SG/LS group (p=0.004); among the patients using incorrect LT4 assumption, TSH was significantly increased in those on tablet (p=0.0029) and stable in those on SG/LS (p=0.36). Conclusion. The performance of nonsolid LT4 formulations is not influenced by correct or incorrect use of therapy. On the contrary, LT4 tablet does not guarantee euthyroidism when it is ingested without waiting for at least 30 minutes before breakfast. These new data, obtained in a real-life scenario, suggest that LT4 SG/LS should be regarded as first-line therapy for treating adults with newly diagnosed hypothyroidism.

Background: Italian consensus for the classification and reporting of thyroid cytology (ICCRTC) has been used in almost all Italian institutions since 2014. High reliability of ICCRTC in classifying low and high risk indeterminate nodules (Tir 3A and Tir 3B, respectively) was demonstrated. Here we reviewed our casuistry of thyroid indeterminate lesions to analyze the histologic outcome.Methods: All lesions undergone FNA and final histology at S. Andrea Hospital of Rome after a cytologic assessment of Tir 3A and Tir 3B, according to ICCRTC, were included in the study.Results: A number of 157 indeterminate FNA was found after the introduction of ICCRTC. Of these, 75 undergone surgery and were finally included for the study. At histology we found a 33.3% of cancers and a 67.7% of benign lesions. Out of the overall series, 25 were classified as Tir 3A and 50 as Tir 3B. Cancer rate observed in Tir 3A (1/25, 4%) was significantly (p = 0.0002) lower than that of Tir 3B (24/50, 48%). No significant difference was found in age and size between the two subcategories.Conclusions: We confirm in our series that Italian consensus for the classification and reporting of thyroid cytology allows to discriminate indeterminate lesions at low and high risk of malignancy.

BackgroundVandetanib is the most largely used tyrosine kinase inhibitor (TKI) in patients with locally advanced and/or metastatic medullary thyroid cancer (MTC). Here, we conducted a systematic review on its efficacy and attempted to perform a meta-analysis adopting standardized RECIST criteria as end-points.MethodsThe terms “medullary thyroid” and “protein kinase inhibitor” (then including all TKIs) were searched in PubMed, ClinicalTrials.gov, and CENTRAL. Only original studies reporting the use of Vandetanib as single agent in MTC were included. The last search was performed on October 31, 2017 and registered in PROSPERO on December 12, 2017 (n = CRD42017081537).ResultsThe search revealed 487 articles, and, after removing duplicates, reading title and abstract, and screening the eligible papers, 10 studied were finally included. Two papers were randomized controlled trials and eight were observational longitudinal studies. No data were available for overall survival. No heterogeneity nor publication bias were recorded in the pooled rate of complete response (0.7%) and stable disease (47%). Mild to moderate heterogeneity were recorded in the pooled rate of other endpoints. Data of the studies did not allow to perform a meta-analysis of time-to-event outcomes.ConclusionVandetanib should be considered as a promising treatment in advanced MTC. However, data based on RECIST endpoints do not currently provide high-level evidence on its efficacy.

BackgroundLevothyroxine sodium (LT4) is the therapy of choice for hypothyroidism. In the last decade, new LT4 formulations, such as liquid and softgel capsules, became available. Even if some evidence has been reached in the efficacy of liquid LT4 in patients with suboptimal TSH on tablet LT4, the usefulness of softgel LT4 has been rarely studied. This study aimed at evaluating the effect of switching from tablet to softgel LT4 patients without increased need for LT4. TSH was used as proxy of LT4 bioavailability and effectiveness.MethodsDuring the period from April to August 2017, 19 patients on tablet LT4 treatment for hypothyroidism, mostly due to autoimmune thyroiditis, were enrolled. Subjects with causes of malabsorption or increased requirement of LT4 were previously excluded. Patients finally included were asked to switch from tablet to softgel LT4 formulation at unchanged dose and ingestion fashion (30 min before breakfast). TSH was measured with chemiluminescence immunoassays.ResultsAccording to exclusion and inclusion criteria, 19 patients were finally selected. One of these had headache 4 days later and come back to tablet LT4, and 18 of them (16W/2M; mean age = 55 years; BMI 22.7 kg/m2) completed the study. They were treated with a median LT4 dose of 88 μg/day and showed a median TSH value of 3.33 mIU/L. The rate of cases with TSH ≤ 4.0 mIU/L was 61.1% (11/18 cases). When patients were re-evaluated after 3 months of softgel LT4, we observed that TSH reached levels under 4.0 mIU/L in 16/18 (88.9%) patients, TSH was lower in 11 cases, and in 6 out of 7 patients with pre-switch TSH values over the normal range. Overall, TSH values on softgel LT4 (median 1.90 mIU/L) was significantly lower from that observed during tablet LT4 (p = 0.0039).ConclusionThese data show that hypothyroid patients with no proven malabsorption may have an improved TSH following 3 months from the switch from tablet to softgel LT4 preparation at unchanged dose.

BackgroundIn the last years, levothyroxine (LT4) has been commercialized also in liquid formulation, which is less sensitive to the factors known to reduce the absorption of tablet LT4. To date, there is no robust information that liquid LT4 can improve pharmacologic thyroid homeostasis of patients with reduced efficacy of tablet LT4. This analysis aimed at achieving solid evidence that switching thyroxine treatment from tablet to liquid preparation improves patients’ TSH levels.MethodsThe search was performed in PubMed/MEDLINE and Scopus database based on the terms “thyroid,” “levothyroxine,” and “liquid,” and updated until September 25, 2017. Studies were included only if they described patients with suboptimal TSH on tablet LT4, subsequently switched to liquid LT4.ResultsThe literature search retrieved 462 articles and six were finally included. The pooled mean difference of TSH value between tablet and liquid LT4 was 4.23 mIU/L (95% CI from 3.69 to 4.77). Mild heterogeneity was found (I2 60%). Overall mean difference of TSH was significant (p